ObjectiveTo establish a tumor prognostic risk assessment model related to target genes of the miR-34 family. MethodsTarget genes of the miR-34 family were screened， and the scores of miR-34 target genes were assessed in 16 tumor types. Univariate Cox regression analysis was used to identify the tumor type with the strongest correlation between miR-34 target gene scores and overall survival （OS）. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses were performed to elucidate the functional roles and signaling pathways of miR-34 target genes. A prognostic risk model based on the miR-34 target genes was constructed using univariate Cox and LASSO regression analyses. Quantitative real-time PCR （qPCR） and dual-luciferase reporter assays were conducted to validate whether the target genes bind to miR-34 and measure their RNA expression levels in the relevant tumors. Additionally， the risk score was integrated with other clinical indicators to develop a nomogram prediction model for patient survival. ResultsA total of 65 target genes of the miR-34 family were screened. The cancer type exhibiting stronger correlation between the target gene scores and OS was lung adenocarcinoma （P = 0.003， HR= 5.150）. Furthermore， miR-34 target genes were predominantly enriched in oxidative stress pathways and various tumor-related processes. Three genes， LDHA， GALNT7， and SATB2， were identified as core components of the prognostic analysis model for lung adenocarcinoma. Additionally， the constructed nomogram model demonstrated robust predictive performance. ConclusionThe risk model and prognosis model of lung adenocarcinoma constructed based on the key target genes of miR-34 have good predictive performance.

AIM:To automatically identify and quantitatively assess myopia-related fundus structural changes by combining non-mydriatic color fundus photography with an artificial intelligence(AI)-powered quantitative fundus analysis system and to further analyze the correlations between these fundus parameters and spherical equivalent(SE), axial length(AL), and age, providing the objective basis for monitoring myopia progression and supporting the formulation of personalized myopia prevention and control strategies. METHODS:A cross-sectional study was conducted enrolling myopic patients aged 18-50 y who underwent myopia screening from March 2023 to December 2023. Patients were stratified into three groups based on SE: the -3.00 D

Osteoarthritis (OA), a highly prevalent degenerative joint disease worldwide, is defined by articular cartilage degradation, abnormal bone remodeling, and persistent chronic inflammation. It severely compromises patients’ quality of life, and currently, there is no radical cure. Abnormal mechanical stress is widely regarded as a core driver of OA pathogenesis, and the exploration of mechanical signal perception and transduction mechanisms has become crucial for deciphering OA’s pathophysiological processes. Piezo1, a key mechanosensitive cation channel belonging to the Piezo protein family, has recently gained significant attention due to its pivotal role in mediating cellular responses to mechanical stimuli in joint tissues. This review systematically examines Piezo1’s expression patterns, regulatory mechanisms, and pathological functions in OA, with a particular focus on its dual roles in modulating chondrocyte homeostasis and bone metabolism disorders, while also delving into the underlying molecular signaling pathways and potential therapeutic implications. Piezo1, consisting of approximately 2 500 amino acids and forming a unique trimeric propeller-like structure, is widely expressed in chondrocytes, osteocytes, mesenchymal stem cells, and synovial cells. It exhibits permeability to cations such as Ca²⁺, K⁺, and Na⁺, and directly responds to membrane tension changes induced by mechanical stimuli like fluid shear stress and mechanical overload. In OA patients and animal models, Piezo1 expression is significantly upregulated, especially in cartilage regions subjected to abnormal mechanical stress (e.g., human temporomandibular joint cartilage). This overexpression is closely associated with aggravated cartilage degeneration, increased chondrocyte apoptosis, accelerated cellular senescence, and intensified inflammatory responses. Mechanical overload and pro-inflammatory cytokines (e.g., IL-1β) are key inducers of Piezo1 upregulation: IL-1β activates the PI3K/AKT/mTOR signaling pathway to enhance Piezo1 expression, forming a pathogenic positive feedback loop that inhibits chondrocyte autophagy, promotes apoptosis, and further accelerates joint degeneration. Mechanistically, Piezo1 mediates OA progression through multiple interconnected pathways. When activated by mechanical stress, Piezo1 triggers excessive Ca²⁺ influx, leading to endoplasmic reticulum stress (ERS) and mitochondrial dysfunction, which directly induce chondrocyte apoptosis. This process involves the activation of downstream signaling cascades such as cGAS-STING and YAP-MMP13/ADAMTS5. YAP, a transcriptional regulator, upregulates the expression of matrix metalloproteinase 13 (MMP13) and aggrecanase (ADAMTS5), thereby accelerating cartilage matrix degradation. Additionally, Piezo1-driven Ca²⁺ overload promotes the accumulation of reactive oxygen species (ROS) and upregulates senescence markers (p16 and p21), accelerating chondrocyte senescence via the p38MAPK and NF-κB pathways. Senescent chondrocytes secrete senescence-associated secretory phenotype (SASP) factors (e.g., IL-6, IL-1β), further amplifying joint inflammation. In terms of bone metabolism, Piezo1 maintains joint homeostasis by promoting the differentiation of fibrocartilage stem cells into chondrocytes and balancing bone formation and resorption through regulating the FoxC1/YAP axis and RANKL/OPG ratio. Therapeutically, targeting Piezo1 shows promising potential. Preclinical studies have demonstrated that Piezo1 inhibitors (e.g., GsMTx4) can reduce joint damage and alleviate pain in OA mice. Simultaneously, siRNA-mediated co-silencing of Piezo1 and TRPV4 (another mechanosensitive channel) decreases intracellular Ca²⁺ concentration, inhibits chondrocyte apoptosis, and promotes cartilage repair. Conditional knockout of Piezo1 using Gdf5-Cre transgenic mice alleviates cartilage degeneration in post-traumatic OA models by downregulating MMP13 and ADAMTS5 expression. Despite existing challenges, such as off-target effects of inhibitors, inefficient local drug delivery, and interindividual genetic variability, strategies like developing selective Piezo1 antagonists, optimizing targeted nanocarriers, and combining Piezo1-targeted therapy with physical therapy provide viable avenues for clinical translation. The authors propose that Piezo1 serves as a critical therapeutic target for OA, and future research should focus on deciphering its context-dependent regulatory networks, developing tissue-specific intervention strategies, and validating their efficacy and safety in clinical trials to address the unmet medical needs of OA patients.

