Volume 139 · Issue 17 · 2026

Musculoskeletal disorders (MSDs) represent a diverse group of conditions affecting bones, cartilage, intervertebral discs, tendons, muscles, and related structures, and continue to be a leading cause of global disability. Despite advancements in surgery and pharmacotherapy, issues such as incomplete regeneration, limited longevity, and procedure-related complications remain unresolved. As a result, hydrogel technologies have garnered increasing attention due to their hydrated three-dimensional networks, customizable mechanical properties, and extracellular matrix (ECM)-mimicking features. Hydrogels have been developed in various forms, including injectable systems, scaffolds, and patches, to facilitate tissue regeneration, deliver bioactive molecules, modulate inflammation, and provide mechanical or interfacial support. This review comprehensively examines recent advancements in hydrogel technologies for MSD treatment, focusing on bone and cartilage repair, osteoarthritis management, intervertebral disc regeneration, tendon and muscle healing, and spinal dural repair. It covers laboratory studies, preclinical animal trials, and clinically approved or translational products. By critically evaluating representative materials, design strategies, and disease-specific requirements, this review highlights the therapeutic potential and translational barriers of current hydrogel systems. Challenges such as mechanical durability, spatiotemporal control of bioactivity, scalable manufacturing, and clinically relevant evaluation are addressed, providing insights into the development of next-generation hydrogels for MSDs.

Allergen immunotherapy (AIT) remains the only disease-modifying treatment for immunoglobulin (Ig) E-mediated allergic diseases, including allergic rhinitis (AR), asthma, food allergy, and atopic dermatitis (AD). This review provides a comprehensive update on recent advances in AIT, focusing on immunological mechanisms, novel vaccines, biomarkers, clinical outcomes across different diseases, and emerging combination strategies with biologics. We discussed the pivotal roles of regulatory T and B cells, innate lymphoid cells (ILCs), and blocking antibodies (immunoglobulin G4 [IgG4], immunoglobulin A [IgA]) in establishing long-term tolerance. Novel allergen vaccines—including recombinant and hypoallergenic derivatives, virus-like particle (VLP) conjugates, and transgenic peptide vaccines—aim to improve safety and efficacy. We critically evaluate current biomarkers for predicting and monitoring AIT response, such as the allergen-specific IgE (sIgE)/total immunoglobulin E (tIgE) ratio, basophil activation test, and cellular markers. Clinical evidence supports AIT efficacy in asthma, AR, and AD, with emerging applications in food allergies. Furthermore, combining AIT with biologics (e.g., anti-IgE and anti-interleukin [IL]-4/IL-4 receptor [IL-4R]) shows promise in enhancing safety and efficacy, particularly in severe asthma. Despite these advances, challenges remain in patient selection, treatment duration, and extract standardization. Future research should prioritize predictive biomarkers, short-course regimens, and synergistic biologic-AIT approaches.

Hematopoietic stem cell transplantation (HSCT) is a foundational treatment for hematological disorders. While its efficacy is established, the conditioning regimens required for HSCT (high-dose chemotherapy and radiotherapy), along with transplant-related immunological and metabolic changes, can induce significant neurological complications. These treatment-related effects necessitate a comprehensive evaluation of their impact on brain structure and function. A synthesis of current evidence on these neurological outcomes is essential to guide clinical practice and future research. This review synthesizes literature on the effects of HSCT-associated treatments on neuroanatomy, cognitive performance, and long-term neurological sequelae. Evidence indicates consistent reductions in gray-matter volume, particularly within frontal, temporal, and parietal cortices, alongside diffuse white-matter alterations affecting major commissural and association tracts. These structural changes correlate with clinically meaningful deficits in attention, executive function, and memory. The underlying pathogenic mechanisms are multifactorial, involving direct neurotoxicity from conditioning regimens, systemic and neuroinflammatory responses, and oxidative stress. The findings underscore the importance of integrating thorough neurological evaluation and longitudinal monitoring into routine care for HSCT recipients. Future research should elucidate detailed mechanisms and develop personalized, evidence-based neuroprotective and rehabilitative strategies. A deeper understanding of these neurological consequences is paramount for improving outcomes and long-term quality of life.

