Objective To investigate the expression level and clinical significance of microRNA(miR)-181c and microRNA(miR)-578 in the serum of patients with sepsis complicated by acute kidney injury(AKI).Methods Eighty patients with sepsis complicated by AKI(AKI group)and 80 patients with simple sepsis(non AKI group)who were hospitalized in Sinopharm Gezhouba Central Hospital from January 2022 to December 2022 were collected as research subjects.The serum levels of miR-181c and miR-578 in two groups were detected and compared.Logistic regression was applied to analyze the influencing factors of sepsis patients complicated by AKI.Receiver operating characteristic(ROC)curve was applied to analyze the predictive value of serum miR-181c and miR-578 levels for patients with sepsis complicated by AKI.Results The proportion of pulmonary infection,the level of arterial blood lactic acid,creatinine,urea nitrogen and APACHEⅡ score in AKI group were higher than those in non-AKI group,and the oxygenation index was lower,the differences were statistically significant(χ2=7.364,t=14.298,26.691,17.925,7.104,12.676,all P＜0.05).The serum miR-181c level in the AKI group(1.47±0.36)was higher than that in the non AKI group(1.03±0.28),the serum miR-578 level(0.76±0.19)was lower than that in the non AKI group(1.05±0.31),and the differences were statistically significant(t=8.629,7.134,all P=0.000).Logistic regression analysis showed that miR-181c[OR(95%CI):2.984(1.628～5.468)],pulmonary infection[OR(95%CI):1.946(1.250～3.031)],arterial blood lactic acid[OR(95%CI):1.457(1.073～1.978)],and APACHE Ⅱ score[OR(95%CI):2.283(1.393～3.741)]were risk factors for AKI in sepsis patients(all P＜0.05);miR-578[OR(95%CI):0.742(0.631～0.873)]and oxygenation index[OR(95%CI):0.342(0.130～0.904)]were protective factors(all P＜0.05).The combined prediction of serum miR-181c and miR-578 for AKI in sepsis patients had an AUC of 0.915,a sensitivity and a specificity of 83.65%,88.75%,respectively,which was superior to their individual predictions(Z=3.118,3.460,P=0.002,0.001).Conclusion The serum miR-181c expression is obviously up-regulated and miR-578 expression is obviously down-regulated in patients with sepsis complicated by AKI.The combination of the two has good reference value for predicting sepsis complicated by AKI.

Objective:To evaluate the clinical value of the adjusted global antiphospholipid syndrome score (aGAPSS) in patients with persistent antiphospholipid antibodies (aPL).Methods:The clinical data of patients who were continuously positive for aPL from May 2012 to August 2022 were retrospectively analyzed, except for patients complicated with connective tissue diseases. Demographic data, traditional cardiovascular thrombosis risk factors, aPL profile, and clinical manifestations included and not included in antiphospholipid syndrome (APS) were collected, and aGAPSS was calculated for all patients according to risk indicators and the correlation with clinical manifestation was analyzed through rank sum test. The diagnostic value of aGAPSS for different clinical manifestations was evaluated by the receiver operator characteristic (ROC) curve.Results:A total of 67 patients with persistent aPL were enrolled, including 15 patients with persistent extra-criteria positive aPL but did not meet the APS classification criteria and 52 patients with a clear diagnosis of primary APS, of which 20 had a history of thrombosis, 36 had a history of pregnancy morbidity, and 24 had extra-criteria clinical manifestations. Patients with history of any thrombosis or arterial thrombosis scored significantly higher than those with no history of thrombosis [any history of thrombosis 11.50 (8.25, 13.00) vs 8.00 (4.00, 13.00), Z=2.33, P=0.020; arterial thrombosis history 11.00 (9.00, 14.00) vs 8.00 (4.00, 13.00), H=6.21, P=0.043]. The aGAPSS score of patients with extra-criteria clinical manifestations was significantly higher than that of patients without corresponding clinical manifestations [13.00 (8.25, 13.00) vs 8.00 (4.00, 11.00), Z=2.81, P=0.005], and the aGAPSS score of patients with thrombocytopenia was significantly higher than that of patients without thrombocytopenia [12.50 (8.00, 13.25) vs 8.00 (4.00, 13.00), Z=2.23, P=0.026]. A subgroup analysis of pregnant women found no statistically significant difference in aGAPSS scores between groups with or without a history of pregnancy morbidity. With thrombosis as the endpoint event, aGAPSS had the highest diagnostic value at 10 points(sensitivity and specificity were 65.00% and 77.78%, respectively). Conclusion:In patients with postivity aPL positivity, aGAPSS score is correlated with thrombosis history and extra-criteria clinical manifestations, especially thrombocytopenia.

