The proliferation/migration ability mediated by CD151/PI3K/AKT pathway determines the therapeutic effect of hUC-MSCs transplantation on rheumatoid arthritis.

OBJECTIVE: To elucidate the underlying mechanism by which the proliferation and migration abilities of human umbilical cord mesenchymal stem cells (hUC-MSCs) determine their therapeutic efficacy in rheumatoid arthritis treatment. METHODS: The DBA/1J mice were utilized to establish a collagen-induced RA (CIA) mouse model and to validate the therapeutic efficacy of hUC-MSCs transfected with CD151 siRNA. RNA-seq, QT-PCR and western blotting were utilized to evaluate the mRNA and protein levels of the PI3K/AKT pathway, respectively. RESULTS: IFN-γ significantly enhanced the proliferation and migration abilities of hUC-MSCs, up-regulating the expression of CD151, a gene related to cell proliferation and migration. Effective inhibition of this effect was achieved through CD151 siRNA treatment. However, IFN-γ did not affect hUC-MSCs differentiation or changes in cell surface markers. Additionally, transplantation of CD151-interfered hUC-MSCs (siRNA-CD151-hUC-MSCs) resulted in decreased colonization in the toes of CIA mice and worse therapeutic effects compared to empty vector treatment (siRNA-NC-hUC-MSCs). CONCLUSION: IFN-γ facilitates the proliferation and migration of hUC-MSCs through the CD151/PI3K/AKT pathway. The therapeutic efficacy of siRNA-CD151-hUC-MSCs was found to be inferior to that of siRNA-NC-hUC-MSCs.

Recurrent stroke shortly after mechanical thrombectomy secondary to carotid web: A case report.

RATIONALE: Carotid web, a known source of thrombus for embolic stroke, presents a considerable risk of stroke recurrence. While case reports have demonstrated the safety and effectiveness of mechanical thrombectomy in treating carotid web-related stroke, the need for concurrent carotid artery stenting to prevent recurrent stroke immediately after thrombectomy remains unclear. This study aims to underscore the importance of immediate carotid artery stenting in preventing recurrent stroke following mechanical thrombectomy in patients with carotid web-related stroke. PATIENT CONCERNS: A 43-year-old woman with acute onset of left limb weakness and slurred speech within 3 hours was admitted to the emergency department. DIAGNOSES: Computed tomographic angiography confirmed the M1 segment occlusion of the right middle cerebral artery. INTERVENTIONS: The patient received intravenous thrombolysis in the local hospital and mechanical thrombectomy in our stroke center. OUTCOMES: Three days post-mechanical thrombectomy, there was a sudden exacerbation of her neurological deficit symptoms. A reexamination via computed tomographic angiography revealed a re-occlusion in M1 segment of the right middle cerebral artery, despite the implementation of stringent anticoagulation therapy for carotid web-related stroke. LESSONS: Stroke patients with carotid web had a high risk of stroke recurrence and it was necessary to conduct carotid artery stenting to prevent stroke recurrence secondary to the carotid web immediately after mechanical thrombectomy.

[Effects of Biochar Application on Physicochemical Properties and Bacterial Communities of Microplastic-contaminated Calcareous Soil].

Microplastics are widely distributed in the soil environment, threatening the soil ecological environment system and changing soil physicochemical properties and microbial characteristics. Biochar is often used as a soil amendment to improve soil quality due to its special pore structure and good soil nutrient retention ability. However, the understanding of the effects and mechanisms of biochar application on the physicochemical properties and bacterial communities of microplastic-contaminated soils is still very limited. Therefore, a 21-day micro-soil culture experiment was conducted to analyze the effects of biochar application on physicochemical properties and bacterial community changes in soil contaminated with different concentrations of microplastics using 16S rRNA high-throughput sequencing technology. The results revealed that the application of biochar slowed down the decrease in nitrate nitrogen and Olsen-P contents in microplastic-contaminated soil and increased the total phosphorus content. Biochar addition increased the relative abundance of tolerant phylum such as Acidobacteriota, Actinobacteriota, and Bacteroidota in microplastic-contaminated calcareous soil. Proteobacteria, Acidobacteriota, and Actinobacteriota were the dominant bacteria of the soil bacterial community in each treatment on day 7 and day 21. Compared with that on day 7, the relative abundance of Proteobacteria and Firmicutes significantly decreased, and the relative abundance of Acidobacteriota, Actinobacteriota, Bacteroidota, Chloroflexi, and Myxococcota increased on day 21. Biochar application also increased the relative abundance of Lysobacter in microplastic-contaminated soils. This study demonstrated that the application of biochar increased microplastic-resistant bacteria, enhanced the stability of microplastic-contaminated soil, and slowed down the pollution of microplastics to the soil. Moreover, biochar had great potential to improve the quality of microplastic-contaminated calcareous soil.

