Multivariate logistic regression analysis of poor prognosis of dermatomyositis and clinical value of ferritin/Kl-6 in predicting prognosis.

BACKGROUND: Dermatomyositis (DM) is a rare inflammatory disease. Our research focuses on predicting poor prognosis in DM patients and evaluating the prognostic significance of ferritin and Salivary Sugar Chain Antigen-6 (KL-6) through multivariate logistic regression analysis. METHODS: Between February 2018 and April 2020, 80 DM patients at our hospital were categorized into MDA5 positive (n = 20) and negative (n = 60) groups. We conducted multivariate logistic regression to determine DM's poor prognosis risk factors and evaluate ferritin/KL-6's predictive value for prognosis. RESULTS: Analysis showed no gender, age, body mass index (BMI), or lifestyle (smoking, drinking) differences, nor in dyspnea, muscle weakness, skin ulcers, and acetylcysteine treatment effects (p > 0.05). Significant differences emerged in arrhythmias, interstitial pneumonia, C-reactive protein, albumin, and lactate dehydrogenase levels (p < 0.05). Before treatment, differences were negligible (p > 0.05), but post-treatment, serum KL-6 and ferritin levels dropped. MDA5 positive patients had elevated serum KL-6 and ferritin levels than survivors (p < 0.05), with a strong correlation to DM. Combined diagnosis using serum KL-6 and ferritin for DM prognosis showed area under curves of 0.716 and 0.634, significantly outperforming single-index diagnoses with an area under curve (AUC) of 0.926 (p < 0.05). CONCLUSION: Serum KL-6 and ferritin show marked abnormalities in DM, useful as indicators for evaluating polymyositis and DM conditions. However, the study's small sample size is a drawback. Expanding the sample size is essential to monitor serum KL-6 and ferritin changes in DM patients under treatment more closely, aiming to improve clinical assessment and facilitate detailed research.

Clinical Value of sTREM-1, PCT, and 1,3-ß-D Glucan in Diagnosis of Immune-Associated Pulmonary Interstitial Disease with Fungal Infection.

Background: Fungal infection in the lungs can cause fungal infectious diseases. This disease develops rapidly and involves a wide range. Pathogenic fungi are also more serious types of pathogenic bacteria. If it invades deep organs and tissues, it will endanger life, so it needs timely diagnosis. Aim: To investigate the diagnostic value of serum soluble myeloid cell triggering receptor-1 (sTREM-1), procalcitonin (PCT), and 1,3-ß-D glucan detection in immune related lung disease complicated with fungal infection. Methods: In this study, a case-control study was conducted. 50 patients with immune-related pulmonary disease complicated with fungal infection (infection group) diagnosed by sputum culture in our hospital from January 2017 to December 2021 were selected as the control group, and 50 patients with immune-related pulmonary disease without fungal infection were selected as the control group. The levels of sTREM-1, PCT, and 1,3-ß-D glucan were compared in the two groups. The receiver operating characteristic (ROC) was used to analyze the value of the three indicators in the diagnosis of immune-related pulmonary disease complicated with fungal infection, and the changes of the three indicators before and after treatment were compared. Results: The levels of sTREM-1, PCT, and 1,3-ß-D glucan in the infection group were higher than those in the control group (P < 0.05). The levels of sTREM-1, PCT, and 1,3-ß-D glucan in the infection group after treatment were significantly lower than those before treatment (P < 0.05). The AUC value of sTREM-1 in the diagnosis of immune-related pulmonary diseases complicated with fungal infection was 0.980, the sensitivity was 97.11%, and the specificity was 83.06%. The AUC value of PCT in the diagnosis of immune-related pulmonary diseases complicated with fungal infection was 0.860, the sensitivity was 80.00%, and the specificity was 72.41%. The AUC value of 1,3-ß-D glucan in the diagnosis of immune-related pulmonary diseases complicated with fungal infection was 0.993, the sensitivity was 98.74%, and the specificity was 99.16%. The levels of sTREM-1, PCT, and 1,3-ß-D glucan in the infection group after treatment were considerably lower than those before treatment, and the difference was statistically significant (P < 0.05). Conclusion: The detection of sTREM-1, PCT, and 1,3-ß-D glucan levels has high clinical value for the diagnosis of immune-related pulmonary diseases complicated with fungal infection.

Incidental Finding: Urine Alzheimer-Associated Neuronal Thread Protein (AD7c-NTP) and Serum Vitamin D25.

