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Abstract Background To analyze the risk factors for the development of avascular necrosis (AVN) of the femoral head after reduction surgery in children with developmental hip dysplasia (DDH), and to establish a prediction nomogram. Methods The clinical data of 134 children with DDH (169 hips) treated with closure reduction or open reduction from December 2016 to December 2019 were retrospectively analyzed. Independent risk factors for AVN after DDH reduction being combined with cast external immobilization were determined by univariate analysis and multivariate logistic regression and used to generate nomograms predicting the occurrence of AVN. Results A total of 169 hip joints in 134 children met the inclusion criteria, with a mean age at surgery of 10.7 ± 4.56 months (range: 4–22 months) and a mean follow-up duration of 38.32 ± 27.00 months (range: 12–94 months). AVN developed in 42 hip joints (24.9%); univariate analysis showed that the International Hip Dysplasia Institute (IHDI) grade, preoperative development of the femoral head ossification nucleus, cartilage acetabular index, femoral head to acetabular Y-shaped cartilage distance, residual acetabular dysplasia, acetabular abduction angle exceeding 60°, and the final follow-up acetabular index (AI) were associated with the development of AVN (P

Immunoregulation and indoleamine 2,3-dioxygenase 1 (IDO1) play pivotal roles in the rejection of allogeneic organ transplantation. This study aims to elucidate the immune-related functional mechanisms of exosomes (Exos) derived from bone marrow–derived mesenchymal stem cells (BMSCs) overexpressing IDO1 in the context of allogeneic heart transplantation (HTx) rejection. A rat model of allogeneic HTx was established. Exos were extracted after transfection with oe-IDO1 and oe-NC from rat BMSCs. Exos were administered via the caudal vein for treatment. The survival of rats was analyzed, and reverse transcription qualitative PCR (RT-qPCR) and immunohistochemistry (IHC) were employed to detect the expression of related genes. Histopathological examination was conducted using hematoxylin and eosin (HE) staining, and flow cytometry was utilized to analyze T-cell apoptosis. Proteomics and RNA-seq analyses were performed on Exos. The data were subjected to functional enrichment analysis using the R language. A protein interaction network was constructed using the STRING database, and miRWalk, TargetScan, and miRDB databases predicted the target genes, differentially expressed miRNAs, and transcription factors (TFs). Exos from BMSCs overexpressing IDO1 prolonged the survival time of rats undergoing allogeneic HTx. These Exos reduced inflammatory cell infiltration, mitigated myocardial damage, induced CD4 T-cell apoptosis, and alleviated transplantation rejection. The correlation between Exos from BMSCs overexpressing IDO1 and immune regulation was profound. Notably, 13 immune-related differential proteins (Anxa1, Anxa2, C3, Ctsb, Hp, Il1rap, Ntn1, Ptx3, Thbs1, Hspa1b, Vegfc, Dcn, and Ptpn11) and 10 significantly different miRNAs were identified. Finally, six key immune proteins related to IDO1 were identified through common enrichment pathways, including Thbs1, Dcn, Ptpn11, Hspa1b, Il1rap, and Vegfc. Thirteen TFs of IDO1-related key miRNAs were obtained, and a TF-miRNA-mRNA-proteins regulatory network was constructed. Exosome miRNA derived from BMSCs overexpressing IDO1 may influence T-cell activation and regulate HTx rejection by interacting with mRNA.

Addressing input saturation, external disturbances, and uncertain system parameters, this paper investigates the position tracking control problem for bilateral teleoperation systems with a time delay communication channel. Based on a composite energy function, we propose an adaptive iterative learning control (AILC) method to achieve the objective of position tracking under the alignment condition. This extends the existing research on the control of nonlinear teleoperation systems with time delay. The saturation constraint property of the Softsign function ensures that no state of the system exceeds its constraints. The controller learns to simultaneously deal with the uncertainty of system parameters online, reject external disturbances, and eliminate positional errors along the time and iteration axes. All signals in the system for any constant time delay are proved to be bounded. Ultimately, the performance of the proposed controller is further verified through numerical simulations.