Multiple lines of evidence of early goose domestication in a 7,000-y-old rice cultivation village in the lower Yangtze River, China.

Poultry are farmed globally, with chicken (Gallus gallus domesticus) being the leading domesticated species. Although domestic chicken bones have been reported from some Early Holocene sites, their origin is controversial and there is no reliable domestic chicken bone older than the Middle Holocene. Here, we studied goose bones from Tianluoshan­a 7,000-y-old rice cultivation village in the lower Yangtze River valley, China­using histological, geochemical, biochemical, and morphological approaches. Histological analysis revealed that one of the bones was derived from a locally bred chick, although no wild goose species breed in southern China. The analysis of oxygen-stable isotope composition supported this observation and further revealed that some of the mature bones were also derived from locally bred individuals. The nitrogen-stable isotope composition showed that locally bred mature birds fed on foods different from those eaten by migrant individuals. Morphological analysis revealed that the locally bred mature birds were homogenous in size, whereas radiocarbon dating clearly demonstrated that the samples from locally bred individuals were ∼7,000 y old. The histological, geochemical, biochemical, morphological, and contextual evidence suggest that geese at Tianluoshan village were at an early stage of domestication. The goose population appears to have been maintained for several generations without the introduction of individuals from other populations and may have been fed cultivated paddy rice. These findings indicate that goose domestication dates back 7,000 y, making geese the oldest domesticated poultry species in history.

ANA-positive primary immune thrombocytopaenia: a different clinical entity with increased risk of connective tissue diseases.

OBJECTIVE: Primary immune thrombocytopaenia (ITP) is highly heterogeneous. ANA-positive primary ITP may resemble the preclinical stage of connective tissue diseases (CTDs), but is still considered primary ITP due to a controversial CTD risk assessment in this group. The objective of this study was to clarify the risk of CTD in ANA-positive patients with primary ITP. METHODS: We performed a retrospective cohort study and a meta-analysis. 586 patients with newly diagnosed primary ITP were followed up and Cox regression analyses were used to analyse the associations of ANA positivity and other immune parameters with CTD development. RESULTS: The mean follow-up time was 37 (19-56) months. ANA was positive in 21.33% (125 of 586) of patients with primary ITP in our retrospective cohort, and the overall rate of ANA positivity in the meta-analysis was 17.06% (369 of 2163). The adjusted HR for CTD in ANA-positive primary ITP was 6.15 (95% CI 2.66 to 14.23, p<0.001). Five patients in the ANA-positive group developed SLE (5 of 125, 4.0%), significantly higher than in the ANA-negative group (0 of 461, 0%). A clinical model combining ANA, anti-Sjogren's syndrome A antibody and C3 was successfully developed to predict the risk of CTD in patients with primary ITP. Increased risk of CTD (risk ratio=12.43, 95% CI 7.91 to 19.55, p<0.00001), especially SLE (risk ratio=30.41, 95% CI 13.23 to 69.86, p<0.00001), among ANA-positive patients with primary ITP was confirmed by a meta-analysis of previous studies and the present study. CONCLUSIONS: The findings suggest that ANA-positive primary ITP is a clinical entity distinct from other primary ITPs and is associated with increased risk of developing CTDs, especially SLE.

Neurological Involvement in Patients With Primary Sjögren's Syndrome.

BACKGROUND/OBJECTIVE: The neurological involvement associated with primary Sjögren's syndrome (pSS) can be life threatening. However, the specific characteristics of pSS-related neurological involvement remain obscure. This study aimed at determining the clinical characteristics of this neurological involvement in patients with pSS. METHODS: The clinical data of 205 patients with pSS who were admitted to our department between January 2015 and June 2017 were studied. Characteristics and laboratory findings of pSS patients with neurological abnormalities were compared with pSS patients without. RESULTS: Forty of the 205 patients with pSS exhibited neurological abnormalities (19.51%); of these, 13 patients exhibited central nervous system (CNS) involvement only, 20 patients exhibited peripheral nervous system (PNS) involvement only, and 7 patients exhibited both, yielding a total of 20 (9.76%) patients with CNS involvement and 27 (13.17%) patients with PNS involvement. The titers of anti-Sjögren's syndrome type A (SSA) antibodies were significant higher while the presence of anti-Sjögren's syndrome type B (SSB) antibodies was significant lower in patients with vs. without neurological involvement. Similar results were found in patients with CNS involvement. No significant differences between patients with and without neurological involvement were found for the other clinical parameters examined. CONCLUSIONS: Neurological involvement in patients with pSS is common and needs to be carefully evaluated. Patients with pSS with a high titer of anti-SSA and low presence of anti-SSB antibodies might have a relatively high risk of developing neurological involvement. Future studies should focus on identifying biomarkers that may aid in the early diagnosis of neurological involvement in patients with pSS.

