Female ; Humans ; Uterine Neoplasms/pathology* ; Uterus/pathology* ; Neoplasms, Connective and Soft Tissue

INTRODUCTION: There is a paucity of information on the cytokine, complement, endothelial activation, and coagulation profiles of multisystem inflammatory syndrome in adults (MIS-A), a rare but serious complication following recovery from SARS-CoV-2 infection. We aim to examine the immune biomarker and coagulation profiles in association with the clinical presentation and course of MIS-A. METHOD: The clinical features of MIS-A patients admitted to our tertiary hospital were documented. Their levels of interleukin (IL)-1β, IL-6, IL-10, IL-17, IL-18, interferon-α (IFN-α), IFN-γ, interferon gamma-induced protein 10 (IP-10), tumour necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, complement activation product (complement 5a [C5a]), and endothelial biomarker intercellular adhesion molecule-1 (ICAM-1) levels were assayed. The haemostatic profile was assessed with standard coagulation testing and thromboelastography. RESULTS: Three male patients were diagnosed with MIS-A at our centre from January to June 2022 with a median age of 55 years. All had tested positive for SARS-CoV-2 12-62 days prior to MIS-A presentation, with gastrointestinal and cardiovascular systems as the most commonly involved. Levels of IL-6, IL-10, IL-18, IP-10 and MCP-1 were raised whereas IL-1β, IFN-α, IFN-γ, IL-17 and TNF-α remained normal. Markedly elevated levels of C-reactive protein (CRP), ferritin and ICAM-1 were present in all. C5a was elevated in 2 patients. A hypercoagulable state was demonstrated by raised levels of D-dimer, factor VIII, von Willebrand factor antigen, and ristocetin cofactor with corresponding raised parameters in thromboelastography in the 2 patients who had their coagulation profile assessed. CONCLUSION MIS-A patients demonstrate activation of pro-inflammatory cytokines, endotheliopathy, complement hyperactivation and hypercoagulability.
Humans ; Adult ; Male ; Middle Aged ; COVID-19/complications* ; Interleukin-10 ; Interleukin-18 ; Intercellular Adhesion Molecule-1 ; Interleukin-17 ; Chemokine CXCL10 ; Interleukin-6 ; SARS-CoV-2 ; Connective Tissue Diseases ; Hemostatics

The present study aimed to assess the molecular profiles of subepithelial connective tissue grafts (CTGs) obtained at different locations and depths in the human palate. Sixty-four CTGs belonging to anterior deep (AD), anterior superficial (AS), posterior deep (PD), and posterior superficial (PS) groups were subjected to RNA-Sequencing and their transcriptomes were analyzed computationally. Functional correlations characterizing the CTG groups were validated by cell biological experiments using primary human palatal fibroblasts (HPFs) extracted from the CTGs. A clearly more pronounced location-dependent than depth-dependent difference between the grafts, with a minimal number of genes (4) showing no dependence on the location, was revealed. Epithelial, endothelial, and monocytic cell migration was strongly (P < 0.001) potentiated by AD- and PS-HPFs. Moreover, significantly increased expression of genes encoding C-C and C-X-C motif chemokine ligands as well as significantly (P < 0.01) activated p38 signaling suggested immunomodulatory phenotype for AD- and PS-HPFs. Increased growth factor gene expression and significantly activated (P < 0.001) Erk and Akt signaling in HPFs originating from A-CTGs implied their involvement in cell survival, proliferation, and motility. Prominent collagen-rich expression profile contributing to high mechanical stability, increased osteogenesis-related gene expression, and strongly activated (P < 0.001) Smad1/5/8 signaling characterized HPFs originating from P-CTGs. The present data indicate that in humans, differences between palatal CTGs harvested from different locations and depths appear to be location- rather than depth-dependent. Our findings provide the basis for future personalization of the therapeutic strategy by selecting an optimal graft type depending on the clinical indications.
Humans ; Connective Tissue/transplantation* ; Palate ; Collagen ; Fibroblasts ; Signal Transduction

