[miR-185-5p alleviates the inflammatory response of acute gouty arthritis by inhibiting of IL-1ß].

Objective To investigate the relationship between interleukin-1ß (IL-1ß) and miR-185-5p in the process of joint injury in acute gouty arthritis (AGA). Methods The serum miR-185-5p levels of 89 AGA patients and 91 healthy volunteers were detected by real-time quantitative PCR. The correlation between miR-185-5p expression level and VAS score or IL-1ß expression level was evaluated by Pearson correlation coefficient method. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of miR-185-5p in AGA. THP-1 cells were induced by sodium urate (MSU) to construct an in vitro acute gouty inflammatory cell model. After the expression level of miR-185-5p in THP-1 cells was upregulated or downregulated by transfection of miR-185-5p mimics or inhibitors in vitro, inflammatory cytokines of THP-1 cells, such as IL-1ß, IL-8 and tumor necrosis factor α (TNF-α), were detected by ELISA. The luciferase reporter gene assay was used to determine the interaction between miR-185-5p and the 3'-UTR of IL-1ß. Results Compared with the healthy control group, the expression level of serum miR-185-5p in AGA patients was significantly reduced. The level of serum miR-185-5p was negatively correlated with VAS score and IL-1ß expression level. The area under the curve (AUC) was 0.905, the sensitivity was 80.17% and the specificity was 83.52%. Down-regulation of miR-185-5p significantly promoted the expression of IL-1ß, IL-8 and tumor necrosis factor (TNF-α), while overexpression of miR-185-5p showed the opposite results. Luciferase reporter gene assay showed that IL-1ß was the target gene of miR-185-5p, and miR-185-5p negatively regulated the expression of IL-1ß. Conclusion miR-185-5p alleviates the inflammatory response in AGA by inhibiting IL-1ß.

Tuning the number of redox groups in the cathode toward high rate and long lifespan zinc-ion batteries.

We synthesized a small molecule, DBPTO, and used it as a cathode material in aqueous zinc-ion batteries. DBPTO presented a high reversible capacity of 382 mA h g-1 at 0.05 A g-1 and a long lifespan of over 60 000 cycles. In the same π-conjugated skeleton, DBPTO (containing four CO and two CN groups) shows a narrower energy gap than TAPQ (containing CO and four CN groups), which leads to the superior rate and cycling performance of DBPTO. The mechanism of charge storage of DBPTO also revealed that H+ and Zn2+ coordinated with the CO and CN sites by ex situ structural characterization and DFT calculations. Our results provide new insights into the design of organic cathodes with a high rate capability and long lifespan. Further efforts will focus on a deeper understanding of the charge storage mechanism.

Association between immunoglobulin G N-glycosylation and lupus nephritis in female patients with systemic lupus erythematosus: a case-control study.

Background: Lupus nephritis (LN) is a crucial complication of systemic lupus erythematosus (SLE) and has important clinical implications in guiding treatment. N-glycosylation of immunoglobulin G (IgG) plays a key role in the development of SLE by affecting the balance of anti-inflammatory and proinflammatory responses. This study aimed to evaluate the performance of IgG N-glycosylation for diagnosing LN in a sample of female SLE patients. Methods: This case-control study recruited 188 women with SLE, including 94 patients with LN and 94 age-matched patients without LN. The profiles of plasma IgG N-glycans were detected by hydrophilic interaction chromatography with ultra-performance liquid chromatography (HILIC-UPLC). A multivariate logistic regression model was used to explore the associations between IgG N-glycans and LN. A diagnostic model was developed using the significant glycans as well as demographic factors. The performance of IgG N-glycans in the diagnosis of LN was evaluated by receiver operating characteristic (ROC) curve analysis, and the area under the curve (AUC) and its 95% confidence interval (CI) were calculated. Results: There were significant differences in 9 initial glycans (GP2, GP4, GP6, GP8, GP10, GP14, GP16, GP18 and GP23) between women with SLE with and without LN (P < 0.05). The levels of sialylated, galactosylated and fucosylated glycans were significantly lower in the LN patients than in the control group, while bisected N-acetylglucosamine (GlcNAc) glycans were increased in LN patients (P < 0.05). GP8, GP10, GP18, and anemia were included in our diagnostic model, which performed well in differentiating female SLE patients with LN from those without LN (AUC = 0.792, 95% CI: 0.727 to 0.858). Conclusion: Our findings indicate that decreased sialylation, galactosylation, and core fucosylation and increased bisecting GlcNAc might play a role in the development of LN by upregulating the proinflammatory response of IgG. IgG N-glycans can serve as potential biomarkers to differentiate individuals with LN among SLE patients.