Characteristics of the Urinary Microbiome From Patients With Gout: A Prospective Study.

The role of host microbes in the pathogenesis of several diseases has been established, and altered microbiomes have been related to diseases. However, the variability of the urinary microbiome in individuals with gout has not been evaluated to date. Therefore, we conducted the present prospective study to characterize the urinary microbiome and its potential relation to gout. Urine samples from 30 patients with gout and 30 healthy controls were analyzed by Illumina MiSeq sequencing of the 16S rRNA hypervariable regions, and the microbiomes were compared according to alpha-diversity indices, complexity (beta diversity) with principal component analysis, and composition with linear discriminant analysis effect size. The most significantly different taxa at the phylum and genus levels were identified, and their potential as biomarkers for discriminating gout patients was assessed based on receiver operating characteristic (ROC) curve analysis. Compared with the healthy controls, there was a dramatic decrease in microbial richness and diversity in the urine of gout patients. The phylum Firmicutes and its derivatives (Lactobacillus_iners, Family_XI, and Finegoldia), the phylum Actinobacteria and its derivatives (unidentified_Actinobacteria, Corynebacteriales, Corynebacteriale, Corynebacterium_1, and Corynebacterium_tuberculostearicum), and the genera Prevotella and Corynebacterium_1 were significantly enriched in the urine of gout patients. ROC analysis indicated that the top five altered microbial genera could be reliable markers for distinguishing gout patients from healthy individuals. These findings demonstrate that there are specific alterations in the microbial diversity of gout patients. Thus, further studies on the causal relationship between gout and the urinary microbiome will offer new prospects for diagnosing, preventing, and treating gout.

Clinical Characteristics of Secondary Immune Thrombocytopenia Associated With Primary Sjögren's Syndrome.

Objective: Clinical characteristics of immune thrombocytopenia (ITP) associated with primary Sjögren's syndrome (pSS) have not been clearly defined. This study aimed to evaluate the prevalence and clinical characteristics of secondary ITP in patients with pSS. Methods: 291 pSS patients in our hospital were retrospectively analyzed. Clinical manifestations and laboratory findings were compared between pSS patients with and without ITP. Results: The prevalence of secondary ITP in pSS patients was 12.03%. Compared to pSS patients without ITP, pSS patients with ITP were younger and had higher disease activity. The prevalence of interstitial lung diseases (ILD) was significantly lower in pSS patients with ITP (30.43 vs. 54.95%; P = 0.029), and it was the same with arthritis (17.14 vs. 3.9.11%; P = 0.014) and dry eye (33.33 vs. 54.17%, P = 0.027) compared with those without ITP. Serum creatinine level was lower in pSS patients with ITP (P = 0.009), while positivity of anti-histone autoantibodies was higher in pSS patients with ITP (P = 0.025). Conclusion: This study is an initial report describing clinical features of ITP in pSS. The lower incidence of ILD and arthritis among pSS patients with ITP indicated potential active roles of platelets in the pathogenesis of fibrosis or inflammatory arthritis, which may open the way for further experimental and clinical work.

Antinuclear antibodies positivity is a risk factor of recurrent pregnancy loss: A meta-analysis.

