Disease computable phenotype is a data model designed to identify specific clinical conditions or characteristics, which automatically extracts information from clinical databases such as electronic health records through algorithms. Phenotypic data for rare diseases often reside in unstructured text. Due to the scarcity of rare disease cases, atypical symptoms, and insufficient physician experience, misdiagnosis and underdiagnosis rates remain high. In this context, the application of computable phenotype technology holds promise for improving the accuracy and efficiency of rare disease diagnosis. This article reviews the current research status, challenges, and opportunities of computable phenotype technology in biomedicine, particularly in the field of rare diseases, and proposes a development and validation framework for rare disease computable phenotypes, aiming to provide research and development insights for computable phenotypes to empower the diagnosis and treatment of rare diseases.

Pneumocystis jirovecii pneumonia (PJP) is an opportunistic pulmonary infection that commonly occurs in immunocompromised children. We report a case of infantile leukemia complicated by PJP and review the relevant literature. A summary and analysis of 10 infantile leukemia patients with PJP infection (9 cases reported in the literature and 1 case from our center) showed that PJP mostly occurred in the early stages of chemotherapy (80%, 8/10). The main clinical manifestations were dyspnea (100%, 10/10) and hypoxemia (50%, 5/10), while pulmonary imaging findings lacked specificity. In most cases (50%, 5/10), diagnosis was established by identifying pathogens in bronchoalveolar lavage fluid under microscopy. In our case, diagnosis was confirmed using targeted next-generation sequencing (tNGS) of bronchoalveolar lavage fluid. Treatment with intravenous sulfamethoxazole complex was administered in 8 patients, all of whom eventually recovered. PJP may occur in the early stages of chemotherapy for infantile leukemia, thus early prevention is necessary. tNGS facilitates early diagnosis of PJP, and sulfamethoxazole complex remains an effective therapeutic option.
Humans ; Infant ; Bronchoalveolar Lavage Fluid/microbiology* ; Immunocompromised Host ; Leukemia/complications* ; Pneumocystis carinii/isolation & purification* ; Pneumonia, Pneumocystis/diagnosis* ; Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use*

Objective:To describe a novel approach for intractable Meniere's disease exclusively through a transcanal endoscopic ear surgery（TEES）. Methods:This retrospective chart review included patients with intractable Menière's disease who underwent endoscopic transcanal labyrinthectomy in the Department of Otolaryngology Head and Neck Surgery, Guangxi Hospital Division, First Affiliated Hospital, Sun Yat-sen University, between February 2023 and October 2024. The first 70-year-old woman and the other 67-year-old woman, who underwent multiple conservative treatment and chemical labyrinthectomy during outpatient and hospitalization, had frequent vertigo, tinnitus and severe sensorineural deafness. The TEES approach provided a wide exposure of the oval window. The incus and the stapes were removed, expanded the oval window. The perilymph was suctioned, The saccule, utricule, macula utriculi and macula sacculi were removed. The ampulla tissue of the three semicircular canal were destroyed with the right-angle crochet. The oval window was obliterated using the perichondrium of the tragal cartilage and cartilage. Results:Two patients underwent endoscopic transcanal labyrinthectomy, and no intraoperative or postoperative complications were observed. Vertigo was controlled in 2 patients during the follow-up of 6 to 12 months. Two patients complained of total hearing loss after surgery. Conclusion:Even though this study presents a limited number of cases, endoscopic transcanal labyrinthectomy is a promising, safe, and effective procedure in selected cases. Additional studies are needed to determine the risk-benefit profile of this technique.
Humans ; Aged ; Female ; Meniere Disease/surgery* ; Retrospective Studies ; Endoscopy/methods* ; Otologic Surgical Procedures/methods* ; Ear, Inner/surgery* ; Treatment Outcome

Autoimmune diseases, cancers, and viral infections pose significant global health threats, characterized by chronic pathology, unregulated cellular proliferation, and rapid transmission, respectively, requiring urgent early warning and treatment strategies. Antibodies, primarily classified into autoantibodies and therapeutic antibodies based on their clinical roles, provide essential information and show considerable value in the precise diagnosis and treatment of these serious diseases. Among the technologies utilized in bioanalysis, electrochemical biosensors, with their unique advantages of rapid response, high sensitivity, miniaturization, cost-effectiveness and user-friendly operation, have been developed as a trending technology for precise diagnostic and therapeutic drug monitoring. This review systematically summarizes the relationships and roles of clinically relevant antibodies in autoimmune diseases, cancers, and viral infections, while detailing the composition, strategies, development, and application trends of relevant electrochemical biosensors. Furthermore, it highlights the remaining challenges and opportunities for the advancement and prospects of electrochemical sensors in the context of clinically relevant antibodies.

Chemotherapy remains a primary treatment option for hepatocellular carcinoma (HCC), yet its clinical benefits are often unsatisfactory. Utilizing arsenic trioxide (ATO) as a model, this study elucidates the role of autophagy inhibition in modulating the cellular response to chemotherapy, shifting cell death from apoptosis to pyroptosis via the caspase-3-GSDME pathway, thereby augmenting the anti-tumor efficacy. Building upon these findings, an ATO nanomedicine delivery system capable of autophagy inhibition to promote pyroptosis for enhanced tumor treatment was developed. Folic acid-modified albumin served as the stabilizer for nano self-assemblies formed through ion pairing between Mn²⁺ and ATO, encapsulating DNAzyme (Dz) targeting Beclin 1, a key autophagy regulator. Characterization studies confirmed efficient encapsulation of ATO and Dz within nanoparticles, designed to disintegrate in the intracellular microenvironment, releasing the all-active components, i.e., ATO, Mn²⁺, and Dz. Mn²⁺ acted as a metal cofactor to activate Dz for Beclin 1 mRNA cleavage, inhibiting autophagy and augmenting ATO-induced cell pyroptosis. Elevated cell pyroptosis levels not only enhance ATO's direct tumor cell killing capacity but also trigger anti-tumor immune responses, synergistically enhancing efficacy. Upon intravenous injection, the nanomedicine accumulated in tumor tissue and targeted liver cancer cells. Compared to free ATO, the nanomedicine exhibited significantly improved in vivo anti-tumor effects, achieving a 100% 45-day survival rate in mice with favorable biosafety profiles. This study offers novel insights into tumor chemotherapy sensitization and presents a promising strategy for ATO nanoformulation development.

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis

To summarize the applications of data-intelligence technology in diagnosing lysosomal storage disease(LSD), analyze their opportunities and challenges in clinical practice as well as their development trends, and provide insights and recommendations for advancing digitally driven auxiliary diagnostic technologies.