Toward Energy-Efficient Routing of Multiple AGVs with Multi-Agent Reinforcement Learning.

This paper presents a multi-agent reinforcement learning (MARL) algorithm to address the scheduling and routing problems of multiple automated guided vehicles (AGVs), with the goal of minimizing overall energy consumption. The proposed algorithm is developed based on the multi-agent deep deterministic policy gradient (MADDPG) algorithm, with modifications made to the action and state space to fit the setting of AGV activities. While previous studies overlooked the energy efficiency of AGVs, this paper develops a well-designed reward function that helps to optimize the overall energy consumption required to fulfill all tasks. Moreover, we incorporate the e-greedy exploration strategy into the proposed algorithm to balance exploration and exploitation during training, which helps it converge faster and achieve better performance. The proposed MARL algorithm is equipped with carefully selected parameters that aid in avoiding obstacles, speeding up path planning, and achieving minimal energy consumption. To demonstrate the effectiveness of the proposed algorithm, three types of numerical experiments including the ϵ-greedy MADDPG, MADDPG, and Q-Learning methods were conducted. The results show that the proposed algorithm can effectively solve the multi-AGV task assignment and path planning problems, and the energy consumption results show that the planned routes can effectively improve energy efficiency.

Inhibition of SK2 and ER stress ameliorated inflammation and apoptosis in liver ischemia-reperfusion injury.

Ischemia-reperfusion injury (IRI) remains a major cause of mortality and morbidity after liver surgery. Endoplasmic reticulum (ER) stress is a critical mechanism of inflammatory injury during hepatic IRI. In this study, we investigated the effect of sphingosine kinases 2 (SK2) on ER stress and hepatic IRI. We established hepatic IRI mice and hepatocellular hypoxia/reoxygenation in vitro model. We observed the SK2 and ER stress protein IRE1α expression. Then, we used an SK2 inhibitor and knocked down IRE1α/SK2, to observe the effect of SK2 during IRI. Our results showed that the expression of ER stress and SK2 was significantly elevated during hepatic IRI. Inhibition of SK2 ameliorated liver inflammation and reduced cell apoptosis in hepatic IRI mice. Consistently, we found that the inhibition of IRE1α also downregulated SK2 expression and reduced mitochondrial membrane permeability. Furthermore, the knockdown of SK2 could also reduce cell damage and reduce the expression of inflammatory factors but did not influence ER stress-related signaling pathway. Taken together, our results suggested that ER stress and SK2 played important and regulatory roles in hepatic IRI. Inhibition of ER stress and SK2 could significantly improve liver function after hepatic IRI.

Bending-Sensitive Optical Waveguide Sensor With Carbon-Fiber Layer for Monitoring Grip Strength.

With the gradual popularity of wearable devices, the demand for high-performance flexible wearable sensors is also increasing. Flexible sensors based on the optical principle have advantages e.g. anti-electromagnetic interference, antiperspirant, inherent electrical safety, and the potential for biocompatibility. In this study, an optical waveguide sensor integrating a carbon fiber layer, fully constraining stretching deformation, partly constraining pressing deformation, and allowing bending deformation, was proposed. The sensitivity of the proposed sensor is three times higher than that of the sensor without a carbon fiber layer, and good repeatability is maintained. We also attached the proposed sensor to the upper limb to monitor grip force, and the sensor signal showed a good correlation with grip force (the R-squared of the quadratic polynomial fitting was 0.9827) and showed a linear relationship when the grip force was greater than 10N (the R-squared of the linear fitting was 0.9523). The proposed sensor has the potential for applications in recognizing the intention of human movement to help the amputees control the prostheses.

