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Abstract Objectives To systematically evaluate the therapeutic effect of electrical stimulation combined with pelvic floor muscle exercise on female pelvic floor dysfunction (PFD). Methods Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was applied. A computer-based retrieval was performed in the databases of PubMed, Web of Science, Embase, and Cochrane Library from database establishment to September 15, 2023, to identify randomized controlled trials on electrical stimulation combined with pelvic floor muscle function exercise on female PFD. Literature screening, data extraction, and quality evaluation were performed independently by two researchers, and meta-analysis was performed using the statistical software Stata15.0. Results 1. In total, 12 randomized controlled trials were included, involving 721 female patients. The overall quality of methodologies employed in the included studies was relatively high. 2. Meta-analysis results showed that electrical stimulation combined with pelvic floor muscle exercise could effectively mitigate the severity of female PFD (SMD = -1.01, 95% CI − 1.78, − 0.25, P 0.05). Conclusions Compared with pelvic floor muscle exercise alone, electrical stimulation combined with pelvic floor muscle exercise could effectively mitigate the severity of female PFD. It had a notable positive impact on enhancing pelvic floor muscle strength in female patients, although it did not significantly improve quality of life. Future high-quality studies are warranted.

Abstract Introduction The prognostic value of multifocality in paediatric papillary thyroid carcinoma (PTC) patients remains a subject of debate. This study aimed to explore the clinical significance and prognostic value of multifocality in children and adolescents with PTC. Methods This study retrospectively analysed the clinicopathological characteristics and postoperative follow-up data of 338 PTC patients aged ≤ 20 years from May 2012 to July 2022. The clinical and pathological characteristics of 205 patients with unifocal lesions and 133 patients with multifocal lesions were compared. A logistic regression model evaluated the relationship between multifocal lesions and disease recurrence/persistence in children and adolescents with PTC. Based on the median follow-up time of children with multifocal PTC, 114 patients with multifocal PTC older than 20 years were added, and the clinicopathological characteristics were compared between the 133. paediatric/adolescent patients and 114 adult patients with multifocal PTC. Results Among the paediatric and adolescent patients, over a median follow-up time of 49 months, 133 had multifocal disease and 205 had unifocal disease. Multifocal PTC patients exhibited stronger invasiveness in the form of extrathyroidal extension, tumour diameter, lymph node metastasis, and distant metastasis. Multifocality (OR 2.68; p = 0.017), lateral lymph node metastasis (OR 2.85; p = 0.036), and distant metastasis (OR 4.28; p = 0.010) were identified as independent predictive factors for the recurrence/persistence of disease. Comparing the paediatric/adolescent vs. adult multifocal patients, the former demonstrated greater tumour invasiveness. Lateral lymph node metastasis (OR 6.36; P = 0.012) and distant metastasis (OR 3.70; P = 0.027) were independent predictive factors for recurrence/persistence of disease in multifocal patients, while age was not (OR 0.95; P = 0.455). Conclusion Tumour multifocality independently predicts persistent/recurrent disease in paediatric and adolescent PTC patients.

IntroductionThyroid cancer (THCA) is the most common endocrine tumor. Coagulation may be associated with the development of cancer, but its role in THCA patients is not yet clear.MethodsIn this study, we determined the predictive value of coagulation biomarker D-dimer for THCA patient lateral lymph node metastasis (LLNM) through receiver operating characteristics (ROC) analysis and logistic regression analysis. Subsequently, this study used the TCGA database to identify coagulation-related molecular subtypes through consensus clustering analysis and compared their prognosis. We identified coagulation-related genes (CRGs) associated with prognosis in thyroid cancer through gene expression data and clinical information, and constructed a prognostic model by selecting the prognostic CRGs using LASSO regression. Patients were divided into high-risk and low-risk groups based on the median score. Subsequently, prognosis, clinical characteristics, gene mutation occurrence, immune infiltration, function, and drug sensitivity of the two groups were analyzed. We also constructed a nomogram combining the model and clinical features. Finally, the expression of the prognostic CRGs was validated by RT-qPCR.ResultsD-dimers had better performance in predicting LLNM(the area under the curve was 0.656 (95% CI 0.580-0.733), with a cut-off value of 0.065 mg/l), and D-dimer>0.065mg/l was an independent predictor of LLNM. Then, we selected 8 prognostic CRGs to construct a predictive model. The prognosis of low-risk group patients was significantly better than that of high-risk group (P

