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.

Drug-target interaction (DTI) is fundamental to novel drug research and development (R &D), playing a critical role in elucidating drug mechanisms of action and improving the cost-effectiveness of drug discovery. Although China has seen rapid accumulation of drug-target resources in recent years, the industry still faces challenges such as a shortage of original targets and excessively high target concentration. The rapid advancement of artificial intelligence (AI) has provided an efficient technological pathway for DTI prediction, establishing it as a core tool for accelerating drug discovery. This paper systematically reviews the fundamental data support framework for DTI prediction tasks, elaborating in detail on three core data types— drug characterization, target characterization, and drug-target associations-as well as the classification and application boundaries of mainstream benchmark datasets tailored to different tasks within the field. On this basis, it comprehensively surveys the technological evolution of AI-driven DTI prediction, summarizing the core paradigms and technical advances of traditional machine learning and deep learning methods in a single-modality setting, alongside cutting-edge multimodal approaches that integrate two modalities (cross-subject/within-subject fusion) and three or more modalities for multidimensional information integration. Finally, this paper analyzes the current major challenges in data quality, model generalizability and interpretability, and real-world deployment, while also discussing future trends in standardized dataset construction, generative AI, and large-scale biomedical foundation models, aiming to provide a reference for both research and industrial applications in the AI-driven DTI prediction field.

Human commensal microbiota exists in the gastrointestinal tract, oral cavity, ocular surface, and intraocular organs.Gastrointestinal commensal microbiota can cause glaucomatous optic nerve damage through autoimmune injury mechanisms, inflammation, or oxidative stress.The imbalance of intestinal microbiota represented by Helicobacter pylori infection may affect the function of trabecular cells by releasing inflammatory mediators and vasoactive substances.The resulting active metabolites affect the oxidative stress and apoptosis of trabecular cells.Autoimmune activation of glial cells leads to apoptosis of retinal ganglion cells.The imbalance of oral symbiotic microbiota can mediate the activation of microglia in the retina and optic nerve and the loss of retinal ganglion cells through the body's immune response.Bacterial products' toxic effects lead to optic nerve degeneration and induce chronic subclinical systemic inflammatory vascular endothelial cell dysfunction resulting in optic nerve damage.Ocular surface commensal microbiota mainly causes optic nerve damage through immune response, but whether it is related to intraocular diseases such as glaucoma remains to be studied.The imbalance of intraocular symbiotic microbiota is a specific characteristic of glaucoma.The changes in the intraocular immune microenvironment caused by intraocular microbiota may involve the complex effects of multiple inflammatory mediators and multiple molecular pathways.This article reviews the recent research in these areas, the extraocular, ocular surface, and intraocular symbiotic microbiota and their metabolites may directly or indirectly play a specific role in the pathogenesis of glaucoma.The comprehensive study and analysis of the microbiome of each part of the same individual in the future will provide a new angle to explore the cause and pathogenesis of glaucoma and provide new research ideas for the diagnosis and treatment of glaucoma.

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 analyze the clinical features and genetic sequencing results of a patient with Kallmann syndrome(KS) carrying digenic mutations who initially presented with osteoporosis, and to enhance awareness of this disease phenotype.Methods:Clinical data were collected, and peripheral blood DNA was extracted for whole-exome sequencing. Relevant literature was reviewed to summarize phenotypes associated with digenic/oligogenic variants involving CHD7.Results:The patient exhibited back pain, delayed development of secondary sexual characteristics, and hyposmia. Laboratory tests revealed reduced sex hormones and gonadotropin levels, while pituitary imaging was unremarkable. Bone mineral density imaging confirmed osteoporosis, and thoracolumbar X-rays showed multiple vertebral compression fractures. Genetic analysis identified a heterozygous splice-site mutation in CHD7(c.2698-1G>T) and a heterozygous missense mutation in WDR11(c.439G>A: p.D147N). According to ACMG criteria, the CHD7 mutation was classified as pathogenic, while the WDR11 variant was defined as a variant of uncertain significance(VUS). Literature review indicated that 40% of KS patients with digenic/oligogenic variants involving CHD7 presented with hearing or ocular abnormalities.Conclusion:This study reports a novel CHD7 mutation and a previously undescribed digenic combination of CHD7 and WDR11 variants in a KS patient. CHD7 variants may be implicated in auditory or ocular involvement in KS cases with digenic/oligogenic inheritances. KS patients may also manifest skeletal abnormalities in addition to hypogonadotropic hypogonadism. Tailored management of sex hormones and osteoporosis therapies across life stages is essential for optimizing bone health in KS.