BACKGROUND: National and international experts have been attempting to find diagnostic tools for the early identification of symptoms to facilitate early identification and intervention of the disease. OBJECTIVE: Detection of urine Alzheimer-associated neuronal thread protein (AD7c-NTP) and serum 25-hydroxyvitamin D (25(OH)D) in the diagnosis of Alzheimer's disease (AD). METHODS: Subjects aged >50 years who underwent a physical examination at the Taihu Sanatorium of Jiangsu Province, had no clinical evidence of AD-related issues, and had normal Mini-Mental State Exam and Montreal Cognitive Assessment scores were enrolled in the present study. There were 35 males and 15 females, who were aged 51-91 years. Urine AD7c-NTP levels and serum 25(OH)D concentrations were measured. RESULTS: The Pearson correlation analysis revealed that the urine AD7c-NTP levels in these subjects were negatively correlated with the serum 25(OH)D concentrations (r = -0.460, p < 0.001). CONCLUSION: Combined with previous studies, it was considered that cognitive function might be the only link for the correlation between AD7c-NTP and 25(OH)D. This finding might provide a starting point to investigate the potential value of the interaction between urine AD7c-NTP and serum 25(OH)D in chronic diseases. Further large-scale studies are needed to validate the results of the present study.

miR-150-5p inhibits osteogenic differentiation of fibroblasts in ankylosing spondylitis by targeting VDR.

Dysregulated microRNAs (miRNAs or miRs) serve potential roles in inflammatory systemic disease, including ankylosing spondylitis (AS). The aim of the present study was to investigate the potential function of miR-150-5p in osteogenic differentiation of AS fibroblasts and its underlying mechanism. The expression of miR-150-5p and vitamin D receptor (VDR) in AS joint capsules and fibroblasts was detected by reverse transcription-quantitative (RT-q)PCR and western blotting. Following overexpression of miR-150-5p, the alteration in osteogenic gene expression was detected by RT-qPCR, western blotting and alkaline phosphatase activity assay, as well as alizarin red staining. The association between miR-150-5p and VDR was confirmed by luciferase assay and rescue experiments were performed. Patients with AS exhibited decreased expression of miR-150-5p in joint capsules. Treatment with bone morphogenic protein 2 (BMP-2) and transforming growth factor-ß1 (TGF-ß1) led to downregulation of miR-150-5p in AS fibroblasts. Enforced expression of miR-150-5p attenuated osteogenic differentiation of AS fibroblasts. These results demonstrated that miR-150-5p inhibited osteogenic differentiation of AS fibroblasts by targeting VDR. miR-150-5p overexpression decreased osteogenic transformation of fibroblasts by decreasing VDR expression in AS.

Serum progranulin level is associated with disease activity following orthopedic surgery in rheumatoid arthritis patients.

BACKGROUND: Few studies have focused on the ability of progranulin to predict postoperative disease activity in rheumatoid arthritis (RA) patients who have undergone surgery. This study evaluated serum progranulin levels in active RA patients and analyzed its relationship with postoperative disease activity. METHODS: One hundred thirty-two patients with active RA and 72 healthy subjects were included in this study. Serum progranulin was measured, and clinical data were collected. The postoperative 1-year Disease Activity Score in 28 joints calculated with C-reactive protein (DAS28-CRP) scores was evaluated as an indicator of disease activity. The predictive value of progranulin in postoperative 1-year disease activity in RA patients was also analyzed. RESULTS: Serum progranulin was significantly associated with the postoperative 1-year RA disease activity. The mean serum progranulin level in patients with a high disease activity was significantly higher than that of RA patients with low-to-moderate disease activity (54.2 ± 10.6 ng/mL vs. 46.7 ± 8.8 ng/mL). Serum progranulin was also evaluated as an independent predictive factor for postoperative 1-year RA disease activity in multivariate analysis (odds ratio [OR], 2.21; 95% confidence interval [CI], 1.02-8.85). CONCLUSIONS: Serum progranulin levels may be a promising indicator of postoperative disease activity in RA patients who underwent orthopedic surgery.

Drug screening and identification of key candidate genes and pathways of rheumatoid arthritis.

