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To investigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) for managing upper limb muscular spasticity after stroke, and to examine its therapeutic effects on spasticity and motor function in the upper limb. A total of 110 post-stroke patients with upper limb spasticity were randomly assigned to the experimental or the control group. The experimental group received rTMS in conjunction with conventional rehabilitation therapy. The affected side of the head received daily treatment for 20 min each at Erb’s point and the stimulation point, totaling 15 sessions over six days per week. The stimulation frequencies were 10 Hz (high frequency, M1 region) and 1 Hz (low frequency, Erb’s point), with an intensity at 120% of the threshold. The control group received sham stimulation alongside conventional rehabilitation therapy. Assessments including the Modified Ashworth Scale (MAS) and Fugl-Meyer Assessment for Upper Extremity (FM-UE), were also conducted before treatment initiation and after 15 rounds of rTMS. Post hoc subgroup analyses were conducted using independent-sample t -tests for FM-UE scores and Mann-Whitney U tests for MAS scores to assess heterogeneity in treatment responses by stroke type (cerebral infarction vs. intracerebral hemorrhage). Among these 110 patients, 25 patients were excluded from the study for various reasons. Hence, 53 patients were included in the control group and 32 patients were included in the experimental group. Following 15 rounds of rTMS, the experimental group exhibited a reductions in MAS score ( P  = 0.004). FM-UE scores increased significantly in both groups (both P  < 0.05), with significant improvement observed in the experimental group ( P  < 0.05). Subgroup analyses revealed no significant differences in FM-UE or MAS outcomes between stroke types, likely due to the limited sample size of intracerebral hemorrhage participants (experimental group: n  = 8; control group: n  = 16). rTMS effectively alleviates upper limb spasticity and enhances motor function after stroke by modulating cortical and spinal nerve excitability.

Differences in the clinical efficacy and adverse drug reactions (ADRs) of eltrombopag (ELT) in children with immune thrombocytopenia (ITP) may be positively correlated with the serum trough concentration of ELT. Individual pharmacokinetic variations primarily contribute to differences in ELT concentration among individuals. This study is the first to establish an expected concentration reference range for ELT in treating pediatric persistent/chronic ITP (P/CITP) across different age-groups. A total of 94 patients with 111 serum trough concentrations were analyzed to validate this range. The median age of patients was 7.68 (5.35, 10.21) years, and 44.7% (42/49) of them were male. Subgroup analyses revealed significant differences in ELT concentration related to the age, efficacy, and ADR occurrence. The expected concentration reference range was determined using the dose-related concentration (DRC) factor combined with the ELT dosage. The DRC factor ranges were as follows: 0.083-0.216 (mg/L)/mg in children aged 1-6 years, 0.058-0.125 (mg/L)/mg in children aged 7-12 years, and 0.043-0.097 (mg/L)/mg in children aged 13-18 years. Among patients with measured trough concentrations within the expected reference range, 84.3% (59/70) achieved response/complete response (R/CR) and 88.6% (62/70) did not experience ADR. Serum trough concentration monitoring based on the established reference ranges could enhance the precision of individualized ELT therapy in pediatric ITP patients.

Background Human periodontal ligament stem cells (hPDLSCs) are ideal seed cells for periodontal regeneration. A greater understanding of the dynamic protein profiles during osteogenic differentiation contributed to the improvement of periodontal regeneration tissue engineering. Methods Tandem Mass Tag quantitative proteomics was utilized to reveal the temporal protein expression pattern during osteogenic differentiation of hPDLSCs on days 0, 3, 7 and 14. Differentially expressed proteins (DEPs) were clustered and functional annotated by Gene Ontology (GO) terms. Pathway enrichment analysis was performed based on the Kyoto Encyclopedia of Genes and Genomes database, followed by the predicted activation using Ingenuity Pathway Analysis software. Interaction networks of redox-sensitive signalling pathways and oxidative phosphorylation (OXPHOS) were conducted and the hub protein SOD2 was validated with western blotting. Results A total of 1024 DEPs were identified and clustered in 5 distinctive clusters representing dynamic tendencies. The GO enrichment results indicated that proteins with different tendencies show different functions. Pathway enrichment analysis found that OXPHOS was significantly involved, which further predicted continuous activation. Redox-sensitive signalling pathways with dynamic activation status showed associations with OXPHOS to various degrees, especially the sirtuin signalling pathway. SOD2, an important component of the sirtuin pathway, displays a persistent increase during osteogenesis. Data are available via ProteomeXchange with identifier PXD020908. Conclusion This is the first in-depth dynamic proteomic analysis of osteogenic differentiation of hPDLSCs. It demonstrated a dynamic regulatory mechanism of hPDLSC osteogenesis and might provide a new perspective for research on periodontal regeneration. Graphical abstract

