ABSTRACT
OBJECTIVE@#To investigate the predictive value of blood cell ratios and inflammatory markers for adverse prognosis in patients with primary Sjögren's syndrome (PSS) combined with coronavirus disease 2019 (COVID-19).@*METHODS@#We retrospectively collected clinical data from 80 patients with PSS and COVID-19 who visited the Rheumatology and Immunology Department of the First Affiliated Hospital of Nanchang University from December 2022 to February 2023. Inclusion criteria were (1) meeting the American College of Rheumatology (ACR) classification criteria for Sjögren's syndrome; (2) confirmed diagnosis of COVID-19 by real-time reverse transcription polymerase chain reaction or antigen testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); (3) availability of necessary clinical data; (4) age > 18 years. According to the clinical classification criteria of the "Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (trial the 10th Revised Edition)", the patients were divided into the mild and severe groups. Disease activity in primary Sjögren' s syndrome was assessed using the European League Against Rheumatism (EULAR) Sjögren' s syndrome disease activity index (ESSDAI). Platelet-lymphocyte ratio (PLR), C-reactive protein-lymphocyte ratio (CLR), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and other laboratory data were compared between the two groups within 24-72 hours post-infection.@*RESULTS@#The mild group consisted of 66 cases with an average age of (51. 52±13. 16) years, and the severe group consisted of 14 cases with an average age of (52.64±10.20) years. Disease activity, CRP, platelets, PLR, and CLR were significantly higher in the severe group compared with the mild group (P < 0.05). Univariate analysis using age, disease activity, CRP, platelets, PLR, and CLR as independent variables indicated that disease activity, CRP, PLR, and CLR were correlated with the severity of COVID-19 (P < 0.05). Multivariate logistic regression analysis further confirmed that PLR (OR=1.016, P < 0.05) and CLR (OR=1.504, P < 0.05) were independent risk factors for the severity of COVID-19 in the critically ill patients. Receiver operator characteristic (ROC) curve analysis showed that the area under the curve (AUC) for PLR and CLR was 0.708 (95%CI: 0.588-0.828) and 0.725 (95%CI: 0.578-0.871), respectively. The sensitivity for PLR and CLR was 0.429 and 0.803, respectively, while the highest specificity was 0.714 and 0.758, respectively. The optimal cutoff values for PLR and CLR were 166.214 and 0.870, respectively.@*CONCLUSION@#PLR and CLR, particularly the latter, may serve as simple and effective indicators for predicting the prognosis of patients with PSS and COVID-19.
Subject(s)
Humans , Adult , Middle Aged , Sjogren's Syndrome/diagnosis , Retrospective Studies , C-Reactive Protein , COVID-19 , SARS-CoV-2ABSTRACT
Osteonecrosis of femoral head (ONFH) is one of the complications of systemic lupus erythematosus (SLE), which is characterized by complex pathogenesis and difficult treatment, and is the main cause of SLE-induced disability. Previous studies have confirmed that the JAK/STAT signaling pathway is involved in the pathological process of SLE, and the activation of JAK/STAT has also been found to be related to the occurrence of ONFH. Therefore, we speculated that the JAK/STAT signaling pathway may play an important role in the occurrence and development of SLE-ONFH. 30 female MRL/lpr mice were randomly divided into three groups: the model group (Lipopolysaccharide/24 hours, twice + Methylprednisolone/24 hours, 3 times), the control group (equal amount of PBS) and the treatment group (the model group + JAK1/2 inhibitors Baricitinib/day, 6 weeks), with 10 mice in each group. The results showed that the grip value of the model group was significantly lower than that of the control group at the 4th and 6th week (P < 0. 05), and that of the treatment group was better than that of the model group at the 6th week (P < 0. 05). At the 6th week, the mice were sacrificed to take the bilateral femoral head, and the morphology and HE staining pathological changes of the femoral head were observed. The results showed that the femoral head of the control group was spherical, transparent, hard and without cartilage defects, while that of the model group was irregular, rough, gray in color and partial defects of the femoral head. The performance of the mice in the treatment group was basically similar to that in the model group. And the overall appearance of the femoral head was more irregular than that in the control group. The color was darker than that in the control group, and there was a partial defect of the femoral head, but the degree was not as serious as that in the model group. The empty bone lacuna rate in the model group and treatment group were significantly higher than that in the control group (P < 0. 05), and the empty bone lacuna rate in the treatment group was lower than that in the model group (P < 0. 05). Western blotting, ELISA and RT-qPCR were used to detect the protein expression, phosphorylation levels, mRNA expression of the JAK/STAT pathway (JAK1, JAK2, JAK3, STAT3) in local bone tissues, and the expression of IL-6 and TNF- α in serum and local tissues. The mRNA expression of IL-6, TNF-α and STAT3 in bone tissues of the model group were significantly higher than that of the control group and treatment group, and the content of serum IL-6 and TNF- α of the model group were significantly higher than that of the treatment group and control group. The cartilage catabolic metabolites ADAMTS-4, MMP-13 and JAK/STAT pathway related proteins JAK1, p-JAK1, JAK2, p-JAK2, STAT3 and pSTAT3 in the model group were significantly higher than those in the control group and treatment group. In summary, the JAK/STAT signaling pathway is involved in the pathogenesis of ONFH in MRL/lpr lupus erythematosus mice. Selective JAK1/2 inhibitors can effectively inhibit ONFH inflammation, improve bone structures and joint functions, and may become an effective therapeutic drug for SLE ONFH.