Rheumatoid arthritis (RA), which normally manifests as a multi­joint inflammatory reaction, is a common immunological disease in clinical practice. However, the pathogenesis of RA has not yet been fully elucidated. Rituximab (RTX) is an effective drug in the treatment of RA, however its therapeutic efficacy and mechanism of action require further investigation. Thus, the present study aimed to screen the candidate key regulatory genes and explain the potential mechanisms of RA. Gene chips of RA and normal joint tissues were analyzed and, gene chips of RTX before and after treatment were investigated. In the present study, strong evidence supporting the pathogenesis of RA and mechanism of action of RTX were also revealed. Differentially expressed genes (DEGs) were analyzed using the limma package of RStudio software. A total of 1,150 DEGs were detected in RA compared with normal joint tissues. The upregulated genes were enriched in 'interleukin­12 production', 'I­κB kinase/NF­κB signaling', 'regulation of cytokine production involved in immune response' and 'cytokine metabolic process'. Functional enrichment analysis showed that RTX was primarily involved in the inhibition of 'adaptive immune response', 'B cell activation involved in immune response' and 'immune effector process'. Subsequently, leukocyte immunoglobulin­like receptor subfamily B member 1 (LILRB1), a hub gene with high connectivity degree, was selected, and traditional Chinese medicine libraries were molecularly screened according to the structure of the LILRB1 protein. The results indicated that kaempferol 3­O­ß­D­glucosyl­(1→2)­ß­D­glucoside exhibited the highest docking score. In the present study, the DEGs and their biological functions in RA and the pharmacological mechanism of RTX action were determined. Taken together, the results suggested that LILRB1 may be used as a molecular target for RA treatment, and kaempferol 3­O­ß­D­glucosyl­(1→2)­ß­D­glucoside may inhibit the pathological process of RA.

Active vitamin D activates chondrocyte autophagy to reduce osteoarthritis via mediating the AMPK-mTOR signaling pathway.

Osteoarthritis (OA) is a common joint degenerative disease. Vitamin D (VD) is essential for bone health. We hypothesized that active VD could be used as a therapeutic treatment for OA. Low serum levels of 25-hydroxyvitamin D [25(OH)D] have been found in patients with OA, and thus the serum level of VD could be diagnostic of OA. To test this, we established a mouse model of OA. The results from staining with hematoxylin-eosin and Safranin O - Fast Green indicated that active VD reduced the symptoms of OA in mice. The results from Western blotting indicated that treatment with VD increased the activity of the p-AMPK-AMPK signaling pathway and decreased the p-mTOR-mTOR pathway; it also increased the ratio of LC3II:LC3I antibodies and the protein expression levels of Beclin-1, but decreased the level of p62. Further, treatment with VD reduced the levels of tumor necrosis factor-α and interleukin-6 both in cartilage tissues and in chondrocytes. Administration of the AMPK inhibitor compound C and autophagy inhibitor 3-methyladenine (3-MA) reversed these changes following VD treatment. In addition, the results from transfection with mRFP-GFP-LC3 indicated that active VD led to autophagosome aggregation in OA chondrocytes. 3-MA inhibited cell autophagy and promoted inflammation in OA. This study provides evidence that active VD activate chondrocyte autophagy to reduce OA inflammation via activating the AMPK-mTOR signaling pathway. Treatment with active VD could be a novel therapeutic option for OA.

Clinicopathologic study of endometrial dedifferentiated endometrioid adenocarcinoma: a case report.

In 2006, dedifferentiated endometrioid adenocarcinoma (undifferentiated carcinoma associated with low-grade endometrioid carcinoma) of the uterus was first proposed. Dedifferentiated endometrioid carcinoma is part of the spectrum of undifferentiated carcinoma of the endometrium which is a highly aggressive tumor even when the undifferentiated component represents only 20% of the entire neoplasm. Therefore, accurate diagnosis and appropriate classification of this neoplasm are important in patient management. Lack of the recognition may lead to misclassification of dedifferentiated endometrioid adenocarcinoma as a pure endometrioid adenocarcinoma which is less aggressive. Only 4 papers have appeared in the literature so far on the topic of dedifferentiated endometrioid carcinoma. We report herein a first case of endometrial dedifferentiated endometrioid carcinoma in a 51-year old woman in Chinese population. We performed immunoperoxidase studies for 12 markers. Among them, cytokeratins, keratin 7, keratin 18, EMA, estrogen receptor (ER), progesterone receptor (PR), and vimentin show significantly differential expression between differentiated and undifferentiated area.

Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman Disease): A case report and review of 49 cases with fine needle aspiration cytology.

Rosai-Dorfman disease (RDD), a rare, benign, self-limiting histiocytic proliferative disorder, can be encountered in both nodal and extranodal locations, and fine needle aspiration (FNA), a simple, accurate and economic tool, has been widely used for the diagnosis of superficial and deep-seated lesions. Familiarity with the cytomorphologic features of RDD is important as prognosis and treatment are quite different from other benign or malignant diseases for which it may clinically masquerade. Although large numbers of RDD cases have been reported, review of the literature has revealed 49 reported cases of RDD diagnosed by FNA. Here, we report a case of RDD with nasal and sinus involvement. The patient was seen at our institution, carrying a diagnosis of inflammatory pseudotumor rendered by an outside institution, based on material obtained by nasal and sinus surgical biopsies. Cervical lymph node FNA performed at our institution revealed typical features of RDD. The case, as well as a brief review of the literature and 49 RDD cases with FNA cytology, will be discussed.