BACKGROUND: Growing evidence suggests that long non-coding RNAs (lncRNAs) exert pivotal roles in fostering chemoresistance across diverse tumors. Nevertheless, the precise involvement of lncRNAs in modulating chemoresistance within the context of gallbladder cancer (GBC) remains obscure. This study aimed to uncover how lncRNAs regulate chemoresistance in gallbladder cancer, offering potential targets to overcome drug resistance. METHODS: To elucidate the relationship between gemcitabine sensitivity and small nucleolar RNA host gene 1 ( SNHG1 ) expression, we utilized publicly available GBC databases, GBC tissues from Renji Hospital collected between January 2017 and December 2019, as well as GBC cell lines. The assessment of SNHG1, miR-23b-3p, and phosphatase and tensin homolog (PTEN) expression was performed using in situ  hybridization, quantitative real-time polymerase chain reaction, and western blotting. The cell counting kit-8 (CCK-8) assay was used to quantify the cell viability. Furthermore, a GBC xenograft model was employed to evaluate the impact of SNHG1 on the therapeutic efficacy of gemcitabine. Receiver operating characteristic (ROC) curve analyses were executed to assess the specificity and sensitivity of SNHG1. RESULTS: Our analyses revealed an inverse correlation between the lncRNA SNHG1 and gemcitabine resistance across genomics of drug sensitivity in cancer (GDSC) and Gene Expression Omnibus (GEO) datasets, GBC cell lines, and patients. Gain-of-function investigations underscored that SNHG1 heightened the gemcitabine sensitivity of GBC cells in both in vitro and in vivo  settings. Mechanistic explorations illuminated that SNHG1 could activate PTEN -a commonly suppressed tumor suppressor gene in cancers-thereby curbing the development of gemcitabine resistance in GBC cells. Notably, microRNA (miRNA) target prediction algorithms unveiled the presence of miR-23b-3p binding sites within SNHG1 and the 3'-untranslated region (UTR) of PTEN . Moreover, SNHG1 acted as a sponge for miR-23b-3p, competitively binding to the 3'-UTR of PTEN , thereby amplifying PTEN expression and heightening the susceptibility of GBC cells to gemcitabine. CONCLUSION The SNHG1/miR-23b-3p/PTEN axis emerges as a pivotal regulator of gemcitabine sensitivity in GBC cells, holding potential as a promising therapeutic target for managing GBC patients.
Humans ; Deoxycytidine/pharmacology* ; PTEN Phosphohydrolase/genetics* ; Gemcitabine ; RNA, Long Noncoding/metabolism* ; MicroRNAs/genetics* ; Gallbladder Neoplasms/genetics* ; Cell Line, Tumor ; Animals ; Mice ; Drug Resistance, Neoplasm/genetics* ; Mice, Nude ; Antimetabolites, Antineoplastic ; Gene Expression Regulation, Neoplastic