OBJECTIVE: Immunologic mechanisms have been proposed as part of the pathogenesis mechanisms involved in recurrent pregnancy loss (RPL). Presence of positive antinuclear antibodies (ANA) is regarded as a typical feature of autoimmunity. Many studies had tried to clarify the association of ANA with RPL, but the conclusions were controversial. The aim of this meta-analysis was to assess whether ANA was positively associated with increased RPL risk. METHODS: We searched PubMed and Embase databases for relevant literatures on the association between ANA positivity and RPL. The odds ratios (OR) with 95% confidence intervals (95%CI) were pooled using meta-analysis, and either fixed-effect or random-effect model was used based on heterogeneity across the included studies. RESULTS: Twenty-one studies with 5038 participants (including 2683 RPL patients and 2355 controls) met the inclusion criteria were included. The total positive rate of ANA was 22.0% (591/2683) in RPL group, and 8.3% (196/2355) in the control group. RPL patients had a significantly higher ANA positive rate than controls (OR = 2.97, 95%CI 1.91-4.64, P<0.00001; I² = 75%), and a significant association between positive ANA and unexplained RPL was also observed (OR = 3.27, 95%CI 2.01-5.31, P<0.00001; I² = 70%). ANA positivity was also significantly associated with increased risk of RPL in women without defined autoimmune diseases (OR = 2.23, 95%CI 1.40-3.55, P=0.0007). Subgroup analysis demonstrated low titers of ANA (1:40≤ANA≤1: 80) were not associated with RPL (OR = 2.44, 95%CI 0.42-14.06, P=0.32), while higher ANA titer (≥1:160) had a significant association with RPL (OR = 45.89, 95%CI 8.44-249.45, P<0.00001). A higher rate of homogenous pattern in RPL patients was observed (OR = 4.89, 95%CI 2.20-10.87, P<0.001), and no significant difference in speckled pattern or nucleolar pattern was found. CONCLUSIONS: This study demonstrated that ANA positivity was positively associated with increased RPL risk. ANA positivity is an important risk factor for RPL which needed to be screened among women with RPL.

Efficiency of Therapeutic Plasma-Exchange in Acute Interstitial Lung Disease, Associated With Polymyositis/Dermatomyositis Resistant to Glucocorticoids and Immunosuppressive Drugs: A Retrospective Study.

Interstitial lung disease (ILD) is a life-threating complication, commonly associated with polymyositis (PM), and dermatomyositis (DM). A subset of acute ILD associated with PM/DM patients are refractory to conventional treatment, and leads to a high rate of mortality. The efficacy of therapeutic plasma-exchange (TPE) as a PM/DM treatment to improve muscle involvement is controversial due to a lack of evidence. However, in recent reports, TPE has been effective in improving lung involvement. To evaluate the efficacy of this therapy, we retrospectively studied TPE treatment outcomes for in 18 acute PM/DM-ILD patients who were resistant to conventional therapies. Five patients were diagnosed with DM (27.8%), 11 with CADM (61.1%), and two with PM (11.1%). Among 18 patients, 11 (61.1%) achieved satisfactory improvement after four or more rounds of TPE, whereas seven died due to respiratory failure. We also analyzed risk factors to predict unresponsiveness to TPE in these patients. Notably, the prevalence of subcutaneous/mediastinal emphysema was significantly higher in the non-responsive group (6/7, 85.7%) than in the responsive group (2/11, 18.2%; P = 0.013); moreover, patients with this complication were mainly in the CADM subgroup (6/8, 75%). Subcutaneous/mediastinal emphysema and increased serum ferritin levels were shown to be poor prognostic factors, predictive of unresponsiveness to TPE, in PM/DM patients. No autoantibodies were found to be associated with TPE outcome, although we only investigated anti-Jo-1 and anti-Ro antibodies; the clinical significance of other myositis-specific autoantibodies, especially anti-melanoma differentiation-associated gene 5 (MDA5) antibody, is not known. Our results indicate that TPE might be an alternative treatment for acute PM/DM-ILD patients resistant to conventional therapies, except for those with subcutaneous/mediastinal emphysema and high serum ferritin levels.

Differentiation between recurrent gliomas and radiation necrosis using arterial spin labeling perfusion imaging.

Arterial spin labeling (ASL) magnetic resonance (MR) perfusion imaging has been proposed as an effective method to measure brain tumor perfusion. The aim of the present study was to evaluate the utility of this technique in the differentiation of recurrent gliomas from radiation necrosis. Twenty-one patients with surgically treated primary gliomas, including 16 cases of recurrent glioma and 5 of radiation necrosis were examined using 3.0T MR imaging (MRI). ASL and dynamic susceptibility contrast-weighted (DSC) perfusion MRI scans were performed. Maps of normalized cerebral blood flow (CBF) in ASL imaging and cerebral blood volume (CBV) in DSC imaging were computed and analyzed in the regions of interest. In cases of glioma recurrence, the normalized ASL-CBF ratio (4.45±2.72) was higher than that in cases of radiation injury (1.22±0.61) (P<0.01). The normalized DSC-relative CBV ratio was also significantly higher in glioma recurrence (3.38±2.08) than it was in radiation injury (1.09±0.55) (P<0.05). A close linear correlation was found between the ASL and DSC MRI techniques (linear regression coefficient, R=0.85; P=0.005) in the differentiation of recurrent glioma from radiation injury. The results indicate that ASL perfusion is an accurate method of distinguishing between glioma recurrence and radiation necrosis.