Background: Guselkumab is effective in treating moderate-to-severe plaque psoriasis; however, data from randomized controlled trials in the Chinese population are limited. This study evaluated and verified the efficacy and safety profile of guselkumab in Chinese patients with moderate-to-severe plaque psoriasis. Methods: This was a randomized, double-blind, placebo-controlled, phase 4 study. Patients with moderate-to-severe plaque psoriasis were randomized 2:1 to the guselkumab group (guselkumab 100 mg by subcutaneous injection at weeks 0 and 4, then every 8 weeks thereafter through week 44) or the placebo-to-guselkumab group (placebo at weeks 0, 4, and 12, then guselkumab at weeks 16, 20, 28, 36, and 44). Coprimary efficacy endpoints were the proportion of patients achieving Psoriasis Area and Severity Index (PASI) 90 response and the proportion of patients achieving Investigator’s Global Assessment (IGA) 0/1 response at week 16. Results: Among the 419 patients screened for eligibility between August 25, 2021, and July 21, 2022, 327 patients were enrolled. All 327 randomized patients (mean age, 41.5 [standard deviation, 12.7] years; 259 [79.2%] men) were treated and included in the analyses. At week 16, 103/110 patients assigned to the placebo group at baseline started guselkumab treatment. Most patients completed the study (210 in guselkumab group and 101 in placebo-to-guselkumab group). Significantly higher proportions of patients with guselkumab achieved PASI 90 (82.4% vs. 2.0%; P <0.001) and IGA score 0/1 (88.8% vs. 7.1%; P <0.001) compared with placebo at week 16. At week 48, response rates were maintained in the guselkumab group (PASI 90: 79.2%; IGA 0/1: 82.4%) and increased in the placebo-to-guselkumab group (PASI 90: 80.2%; IGA 0/1: 86.3%). During the first 16 weeks, the incidence of adverse events was comparable between groups (41.9% guselkumab vs. 39.1% placebo) and the incidence of serious adverse events was low (0.9% vs. 5.5%), respectively. Conclusion: Guselkumab was highly effective and displayed a favorable safety profile for the treatment of moderate-to-severe plaque psoriasis in Chinese patients.

Background: Neonatal encephalopathy (NE) due to birth asphyxia and trauma has become the second leading cause of global neonatal and under-5 deaths. However, comprehensive data on the global NE burden are scarce. This study aimed to determine the global, regional, and national trends in NE burden from 1990 to 2019, utilizing the 2019 Global Burden of Disease (GBD) study data. Methods: Annual incident cases, deaths, disability-adjusted life years (DALYs), and age-standardized rates (incidence [ASIR], mortality [ASMR], DALYs) of NE were collected from the 2019 GBD study. The percentage of relative changes and estimated annual percentage changes (EAPCs) were calculated to assess temporal trends. Results: NE global incident cases increased from 1.33 million in 1990 to 1.38 million in 2019, with a 4.87% rise in ASIR. Global NE deaths remained at 0.57 million in 2019, despite a 29.88% reduction from 1990. Significant annual reductions in ASMR and DALYs were observed post-2005. South Asia and sub-Saharan Africa accounted for 80.00% of global NE cases, with South Asia, Eastern and Western sub-Saharan Africa contributing to 81.42% of global deaths and 79.50% of DALYs. NE-related deaths comprised 22.76% and 11.24% of neonatal and under-5 mortality. There were 3.91 million epilepsy, 4.23 million developmental intellectual disability, and 0.57 million blindness cases caused by NE globally in 2019. Conclusions: Despite a significant reduction in NE mortality from 1990 to 2019, the ongoing rise in incidence, particularly in South Asia and sub-Saharan Africa, is alarming. Targeted initiatives to prevent NE are needed, especially tailored to high-burden regions.