BACKGROUND: Vaccination has been shown effective in controlling the global coronavirus disease 2019 (COVID-19) pandemic and reducing severe cases. This study was to assess the flare and change in disease activity after COVID-19 vaccination in patients with stable rheumatoid arthritis (RA). METHODS: A prospective cohort of RA patients in remission or with low disease activity was divided into a vaccination group and a non-vaccination group based on their COVID-19 vaccination status. Each of them was examined every 3 to 6 months. In the vaccination group, disease activity was compared before and after vaccination. The rates of flare defined as disease activity scores based on 28-joint count (DAS28) >3.2 with ΔDAS28 ≥0.6 were compared between vaccination and non-vaccination groups. RESULTS: A total of 202 eligible RA patients were enrolled. Of these, 98 patients received no vaccine shot (non-vaccination group), and 104 patients received two doses of vaccine (vaccination group). The median time interval from pre-vaccination visit to the first immunization and from the second dose of vaccine to post-vaccination visit was 67 days and 83 days, respectively. The disease activity scores at pre-vaccination and post-vaccination visits in the vaccination group patients were similar. At enrollment, gender, RA disease course, seropositivity, and disease activity were comparable across the two groups. Flare was observed in five (4.8%) of the vaccination group patients and nine (9.2%) of the non-vaccination group patients at post-vaccination assessment ( P  = 0.221). In terms of safety, 29 (27.9%) patients experienced adverse events (AEs) after vaccination. No serious AEs occurred. CONCLUSIONS COVID-19 vaccinations had no significant effect on disease activity or risk of flare in RA patients in remission or with low disease activity. Patients with stable RA should be encouraged to receive the COVID-19 vaccination.
Humans ; Arthritis, Rheumatoid ; Cohort Studies ; COVID-19/prevention & control* ; COVID-19 Vaccines/adverse effects* ; East Asian People ; Prospective Studies ; Vaccination/adverse effects*

Autoimmune hepatitis (AIH) is a severe globally distributed liver disease that could occur at any age. Human menstrual blood-derived stem cells (MenSCs) have shown therapeutic effect in acute lung injury and liver failure. However, their role in the curative effect of AIH remains unclear. Here, a classic AIH mouse model was constructed through intravenous injection with concanavalin A (Con A). MenSCs were intravenously injected while Con A injection in the treatment groups. The results showed that the mortality by Con A injection was significantly decreased by MenSCs treatment and liver function tests and histological analysis were also ameliorated. The results of phosphoproteomic analysis and RNA-seq revealed that MenSCs improved AIH, mainly by apoptosis and c-Jun N-terminal kinase/mitogen-activated protein signaling pathways. Apoptosis analysis demonstrated that the protein expression of cleaved caspase 3 was increased by Con A injection and reduced by MenSCs transplantation, consistent with the TUNEL staining results. An AML12 co-culture system and JNK inhibitor (SP600125) were used to verify the JNK/MAPK and apoptosis signaling pathways. These findings suggested that MenSCs could be a promising strategy for AIH.
Mice ; Animals ; Humans ; Hepatitis, Autoimmune/pathology* ; Signal Transduction ; Disease Models, Animal ; Stem Cells

Natural extracellular vesicles (EVs) play important roles in many life processes such as in the intermolecular transfer of substances and genetic information exchanges. Investigating the origins and working mechanisms of natural EVs may provide an understanding of life activities, especially regarding the occurrence and development of diseases. Additionally, due to their vesicular structure, EVs (in small molecules, nucleic acids, proteins, etc.) could act as efficient drug-delivery carriers. Herein, we describe the sources and biological functions of various EVs, summarize the roles of EVs in disease diagnosis and treatment, and review the application of EVs as drug-delivery carriers. We also assess the challenges and perspectives of EVs in biomedical applications.