OBJECTIVE: To investigate the significance of anti-histidyl tRNA synthetase (Jo-1) antibody in idiopathic inflammatory myopathies (IIM) and its diseases spectrum. METHODS: We enrolled all the patients who were tested positive for anti-Jo-1 antibody by immunoblotting in Peking University People's Hospital between 2016 and 2022. And the patients diagnosed with anti-synthetase antibody syndrome (ASS) with negative serum anti-Jo-1 antibody were enrolled as controls. We analyzed the basic information, clinical characteristics, and various inflammatory and immunological indicators of the patients at the onset of illness. RESULTS: A total of 165 patients with positive anti-Jo-1 antibody were enrolled in this study. Among them, 80.5% were diagnosed with connective tissue disease. And 57.6% (95/165) were diagnosed with IIM, including ASS (84/165, 50.9%), immune-mediated necrotizing myopathy (7/165, 4.2%) and dermatomyositis (4/165, 2.4%). There were 23.0% (38/165) diagnosed with other connective tissue disease, mainly including rheumatoid arthritis (11/165, 6.7%), undifferentiated connective tissue disease (5/165, 3.0%), interstitial pneumonia with autoimmune features (5/165, 3.0%), undifferentiated arthritis (4/165, 2.4%), Sjögren's syndrome (3/165, 1.8%), systemic lupus erythematosus (3/165, 1.8%), systemic vasculitis (3/165, 1.8%), and so on. Other cases included 3 (1.8%) malignant tumor patients, 4 (2.4%) infectious cases and so on. The diagnoses were not clear in 9.1% (15 /165) of the cohort. In the analysis of ASS subgroups, the group with positive serum anti-Jo-1 antibody had a younger age of onset than those with negative serum anti-Jo-1 antibody (49.9 years vs. 55.0 years, P=0.026). Clinical manifestations of arthritis (60.7% vs. 33.3%, P=0.002) and myalgia (47.1% vs. 22.2%, P=0.004) were more common in the ASS patients with positive anti-Jo-1 antibody. With the increase of anti-Jo-1 antibody titer, the incidence of the manifestations of arthritis, mechanic hands, Gottron sign and Raynaud phenomenon increased, and the proportion of abnormal creatine kinase and α-hydroxybutyric dehydrogenase index increased in the ASS patients. The incidence of myalgia and myasthenia were significantly more common in this cohort when anti-Jo-1 antibody-positive ASS patients were positive for one and more myositis specific antibodies/myositis associated autoantibodies (P < 0.05). CONCLUSION The disease spectrum in patients with positive serum anti-Jo-1 antibody includes a variety of diseases, mainly ASS. And anti-Jo-1 antibody can also be found in many connective tissue diseases, malignant tumor, infection and so on.
Humans ; Middle Aged ; Myalgia ; Myositis/epidemiology* ; Autoantibodies ; Connective Tissue Diseases ; Arthritis, Rheumatoid ; Neoplasms