ABSTRACT
Systemic sclerosis (SSc) is a chronic autoimmune disease that can involve multiple organs throughout the body. It is characterized by extensive vascular disease and fibrosis of the skin and internal organs, but its mechanism is still unclear. Studies have confirmed that the Wnt pathway is involved in SSc fibrosis, but its pathological role in vascular lesions has not been reported. In this study, the bleomycin (BLM)-induced SSc mouse model was used to investigate the role of Wnt pathway in SSc cutaneous vascular lesions. Eighteen BALB/C mice were randomly divided into control, model and treatment groups. The control group of mice was injected with PBS 100 μL/d. The model group was injected with BLM 100 μL/d at a concentration of 1 mg/mL. The treatment group of mice received injection of BLM 100 μL as the model group of mice and retroperitoneal injection of iCRT3 (Wnt and beta-catenin inhibitors) 5 mg/kg/d. Mice were sacrificed on day 28. The thickness of dorsal dermis and epidermis in the model group induced by BLM was significantly higher than that in the control group (P <0. 05). The skin appendages such as sebaceous glands and hair follicles in the model group were significantly reduced. At the same time, the thickness of fat layer became thinner and surrounded by fibrous tissue, and the collagen deposition in the model group was higher than that in the control group. It was identified at the histological level by immunohistochemical staining that α-SMA expression in model group and treatment group α-SMA is highly expressed in skin tissues, and the positive expression of α-SMA around blood vessels was significantly higher than that in the control group. In addition, the expression of IL-6 and IL-17 in serum of model group was significantly higher than that in control group (P<0. 05), and the expression of IL-6 and IL-17 in serum of treatment group was significantly lower than that in model group (P<0. 05). Furthermore, q-PCR analysis showed that the mRNA levels of β-catenin in the skin microvessels of the mice were higher in the model and the treatment groups as compared with the control group. The protein levels of Wnt5A, β-catenin, α-SMA and col1A1 were analyzed by Western blotting and results showed that the levels of fibrosis-related proteins, α-SMA and col1A1, were increased in the model group injected with BLM as compared with the control group (P<0. 05), whereas iCRT3 treatment attenuated the upregulation of α-SMA and col1A1 induced by BLM in the treatment group (P<0. 05). The levels of Wnt pathway-related proteins β-catenin and Wnt5A were significantly increased in the model group as compared with the control (P<0. 05). This study suggests that BLM can successfully induce the skin phenotype of mice with systemic sclerosis. Abnormal activation of Wnt signaling pathway is involved in BLM-induced skin microangiopathy in mice with scleroderma, and the specific Wnt pathway inhibitor iCRT3 can reduce BLM-induced scleroderma. The expression of α-SMA and col1A1 proteins in mouse skin microvessels can improve the microvascular lesions of mouse skin. Inhibition of Wnt pathway may directly or indirectly down-regulate the abnormal expression of cytokines IL-6 and IL-17, and interfere with BLM-induced progression of vascular lesions in mice.