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.

Multidrug-resistant (MDR) bacterial infections have emerged as a serious challenge of global public health crisis. The overuse and misuse of conventional antibiotics have dramatically accelerated the emergence, evolution and worldwide spread of drug-resistant bacterial strains, necessitating urgent exploration of novel antibacterial strategies. Bacteriophages serve as natural bacterial predators offering distinct advantages including high host specificity, autonomous self-replication capabilities and cost-effective large-scale production. However, wild-type phages present significant clinical limitations due to their narrow host ranges, susceptibility to rapid immune clearance and poor penetration of bacterial biofilms, which severely restrict their therapeutic applications. The convergence of synthetic biology, nanotechnology and advanced gene editing technologies has accelerated the development of engineered bacteriophage platforms, providing programmable, scalable and clinically translatable pathways to overcome these inherent biological constraints. Here, we systematically delineate four fundamental strategies for engineered bacteriophage development. Chemical modification utilizes reactive functional groups such as amino, carboxyl and thiol moieties on capsid proteins through esterification, amidation or click chemistry reactions to achieve precise drug conjugation and surface functionalization. In vivo editing encompasses ultraviolet or chemical mutagenesis for random mutation induction, homologous recombination for targeted genetic alterations, recombineering methodologies including electroporation-mediated bacteriophage recombination engineering, and CRISPR-Cas systems for precise genome editing to enable exact genetic reconstruction and host range reprogramming. In vitro synthesis leverages genome engineering platforms where intact phage genomes are transferred into yeast or host bacteria to facilitate highly efficient homologous recombination, enabling large DNA fragment assembly and cross-gene host range expansion without bacterial toxicity constraints. Directed evolution combines artificial selection through mutation library screening with rational design approaches involving chimeric receptor binding protein construction or site-specific mutagenesis, effectively balancing the discovery of unknown adaptive pathways with targeted host specificity modification. Moreover, we comprehensively discuss therapeutic applications across diverse clinical scenarios. Engineered bacteriophage effectively disrupt bacterial biofilms through sophisticated functionalized delivery platforms including nanozyme-conjugated phages, phage-liposome nanoconjugates and bio-responsive hydrogels, demonstrating significantly enhanced bactericidal efficiency compared to unmodified free phages. These bioengineered vectors attenuate bacterial virulence and resensitize pathogens to antibiotics by delivering CRISPR-Cas systems or base editors to disrupt critical virulence factors such as pili, capsule synthesis machineries and quorum sensing systems, or by inactivating antibiotic resistance determinants including beta-lactamase genes. As an intelligent nanomedicine delivery platform, engineered bacteriophage enable precise pathogen elimination an through photocatalytic reactive oxygen species generation, immunomodulatory interventions, or controlled release of antibacterial drugs. Furthermore, oral administration of engineered bacteriophage facilitates microbiota modulation, which selectively eliminate intestinal pathogens while preserve beneficial commensal microbiota, thereby restoring microbial community balance and preventing complications associated with dysbiosis. Finally, we critically analyze persistent challenges including host strain matching complexity, evolution of bacterial resistance mechanisms, pharmacokinetic optimization requirements, optimal administration route selection, large-scale production quality control standards and clinical dosing determination protocols. Through multidisciplinary integration of synthetic biology, infectious disease medicine and immunology, future translational medicine studies of bacteriophage should establish comprehensive technical platforms encompassing rapid phage screening, intelligent rational design, rigorous in vivo evaluation and standardized clinical validation processes, ultimately advancing engineered bacteriophage from laboratory innovations to clinically approved therapeutics for effectively combating MDR bacterial infections.

Purpose: This study aimed to evaluate the safety and efficacy of gemcitabine and cisplatin (GP) regimen in combination with immune checkpoint inhibitor sintilimab as neoadjuvant therapy for muscle-invasive bladder cancer (MIBC) patients and the feasibility of the following selective bladder sparing surgery. Materials and Methods: Patients with histopathologically confirmed urothelial carcinoma without distant metastases (T2-4a, N ≤ 1, M0, American Joint Committee of Cancer 8th) and with adequate organ function will be enrolled. The therapeutic regimen was sintilimab 200 mg once on day 8, gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 once on days 1 and 8, every 21 days for four cycles. The primary endpoint was pathologic complete response (pCR, pT0N0) rate. The secondary end points were ypT < 2 rate, R0 resection rate, event-free survival, and safety. Results: From May 4, 2020, to May 20, 2023, 55 patients were enrolled. Forty-six patients were evaluated for efficacy. Among the 42 patients who underwent surgery, 16 patients (38.0%) achieved pCR. Thirty-three patients (78.6%) achieved pT < 2. With a median follow-up of 15.7 months, the 1-year event-free survival was 91.3%. Notwithstanding the poor pathological baseline characteristic of a high T3-T4a proportion (39.1%), a promising bladder preservation (including 22 patients transurethral resection of bladder tumor, 5 patients partial cystectomy, and 4 surveillances) rate was achieved (67.4%). The most common grade ≥ 3 treatment-related adverse events was neutropenia (n=15, 27.3%), which was related to chemotherapy. There were no grade 3 immune-related adverse events. Conclusion Neoadjuvant GP plus sintilimab is a promising regimen for MIBC patients, with relatively high pT < 2 rate and triggering the emerging roles for the multi-disciplinary team decision-making for bladder sparing surgery.