OBJECTIVE: To investigate the fetal and maternal outcomes, risk factors of disease progression and adverse pregnancy outcomes (APOs) in patients with undifferentiated connective tissue disease (UCTD). METHODS: This retrospective study described the outcomes of 106 pregnancies in patients with UCTD. The patients were divided into APOs group (n=53) and non-APOs group (n=53). The APOs were defined as miscarriage, premature birth, pre-eclampsia, premature rupture of membranes (PROM), intrauterine growth restriction (IUGR), postpartum hemorrhage (PPH), and stillbirth, small for gestational age infant (SGA), low birth weight infant (LBW) and birth defects. The differences in clinical manifestations, laboratory data and pregnancy outcomes between the two groups were compared. Logistic regression analysis was performed to analyze the risk factors for APOs and the progression of UCTD to definitive CTD. RESULTS: There were 99 (93.39%) live births, 4 (3.77%) stillbirths and 3 (2.83%) miscarriage, 20 (18.86%) preterm delivery, 6 (5.66%) SGA, 17 (16.03%) LBW, 11 (10.37%) pre-eclampsia, 7 (6.60%) cases IUGR, 19 (17.92%) cases PROM, 10 (9.43%) cases PPH. Compared with the patients without APOs, the patients with APOs had a higher positive rate of anti-SSA antibodies (73.58% vs. 54.71%, P=0.036), higher rate of leukopenia (15.09% vs. 3.77%, P=0.046), lower haemoglobin level [109.00 (99.50, 118.00) g/L vs. 124.00 (111.50, 132.00) g/L, P < 0.001].Multivariate Logistic regression analysis showed that leucopenia (OR=0.82, 95%CI: 0.688-0.994) was an independent risk factors for APOs in UCTD (P=0.042). Within a mean follow-up time of 5.00 (3.00, 7.00) years, the rate of disease progression to a definite CTD was 14.15%, including 8 (7.54%) Sjögren's syndrome, 4 (3.77%) systemic lupus erythematosus (SLE), 4 (3.77%) rheumatoid arthritis and 1 (0.94%) mixed connective tissue disease. Multivariate Cox proportional risk regression analysis showed that Raynaud phenomenon (HR=40.157, 95%CI: 3.172-508.326) was an independent risk factor for progression to SLE. CONCLUSION Leukopenia is an independent risk factor for the development of APOs in patients with UCTD. Raynaud's phenmon is a risk factor for the progression of SLE. Tight disease monitoring and regular follow-up are the key measures to prevent adverse pregnancy outcomes and predict disease progression in UCTD patients with pregnancy.
Pregnancy ; Infant, Newborn ; Female ; Humans ; Pregnancy Outcome ; Retrospective Studies ; Abortion, Spontaneous/etiology* ; Undifferentiated Connective Tissue Diseases ; Pre-Eclampsia/epidemiology* ; Lupus Erythematosus, Systemic ; Risk Factors ; Leukopenia ; Pregnancy Complications/epidemiology* ; Disease Progression ; Connective Tissue Diseases/epidemiology*

Objective: To analyze the clinical characteristics of children with multisystem inflammatory syndrome (MIS-C) associated with SARS-CoV-2 in China, and to improve the understanding of MIS-C among pediatricians. Methods: Case series study.Collect the clinical characteristics, auxiliary examinations, treatment decisions, and prognosis of 64 patients with MIS-C from 9 hospitals in China from December 2022 to June 2023. Results: Among the 64 MIS-C patients, 36 were boys and 28 were girls, with an onset age being 2.8 (0.3, 14.0) years. All patients suffered from fever, elevated inflammatory indicators, and multiple system involvement. Forty-three patients (67%) were involved in more than 3 systems simultaneously, including skin mucosa 60 cases (94%), blood system 52 cases (89%), circulatory system 54 cases (84%), digestive system 48 cases (75%), and nervous system 24 cases (37%). Common mucocutaneous lesions included rash 54 cases (84%) and conjunctival congestion and (or) lip flushing 45 cases (70%). Hematological abnormalities consisted of coagulation dysfunction 48 cases (75%), thrombocytopenia 9 cases (14%), and lymphopenia 8 cases (13%). Cardiovascular lesions mainly affected cardiac function, of which 11 patients (17%) were accompanied by hypotension or shock, and 7 patients (12%) had coronary artery dilatation.Thirty-six patients (56%) had gastrointestinal symptoms, 23 patients (36%) had neurological symptoms. Forty-five patients (70%) received the initial treatment of intravenous immunoglobulin in combination with glucocorticoids, 5 patients (8%) received the methylprednisolone pulse therapy and 2 patients (3%) treated with biological agents, 7 patients with coronary artery dilation all returned to normal within 6 months. Conclusions: MIS-C patients are mainly characterized by fever, high inflammatory response, and multiple organ damage. The preferred initial treatment is intravenous immunoglobulin combined with glucocorticoids. All patients have a good prognosis.
Male ; Child ; Female ; Humans ; Immunoglobulins, Intravenous/therapeutic use* ; Blood Coagulation ; COVID-19 ; China/epidemiology* ; Connective Tissue Diseases ; Coronary Aneurysm ; Fever ; Systemic Inflammatory Response Syndrome/therapy*