Combining a machine-learning derived 4-lncRNA signature with AFP and TNM stages in predicting early recurrence of hepatocellular carcinoma.

BACKGROUND: Near 70% of hepatocellular carcinoma (HCC) recurrence is early recurrence within 2-year post surgery. Long non-coding RNAs (lncRNAs) are intensively involved in HCC progression and serve as biomarkers for HCC prognosis. The aim of this study is to construct a lncRNA-based signature for predicting HCC early recurrence. METHODS: Data of RNA expression and associated clinical information were accessed from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) database. Recurrence associated differentially expressed lncRNAs (DELncs) were determined by three DEG methods and two survival analyses methods. DELncs involved in the signature were selected by three machine learning methods and multivariate Cox analysis. Additionally, the signature was validated in a cohort of HCC patients from an external source. In order to gain insight into the biological functions of this signature, gene sets enrichment analyses, immune infiltration analyses, as well as immune and drug therapy prediction analyses were conducted. RESULTS: A 4-lncRNA signature consisting of AC108463.1, AF131217.1, CMB9-22P13.1, TMCC1-AS1 was constructed. Patients in the high-risk group showed significantly higher early recurrence rate compared to those in the low-risk group. Combination of the signature, AFP and TNM further improved the early HCC recurrence predictive performance. Several molecular pathways and gene sets associated with HCC pathogenesis are enriched in the high-risk group. Antitumor immune cells, such as activated B cell, type 1 T helper cell, natural killer cell and effective memory CD8 T cell are enriched in patients with low-risk HCCs. HCC patients in the low- and high-risk group had differential sensitivities to various antitumor drugs. Finally, predictive performance of this signature was validated in an external cohort of patients with HCC. CONCLUSION: Combined with TNM and AFP, the 4-lncRNA signature presents excellent predictability of HCC early recurrence.

Different responses of Japanese encephalitis to weather variables among eight climate subtypes in Gansu, China, 2005-2019.

This study evaluated epidemic temporal aspects of Japanese encephalitis (JE) and investigated the weather threshold of JE response across eight climate subtypes between 2005 and 2019 in Gansu Province, China. Epidemiological data were collected from the China Information System for Disease Control and Prevention (CISDCP). Three epidemic temporal indices [frequency index (α), duration index (ß), and intensity index (γ)] were adopted for the comparison of epidemic features among different climate subtypes. In addition, the local indicators of spatial association (LISA) technique was used to detect the hot-spot areas. The category and regression tree (CART) model was used to detect the response threshold of weather variables in hot-spot areas across climate subtypes. Among eight climate subtypes in Gansu, in most hot-spot areas (i.e., high-high clusters), α, ß, and γ were detected in the climate subtypes of subtropical winter dry (Cwa), temperate oceanic continental (Cwb), and continental winter dry (Dwa and Dwb). According to the CART analysis, a minimum monthly temperature is required for Japanese encephalitis virus (JEV) transmission, with different threshold values among the climatic subtypes. In temperate climate zones (Cwa and Cwb), this threshold is 19 °C at a 1-month lag. It is lower in continental winter dry climate zones: 18 °C in Dwa (snow climate, dry winter, and hot summer) and 16 °C in Dwb (snow climate, dry winter, and warm summer). Additionally, some areas of the areas with temperate arid (BWk and BSk) had the first JE cases. Further studies to detect whether the climate change influence the JEV's distribution in Gansu Province are needed.

Congruence couple therapy for alcohol use and gambling disorders with comorbidities (part I): Outcomes from a randomized controlled trial.

