An innovative immunotherapeutic strategy for rheumatoid arthritis: Selectively suppressing angiogenesis and osteoclast differentiation by fully human antibody targeting thymocyte antigen-1.

Thymocyte antigen-1 (THY-1)is a potential target for rheumatoid arthritis (RA) treatment, and THY-1 positive fibroblast-like synoviocytes (FLS) are enriched in the synovium of RA patients and participate in angiogenesis to accelerate RA progression. In this study, we screened an antibody targeting THY-1 (THY-1 Ab) and explored its mechanism in alleviating RA progression. THY-1 Ab was screened from ScFv phage antibody library by phage display technology (PDT). THY-1 Ab-treated collagen induced arthritis (CIA) mice had lower degree of arthritis scores. We explore the mechanism of THY-1 Ab in alleviating RA progression. THY-1 Ab can remarkably inhibit the secretion of pro-inflammatory factors and promote the secretion of anti-inflammatory factors. Further experiments showed that THY1 Ab downregulated the expression of JUNB by the hsa_circ_0094342/miRNA-155-5P/SPI1 axis, inhibited RA angiogenesis and osteoclast differentiation, and relieved RA progression. These findings support that THY-1 Ab is a promising therapeutic antibody for RA treatment.

Prognostic Nutritional Index and Major Cardiovascular Events in Patients Undergoing Invasive Coronary Angiography: A Clinical Retrospective Study.

We aimed to examine whether prognostic nutritional index (PNI) could serve as an auxiliary predictor for major cardiovascular events (MCEs) in patients undergoing invasive coronary angiography (ICA). A total of 485 participants were enrolled, divided into low-PNI (≥47.40) and high-PNI (<47.40) groups. ICA determined the stenotic vessels of coronary artery disease. The primary outcome was incidental MCEs, a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, or rehospitalization of in-stent restenosis. There were 47 (9.69%) MCEs during the 3.78-years follow-up. The cumulative incidence of MCEs was significantly higher in the low-PNI patients compared with the high-PNI patients (17.07% vs. 7.18%, p = 0.001). Malnutrition risk (low PNI) was significantly and independently associated with a higher risk of MCEs (hazard ratios: 2.593, 95% confidence intervals [CI]: 1.418−4.742). Combined use of the number of stenotic vessels with malnutrition risk showed a higher capacity to predict the MCEs than the presence of stenotic vessels alone (areas under the receiver operator characteristic curve: 0.696 [95% CI, 0.618−0.775] vs. 0.550 [95% CI, 0.466−0.633], p = 0.013). In conclusion, lower PNI levels may predict a higher risk of cardiovascular events in patients undergoing ICA, which supports the necessity of the risk assessment of nutrition status and guide the clinical treatment on strengthening nutritional support before ICA is performed, as well as nutritional intervention after ICA.

Risk Factors and Prognostic Analysis of Gastrointestinal Stromal Tumor Recurrence-Metastasis.

Objective: Gastrointestinal stromal tumors (GISTs) are potential malignancies that occur in the digestive tract. This study aimed to investigate the risk factors and prognosis of recurrence and metastasis of gastrointestinal stromal tumor (GIST). Methods: From January 2018 to December 2019, 422 patients with GIST who received surgery in the First Affiliated Hospital of Wenzhou Medical University were enrolled. Their clinical data were retrospectively analyzed, and their follow-ups were continued until March 31, 2022. Subsequently, univariate and multivariate Cox analyses, survival curves, and nomograms were adopted to explore the relationship between clinicopathological characteristics and recurrence or metastasis in patients with GIST. Results: Univariate and multivariate Cox analysis exhibited that the prognosis of patients was affected by tumor rupture (P = 0.040), tumor location (P < 0.001), tumor diameter (P = 0.016), mitotic figures (P < 0.001), and risk grade (P < 0.009). The above variables were selected to create the nomogram for 3-year disease-free survival (DFS). The 3-year the ROC (receiver operating characteristic) curves of the nomogram were (0.878 95% confidence interval [CI]: 0.871-0.939). Conclusion: Collectively, risk factors affecting postoperative recurrence or metastasis of GIST consist of primary site of tumors, tumor rupture, tumor diameter >10 cm, high-risk tumor classification, and mitotic figures ≥10 per 50 HPFs. And the application of nomogram may help physicians provide individualized diagnosis and treatment for patients with GISTs following surgical resection.

