Investigating the influence of excavating a tunnel undercrossing an existing tunnel at zero distance.

In urban areas with limited underground space, the new tunnel construction introduces additional loads and displacements to existing tunnels, raising serious safety concerns. These concerns become particularly pronounced in the case of closely undercrossing excavation at zero-distance. The conventional elastic foundation beam model, which assumes constant reaction coefficients for the subgrade, fails to account for foundation loss. In this study, the existing tunnel is modeled as an Euler-Bernoulli beam supported by the Pasternak elastic foundation, and the foundation loss caused by zero-distance undercrossing excavations is considered. Furthermore, an analytical solution is proposed to evaluate the mechanical response in segments, by establishing governing differential equations and boundary conditions for the excavation and neutral zones, and underpinning loads are also considered. The analytical solution is validated in two case studies. Finally, a parametric analysis is performed to explore the influence of various parameters on the mechanical response of the existing tunnel.

Comprehensive analysis identifies crucial genes associated with immune cells mediating progression of carotid atherosclerotic plaque.

BACKGROUNDS: Carotid atherosclerosis is prone to rupture and cause ischemic stroke in advanced stages of development. Our research aims to provide markers for the progression of atherosclerosis and potential targets for its treatment. METHODS: We performed a thorough analysis using various techniques including DEGs, GO/KEGG, xCell, WGCNA, GSEA, and other methods. The gene expression omnibus datasets GSE28829 and GSE43292 were utilized for this comprehensive analysis. The validation datasets employed in this study consisted of GSE41571 and GSE120521 datasets. Finally, we validated PLEK by immunohistochemistry staining in clinical samples. RESULTS: Using the WGCNA technique, we discovered 636 differentially expressed genes (DEGs) and obtained 12 co-expression modules. Additionally, we discovered two modules that were specifically associated with atherosclerotic plaque. A total of 330 genes that were both present in DEGs and WGCNA results were used to create a protein-protein network in Cytoscape. We used four different algorithms to get the top 10 genes and finally got 6 overlapped genes (TYROBP, ITGB2, ITGAM, PLEK, LCP2, CD86), which are identified by GSE41571 and GSE120521 datasets. Interestingly, the area under curves (AUC) of PLEK is 0.833. Besides, we found PLEK is strongly positively correlated with most lymphocytes and myeloid cells, especially monocytes and macrophages, and negatively correlated with most stromal cells (e.g, neurons, myocytes, and fibroblasts). The expression of PLEK were consistent with the immunohistochemistry results. CONCLUSIONS: Six genes (TYROBP, ITGB2, ITGAM, PLEK, LCP2, CD86) were found to be connected with carotid atherosclerotic plaques and PLEK may be an important biomarker and a potential therapeutic target.

Rapidly progressive interstitial lung disease risk prediction in anti-MDA5 positive dermatomyositis: the CROSS model.

Background: The prognosis of anti-melanoma differentiation-associated gene 5 positive dermatomyositis (anti-MDA5+DM) is poor and heterogeneous. Rapidly progressive interstitial lung disease (RP-ILD) is these patients' leading cause of death. We sought to develop prediction models for RP-ILD risk in anti-MDA5+DM patients. Methods: Patients with anti-MDA5+DM were enrolled in two cohorts: 170 patients from the southern region of Jiangsu province (discovery cohort) and 85 patients from the northern region of Jiangsu province (validation cohort). Cox proportional hazards models were used to identify risk factors of RP-ILD. RP-ILD risk prediction models were developed and validated by testing every independent prognostic risk factor derived from the Cox model. Results: There are no significant differences in baseline clinical parameters and prognosis between discovery and validation cohorts. Among all 255 anti-MDA5+DM patients, with a median follow-up of 12 months, the incidence of RP-ILD was 36.86%. Using the discovery cohort, four variables were included in the final risk prediction model for RP-ILD: C-reactive protein (CRP) levels, anti-Ro52 antibody positivity, short disease duration, and male sex. A point scoring system was used to classify anti-MDA5+DM patients into moderate, high, and very high risk of RP-ILD. After one-year follow-up, the incidence of RP-ILD in the very high risk group was 71.3% and 85.71%, significantly higher than those in the high-risk group (35.19%, 41.69%) and moderate-risk group (9.54%, 6.67%) in both cohorts. Conclusions: The CROSS model is an easy-to-use prediction classification system for RP-ILD risk in anti-MDA5+DM patients. It has great application prospect in disease management.