Malignant proliferating liver cancer cells possess the ability to detect and respond to various body signals, thereby facilitating tumor growth, invasion, and metastasis. One crucial mechanism through which hepatocellular carcinoma (HCC) cells interpret these signals is crosstalk. Within liver cancer tissues, cancer cells engage in communication with hepatic stellate cells (HSCs), tumor-associated macrophages (TAMs), and immune cells. This interaction plays a pivotal role in regulating the proliferation, invasion, and metastasis of HCC cells. Crosstalk occurs in multiple ways, each characterized by distinct functions. Its molecular mechanisms primarily involve regulating immune cell functions through the expression of specific receptors, such as CD24 and CD47, modulating cell functions by secreting cytokines like transforming growth factor-β (TGF-β) and platelet-derived growth factor (PDGF), and mediating cell growth and proliferation by activating pathways such as Wnt/β-catenin and Hedgehog. A comprehensive understanding of the mechanisms and interactions within crosstalk is essential for unraveling the pathogenesis of HCC. It also opens up new avenues for the development of innovative therapeutic strategies. This article reviews the relationship between crosstalk and the progression of HCC, offering insights and inspiration for future research.
Humans ; Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Hepatic Stellate Cells/physiology* ; Disease Progression ; Signal Transduction/physiology* ; Transforming Growth Factor beta/metabolism* ; Cell Proliferation ; Hedgehog Proteins/metabolism* ; Tumor-Associated Macrophages ; Platelet-Derived Growth Factor/metabolism* ; Cell Communication/physiology*

Juvenile idiopathic arthritis (JIA) is the most common condition of chronic rheumatic disease in children. JIA is an autoimmune or autoinflammatory disease, with unclear mechanism and limited treatment efficacy. Recent studies have found a number of alterations in gut microbiota and its metabolites in children with JIA, which are related to the development and progression of JIA. This review focuses on the influence of the gut microbiota and its metabolites on immune function and the intestinal mucosal barrier and discuss the key role of the gut-joint axis in the pathogenesis of JIA and emerging treatment methods based on gut microbiota and its metabolites. This review could help elucidate the pathogenesis of JIA and identify the potential therapeutic targets for the prevention and treatment of JIA.
Humans ; Arthritis, Juvenile/physiopathology* ; Gastrointestinal Microbiome/physiology* ; Child ; Intestinal Mucosa

Purpose: We used bioinformatics methods and Mendelian randomization (MR) analysis to investigate the hub genes involved in acute myeloid leukemia (AML) and their causal relationship with hemolysis, to explore a new direction for molecular biology research of AML. Methods: We first differentially analyzed peripheral blood samples from 62 healthy volunteers and 65 patients with AML from the Gene Expression Omnibus database to obtain differentially expressed genes (DEGs), and intersected them with genes sourced from weighted gene co-expression network analysis (WGCNA) and the GeneCards database to obtain target genes. Target genes were screened using protein–protein interaction (PPI) network analysis and ROC curves to identify genes associated with AML. Finally, we analyzed the correlation between genes and immune cells and the relationship between toll-like receptor 4 (TLR4) and AML using MR. Results: We compared peripheral blood expression profiles using an array of 62 healthy volunteers (GSE164191) and 65 patients with AML (GSE89565) (M0:25; M1:11; M2:10; M3:1; M4:7; M4 eo t [16;16] ou inv [16]:4; M5:6; M6:1) and obtained 7,339 DEGs (3,733 upregulated and 3,606 downregulated). We intersected these DEGs with 4,724 genes from WGCNA and 1,330 genes related to hemolysis that were identified in the GeneCards database to obtain 190 target genes. After further screening these genes using the PPI network, we identified TLR4, PTPRC, FCGR3B, STAT1, and APOE, which are closely associated with hemolysis in patients with AML. Finally, we found a causal relationship between TLR4 and AML occurrence using MR analysis (p < 0.05). Conclusion We constructed a WGCNA-based co-expression network and identified hemolysis-associated AML genes.

Purpose: To investigate the short-term outcomes of intravitreal injections of the ranibizumab biosimilar SB11 in patients with neovascular age-related macular degeneration (AMD). Methods: This retrospective comparative study assessed changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) in patients diagnosed with neovascular AMD who received three monthly injections of SB11. The outcomes were compared to those of patients who received the same treatment using the ranibizumab originator. Within the SB11 group, comparisons were made between BCVA and CRT at diagnosis and after three injections. The proportion of patients with resolved subretinal fluid/intraretinal fluid was also evaluated. Results: The study included 46 eyes. In the SB11 group (n = 23), the average BCVA improved significantly from a baseline of logarithm of minimal angle of resolution 0.54 ± 0.42 to 0.40 ± 0.32 after three injections (p = 0.008). The average CRT decreased significantly from 447.4 ± 167.7 µm at baseline to 267.9 ± 66.9 µm after treatment (p < 0.001). Complete resolution of macular edema was observed in 19 eyes (82.7%). No significant differences were found in the degree of change in BCVA (p = 0.883) and CRT (p = 0.629) when compared to the ranibizumab originator group (n = 23). No complications such as intraocular inflammation or retinal detachment were noted. Conclusions Treatment with SB11 loading injections in neovascular AMD led to significant improvements in vision and reductions in macular thickness. The extent of improvement was comparable to that achieved with the ranibizumab originator and no severe complications were observed.