Background: Refractory epilepsy remains a global clinical challenge. This first-in-human cohort study aimed to evaluate the efficacy and safety of washed microbiota transplantation (WMT) in the treatment of epilepsy. Methods: A prospective, single-center, open-label study of WMT in patients with epilepsy was conducted at the Second Affiliated Hospital of Nanjing Medical University from November 2016 to November 2023. The primary outcome was the clinical response rate (≥50% reduction in seizure frequency) at one month post-WMT. Parallel experiments using a pentylenetetrazole-induced epileptic mouse model were performed to validate clinical findings and investigate the role of specific core bacterial species. Results: Among 21 patients (mean age, 18.9 years), including 18 with refractory epilepsy, the clinical response rates were 43% (9/21), 57% (12/21), and 38% (8/21) at one, three, and six months post-WMT, respectively. A second maintenance WMT course at three months was associated with a higher response rate at six months compared to no maintenance therapy (odds ratio [OR] >999, 95% confidence interval [CI]: [1.12, +infinity], P = 0.080). WMT significantly increased Akkermansia muciniphila (A. muciniphila) levels in responders (P = 0.038). A higher baseline A. muciniphila abundance was associated with improved clinical outcomes (Z = 3.28, P = 0.001). The preclinical study confirmed that A. muciniphila augmented the effects of WMT against seizures, significantly reducing seizure severity and duration, and prolonging seizure latency. Conclusions: Integrating clinical and preclinical findings, this study demonstrates that A. muciniphila synergistically enhances the effects of WMT against epileptic seizures. This study provides evidence for a new concept of microbiome-based therapeutics in epilepsy treatment.

Background: Bladder cancer (BCa) is the most common genitourinary malignancy and causes substantial economic losses worldwide. Recent studies suggest overexpression of circCD2AP in BCa, but its mechanistic contributions to carcinogenesis and ferroptosis regulation remain unclear. Methods: From August 2021 to January 2024, 98 pairs of BCa and adjacent normal tissue samples were collected from the Third Xiangya Hospital, Central South University. Gene/protein expression, lipid reactive oxygen species (ROS) levels, and cell viability were analyzed. Interactions among circCD2AP/YTH domain-containing protein 1 (YTHDC1), circCD2AP, insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), and IGF2BP3/forkhead box C1 (FOXC1) were validated, along with circCD2AP-IGF2BP3 colocalization. FOXC1 binding sites in the Parkinson’s disease protein 7 (PARK7) promoter were mapped. N6-methyladenosine (m6A) modifications on circCD2AP were quantified via methylated RNA immunoprecipitation polymerase chain reaction. Results: circCD2AP was significantly upregulated in BCa and positively correlated with PARK7 expression (R2 = 0.1357, P = 0.0002). Patients with high circCD2AP expression showed poorer survival rates. CircCD2AP knockdown sensitized BCa cells to ferroptosis inducers (erastin and Ras-selective lethal small molecule 3). Methyltransferase-like 3 (METTL3) knockdown inhibited circCD2AP m6A modification and relative expression. YTHDC1 mediated m6A-dependent cytoplasmic export of circCD2AP (2.8-fold increase). Besides, circCD2AP stabilized FOXC1 messenger RNA (mRNA), and FOXC1 bound the PARK7 promoter to enhance its expression. Knockdown of FOXC1 or PARK7 blocked the antiferroptotic effect of circCD2AP overexpression in BCa cells. Knockdown of METTL3 or circCD2AP reduced tumor burden in mice, decreasing both volume (approximately 48.3% or 56.4%) and weight (approximately 65.3% or 58.7%) through FOXC1/PARK7-mediated ferroptosis. Conclusions: METTL3-mediated m6A modification drives circCD2AP overexpression, which is subsequently exported to the cytoplasm with enhanced efficiency mediated by YTHDC1. Cytoplasmic circCD2AP stabilizes FOXC1 mRNA, enabling FOXC1-dependent transcriptional activation of PARK7. This axis suppresses ferroptosis and promotes BCa progression, revealing a novel therapeutic target.