Classifying systemic lupus erythematosus using laboratory items alone: a preliminary study.

OBJECTIVES: To explore the performance of laboratory items alone in systemic lupus erythematosus (SLE) classification. METHODS: Our cohort consisted of 352 and 385 (control) patients with and without SLE. This study evaluated the performance of the American College of Rheumatology (ACR)-1997, Systemic Lupus International Collaborating Clinics (SLICC)-2012, European League Against Rheumatism (EULAR)/ACR-2019, and Systemic Lupus Erythematosus Risk Probability Index (SLERPI) using laboratory items alone, including blood and urine test results. RESULTS: The median ratio of laboratory items/total items was 66.7%, 75.0%, 60.4%, and 77.4% in ACR-1997, SLICC-2012, EULAR/ACR-2019, and SLERPI, respectively. After including laboratory items alone, the sensitivity of ACR-1997, SLICC-2012, EULAR/ACR-2019, and SLERPI was 31.3% (95% confidence interval [CI]: 26.4%-36.4%), 79.8% (95% CI: 75.3%-83.9%), 75.9% (95% CI: 71.0%-80.2%), and 85.2% (95% CI: 81.1%-88.8%), respectively. We referenced the SLERPI and removed the additional restrictions, i.e., SLICC-2012 criteria only needs to fulfill at least four items (mSLICC-2012) and EULAR/ACR-2019 criteria needs to have ≥ 10 points (mEULAR/ACR-2019) to qualify for SLE classification. The mSLICC-2012 and mEULAR/ACR-2019 criteria, including laboratory items alone, newly identified 13 and 25 patients, respectively. Based on laboratory items alone, the combination of mSLICC-2012, mEULAR/ACR-2019, and SLERPI identified 348 patients with an improved sensitivity of 90.6% (95% CI: 87.1%-93.5%). Patients, who were classified according to the mEULAR/ACR-2019 criteria, all met the other criteria. CONCLUSION: Incorporating laboratory items alone was clinically feasible to help identify SLE. SLERPI and SLICC-2012, using laboratory items alone, were more worthwhile to promote in the clinic compared with EULAR/ACR-2019. Key Points • Laboratory items play a crucial role in the SLE classification criteria, and incorporating laboratory items alone was clinically feasible to help in the identification of SLE. • The SLERPI and SLICC-2012, using laboratory items alone, were more worthwhile to promote in the clinic compared with EULAR/ACR-2019, and the combination of the two could further improve the sensitivity. • The relative simplicity of evaluating laboratory indices may help nonrheumatologists and inexperienced rheumatologists to identify SLE more quickly, thereby reducing the risk of delayed diagnosis in patients.

Tumour-associated antigens in systemic lupus erythematosus: association with clinical manifestations and serological indicators.

OBJECTIVES: To explore the relationship of tumour-associated antigens (TAAs) with the clinical manifestations and serological markers of SLE. METHODS: This was a retrospective study. Clinical data of SLE patients were extracted from the electronic medical records, including serum levels of TAAs such as alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), cancer antigen (CA) 19-9, CA125, CA15-3 and cytokeratin 19-fragments (CYFRA21-1). TAA positivity was defined as serum level exceeding the upper limit of the corresponding reference range. RESULTS: A total of 149 SLE patients (SLE group) and 149 age- and sex-matched healthy subjects (control group) were enrolled. Compared with healthy controls, the SLE group had higher positivity rates for CA19-9 and CYFRA21-1, and elevated serum levels of CA125, CA15-3 and CYFRA21-1. SLE patients with TAA positivity were older, had a higher prevalence of serous effusion, pericardial effusion, albuminuria and thrombocytopenia, and lower positivity rate for anti-dsDNA than patients without TAA positivity. The levels of serum creatinine (SCR), blood urea nitrogen, glutamic oxalate transaminase and 24-h urinary protein were also higher in SLE patients with TAA positivity, but platelet count and serum albumin levels were lower. On logistic regression, thrombocytopenia and SCR levels were identified as independent risk factors for TAA positivity. CA125 positivity rate and serum levels of CA125 were associated with SLE disease activity. CONCLUSION: The positivity rates and serum levels of some TAAs were elevated in SLE, and thrombocytopenia and SCR levels were independent risk factors for TAA positivity.