BackgroundBreast cancer is one of the most common female malignancies. This study explored the underlying mechanism through which the two plant compounds (Brucaine D and Narclasine) inhibited the proliferation of breast cancer cells.ObjectiveThe purpose of this study was to explore the effect of Brucaine D and Narclasine on breast cancer development and their potential drug targets.MethodsGSE85871 dataset containing 212 samples and the hallmark gene set "h.all.v2023.1.Hs.symbols.gmt" were downloaded from the Gene Expression Omnibus (GEO) database and the Molecular Signatures Database (MSigDB) database, respectively. Principal component analysis (PCA) was applied to classify clusters showing similar gene expression pattern. Single sample gene set enrichment analysis (ssGSEA) was used to calculate the hallmark score for different drug treatment groups. The expressions of genes related to angiogenesis, glycolysis and cell cycle were detected. Protein-protein interaction (PPI) network analysis was performed to study the interaction of the hub genes. Then, HERB database was employed to identify potential target genes for Narclasine and Bruceine D. Finally, in vitro experiments were conducted to validate partial drug-target pair.ResultsPCA analysis showed that the significant changes in gene expression patterns took place in 6 drugs treatment groups (Narciclasine, Bruceine D, Japonicone A, 1beta-hydroxyalatolactone, Britanin, and four mixture drugs) in comparison to the remaining drug treatment groups. The ssGSEA pathway enrichment analysis demonstrated that Narciclasine and Bruceine treatments had similar enriched pathways, for instance, suppressed pathways related to angiogenesis, Glycolysis, and cell cycle, etc.. Further gene expression analysis confirmed that Narciclasine and Bruceine had a strong ability to inhibit these cell cycle genes, and that MYC, CHEK2, MELK, CDK4 and EZH2 were closely interacted with each other in the PPI analysis. Drug target prediction revealed that Androgen Receptor (AR) and Estrogen Receptor 1 (ESR1) were the targets for Bruceine D, and Cytochrome P450 3A4 enzyme (CYP3A4) was the target for Narciclasine. Cell experiments also confirmed the connections between Narciclasine and CYP3A4.ConclusionThe present study uncovered that Narciclasine and Bruceine D could inhibit the growth of breast cancer and also predicted the potential targets for these two drugs, providing a new therapeutic direction for breast cancer patients.

Background This study aimed to investigate the effect of double-lumen irrigation-suction tube (DLIST) in the management of surgical site infections (SSIs) after enterocutaneous fistula (ECF) excisions. Method From January 2016 to December 2017 medical records of patients with ECF excisions were reviewed. Patients with primary superficial SSI were divided into group a (treated with DLIST) and b (treated with delayed primary closures). Patients with primary deep SSI were divided into group A (treated with DLIST) and B (treated with vacuum-assisted closure [VAC]). The effect of the DLIST was evaluated. Results There were 32 in group a and 27 in group b. The therapeutic time and cost in group a were lower (13.13 ± 2.37 d vs. 24.89 ± 7.44 d; p