A nonblinded randomized trial was conducted at two Canadian provincial outpatient addiction clinics that tested the effectiveness of a systemic congruence couple therapy (CCT) versus individual-based treatment-as-usual (TAU) on nine clinical outcomes: (1) primary outcomes-alcohol use and gambling, psychiatric symptoms, and couple adjustment; (2) secondary outcomes-emotion regulation, substance use, depression, post-traumatic stress symptoms, and life stress. Data of primary clients and partners (N = 46) were analyzed longitudinally across baseline, posttreatment (5 months), and follow-up (8 months). Alcohol use disorder (95%) and gambling disorder (5%) were in the severe range at baseline, and co-addiction was 27%. Psychiatric comorbidity was 100%, and 18% of couples were jointly addicted. Between-group comparison favored CCT in primary outcomes with medium-to-large effect sizes (Cohen's h = 0.74-1.44). Secondary outcomes were also significantly stronger for CCT (Cohen's h = 0.27-1.53). Within-group, for all primary outcomes, a significant proportion of symptomatic CCT clients and partners improved, converging with ANOVA results of large effect sizes (0.14-0.29). All secondary outcomes improved significantly in CCT with large effect sizes (0.14-0.50). TAU showed significant within-group improvement in alcohol use, other substance use, and life stress with large effect sizes (0.16-0.40). Primary clients and partners made largely equivalent improvement within CCT and within TAU. Results were triangulated with clients' satisfaction ratings and counselors' reports. Overall, significant within-group effects were detected for CCT both clinically and statistically and between-group difference favored CCT. Future trials are required to validate these promising findings.

Ancient Herbal Formula Mahuang Lianqiao Chixiaodou Decoction Protects Acute and Acute-on-Chronic Liver Failure via Inhibiting von Willebrand Factor Signaling.

BACKGROUND: Acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) are characterized by systemic inflammation and high mortality, but there is no effective clinical treatment. As a classic traditional Chinese medicine (TCM) formula, MaHuang-LianQiao-ChiXiaoDou decoction (MHLQD) has been used clinically for centuries to treat liver diseases. METHODS: The LPS/D-GalN-induced ALF mice model and the CCl4+LPS/D-GalN-induced ACLF mice model were used to observe the therapeutic effects of MHLQD on mice mortality, hepatocytes death, liver injury, and immune responses. RESULTS: MHLQD treatment significantly improved mice mortality. Liver injury and systemic and hepatic immune responses were also ameliorated after MHLQD treatment. Mechanistically, proteomic changes in MHLQD-treated liver tissues were analyzed and the result showed that the thrombogenic von Willebrand factor (VWF) was significantly inhibited in MHLQD-treated ALF and ACLF models. Histological staining and western blotting confirmed that VWF/RAP1B/ITGB3 signaling was suppressed in MHLQD-treated ALF and ACLF models. Furthermore, mice treated with the VWF inhibitor ADAMTS13 showed a reduced therapeutic effect from MHLQD treatment. CONCLUSIONS: Our study indicated that MHLQD is an effective herbal formula for the treatment of ALF and ACLF, which might be attributed to the protection of hepatocytes from death via VWF/RAP1B/ITGB3 signaling.

Expression of STING Is Increased in Monocyte-Derived Macrophages and Contributes to Liver Inflammation in Hepatic Ischemia-Reperfusion Injury.

Ischemia/reperfusion (I/R) injury, aggravated by innate immune cell-mediated inflammatory response, is a major problem in liver transplantation. Stimulator of interferon gene (STING) is a crucial regulatory signaling molecule in the DNA-sensing pathway, and its activation can produce strong innate immunity. However, the STING-mediated innate immune pathway in hepatic I/R injury has not been fully elucidated. In this study, we first examined the STING expression changes in the liver tissues of mice after hepatic I/R injury by using quantitative polymerase chain reaction and Western blot assays. We then investigated the role of STING in I/R injury by using a murine hepatic I/R model. STING up-regulation in mouse liver tissues in response to I/R injury and STING deficiency in myeloid cells was found to significantly ameliorate I/R-induced liver injury and inflammatory responses. STING inhibitors were also able to ameliorate hepatic I/R injury. Mechanically, STING may have a protective effect on hepatic I/R injury by the inhibition of hypoxia-inducible factor-1 alpha and enhancement of phosphorylated AMP-activated protein kinase to reduce macrophage activation. These findings show the potential regulatory effects of STING in hepatic I/R and suggest a new method for clinical protection of hepatic I/R injury.