Gender differences in patients with anti-MDA5-positive dermatomyositis: a cohort study of 251 cases.

OBJECTIVE: To investigate the impact of sex differences on the clinical characteristics and prognosis of patients with anti-melanoma differentiation-associated gene 5-positive dermatomyositis (MDA5+ DM). METHODS: We retrospectively analyzed a cohort of 251 patients with MDA5+ DM, including 71 in the male group and 180 in the female group. A multivariate logistic regression model was built to analyze independent risk factors for RPILD in each group. An ROC curve was drawn to evaluate the predictive value of independent risk factors. Kaplan‒Meier analysis was used to compare the cumulative survival rates, while the log-rank test was used to test for significant differences between the two groups. RESULTS: Patients in the male group had a significantly higher prevalence of heliotrope rash, V sign, severe interstitial lung disease (ILD), and rapidly progressive interstitial lung disease (RPILD) than those in the female group. Anti-Ro52 positivity, high CRP level and short disease were identified as independent risk factors for RPILD in both male and female groups by multivariate logistic regression analysis. The mortality rates of males and females were 33.8% and 22.0%, respectively, and the survival time of patients in the male group was shorter than that in the female group. CONCLUSION: Male patients with MDA5+ DM exhibit an increased risk of RPILD, elevated mortality rates and reduced overall survival time compared to their female counterparts, and anti-Ro52 positivity may be an unfavorable prognostic factor for these patients. Key Points • The prevalence of solar rash, V sign, severe interstitial lung disease (ILD) and rapidly progressive interstitial lung disease (RPILD) in anti-MDA5-positive female patients was significantly lower than that in male patients. • Positive Anti-Ro52, high CRP level, and short course of disease were independent risk factors for RPILD in both men and women. • Female patients exhibited a lower mortality rate than male patients (22.0% vs 33.8%) and demonstrated longer survival time.

Association of serum tumor markers with serous effusion in systemic lupus erythematosus.

The objective of this study was to investigate the relationship between serum tumor markers and serous effusion in systemic lupus erythematosus (SLE) patients, thereby contributing preliminary data on the utility of these tumor markers in diagnosing serous effusion. In this retrospective analysis, clinical data of SLE patients were extracted from electronic medical records. This included the levels of serum tumor markers, including pro-gastrin-releasing peptide, neuron-specific enolase (NSE), cytokeratin-19 fragments (CYFRA 21-1), various carbohydrate antigens (CA 153, CA 125, CA 19-9), along with carcinoembryonic antigen, and alpha-fetoprotein. Positivity of tumor markers was established based on serum levels surpassing the upper threshold of the respective reference ranges. This study included 149 eligible patients with SLE, of whom 38 (25.50%) had serous effusion, and the prevalence of pleural, pericardial, and peritoneal effusions was 11.41%, 14.77%, and 6.71%, respectively. The analysis revealed that patients with serous effusion had higher scores on the SLE Disease Activity Index 2000 (SLEDAI 2000) than those without serous effusion. Notably, this disparity remained significant when the serositis score was excluded from the SLEDAI 2000 calculation. The positivity rate and serum levels of CA 125 were higher in patients with serous effusion and pleural effusion. Patients with pericardial effusion demonstrated an elevated CYFRA 21-1 positivity rate and serum CA 125 and CYFRA 21-1 levels compared to patients without pericardial effusion. CA 125 and NSE were higher both in terms of positivity rate and serum levels for patients with peritoneal effusion. Through receiver operating characteristic curve analysis, a moderate relationship was discerned between the conjoined levels of CYFRA 21-1 and CA 125 and the occurrence of pericardial effusion. Additionally, CA 125, NSE, and their combination revealed the moderate diagnostic ability of peritoneal effusion. In summary, this study observed elevated serum levels of various tumor markers in SLE patients exhibiting serous effusion, which is likely attributable to lupus-induced inflammation. These findings suggest that serum tumor markers can be valuable in diagnosing pericardial and peritoneal effusions.