Abstract While hypoxic signaling has been shown to play a role in many cellular processes, its role in metabolism-linked extracellular matrix (ECM) organization and downstream processes of cell fate after musculoskeletal injury remains to be determined. Heterotopic ossification (HO) is a debilitating condition where abnormal bone formation occurs within extra-skeletal tissues. Hypoxia and hypoxia-inducible factor 1α (HIF-1α) activation have been shown to promote HO. However, the underlying molecular mechanisms by which the HIF-1α pathway in mesenchymal progenitor cells (MPCs) contributes to pathologic bone formation remain to be elucidated. Here, we used a proven mouse injury-induced HO model to investigate the role of HIF-1α on aberrant cell fate. Using single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics analyses of the HO site, we found that collagen ECM organization is the most highly up-regulated biological process in MPCs. Zeugopod mesenchymal cell-specific deletion of Hif1α (Hoxa11-CreER T2 ; Hif1a fl/fl ) significantly mitigated HO in vivo. ScRNA-seq analysis of these Hoxa11-CreER T2 ; Hif1a fl/fl mice identified the PLOD2/LOX pathway for collagen cross-linking as downstream of the HIF-1α regulation of HO. Importantly, our scRNA-seq data and mechanistic studies further uncovered that glucose metabolism in MPCs is most highly impacted by HIF-1α deletion. From a translational aspect, a pan-LOX inhibitor significantly decreased HO. A newly screened compound revealed that the inhibition of PLOD2 activity in MPCs significantly decreased osteogenic differentiation and glycolytic metabolism. This suggests that the HIF-1α/PLOD2/LOX axis linked to metabolism regulates HO-forming MPC fate. These results suggest that the HIF-1α/PLOD2/LOX pathway represents a promising strategy to mitigate HO formation.

Abstract The live transport of farmed fish is an important practice in Chinese aquaculture due to consumer preferences in its domestic market. However, live transport can be stressful for fish and may cause many welfare issues. This study aimed to examine the effects of transport density on the welfare of largemouth bass (Micropterus salmoides). Adult fish were allocated to four experimental treatments in a two‐factor design (N = 5 groups per treatment). Factor one was stocking density of either 39 (low density) or 78 (high density) g L−1. Factor two was transport, with half of the fish groups exposed to simulated transport stress for 3 h using a motion platform, and the other half kept in static tanks for the same length of time. Baseline behavior and physiology were determined from a subset of fish after acclimation but before selection into groups and application of transport. To determine the effects of transport, stocking density, and their interaction on the experimental groups, physiological sampling and behavioral recording were carried out immediately after simulated transport, and water quality was measured both before and after transport. Changes in water quality were observed between two timepoints, with decreased dissolved oxygen levels and increased water temperature. Total ammonia nitrogen levels significantly increased in all treatments over time, particularly in the high‐density groups. Fish ventilation rates were significantly elevated in the groups kept at a high stocking density regardless of whether they also experienced transport stress. Fish transported at a high stocking density also showed more fear‐related behaviors such as freezing and thigmotaxis than non‐transported groups. Serum cortisol, catalase, and aspartate transaminase levels were significantly higher in the transported treatment groups compared to the baseline fish, but no difference was found for serum glucose, lactate, and glutathione peroxidase. We concluded that 3 h of simulated transport was stressful to largemouth bass kept at 78 g L−1, as evidenced by altered fish physiological and behavioral indicators of stress, as well as deteriorated water quality. Additionally, we identified a positive correlation between serum and skin mucus samples for cortisol, glucose, and lactate in transported fish, providing important information for developing less invasive methods for the welfare assessment of largemouth bass.

Summary: Heterotopic ossification (HO) is a challenging condition that occurs after musculoskeletal injury and is characterized by the formation of bone in non-skeletal tissues. While the effect of HO on blood vessels is well established, little is known about its impact on lymphatic vessels. Here, we use a mouse model of traumatic HO to investigate the relationship between HO and lymphatic vessels. We show that injury triggers lymphangiogenesis at the injury site, which is associated with elevated vascular endothelial growth factor C (VEGF-C) levels. Through single-cell transcriptomic analyses, we identify mesenchymal progenitor cells and tenocytes as sources of Vegfc. We demonstrate by lineage tracing that Vegfc-expressing cells undergo osteochondral differentiation and contribute to the formation of HO. Last, we show that Vegfc haploinsufficiency results in a nearly 50% reduction in lymphangiogenesis and HO formation. These findings shed light on the complex mechanisms underlying HO formation and its impact on lymphatic vessels.