Objective:To analyze the characteristics of various clinical parameter reflecting the di-sease activity of patients with rheumatoid arthritis (RA) and explore their objectivity and different clinical values.Methods:The clinical data and ultrasonic data of 28 joints of RA patients diagnosed between 2014 and 2018 were collected. The characteristics of clinical indicators were analyzed, and their correlation with total grey scale (GS)/power Doppler (PD) scores of 28 joints was explored. Semi-quantitative score (0-3 points) of GS and PD for synovial hyperplasia was performed on 28 joints of selected patients by ultrasound. Total GS/PD scores include 28 joints. The characteristics of clinical parameters were analyzed, and their correlation with total GS/PD scores of 28 joints was explored. The normal distribution data was represented by mean SD, while the non-normal distribution data was represented by median (interquad interval, IQR). Correlation analysis was performed using 95% Spearman nonparametric correlation coefficient. All statistical tests were bilateral, with a significance of P<0.01. Results:163 RA patients were enrolled. 85% of them were female, with an average age of (52.0±13.0) years and a median course of disease 34(24, 45) months. The disease activity score in 28 joints C-reactive protein (DAS28-CRP), simplified disease activity index (SDAI) and clinical disease activity index (CDAI) were 4.2(2.4, 5.4), 17.9 (5.7, 33.3) and 16.0 (5.0, 28.5), respectively. There was discordance between tender joint count (TJC) and swollen joint count (SJC) in some patients. Eighty-nine (54.6%) patients had higher TJC than SJC, while 19(11.7%) patients had fewer TJC than SJC. The accordance between physician's global assessment (PGA) and evaluator Sglobalassessmentofdiseaseactivity (EGA) was observed in only 61 cases (37.4%). Eighty-nine patients (54.6%) had a higher PGA than EGA. Overall, all the parameters [TJC, SJC, PGA, PGA, erythrocyte sedimentation rate (ESR) and CRP] were positively correlated with the total GS/PD scores ( r>0.50, P<0.01). Composite disease activity scores, DAS28, SDAI and CDAI, were also significantly correlated with total GS/PD scores ( r>0.59, P<0.01). But compared with TJC, the correlation between SJC and GS/PD was better ( r=0.59/0.60, P<0.01; r=0.50/0.51, P<0.01). Similarly, compared with GPA, the correlation between EGA and GS/PD was better ( r=0.66/0.67, P<0.01; r=0.55/0.58, P<0.01). Conclusion:The composite disease activity scores and all their components are significantly correlated with ultrasonic synovitis. Compared with TJC and PGA, SJC, EGA, CRP and ESR show a higher correlation with joint ultrasonic synovitis, and are more objective and meaningful in the evaluation of RA disease activity.

Objective:To explore the clinical and serological evolution of patients with positive antiphospholipid antibodies (aPL), and the factors and therapeutic implications associated with aPL negativization.Methods:Patients with a persistent serological positive aPL according to established criteria between 1997 and 2018 were included. The Lupus anticoagulant (LA), anti-cardiolipid antibody (aCL) and anti-β 2 glycoproteinⅠ (anti-β 2GPⅠ) were tested following the International Society on Thrombosis and Haemostasis guidelines. The patients were classified as aPL negativization if the following aPL tests became negative, on two or more occasions at least 12 weeks apart. Titer more than 40 RU/ml was defined as moderate to high titer for anti-aCL and anti-β 2GPⅠ. For patients receiving warfarin, the results of LA were counted only when international normalized ratio (INR)<1.5. Results:There were 93 patients finally involved. 25% of them were primary APS and 63% were conco-mitant with systemic lupus erythematosus (SLE). After a mean follow-up of 45.0 (45.0) months, the percentage of aPL negativization was 11%(9/83), 26%(18/69), 24%(13/53) for LA, aCL and anti-β 2GP Ⅰ respectively. Multivariate analysis confirmed that double positive of dilute russell's viper venom time (dRVVT) and silica clotting time (SCT) was the only independent protective factor for LA negativization [ OR=0.055, 95% CI (0.006, 0.545); P=0.013]. SLE, moderate to high titer of aCL and number of baseline aPL positivity were independently associated with aCL negativization [ OR=18.2; 95% CI (1.45, 228); P=0.025, for SLE; OR=0.217; 95% CI (0.053, 0.888); P=0.034, for moderate to high titer of aCL; OR=0.198; 95% CI(0.057, 0.689); P=0.011, for number of baseline aPL positivity]. Moderate to high titer of anti-β 2GPⅠ and number of baseline aPL positivity were independent protective factors for anti-β 2GPⅠnegativization [ OR=0.168; 95% CI (0.032, 0.872); P=0.034, for moderate to high titer of anti-β 2GPⅠ; OR=0.243; 95% CI (0.073, 0.813); P=0.022, for number of baseline aPL positivity]. There were no factors related with aPL negativization among 40 triple aPL positive patients. We didn't find any relationship between aPL persistent positivity and further thrombosis/pregnancy morbidity due to limited events. Conclusion:aPLs negativization is common and frequent for aCL. The number of positive antibodies and higher antibody load are associated with persistently positive serology. Patients with SLE are easier to get aCL negativization. Double positive of dRVVT and SCT was a protective factor for LA negativization.