Immunoglobulin G4-related disease (IgG4-RD) is a rare systemic immune-mediated disorder characterized by infiltration of IgG4-positive plasma cells and multiorgan fibrosis. Among them, cases with multiple pancreatic cystic lesions as the prominent manifestation are relatively rare, and they are easily misdiagnosed as pancreatic tumors or pancreatitis in clinical practice. Herein, we report one patient with IgG4-RD admitted to Peking Union Medical College Hospital. The patient initially presented with multiple pancreatic cystic lesions and aneurysmal dilatation of the abdominal aorta, accompanied by markedly elevated serum IgG4 levels. Combined with pathological findings from submandibular gland biopsy, the diagnosis of IgG4-RD was ultimately established. After treatment with a regimen of glucocorticoids combined with cyclophosphamide, the patient′s condition improved. Meanwhile, we performed a literature review of cases with IgG4-RD-related pancreatic cystic lesions, aiming to improve clinicians′ understanding of this rare disease phenotype.

With the rapid development of social economy and the continuous improvement of human living standard, the incidence, fatality and recurrence rates of cardiovascular disease (CVD) are increasing year by year, which seriously affects people's life and health. Conventional therapeutic drugs have limited improvement on the disability rate, so the search for new therapeutic drugs and action targets has become one of the hotspots of current research. In recent years, the therapeutic role of the natural compound rosmarinic acid (RA) in CVD has attracted much attention, which is capable of preventing CVD by modulating multiple signalling pathways and exerting physiological activities such as antioxidant, anti-apoptotic, anti-inflammatory, anti-platelet aggregation, as well as anti-coagulation and endothelial function protection. In this paper, the role of RA in the prevention of CVD is systematically sorted out, and its mechanism of action is summarised and analysed, with a view to providing a scientific basis and important support for the in-depth exploration of the prevention value of RA in CVD and its further development as a prevention drug.

Objective:To examine the funding landscape of the National Natural Science Foundation of China(NSFC)concerning research focused on the elderly as a specific demographic group.It seeks to analyze prevailing research hotspots and to offer insightful research ideas for scholars in this field.Methods:The study employed a retrospective research design.It involved retrieving data on approved projects related to the elderly from the NSFC's official database, covering the period from 2000 to 2020.The data set included variables such as funding year, project title, project category, supporting institution, and funding amount(application codes: H1901, H1902, H1903).Statistical analysis was conducted using Excel software, while visual analysis was performed using CiteSpace software.Results:Between 2000 and 2020, a total of 710 projects focused on geriatrics received funding, amounting to RMB 361, 032, 300, 000.This period exhibited a fluctuating upward trend in both the number of projects and the total funding amount.The primary funding categories were face-to-face projects and youth science fund projects, which together accounted for 44.4%(315/710), 34.4%(244/710)respectively.The distribution of project-relying units demonstrated significant regional imbalance, with Beijing, Zhejiang, Jiangsu, and Shanghai being the predominant areas.Notably, Nanjing Medical University, Peking University, and Shanghai Jiao Tong University ranked as the top three institutions, with funding percentages of 5.9%(42/710), 5.4%(38/710), and 4.5%(32/710), respectively.The research themes encompassed nucleoplasmic interactions, brain networks, and bioinformatics, among others.Conclusions:The NSFC has consistently provided funding for in-depth research in the critical field of geriatrics.The primary research directions focus on aspects such as the mechanisms of aging and the pathogenesis of neurological diseases associated with aging.With the application of innovative technologies and methodologies, significant breakthroughs and achievements are anticipated in geriatrics, contributing to the improvement of health outcomes and the enhancement of the quality of life for the elderly.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Objective:To investigate the epidemiological trends of viral diarrhea pathogens in children in Baotou city, and to provide reference for controlling the prevalence of viral diarrhea and guiding the development of regional vaccines.Methods:Fecal samples were collected from children under five years old hospitalized with viral diarrhea at two sentinel hospitals in Baotou from June 2023 to May 2024. Real-time PCR was used to detect group A rotavirus, norovirus, adenovirus, and astrovirus. Statistical analysis was performed using SPSS 20.0 software, with Chi-square tests conducted to assess differences. A P value<0.05 was considered statistically significant. Results:A total of 246 fecal samples were collected, including 153 from males and 93 from females. Among these, 135 samples tested positive, yielding a positivity rate of 54.88% (135/246). There were 82 positive samples from male children and 53 from female children, with no significant difference between genders. Most positive samples (51.85%, 70/135) tested positive for two viruses. Specifically, co-infections of group A rotavirus with norovirus or adenovirus accounted for 98.57% (69/70) of all co-infected cases. Significant differences in detection rates were observed across age groups (χ 2=29.803, P<0.001), with the highest positivity rates in children under one year old and in the 1-year age group. Seasonality, viral diarrhea in Baotou was more prevalent in winter and spring. The G8P[8] genotype of group A rotavirus was the predominant strain. Conclusions:From June 2023 to May 2024, viral diarrhea in hospitalized children under five years old in Baotou is primarily caused by co-infections of group A rotavirus and norovirus, with a higher incidence in preschool-aged children. The G8P[8] genotype of group A rotavirus is the dominant strain. It is recommended to strengthen vaccination and surveillance efforts for viral diarrhea in preschool children, particularly during the winter and spring seasons.