Background: Colorectal cancer (CRC) is one gastrointestinal malignancy, accounting for 10% of cancer diagnoses and cancer-related deaths worldwide each year. Therefore, it is urgent to identify genes involved in CRC predicting the prognosis.Methods: CRC’s data were acquired from the Gene Expression Omnibus (GEO) database (GSE39582 and GSE41258 datasets) and The Cancer Genome Atlas (TCGA) database. The differentially expressed necroptosis-related genes (DENRGs) were sorted out between tumor and normal tissues. Univariate Cox regression analysis and least absolute shrinkage and selectionator operator (LASSO) analysis were applied to selected DENRGs concerning patients’ overall survival and to construct a prognostic biomarker. The effectiveness of this biomarker was assessed by the Kaplan–Meier curve and the receiver operating characteristic (ROC) analysis. The GSE39582 dataset was utilized as external validation for the prognostic signature. Moreover, using univariate and multivariate Cox regression analyses, independent prognostic factors were identified to construct a prognostic nomogram. Next, signaling pathways regulated by the signature were explored through the gene set enrichment analysis (GSEA). The single sample gene set enrichment analysis (ssGSEA) algorithm and tumor immune dysfunction and exclusion (TIDE) were used to explore immune correlation in the two groups, high-risk and low-risk ones. Finally, prognostic genes’ expression was examined in the GSE41258 dataset.Results: In total, 27 DENRGs were filtered, and a necroptosis-related prognostic signature based on 6 DENRGs was constructed, which may better understand the overall survival (OS) of CRC. The Kaplan–Meier curve manifested the effectiveness of the prognostic signature, and the ROC curve showed the same result. In addition, univariate and multivariate Cox regression analyses revealed that age, pathology T, and risk score were independent prognostic factors, and a nomogram was established. Furthermore, the prognostic signature was most significantly associated with the apoptosis pathway. Meanwhile, 24 immune cells represented significant differences between two groups, like the activated B cell. Furthermore, 32 immune checkpoints, TIDE scores, PD-L1 scores, and T-cell exclusion scores were significantly different between the two groups. Finally, a 6-gene prognostic signature represented different expression levels between tumor and normal samples significantly in the GSE41258 dataset.Conclusion: Our study established a signature including 6 genes and a prognostic nomogram that could significantly assess the prognosis of patients with CRC.

Abstract Vitamin D deficiency has recently become a global public health problem. However, it is still unclear if gene polymorphisms in the vitamin D pathway influence vitamin D levels among pregnant women in Eastern and Central China. The objective of this study was to assess factors influencing vitamin D levels in pregnant women. A total of 326 participants in Shandong and Henan provinces in China were enrolled from August 2017 to April 2019. Serum 25(OH)D levels and single nucleotide polymorphisms (SNPs) in the vitamin D pathway were measured using the blood samples collected in the first trimester, second trimester, and third trimester. Data on demographics, lifestyle, and health behavior were collected using a questionnaire. Statistical analyses were performed using the R software. The prevalence of 25(OH)D deficiency was significantly more severe in pregnant women. The average 25(OH)D value of all enrolled pregnant women was 14.57 ± 7.21 ng/ml (deficiency). Only 15 (4.60%) participants had a 25(OH)D concentration ≥30 ng/ml (sufficient). The prevalence of four ranks of vitamin D levels from severe 25(OH)D deficiency to 25(OH)D sufficiency (

Ferroptosis is a unique way of regulating cell death (RCD), which is quite different from other programmed cell deaths such as autophagy. It presents iron overload, accumulation of reactive oxygen species (ROS), and lipid peroxidation. A ferroptotic cell usually has an intact cell structure as well as shrinking mitochondria with decreased or vanishing cristae, concentrated membrane density, and ruptured outer membrane. Recently, increasing investigations have discovered that tumor cells have a much greater iron demand than the normal ones, making them more sensitive to ferroptosis. In other words, ferroptosis may inhibit the progress of the tumor, which can be used in the therapy of tumor patients, especially for those with chemotherapy resistance. Therefore, ferroptosis has become one hot spot in the field of tumor research in recent years. Colorectal cancer (CRC) is one common type of gastrointestinal malignancy. The incidence of CRC appears to have an upward trend year by year since the enhancement of living standards. Although surgery and chemoradiotherapy have largely improved the prognosis of patients with CRC, some patients still appear to have severe adverse reactions and drug resistance. Moreover, much research has verified that ferroptosis has a necessary association with the occurrence and progression of gastrointestinal tumors. In this review, we provide a comprehensive evaluation of the main mechanisms of iron metabolism, lipid metabolism, and amino acid metabolism involved in the occurrence of ferroptosis, as well as the research progress of ferroptosis in CRC.