Diabetes reduces bone marrow and circulating porcine endothelial progenitor cells, an effect ameliorated by atorvastatin and independent of cholesterol.

Bone marrow derived endothelial progenitor cells (EPCs) are early precursors of mature endothelial cells which replenish aging and damaged endothelial cells. The authors studied a diabetic swine model to determine if induction of DM adversely affects either bone marrow or circulating EPCs and whether a HMG-CoA reductase inhibitor (statin) improves development and recruitment of EPCs in the absence of cholesterol lowering. Streptozotocin was administered to Yorkshire pigs to induce DM. One month after induction, diabetic pigs were treated with atorvastatin (statin, n = 10), ezetimibe (n = 10) or untreated (n = 10) and evaluated for number of bone marrow and circulating EPCs and femoral artery endothelial function. There was no effect of either medication on cholesterol level. One month after induction of DM prior to administration of drugs, the number of bone marrow and circulating EPCs significantly decreased (P < 0.0001) compared to baseline. Three months after DM induction, the mean proportion of circulating EPCs significantly increased in the atorvastatin group, but not in the control or ezetimibe groups. The control group showed progressive reduction in percentage of flow mediated vasodilatation (no dilatation at 3 months) whereas the atorvastatin group and ezetimibe exhibited vasodilatation, 6% and 4% respectively. DM results in significant impairment of bone marrow and circulating EPCs as well as endothelial function. The effect is ameliorated, in part, by atorvastatin independent of its cholesterol lowering effect. These data suggest a model wherein accelerated atherosclerosis seen with DM may, in part, result from reduction in EPCs which may be ameliorated by treatment with a statin.

A study on blood-brain barrier ultrastructural changes induced by cerebral hypoperfusion of different stages.

OBJECTIVES: To evaluate the ultrastructural changes in the blood-brain barrier (BBB) induced by cerebral hypoperfusion of different stages, which may predispose the brain to the formation of vasogenic edema and hemorrhage under cerebral luxury perfusion. METHODS: Twenty cerebral steal models with left neck arteriovenous fistula (AVF) were surgically created in Wistar's rats, leading to a noninfarctional reduction in the cerebral blood flow (CBF) by between 25 and 50%, resulting in cerebral hypoperfusion in the AVF side for 3 days (acute stage), 3 weeks (subacute stage) and 3 months (chronic stage), respectively. Another six sham-operated models were made in age-matched rats as control. The BBB ultrastructural changes were assessed by transmission electron microscopy. Ridit analysis was conducted to compare the positive ratio of ultrastructural changes among multiple groups. RESULTS: Electron microscopy demonstrated no ultrastructural change at the acute stage, however, at the subacute stage, slight vacuolar degeneration was found in the astrocytic foot process layer encircling the capillaries; furthermore, at the chronic stage, the astrocytic foot processes expressed marked vacuolization associated with the adjacent astrocytic degeneration. Meanwhile, in both capillary endothelium and basal lamina layers, no abnormal ultrastructures similar to those in the astrocytic foot processes layer were identified. After cerebral luxury perfusion took place, BBB was disrupted where astrocytic foot processes vacuolization was most distinguished. CONCLUSION: Astrocytes generate ultrastructural abnormality as a result of chronic cerebral hypoperfusion. Astrocytic foot process vacuolization, which constitutes the major ultrastructural change in the BBB, is the extension of the degeneration of astrocyte body. It is inferred that BBB is prone to structure weakness and function instability, which forms the morphological basis of cerebral luxury perfusion.

CD4 and CD8 T-lymphocyte apoptosis can predict radiation-induced late toxicity: a prospective study in 399 patients.