Objective To evaluate the validity of assessing synovitis and tenosynovitis by using musculoskeletal ultrasound scoring systems after standardized training in Chinese doctors.Methods All participants received a 30 minutes' training for the ultrasound scoring systems of synovitis and tenosynovitis.Ten static images were applied to evaluate the changes before and after training,respectively.Each parameter was assessed by a four scale semi-quantitative system recommended by outcomes measures in rheumatoid arthritis clinical trials (OMERACT).Paired t-test was used to assess the differences before and after training.Results Thirteen rheumatologists and two ultrasonographers completed the entire procedure.Significant differences were found before and after training when assessing the severity of gray-scale of synovitis (0.61± 0.30 vs 0.45±0.23;t=2.230,P＜0.05) and power Doppler of synovitis (0.57±0.26 vs 0.31±0.18;t=2.928,P＜0.05) and tenosynotis (0.56±0.15 vs 0.31±0.16;t=5.286,P＜0.05),while no significant difference was found when assessing the gray scale of tenosynovitis (t=-1.679,P＞0.05).Conclusion Standardized training is helpful to improve the validity of ultrasound scoring systems of synovitis and tenosynovitis in Chinese rheumatologists and ultrasonographers.The validity of assessing gray-scale of tenosynovits needs improvement.

Objective To develop the optimal simplified combination of joints for ultrasonographic assessment of joint inflammation of wrists and hands in patients with rheumatoid arthritis (RA).Methods US examination was performed using grey-scale (GSUS) and power Dop.pler (PDUS) semi-quantitative scoring systems with scores 0-3 in 22 joints of 705 RA patients,including all proximal interphalangeal (PIP),metacarpophalangeal (MCP),and bilateral wrist joints.Continuous variables were presented as mean and standard deviation if normally distributed,and dichotomous variables were presented as frequencies.T test and Wilcoxon signed test were applied for statistical analysis.All correlations among US variables were assessed using Spearman's rank correlation test.Candidate joint set was selected by multiple stepwise linear regression analysis.Results Through multiple linear stepwise regression analysis,the standard coefficient of wrist,MCP5,MCP2 and MCP3 joints under GSUS was higher than other joints.And the adjusted R2 of the model composed of wrist,MCP5,MCP2 and MCP3 joints was greater than 0.9.Among the sum GS and PD scores of various selected joint combinations,total score-8 (GS vs PD),including bilateral wrist,MCP2,MCP3,MCP5 joints,not only showed highest sensitivity and negative predictive value (97.3 5％ vs 97.20％;92.67％ vs 97.21％,respectively),but also had the highest correlation with the total score-22 (GS,PD) (r=0.989,0.972,P＜0.01).Conclusion Total score-8,including bilateral wrist,MCP2,MCP3,MCP5 joints,is simple and efficient enough for monitoring active synovitis of wrists and hands in patients with RA in daily practice.

OBJECTIVEThis research aimed to analyze the three-dimensional position of mandibular canal (MC) and man of MC and its relationship with the surrounding structures dibular morphology of normal young males and females by using data from cone beam computed tomography (CBCT), as well as to provide an anatomical basis for clinical surgery of the mandible.

METHODSNormal occlusion and CBCT scans of 29 normal young people were conducted. InVivo 5 software was used to reconstruct the mandible, anchor the points, and measure the jaw shape and three-dimensional course of MC. All measurements were analyzed with SSPS 17.0 software.

RESULTSThe MC lingual bone cortex was thinner than the MC buccal bone cortex, and the distance of the MC to the buccal bone cortex gradually increased. However, the distance of the MC to the tongue bone cortex and alveolar crest gradually decreased from proximal to distal. In addition, the distance of the MC to the mandibular lower margin was minimal at the first molar and reached the maximum at the second premolar. No significant difference was observed among the heights, widths, and thicknesses of the left and right sides of the cortical bone of the mandibular body cross sections. From the midline to the farthest point, the height and lower one-third thickness of the lingual cortical bone of the mandibular body cross sections gradually decreased, whereas the width of the upper cross section and upper one-third thickness of the buccal cortical bone gradually increased. Significant difference was observed in some measured values.

CONCLUSIONAfter MC enter into the mandibular foramen, it moved away from the lingual to the buccal bone but gradually returned to the lingual bone; its general course is closer to the lingual bone. The mandibles of males are thicker than those of females. CBCT can accurately display the course of MC and its relationship with the surrounding structures.

Alveolar Process ; Bicuspid ; Cone-Beam Computed Tomography ; methods ; Dental Pulp Cavity ; Female ; Humans ; Hyoid Bone ; Male ; Mandible ; anatomy & histology ; diagnostic imaging ; Molar ; Software ; Surveys and Questionnaires ; Tongue ; Zygoma