Importance Eltrombopag has been recommended for pediatric immune thrombocytopenia (ITP). Response and adverse drug reactions (ADRs) varied widely between individuals, even at the same dose of eltrombopag. The appropriate eltrombopag concentration in ITP has not been reported. Objective This study aims to explore the appropriate eltrombopag concentration in pediatric ITP. Methods This was a single‐center, prospective cohort study. Children diagnosed with refractory persistent/chronic ITP and platelet count < 30×109/L were treated with eltrombopag and followed up for at least 2 months. Concentration was detected by high‐performance liquid chromatography‐mass spectrometry at least 2 weeks after eltrombopag. The clinical characteristics‐concentration, concentration‐response, and concentration‐ADRs were analyzed. Results A total of 30 patients were enrolled, comprising 13 males and 17 females, with a median age of 72 (45‒94) months. The median dose and concentration were 1.39 (1.09‒1.56) mg/kg and 2.70 (2.25‒4.13) mg/L, respectively. Of the enrolled patients, 14 responded to treatment, whereas 16 did not. Additionally, five experienced adverse drug reactions. No linear correlation was observed between eltrombopag concentration and clinical characteristics. The concentration was lower in the response group than in the nonresponse group, but there was no significant difference (t = 0.755, P = 0.457). Patients who experienced ADRs had a higher concentration than those without ADRs (t = 2.538, P = 0.017). The area under the receiver operating characteristic curve of ADRs was 0.78 (95% confidence interval: 0.56‒1.00). Youden's index identified the cutoff point as 4.33 mg/L, with a sensitivity of 88% and a specificity of 60%. Logistic regression analysis demonstrated that a higher platelet count before eltrombopag predicted a favorable response. Interpretation Eltrombopag proves efficacious and well‐tolerated for treating pediatric ITP. However, prolonged and high‐dose administration may increase the likelihood of ADRs. Thus, examining the appropriate eltrombopag concentration assists in directing individualized management of pediatric ITP.

Long non-coding RNAs (lncRNAs) can potentially regulate all aspects of cellular activity including differentiation and development, metabolism, proliferation, apoptosis, and activation, and benefited from advances in transcriptomic and genomic research techniques and database management technologies, its functions and mechanisms in physiological and pathological states have been widely reported. Liver fibrosis is typically characterized by a reversible wound healing response, often accompanied by an excessive accumulation of extracellular matrix. In recent years, a range of lncRNAs have been investigated and found to be involved in several cellular-level regulatory processes as competing endogenous RNAs (ceRNAs) that play an important role in the development of liver fibrosis. A variety of lncRNAs have also been shown to contribute to the altered cell cycle, proliferation profile associated with the accelerated development of liver fibrosis. This review aims to discuss the functions and mechanisms of lncRNAs in the development and regression of liver fibrosis, to explore the major lncRNAs involved in the signaling pathways regulating liver fibrosis, to elucidate the mechanisms mediated by lncRNA dysregulation and to provide new diagnostic and therapeutic strategies for liver fibrosis.

Objectives. To investigate potential genetic biomarkers of peri-implantitis and target genes for the therapy of peri-implantitis by bioinformatics analysis of publicly available data. Methods. The GSE33774 microarray dataset was downloaded from the Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) between peri-implantitis and healthy gingival tissues were identified using the GEO2R tool. GO enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the DAVID database and the Metascape tool, and the results were expressed as a bubble diagram. The protein-protein interaction network of DEGs was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) and visualized using Cytoscape. The hub genes were screened by the cytoHubba plugin of Cytoscape. The potential target genes associated with peri-implantitis were obtained from the DisGeNET database and the Open Targets Platform. The intersecting genes were identified using the Venn diagram web tool. Results. Between the peri-implantitis group and the healthy group, 205 DEGs were investigated including 140 upregulated genes and 65 downregulated genes. These DEGs were mainly enriched in functions such as the immune response, inflammatory response, cell adhesion, receptor activity, and protease binding. The results of KEGG pathway enrichment analysis revealed that DEGs were mainly involved in the cytokine-cytokine receptor interaction, pathways in cancer, and the PI3K-Akt signaling pathway. The intersecting genes, including IL6, TLR4, FN1, IL1β, CXCL8, MMP9, and SPP1, were revealed as potential genetic biomarkers and target genes of peri-implantitis. Conclusions. This study provides supportive evidence that IL6, TLR4, FN1, IL1β, CXCL8, MMP9, and SPP1 might be used as potential target biomarkers for peri-implantitis which may provide further therapeutic potentials for peri-implantitis.