Potato is a plant with high water requirements. This factor affects not only the weight of potato tubers but also their quality parameters. In order to achieve quantity and quality goal, it is helpful if we apply the principles of precision agriculture, which also contributes to sustainable management of environmental resources. Accurate identification of the water requirements of crops is the basis for determining optimal irrigation doses and dates. After their application, it is possible to assess the effectiveness of irrigation treatments and their impact on the air-water conditions in soil with a root system. The aim of the presented study was to analyse the influence of volumetric soil moisture diversity on the vegetation of early potato varieties. Two potato varieties were subject to investigation: Denar and Julinka. Pot experiments were carried out at the Department of Horticulture of Wroclaw University of Environmental and Life Sciences. Three variants were analysed: one with a low water content in the soil (pF 2.7), one with the optimal water content (pF 2.5) and one with a high water content (pF 2.2). The basis for the selection of the frequency and application rate of water doses was soil moisture measured with an SM150-Kit set. Volumetric moisture was measured with a TDR apparatus. It was found that the water requirements of both potato varieties differ and increase along with the development of the aboveground and underground parts. Moreover, it was shown that the irrigation requirements of cv. Julinka are higher than those of Denar (31.4-33.0% higher), depending on the adopted variant. The research also showed that the most effective method of potato cultivation is to maintain soil moisture at a lower level. This should be taken into account in regions where the cultivation of this species uses supplementation of the water requirements by irrigation.

Diabetic neuropathy affects nearly half of all diabetics and poses a significant threat to public health. Recent preclinical studies suggest that mesenchymal stem cells (MSCs) may represent a promising solution for the treatment of diabetic neuropathy. However, an objective assessment of the preclinical effectiveness of MSCs is still pending. We conducted a comprehensive search of PubMed, Web of Science, Embase, and Cochrane library to identify preclinical studies that investigate the effects of MSCs on diabetic neuropathy up until 15 September 2023. Outcome indicators consisted of motor and sensory nerve conduction velocities, intra-epidermal nerve fiber density, sciatic nerve blood flow, capillary-to-muscle fiber ratio, neurotrophic factors, angiogenic factors and inflammatory cytokines. The literature review and meta-analysis were conducted independently by two researchers. 23 studies that met the inclusion criteria were included in this system review for qualitative and quantitative analysis. Pooled analyses indicated that MSCs exhibited an evident benefit in diabetic neuropathy in terms of motor (SMD = 2.16, 95% CI: 1.71–2.61) and sensory nerve conduction velocities (SMD = 2.93, 95% CI: 1.78–4.07), intra-epidermal nerve fiber density (SMD = 3.17, 95% CI: 2.28–4.07), sciatic nerve blood flow (SMD = 2.02, 95% CI: 1.37–2.66), and capillary-to-muscle fiber ratio (SMD = 2.28, 95% CI: 1.55 to 3.01, p < 0.00001). Furthermore, after MSC therapy, the expressions of neurotrophic and angiogenic factors increased significantly in most studies, while the levels of inflammatory cytokines were significantly reduced. The relevance of this review relies on the fact that summarizes an extensive body of work entailing substantial preclinical evidence that supports the efficacy of MSCs in mitigating diabetic neuropathy. While MSCs emerge as a promising potential treatment for diabetic neuropathy, further research is essential to elucidate the underlying mechanisms and the best administration strategy for MSCs.

A large amount of mine water is generated during coal production, which not only damages the surface environment and ecology but also wastes groundwater resources in the mining area, exacerbating regional water scarcity. In this work, a novel zero liquid discharge technology combining selectrodialysis (SED) and bipolar membrane electrodialysis (BMED) was developed for the resourceful treatment of low-salinity mineralized wastewater. The SED stack had demonstrated to be workable for the elimination of multivalent ions. The BMED stack converts brine into acid and base. After SED, a high pure crude salt (~98%) was attained. Furthermore, under the conditions of a current density of 20 mA/cm2, a flow velocity of 20 L/h, and an initial acid/base concentration of 0.10 mol/L, the maximum concentrations of acid and base were found to be 0.75 mol/L and 0.765 mol/L, respectively, for a feed conductivity of 55 mS/cm. The cost of the entire electrodialysis stage was evaluated to be USD 1.38/kg of NaOH. Therefore, this combined UF-RO-SED-BMED process may be an effective strategy for the sustainable treatment of low-salinity mineralized wastewater.