Hepatocellular carcinoma-derived exosomal miRNA-761 regulates the tumor microenvironment by targeting the SOCS2/JAK2/STAT3 pathway.

BACKGROUND: Exosomes and exosomal microRNAs have been implicated in tumor occurrence and metastasis. Our previous study showed that microRNA-761 (miR-761) is overexpressed in hepatocellular carcinoma (HCC) tissues and that its inhibition affects mitochondrial function and inhibits HCC metastasis. The mechanism by which exosomal miR-761 modulates the tumor microenvironment has not been elucidated. METHODS: Exosomal miR-761 was detected in six cell lines. Cell counting kit-8 (CCK-8) and transwell migration assays were performed to determine the function of exosomal miR-761 in HCC cells. The luciferase reporter assay was used to analyze miR-761 target genes in normal fibroblasts (NFs). The inhibitors AZD1480 and C188-9 were employed to determine the role of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in the transformation of cancer-associated fibroblasts (CAFs). RESULTS: In this study, we characterized the mechanism by which miR-761 reprogrammed the tumor microenvironment. We found that HCC-derived exosomal miR-761 was taken up by NFs. Moreover, HCC exosomes affected the tumor microenvironment by activating NFs via suppressor of cytokine signaling 2 (SOCS2) and the JAK2/STAT3 signaling pathway. CONCLUSIONS: These results demonstrated that exosomal miR-761 modulated the tumor microenvironment via SOCS2/JAK2/STAT3 pathway-dependent activation of CAFs. Our findings may inspire new strategies for HCC prevention and therapy.

A systematic pan-cancer analysis of PXDN as a potential target for clinical diagnosis and treatment.

Peroxidasin (PXDN), also known as vascular peroxidase-1, is a newly discovered heme-containing peroxidase; it is involved in the formation of extracellular mesenchyme, and it catalyzes various substrate oxidation reactions in humans. However, the role and specific mechanism of PXDN in tumor are unclear, and no systematic pan-cancer studies on PXDN have been reported to date. This study employed data from multiple databases, including The Cancer Genome Atlas and The Genotype-Tissue Expression, to conduct a specific pan-cancer analysis of the effects of PXDN expression on cancer prognosis. Further, we evaluated the association of PXDN expression with DNA methylation status, tumor mutation burden, and microsatellite instability. Additionally, for the first time, the relationship of PXDN with the tumor microenvironment and infiltration of fibroblasts and different immune cells within different tumors was explored, and the possible molecular mechanism of the effect was also discussed. Our results provide a comprehensive understanding of the carcinogenicity of PXDN in different tumors and suggest that PXDN may be a potential target for tumor immunotherapy, providing a new candidate that could improve cancer clinical diagnosis and treatment.

An Immunity-Related Gene Model Predicts Prognosis in Cholangiocarcinoma.

The prognosis of patients with cholangiocarcinoma (CCA) is closely related to both immune cell infiltration and mRNA expression. Therefore, we aimed at conducting multi-immune-related gene analyses to improve the prediction of CCA recurrence. Immune-related genes were selected from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and the Immunology Database and Analysis Portal (ImmPort). The least absolute shrinkage and selection operator (LASSO) regression model was used to establish the multi-gene model that was significantly correlated with the recurrence-free survival (RFS) in two test series. Furthermore, compared with single genes, clinical characteristics, tumor immune dysfunction and exclusion (TIDE), and tumor inflammation signature (TIS), the 8-immune-related differentially expressed genes (8-IRDEGs) signature had a better prediction value. Moreover, the high-risk subgroup had a lower density of B-cell, plasma, B-cell naïve, CD8+ T-cell, CD8+ T-cell naïve, and CD8+ T-cell memory infiltration, as well as more severe immunosuppression and higher mutation counts. In conclusion, the 8-IRDEGs signature was a promising biomarker for distinguishing the prognosis and the molecular and immune features of CCA, and could be beneficial to the individualized immunotherapy for CCA patients.