Child ; Humans ; COVID-19 ; Connective Tissue Diseases

OBJECTIVES: To evaluate the effectiveness of an acellular dermal matrix or a connective tissue autograft in the treatment of multiple adjacent gingival recessions through Meta-analysis. METHODS: Randomized controlled trials were screened in four electronic databases in English according to the inclusion and exclusion criteria until April 20, 2022. The main outcome indicators were keratinized gingival tissue width, recession depth, probing depth, clinical attachment level, complete root coverage, and root coverage esthetic score. RESULTS: Seven randomized controlled trials were included. After 12 months, the connective tissue graft in the control group could increase the keratinized gingival tissue width [mean difference (MD)=-0.28 (-0.47, -0.08), P=0.006], reduce the gingival recession depth [MD=0.23 (0.12, 0.35), P<0.000 1], and improve the complete root coverage [risk ratio=0.80, 95% confidence interval (0.69, 0.93), P=0.003] compared with the acellular dermal matrix in the experimental group. No significant difference was found in probing depth, clinical attachment level, and root coverage esthetic score between groups. CONCLUSIONS Connective tissue grafts have advantages in increasing the keratinized gingival tissue width, reducing the gingival recession depth, and improving the complete root coverage in surgeries for treating multiple adjacent gingival recessions. Acellular dermal matrices also have some clinical value in terms of operation simplicity and similar effectiveness.
Humans ; Gingival Recession/surgery* ; Acellular Dermis ; Surgical Flaps ; Esthetics, Dental ; Connective Tissue/transplantation*

Objective: To investigate the clinicopathologic features,diagnosis and prognosis of pericytic tumor of the kidney. Methods: Three cases of pericytic tumor of the kidney (two cases were diagnosed as glomangiomyomas and one case as pericytic tumor,unclassified) were collected from the affiliated Hospital of Qingdao University between January 2014 to May 2021; the clinical and morphologic features, immunohistochemical and molecular characteristics were analyzed and the relevant literature was reviewed. Results: The three patients included one male and two females, with ages ranging from 21 to 70 years. In two patients the tumors were detected incidentally at physical examination and one patient presented with low back discomfort. Imaging showed a rounded nodular soft tissue density shadow in renal parenchyma, and enhancement scan showed uneven delayed enhancement. Grossly, two tumors were located in the renal hilum and one in the renal parenchyma; all were nodular. The tumors were measured in size from 1.6 cm to 5.1 cm (mean 4.1 cm) and showed gray or gray-red cut surface. Histologic examination showed the tumor cells were arranged in solid sheets or small nodules, closely related to vascular wall. Tumor cells were mostly epithelial-like with abundant cytoplasm, light eosinophilia, obscure boundary and round nuclei with visible nucleoli. Vague bundles and fascicular arrangements of smooth muscle component were noted in some areas, with transition of both components. There was no necrosis. By immunohistochemistry, the tumor cells strongly and diffusely expressed vimentin, SMA and collagen Ⅳ, two cases expressed CD34, all three cases expressed PDGFRB to varying extent, and the Ki-67 index was 2%-3%. PCR tests showed absent K-RAS, BRAF V600E gene mutation in all three cases. PDGFRB mutations in exons 3 and 18, respectively were found in two of the three cases by high-throughput sequencing, and no NOTCH 1/2/3 gene fusions were found in any of them. Follow-up information (range: 6-92 months) showed no evidence of local recurrence or distant metastasis in all three patients. Conclusions: Pericytic tumor of the kidney is a rare mesenchymal tumor originating in the kidney with differentiation to smooth muscle, most commonly glomus tumor. The mild pleomorphism, close relationship with vascular wall and spindled smooth muscle components suggest the diagnosis of the tumor. Expression of both epithelial and muscle-associated markers aids the diagnosis. PDGFRB gene mutations may have an important role in the development of this tumor. Most patients have a good prognosis, and a few cases have malignant biological behavior.
Adult ; Aged ; Biomarkers, Tumor/analysis* ; Collagen ; Diagnosis, Differential ; Female ; Glomus Tumor/pathology* ; Humans ; Ki-67 Antigen ; Kidney/pathology* ; Kidney Neoplasms/pathology* ; Male ; Middle Aged ; Neoplasms, Connective and Soft Tissue ; Proto-Oncogene Proteins B-raf ; Receptor, Platelet-Derived Growth Factor beta ; Vimentin ; Young Adult

Chondrosarcoma/surgery* ; Humans ; Neoplasms, Connective and Soft Tissue ; Soft Tissue Neoplasms