Objective:To analyze the epidemiological characteristics of severe fever with thrombocytopenia syndrome (SFTS) in Beijing in 2024, to investigate the infection status of reservoir hosts, vector organisms, and baseline human populations, and provide a scientific basis for formulating prevention and control strategies.Methods:Epidemiological surveys were conducted on all confirmed cases. Serum samples from healthy populations and reservoir hosts were collected for SFTSV antibody detection. Questing ticks were monitored using the flagging method. Real-time fluorescent quantitative PCR was employed to detect SFTSV in cases, reservoir hosts, and ticks. Positive samples underwent whole-genome sequencing and genetic evolution analysis.Results:In 2024, Beijing reported 15 locally infected cases with 4 deaths. The age of onset ranged from 50 to 80 years (median: 66 years). Cases showed a certain degree of geographical clustering, with June being the peak month of onset. The affected population was predominantly farmers, with a male-to-female ratio of 3∶2. Animal contact history emerged as a significant risk factor alongside tick bites. Parthenogenetic tick populations were identified in Pinggu district, while SFTSV-carrying ticks were detected in endemic areas (Mentougou, Shijingshan, and Fengtai Districts). Viral presence was also confirmed in ticks or dogs from non-endemic areas. Sequencing and phylogenetic analysis revealed stable clustering of strains into two distinct genotypes (A and B). Antibody-positive individuals were identified in healthy populations from non-endemic areas.Conclusions:The incidence of SFTS in Beijing is increasing, with natural viral circulation already established in non-endemic regions. Enhanced surveillance and adjusted prevention strategies are urgently needed.

Owing to the insidious onset and limited awareness of early screening,many patients with esophageal squamous cell carcinoma(ESCC)are diagnosed at an advanced stage.Immunochemotherapy is the current standard first-line treatment for advanced ESCC;however,survival outcomes remain suboptimal.Radiotherapy,with its precise local control and potential immunomodulatory effects,is anticipated to act synergistically with immunochemotherapy,offering a novel direction for overcoming survival limitations.This review systematically sum-marizes the progress in the use of radiotherapy as a first-line treatment for advanced ESCC and discusses the synergistic mechanisms,clinical applications,and challenges associated with its combination with immunochemotherapy.

Owing to the insidious onset and limited awareness of early screening,many patients with esophageal squamous cell carcinoma(ESCC)are diagnosed at an advanced stage.Immunochemotherapy is the current standard first-line treatment for advanced ESCC;however,survival outcomes remain suboptimal.Radiotherapy,with its precise local control and potential immunomodulatory effects,is anticipated to act synergistically with immunochemotherapy,offering a novel direction for overcoming survival limitations.This review systematically sum-marizes the progress in the use of radiotherapy as a first-line treatment for advanced ESCC and discusses the synergistic mechanisms,clinical applications,and challenges associated with its combination with immunochemotherapy.

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 analyze the clinical features and genetic sequencing results of a patient with Kallmann syndrome(KS) carrying digenic mutations who initially presented with osteoporosis, and to enhance awareness of this disease phenotype.Methods:Clinical data were collected, and peripheral blood DNA was extracted for whole-exome sequencing. Relevant literature was reviewed to summarize phenotypes associated with digenic/oligogenic variants involving CHD7.Results:The patient exhibited back pain, delayed development of secondary sexual characteristics, and hyposmia. Laboratory tests revealed reduced sex hormones and gonadotropin levels, while pituitary imaging was unremarkable. Bone mineral density imaging confirmed osteoporosis, and thoracolumbar X-rays showed multiple vertebral compression fractures. Genetic analysis identified a heterozygous splice-site mutation in CHD7(c.2698-1G>T) and a heterozygous missense mutation in WDR11(c.439G>A: p.D147N). According to ACMG criteria, the CHD7 mutation was classified as pathogenic, while the WDR11 variant was defined as a variant of uncertain significance(VUS). Literature review indicated that 40% of KS patients with digenic/oligogenic variants involving CHD7 presented with hearing or ocular abnormalities.Conclusion:This study reports a novel CHD7 mutation and a previously undescribed digenic combination of CHD7 and WDR11 variants in a KS patient. CHD7 variants may be implicated in auditory or ocular involvement in KS cases with digenic/oligogenic inheritances. KS patients may also manifest skeletal abnormalities in addition to hypogonadotropic hypogonadism. Tailored management of sex hormones and osteoporosis therapies across life stages is essential for optimizing bone health in KS.