Gut neuroendocrine signaling regulates synaptic assembly in C. elegans.

Synaptic connections are essential to build a functional brain. How synapses are formed during development is a fundamental question in neuroscience. Recent studies provided evidence that the gut plays an important role in neuronal development through processing signals derived from gut microbes or nutrients. Defects in gut-brain communication can lead to various neurological disorders. Although the roles of the gut in communicating signals from its internal environment to the brain are well known, it remains unclear whether the gut plays a genetically encoded role in neuronal development. Using C. elegans as a model, we uncover that a Wnt-endocrine signaling pathway in the gut regulates synaptic development in the brain. A canonical Wnt signaling pathway promotes synapse formation through regulating the expression of the neuropeptides encoding gene nlp-40 in the gut, which functions through the neuronally expressed GPCR/AEX-2 receptor during development. Wnt-NLP-40-AEX-2 signaling likely acts to modulate neuronal activity. Our study reveals a genetic role of the gut in synaptic development and identifies a novel contribution of the gut-brain axis.

A Control Method with Reinforcement Learning for Urban Un-Signalized Intersection in Hybrid Traffic Environment.

To control autonomous vehicles (AVs) in urban unsignalized intersections is a challenging problem, especially in a hybrid traffic environment where self-driving vehicles coexist with human driving vehicles. In this study, a coordinated control method with proximal policy optimization (PPO) in Vehicle-Road-Cloud Integration System (VRCIS) is proposed, where this control problem is formulated as a reinforcement learning (RL) problem. In this system, vehicles and everything (V2X) was used to keep communication between vehicles, and vehicle wireless technology can detect vehicles that use vehicles and infrastructure (V2I) wireless communication, thereby achieving a cost-efficient method. Then, the connected and autonomous vehicle (CAV) defined in the VRCIS learned a policy to adapt to human driving vehicles (HDVs) across the intersection safely by reinforcement learning (RL). We have developed a valid, scalable RL framework, which can communicate topologies that may be dynamic traffic. Then, state, action and reward of RL are designed according to urban unsignalized intersection problem. Finally, how to deploy within the RL framework was described, and several experiments with this framework were undertaken to verify the effectiveness of the proposed method.

Sandplay therapy could be a method to decrease disease activity and psychological stress in children with systemic lupus erythematosus.

OBJECTIVE: Although the prevalence rate of childhood-onset systemic lupus erythematosus (cSLE) is far lower than that of adults, cSLE has a high rate of organ involvement, rapid development and poor prognosis, which is more serious than that in adults. And studies have shown that a wide range of physiological, functional, nerve, and organ damage will have a great impact on the mental health of children. At present, there is no relevant psychological intervention research for cSLE in China. This paper aimed to explore the effect of Sandplay therapy on mental health and disease activity of children with cSLE. METHODS: Forty childrens with cSLE were randomly divided into control group (CG) and intervention group (IG); the CG were treated with glucocorticoid, immunosuppressant and other drugs, while the IG were treated with Sandplay therapy in addition to drug therapy, at the time of 0, 2, and 4 weeks after initial diagnosis, respectively. The questionnaire evaluation and related clinical indicators of the two groups were compared and analyzed (before psychotherapy intervention) at 0, 2, 4, and 12 weeks after initial diagnosis. RESULTS: There was no significant difference between the two groups in the evaluation of questionnaire and related clinical indicators at the time 0, 2 weeks after initial diagnosis respectively. At 12 weeks after the intervention, the score of Short version of the Children's Depression Inventory (CDI-S) in the IG was significantly lower than that in the CG, the score of The Screen for Child Anxiety Related Emotional Disorders (SCARED) scale in the IG was significantly lower than that in the CG, and the Pediatric Quality of Life Inventory (PedsQL 4.0) showed that the scores of social function, school performance, and emotional health of the IG were higher than those of the CG (p < 0.05), and the clinical indexes of the IG were better than those of the CG (p < 0.05). CONCLUSION: Sandplay therapy may help to slow down the occurrence and development of anxiety and depression and reduce disease activity in patients with cSLE.