Background: Sensorineural hearing loss is characterized by irreversible hair cell (HC) degeneration. Ferroptosis, which is marked by the accumulation of reactive oxygen species and elevated levels of lipid peroxidation products, has been shown to contribute to drug-mediated auditory impairment. This study aimed to elucidate the role of mixed-lineage leukemia 1 (MLL1) in HC survival in the auditory system. Methods: The HEI-OC1 auditory cell line and postnatal cochlear explants were evaluated using MM-102, a specific MLL1 histone methyltransferase inhibitor. Western blotting, quantitative polymerase chain reaction, electron microscopy, and immunofluorescence were used to elucidate the role of MLL1 in regulating ferroptosis in HC injury. RNA sequencing (RNA-seq) was used to analyze the molecular mechanisms of MLL1 intervention in HC injury from an epigenetic perspective. Results: Our findings demonstrated that immunofluorescence staining revealed a crucial role of MM-102 in promoting intracellular accumulation of lipid peroxides and ferrous ions. Subsequent analysis showed MLL1 downregulation-induced mitochondrial dysfunction and endoplasmic reticulum (ER) stress, with transmission electron microscopy imaging confirming ultrastructural alterations in mitochondria and ER. Mechanistic investigations identified the PERK–eIF2α–ATF4–Chop signaling axis as the regulatory pathway, evidenced by Western blotting quantification of phosphorylated PERK (p-PERK), ATF4, and Chop levels. RNA-seq analysis revealed 741 differentially expressed genes (335 upregulated and 406 downregulated). Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis specifically highlighted significant enrichment of the PI3K/Akt-Lrp1 pathway, with corresponding activation patterns of phospho (p)-Akt and Lrp1 confirmed through Western blotting analysis. Conclusions: MLL1 downregulation initiates ferroptosis in cochlear HCs. This process is intrinsically associated with the activation of mitochondrial dysfunction and ER stress. The study highlights the importance of MLL1 in HC survival, suggesting its potential as a therapeutic target for treating hearing loss.

Background: Endometriosis (EMs) is one of the most common gynecologic diseases, and the roles of ferroptosis in EMs have not been fully clarified. The induction of ferroptosis has been demonstrated to inhibit the growth of ectopic lesions in EMs. Although acetyl-CoA carboxylase 1 (ACC1), the rate-limiting enzyme for fatty acid biosynthesis, has been shown to regulate ferroptosis, the detailed mechanism involved has not been fully elucidated. In addition, the role of ACC1, encoded by ACACA, in EMs remains unclear. Thus, the present study aimed to explore the role of ACC1 in ferroptosis and the potential therapeutic effect of the ferroptosis inducer the ferroptosis inducer 56 (FIN56) in EMs. Methods: The effects of ACACA, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4), and p38 mitogen-activated protein kinase (MAPK) on FIN56-induced ferroptosis were analyzed in ectopic endometrial stromal cells (ecESCs) through Cell Counting Kit-8 (CCK-8) assays, lipid reactive oxygen species (ROS) assays using flow cytometry, lipid peroxidation malondialdehyde (MDA) assays, and transmission electron microscopy (TEM). RNA sequencing (RNA-seq) and Venn diagram analysis were used to explore the possible ACACA-related genes. Drug inhibitor administration, plasmid overexpression, and small interfering RNA (siRNA) knockdown were used to investigate the role of ACACA and NOX4 in ferroptosis. Immunofluorescence analysis and chromatin immunoprecipitation (ChIP) analysis were subsequently conducted to assess the interaction between AT-rich interaction domain 5A (ARID5A) and NOX4. The effects of ACACA and NOX4 on mitochondrial function were assessed via mitochondrial membrane potential (MMP) analysis, mitochondrial ROS (mtROS) production analysis, and adenosine triphosphate (ATP) assays. Ferro orange staining was used to determine the intracellular levels of iron. An EMs mouse model was generated to evaluate the therapeutic effect of FIN56 in vivo. Results: FIN56 increased intracellular iron levels, lipid peroxidation, and mitochondrial damage, which further triggered ferroptosis in ecESCs. ACACA expression was significantly decreased in ecESCs and ectopic endometrial tissues. Treatment with 5-(tetradecyloxy)-2-furoic acid (TOFA), an allosteric inhibitor of ACC1, alleviated ferroptosis induced by FIN56 in ecESCs. Mechanistically, FIN56 treatment resulted in upregulation of NOX4 expression in ecESCs via activation of the p38 MAPK/ARID5A signaling pathway, which was alleviated by ACACA inhibition. Additionally, ACACA and NOX4 increase ferroptosis-dependent cytotoxicity by impairing mitochondrial function and oxidative stress-induced lipid peroxidation in ecESCs. Finally, the regression of ectopic lesions after FIN56 administration was verified in an EMs mouse model. Conclusions: The findings reveal that ACACA deficiency protected ecESCs from ferroptosis-dependent cytotoxicity through the p38 MAPK/ARID5A/NOX4 pathway. Moreover, ferroptosis induction by FIN56 in the EMs model mice alleviated the disease. Thus, the ferroptosis inducer FIN56 may be a new therapeutic for EMs.