OBJECTIVE: To investigate the safety and effectiveness of using the Taylor spatial frame (TSF) based on the Ilizarov tension-stress principle for treatment of post-burn foot and ankle deformities in adults. METHODS: A clinical data of 6 patients with post-burn foot and ankle deformities treated between April 2019 and November 2023 was retrospectively analyzed. There was 1 male and 5 females with an average age of 28.7 years (range, 20-49 years). There were 3 cases of simple ankle equinus, 2 cases of ankle equinus, midfoot rocker-bottom foot, and forefoot pronation, and 1 case of calcaneus foot and forefoot pronation. Preoperative American Orthopedic Foot and Ankle Society (AOFAS) score was 45.3±18.2, 12-Item Short-Form Health Survey (SF-12)-Physical Component Summary (PCS) score was 34.3±7.3 and Mental Component Summary (MCS) score was 50.4±8.8. Imaging examination showed tibial-calcaneal angle of (79.8±31.5)°, calcaneus-first metatarsal angle of (154.5±45.3)°, talus-first metatarsal angle of (-19.3±35.0)°. Except for 1 case with severe deformity that could not be measured, the remaining 5 cases had talus-second metatarsal angle of (40.6±16.4)°. The deformities were fixed with TSF after soft tissue release and osteotomy. Then, the residual deformities were gradually corrected according to software-calculated prescriptions. TSF was removed after maximum deformity correction and osteotomy healing. External fixation time, brace wearing time after removing the TSF, and pin tract infection occurrence were recorded. Infection severity was evaluated based on Checketts-Otterburns grading. Joint function was evaluated using AOFAS score and SF-12 PCS and MCS scores. Patient satisfaction was assessed using Likert score. Imaging follow-up measured relevant indicators to evaluate the degree of deformity correction. Deformity recurrence was observed during follow-up. RESULTS: The external fixation time was 103-268 days (mean, 193.5 days). The mild pin tract infections occurred during external fixation in all patients, which healed after pin tract care and oral antibiotics. No serious complication such as osteomyelitis, fractures, neurovascular injury, or skin necrosis occurred. After external fixation removal, 3 cases did not wear braces, while the remaining 3 cases wore braces continuously for 6 weeks, 8 weeks, and 3 years, respectively. All patients were followed up 13.9-70.0 months, with an average of 41.7 months. During follow-up, none of the 6 patients had recurrence of foot deformity. At 1 year after operation, the AOFAS score was 70.0±18.1, SF-12-PCS and MCS scores were 48.9±4.5 and 58.8±6.4, respectively, all showing significant improvement compared to preoperative values ( P<0.05). Imaging follow-up showed that all osteotomies healed, and all distraction cases achieved bony union at 6 months after stopping stretching. At 1 year after operation, tibial-calcaneal angle was (117.5±12.8)° and talus-first metatarsal angle was (-3.3±19.3)°, both showing significant improvement compared to preoperative values ( P<0.05). Calcaneus-first metatarsal angle was (132.0±14.4)°, which also improved compared to preoperative values but without significant difference ( P>0.05). Except for 1 case with severe deformity that could not be measured, the remaining 5 cases had talus-second metatarsal angle of (18.0±6.4)°. And there was no significant difference ( P>0.05) between pre-and post-operative data of 4 patients with complete data. At 1 year after operation, 1 patient was satisfied with effectiveness and 5 patients were very satisfied. CONCLUSION The TSF, by applying the Ilizarov tension-stress principle for gradual distraction and multi-planar adjustment, combined with soft tissue release and osteotomy, can effectively correct foot and ankle deformities after burns, especially equinus deformity with contracture of the posterior soft tissues of the lower leg. There are still limitations in treating cases with tight, adherent scars on the dorsum of the foot that require long-distance distraction. If necessary, a multidisciplinary approach combined with microsurgical techniques can be utilized.
Humans ; Adult ; Male ; Female ; Middle Aged ; Retrospective Studies ; External Fixators ; Young Adult ; Burns/complications* ; Foot Deformities, Acquired/etiology* ; Treatment Outcome ; Ilizarov Technique/instrumentation*