Recombinant human thrombopoietin (rhTPO) is commonly used to improve low platelet status in immune thrombocytopenia (ITP), as one protein product, even with a very low rate, there is still the possibility to produce neutralizing antibodies of thrombopoietin (TPO). We described a 7-year-old boy with ITP and normal TPO levels who had previously received rhTPO for 2 weeks but showed persistent thrombocytopenia and was misdiagnosed as acquired amegakaryocytic thrombocytopenia (AATP) and ineffectively treated with cyclosporine A (CsA) in combination with avatrombopag (AVA). As suspicious the TPO neutralizing antibody development as re-test of TPO level is 0, the CD20 + deletion antibody drug rituximab (RTX) was prescribed and received efficacy. rhTPO serves as one bio-protein drug and should be cautious with developing neutralizing antibodies if the drug effect is lost. The tests for antibody and/or TPO level should be done for the diagnosis, and the antibody eradication medication as an anti-CD20 antibody, RTX, should be prescribed to delete thes e neutralizing antibodies to recover the TPO level to reattain the response of ITP treatment.

Poor osseointegration has been regarded as a cause of implant failure in the early stage of healing. Baicalin (BC) is a flavonoid that can promote osteoblastic differentiation. To study the effects of BC coated on implants, this study incorporated BC onto commonly used modified titanium surfaces, such as TiO 2 nanotubes (TNTs), alkali-heated (AH) surfaces and sandblasted acid-etched (SLA) surfaces. The biocompatibility of different titanium surfaces was demonstrated by in vitro study. The effects on osteoblastic differentiation were determined based on ALP activity and the expression of osteogenic proteins. The results revealed that higher concentrations of BC can promote osteoblastic differentiation but also greater inhibition of cell proliferation. Different modified surfaces coated with BC all showed satisfactory biocompatibility. Among them, TNTs with BC coating exhibited optimal incorporation and osteoinduction. It indicates that BC-coated TNTs possess enhanced cell affinity and osteogenesis and have great potential for application in implant dentistry. Graphical abstract

Avatrombopag (AVA), a second-generation thrombopoietin receptor agonist (TPO-RA), has demonstrated efficacy in pediatric persistent/chronic immune thrombocytopenia (ITP). However, critical evidence gaps persist regarding treatment-switching strategies between TPO-RAs, particularly when transitioning from eltrombopag (ELT) or hetrombopag (HET) to AVA. This multicenter cohort study evaluated 55 pediatric ITP patients unresponsive to or relapsing after ELT ( n  = 46) or HET ( n  = 9) who underwent AVA switch therapy. Outcomes included platelet response (≥ 30 × 10⁹/L without rescue therapy), bleeding events, concomitant medication reduction, and safety. Sustained response rates reached 48.4% (ELT-to-AVA) and 33.3% (HET-to-AVA), with median response durations of 10 and 7 days respectively. Platelet elevation during AVA treatment was resolved with dosage changes or discontinuation. AVA significantly reduced bleeding, ITP medications, and rescue therapy, with side effects such as gastrointestinal symptoms, headaches, and fatigue (grades 1–2). AVA demonstrates potential as a safe and effective bridging therapy for TPO-RA refractory pediatric ITP, offering hematological stabilization while reducing treatment burden. These findings address current evidence deficiencies in TPO-RA switching protocols.

Hot compression tests were conducted on an ultrahigh-alloyed Al–Zn–Mg–Cu alloy within a temperature range of 250 to 450°C and a strain rate range of 0.001 to 1 s –1 . The effects of strain rate and temperature on the flow curves were analyzed, along with the relationship between flow stress and microstructural evolution. The results indicate that, except for a strain rate of 1 s –1 across all temperatures, the flow curves following the peak stress do not exhibit monotonic work hardening or dynamic softening. In contrast, continuous work hardening is observed at this strain rate. The diverse shapes of the flow curves are attributed to the various precipitates formed due to the high alloying element content. Dynamic recovery (DRV) is identified as the main flow softening mechanism for the ultrahigh-alloyed Al–Zn–Mg–Cu alloy. While dynamic recrystallization (DRX) contributes to flow softening at a strain rate of 0.001 s –1 , the deformed microstructure becomes the predominant softening mechanism at lower temperatures and higher strain rates. Additionally, the low intensity of isotropic texture at higher temperatures and strain rates facilitates DRX, resulting in a decrease in peak stress.