A Rare Case of Primary Sjogren's Syndrome Coexisting With Gilbert Syndrome.

Gilbert syndrome (GS) is an autosomal recessive inherited bilirubin metabolism disorder characterized by chronic unconjugated hyperbilirubinemia in the absence of hemolysis and liver disease. Primary Sjogren's syndrome (pSS), mainly occurring in women, is a common connective tissue disease (CTD) wherein bilirubin levels are generally reduced. We report a rare case of pSS coexisting with GS. A 35-year-old female patient presented to our hospital with pSS and chronic unconjugated hyperbilirubinemia, for which low-dose methylprednisolone was ineffective. The patient's liver function test results were normal, serological tests for hepatitis virus were negative, and abdominal ultrasound did not indicate abnormal liver morphology. Bone mineral density determination showed that the Z scores of the left femoral neck and lumbar spine were -1.9 and -2.6, respectively, with T scores of -2.1 and -2.8, respectively. Full-exon sequencing revealed a homozygous TA insertion in the TATA box (A(TA)7TAA) and a heterozygous base substitution from C to A at nucleotide position 686 in exon 1 (c.686C>A) in the uridine glucuronosyltransferase 1A1 (UGT1A1) gene. Therefore, the patient was diagnosed with pSS, GS, and osteoporosis. The dose of methylprednisolone was then reduced and gradually stopped, and treatment for osteoporosis was strengthened. To our knowledge, this is the first report of pSS with GS. It is important to clarify the cause of hyperbilirubinemia in patients with CTD, including pSS, which affects the formulation of correct treatment plans.

Systemic Lupus Erythematosus Risk Probability Index: ready for routine use? Results from a Chinese cohort.

OBJECTIVES: To evaluate the performance of Systemic Lupus Erythematosus Risk Probability Index (SLERPI) in patients with SLE using a Chinese cohort. METHODS: The Chinese cohort included 352 patients with and 385 without SLE (control group). The clinical data of patients, including demographic data, clinical findings and serological profiles, were collected. Patients with an SLERPI score >7 were classified as SLE. The performance of the American College of Rheumatology (ACR)-1997, Systemic Lupus International Collaborating Clinics (SLICC)-2012 and European League Against Rheumatism (EULAR)/ACR-2019 criteria were used as references. RESULTS: Of these four classification criteria, SLERPI has the highest sensitivity (98.3% (95% CI 96.3% to 99.4%)), but lowest specificity (89.4% (95% CI 85.8% to 92.2%)). In the control group, patients eligible for the classification criteria for SLE were mainly those with primary Sjogren's syndrome (pSS) and undifferentiated connective tissue disease (UCTD), which adversely affected the specificity of the classification criteria. Moreover, significantly more patients with pSS and UCTD met SLERPI than those who met other classification criteria. After excluding patients with pSS and UCTD from the control group, the specificity and accuracy of SLERPI improved to 94.3% (95% CI 91.0% to 96.6%) and 96.5% (95% CI 95.0% to 97.9%), respectively, and both outperformed the EULAR/ACR-2019 criteria. The time to SLERPI classification was the same as their clinical time to diagnosis in 261 patients, earlier than the clinical diagnosis in 23 patients and later than the clinical diagnosis in 9 patients. A total of 280 patients had the same time to SLERPI classification as EULAR/ACR-2019, 8 patients had earlier than EULAR/ACR-2019 and 1 patient had later than EULAR/ACR-2019. CONCLUSION: SLERPI performed well in patients with SLE, particularly for the earlier diagnosis of SLE.