Objective:To analyze the epidemiological characteristics of influenza-like illness（ILI）and the genetic evolutionary trends of the hemagglutinin（HA）and neuraminidase（NA）genes of influenza A（H3N2）viruses isolated in Baotou during the 2022-2023 influenza season.Methods:Etiological surveillance data for ILI cases in Baotou during the 2022-2023 influenza season were collected from the China Influenza Surveillance Information System. Descriptive statistical analysis was performed on the data. HA and NA genes of 30 influenza A（H3N2）viruses were sequenced. Amino acid variation sites，glycosylation sites，drug resistance genes，and phylogenetic trees were analyzed using MEGA 11 software and the NextClade online analysis tool.Results:A total of 1 443 ILI specimens were tested，of which 241（16.70%）were positive for influenza viruses. Among the positive cases，influenza A（H3N2）virus-positive cases accounted for 75.93%（183/241）. The nucleotide sequence similarity of the HA gene between the 30 influenza A（H3N2）isolates and the vaccine strains A/Hong Kong/2671/2019（H3N2），A/Cambodia/e0826260/2020（H3N2），and A/Darwin/9/2021（H3N2）ranged from 96.83% to 98.77%，while the amino acid sequence similarity ranged from 94.63% to 99.62%. A total of 14 amino acid variation sites and 11 conserved glycosylation sites were identified in the HA gene. For the NA gene，the nucleotide sequence similarity ranged from 98.37% to 99.65%，and the amino acid sequence similarity ranged from 94.64% to 98.28%. A total of three amino acid variation sites and nine conserved glycosylation sites were found in the NA gene. None of the 30 influenza A（H3N2）isolates had mutations associated with drug resistance，and all belonged to the clade 3C.2a1b.2a.2a.3a.1.Conclusions:During the 2022-2023 influenza season in Baotou，the circulating influenza A（H3N2）viruses belong to the same evolutionary clade as the 2021-2022 vaccine strain A/Cambodia/e0826360/2020（H3N2）. The isolates from different sources share a common evolutionary origin；however，variations are observed across the genome in terms of homology，molecular mutations，and glycosylation patterns.

Lung cancer has the highest incidence and mortality among malignant tumors in China.Persistent subsolid nodules(SSNs)are closely associated with early-stage lung adenocarcinoma.Artificial intelligence(AI),as an emerging technology,is capable of performing in-depth analysis of large-scale imaging data through autonomous learning and possesses the ability to predict outcomes from new data,demonstrating great potential and application prospects in the assessment of SSNs.AI can not only effectively assist radiologists in diagnosis and treatment,but also improve work efficiency while reducing misdiagnosis and missed diagnosis rates.This review summarizes the recent applications and research progress of AI in the assessment of SSNs,to provide new insights for the diagnosis and treatment of SSNs.