Circulating lnc-LOC as a novel noninvasive biomarker in the treatment surveillance of acute promyelocytic leukaemia.

BACKGROUND: Acute promyelocytic leukaemia (APL) is a unique subtype of acute myeloid leukaemia (AML) characterized by haematopoietic failure caused by the accumulation of abnormal promyelocytic cells in bone marrow (BM). However, indispensable BM biopsy frequently afflicts patients in leukaemia surveillance, which increases the burden on patients and reduces compliance. This study aimed to explore whether the novel circulating long noncoding RNA LOC100506453 (lnc-LOC) could be a target in diagnosis, assess the treatment response and supervise the minimal residual disease (MRD) of APL, thereby blazing a trail in noninvasive lncRNA biomarkers of APL. METHODS: Our study comprised 100 patients (40 with APL and 60 with non-APL AML) and 60 healthy donors. BM and peripheral blood (PB) sample collection was accomplished from APL patients at diagnosis and postinduction. Quantitative real-time PCR (qRT-PCR) was conducted to evaluate lnc-LOC expression. A receiver operating characteristic (ROC) analysis was implemented to analyse the value of lnc-LOC in the diagnosis of APL and treatment monitoring. For statistical analysis, the Mann-Whitney U test, a t test, and Spearman's rank correlation test were utilized. RESULTS: Our results showed that BM lnc-LOC expression was significantly different between APL and healthy donors and non-APL AML. lnc-LOC was drastically downregulated in APL patients' BM after undergoing induction therapy. Lnc-LOC was upregulated in APL cell lines and downregulated after all-trans retinoic acid (ATRA)-induced myeloid differentiation, preliminarily verifying that lnc-LOC has the potential to be considered a treatment monitoring biomarker. PB lnc-LOC was positively correlated with BM lnc-LOC in APL patients, non-APL AML patients and healthy donors and decreased sharply after complete remission (CR). However, upregulated lnc-LOC was manifested in relapsed-refractory patients. A positive correlation was revealed between PB lnc-LOC and PML-RARα transcript levels in BM samples. Furthermore, we observed a positive correlation between PB lnc-LOC and BM lnc-LOC expression in APL patients, suggesting that lnc-LOC can be utilized as a noninvasive biomarker for MRD surveillance. CONCLUSIONS: Our study demonstrated that PB lnc-LOC might serve as a novel noninvasive biomarker in the treatment surveillance of APL, and it innovated the investigation and application of newly found lncRNAs in APL noninvasive biomarkers used in diagnosis and detection.

The effect of different modes of microneedling technique on random flap survival in rats.

OBJECTIVE: The investigation and practice of physical therapy in flap surgery are still scare. The purpose of this study is to evaluate the impact of different microneedling interventions on survival of random pattern flaps in rats, attempting to determine the optimal microneedling protocols for improvement of flap survival. METHODS: Eighty male Sprague-Dawley rats were randomly divided into four groups, with 20 in each group (group A, B, C, and D). A 3 cm × 9 cm rectangular random flap as the McFarlane flap was adopted in each group. In groups A and B, microneedling treatment was performed before and after surgery, respectively. While animals in group C were received both pre- and postoperative microneedling treatment. Group D was used as a control group, which was only exposed to surgery. Flap survival, flap blood flow, number of capillary formations, the expressions of CD31, CD34, HIF-1α, and vascular endothelial growth factor (VEGF) were detected in each group and compared. RESULTS: On the 7th day postoperatively, significant improvements with microneedling treatment were found in flap survival rate (p = 0.007), blood flow (p = 0.024), the expression levels of CD34 (p = 0.005), and the VEGF (p < 0.01). Furthermore, the VEGF expression level was significantly higher in group B when compared with the other three groups (all p < 0.01). However, there was no significant difference in the number of new blood vessels and other immunohistochemical indicators among the four groups (all p > 0.05). CONCLUSION: Microneedling treatment especially postoperative intervention can significantly improve the survival of random flaps in rats.