PURPOSE: Predicting late effects in patients treated with radiation therapy by assessing in vitro radiation-induced CD4 and CD8 T-lymphocyte apoptosis can be useful in individualizing treatment. EXPERIMENTAL DESIGN: In a prospective study, 399 curatively irradiated patients were tested using a rapid assay where fresh blood samples were in vitro irradiated with 8 Gy X-rays. Lymphocytes were collected and prepared for flow cytometric analysis. Apoptosis was assessed by associated condensation of DNA. The incidences of late toxicities were compared for CD4 and CD8 T-lymphocyte apoptoses using receiver-operating characteristic curves and cumulative incidence. RESULTS: No association was found between early toxicity and T-lymphocyte apoptosis. Grade 2 and 3 late toxicities were observed in 31% and 7% of patients, respectively. More radiation-induced T-lymphocyte apoptosis was significantly associated with less grade 2 and 3 late toxicity (Gray's test, P < 0.0001). CD8 (area under the curve = 0.83) was more sensitive and specific than CD4. No grade 3 late toxicity was observed for patients with CD4 and CD8 values greater than 15% and 24%, respectively. The 2-year cumulative incidence for grade 2 or 3 late toxicity was 70%, 32%, and 12% for patients with absolute change in CD8 T-lymphocyte apoptosis of < or =16, 16 to 24, and >24, respectively. CONCLUSIONS: Radiation-induced T-lymphocyte apoptosis can significantly predict differences in late toxicity between individuals. It could be used as a rapid screen for hypersensitive patients to radiotherapy. In future dose escalation studies, patients could be selected using the apoptosis assay.

Effects of hyperbaric oxygen exposure on experimental head and neck tumor growth, oxygenation, and vasculature.

BACKGROUND: Hyperbaric oxygen (HBO2) is used to promote healing in irradiated tissues, but concern persists about the possibility that it may promote residual tumor growth. METHODS: The tumor growth of SQ20B and Detroit 562 head and neck squamous cell carcinoma xenografts were studied after single-dose irradiation and 5x/week HBO2 treatment at 2.4 atm absolute for 90 minutes. The effect of HBO2 treatment on tumor hypoxia and vasculature was also examined by immunohistochemical analysis. RESULTS: HBO2 treatment increased tumor oxygenation during the treatment interval but did not promote the growth of either irradiated or unirradiated tumors. No increase in tumor vascular endothelial growth factor expression or vascularization was detected. CONCLUSIONS: This study found no evidence for persistent changes in tumor microenvironment or tumor growth promotion caused by hyperbaric oxygen exposure.

Farnesyltransferase inhibitor effects on prostate tumor micro-environment and radiation survival.

BACKGROUND: Ras activation by mutation, overexpression, or receptor signaling can increase tumor cell survival after irradiation. METHODS: We examined whether inhibiting Ras activity with farnesyltransferase inhibitors (FTI) altered the radiosensitivity and tumor micro-environment in prostate tumors. RESULTS: Treatment with FTIs L-744,832 or FTI-277 reduced clonogenic survival of prostate tumor cells expressing oncogenic H-ras after irradiation. PI3-kinase/Akt and MAPK signaling pathways were downregulated by FTIs in these cells. FTI treatment reduced tumor hypoxia and also reduced MMP-9 expression in tumors with activated mutant H-ras. FTI treatment did not, however, increase apoptosis in irradiated intestine, demonstrating that acute radiation injury of this normal tissue was not enhanced by FTIs. CONCLUSIONS: FTIs can enhance the killing of prostate tumors with activated H-Ras. Together with the absence of increased acute toxicity to normal bowel, these results imply that FTI treatment should be further studied as a possible adjuvant to radiotherapy in the treatment of abdominal cancers with activated Ras signaling.

A single low dose of X-rays induces high frequencies of genetic instability (aneuploidy) and heritable damage (apoptosis), dependent on cell type and p53 status.

We harvested and analyzed cells from four different non-transformed cell lines surviving a single X-ray exposure. Evidence of radiation-induced karyotype instability was observed in 100% of C3H 10T1/2 fibroblast clones and 11.3% of V79 fibroblast clones. Heritable damage: predisposition to apoptosis, but not karyotype instability, was induced in TK6 (p53(wt/wt)) and WTK1 (p53(mut/mut)) human B-lymphoblastoid cell clones. The studies indicate: (1) genetic instability and/or heritable damage are induced in cells exposed to radiation at a high frequency, and induction of genetic instability is not limited to morphologically transformed cells [Radiat. Res. 138 (1994) S105; Radiat. Environ. Biophys. 36 (1998) 255]; (2) sensitivity to genetic instability and heritable damage depend on cell type; (3) checkpoint stringency and p53 status significantly influence the frequency of radiation-induced genetic instability and heritable damage; (4) in some cell lines, damage induced by low doses of radiation (below 2 Gy) leads to heritable cytotoxic and genotoxic effects in 100% of cells exposed. The data suggest that mammalian cells misinterpret damage induced by ionizing radiation as if it were a physiological cell signal. This contrasts strongly with the response of mammalian cells to damage induced by other types of DNA-toxic agents where damage-specific repair mechanisms are activated.