Association Between Gamma-Glutamyl Transferase, Total Bilirubin and Systemic Lupus Erythematosus in Chinese Women.

Background: Systemic lupus erythematosus (SLE) affects many organs and systems of the human organism, at present, its specific pathogenesis is not completely clear, but inflammation is considered to be an important factor involved in the pathogenesis and progression of SLE. Gamma-glutamyl transpeptidase (GGT) and total bilirubin (TBIL) have different effects on inflammation: GGT has pro-inflammatory effects, on the contrary, TBIL has anti-inflammatory effects. Study has found that GGT and TBIL play opposite roles in metabolic diseases. However, the roles of them in SLE are unknown. Meanwhile, the relationship between GGT and SLE also remains unexplored. Method: We recruited 341 SLE patients and 332 healthy individuals in Liaocheng People's Hospital from August 2018 to May 2019. We diagnosed SLE using 2019 revised American College of Rheumatology (ACR) SLE criteria, and modeled the study outcomes using logistic regression to explore the respective relationship between GGT, TBIL and SLE. We also analyzed the interaction of GGT and TBIL in the progression of SLE. Results: We found that the levels of CRP, IL-6 and TNF-α in the aggravated group were significantly higher than those in the unaggravated group, the levels of C3 and C4 in the aggravated group were significantly lower than those in the unaggravated group. According to Spearman correlation analysis, GGT is proportional to CRP (rs=0.417) and IL-6 (rs=0.412), inversely proportional to C3 (rs=-0.177) and C4 (rs=0.-132). TBIL was inversely proportional to CRP (rs=-0.328) and TNF(rs=-0.360), and positively proportional to C3 (rs=0.174) and C4 (rs=0.172). In the fully adjusted model, compared to the lowest quartile, the highest quartile of GGT exhibited a positive association with the risk of SLE aggravation (OR=2.99, 95% CI: 1.42-6.31, P<0.001). At the same time, compared to the highest quartile, the quartile lowest of TBIL exhibited a positive association with the risk of SLE aggravation (OR=2.66, 95% CI: 1.27-5.59, P<0.001) in the fully adjusted model. Through interaction analysis, we found that women with high GGT levels had an increased risk of SLE aggravation when they had a low level of TBIL (OR=3.68, 95% CI: 1.51-9.01, for women with Q1 TBIL and Q4 GGT compared to women with Q2-Q4 TBIL and Q1-Q3 GGT, P for interaction <0.001), the combined AUC value (AUCCOMBINED=0.711) of high GGT level and TBIL were higher than their respective values (AUCGGT=0.612, AUCTBIL=0.614). Conclusion: We found that the effects of GGT and TBIL in the progression of SLE are opposite. High GGT level might be a risk factor for SLE aggravation, as GGT levels increased, so did the risk of SLE aggravation. At the same time, we found that low TBIL level might be a risk factor for SLE aggravation. Moreover, high GGT level and low TBIL level had a subadditive effect on the increased risk of SLE aggravation.

COVID-19 or treatment associated immunosuppression may trigger hepatitis B virus reactivation: A case report.

BACKGROUND: Since the initial recognition of coronavirus disease 2019 (COVID-19) in Wuhan, this infectious disease has spread to most areas of the world. The pathogenesis of COVID-19 is yet unclear. Hepatitis B virus (HBV) reactivation occurring in COVID-19 patients has not yet been reported. CASE SUMMARY: A 45-year-old hepatitis B man with long-term use of adefovir dipivoxil and entecavir for antiviral therapy had HBV reactivation after being treated with methylprednisolone for COVID-19 for 6 d. CONCLUSION: COVID-19 or treatment associated immunosuppression may trigger HBV reactivation.