Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Objective: To develop QingNangTCM, a specialized large language model (LLM) tailored for expert-level traditional Chinese medicine (TCM) question-answering and clinical reasoning, addressing the scarcity of domain-specific corpora and specialized alignment. Methods: We constructed QnTCM_Dataset, a corpus of 100 000 entries, by integrating data from ShenNong_TCM_Dataset and SymMap v2.0, and synthesizing additional samples via retrieval-augmented generation (RAG) and persona-driven generation. The dataset comprehensively covers diagnostic inquiries, prescriptions, and herbal knowledge. Utilizing P-Tuning v2, we fine-tuned the GLM-4-9B-Chat backbone to develop QingNangTCM. A multi-dimensional evaluation framework, assessing accuracy, coverage, consistency, safety, professionalism, and fluency, was established using metrics such as bilingual evaluation understudy (BLEU), recall-oriented understudy for gisting evaluation (ROUGE), metric for evaluation of translation with explicit ordering (METEOR), and LLM-as-a-Judge with expert review. Qualitative analysis was conducted across four simulated clinical scenarios: symptom analysis, disease treatment, herb inquiry, and failure cases. Baseline models included GLM-4-9B-Chat, DeepSeek-V2, HuatuoGPT-II (7B), and GLM-4-9B-Chat (freeze-tuning). Results: QingNangTCM achieved the highest scores in BLEU-1/2/3/4 (0.425/0.298/0.137/0.064), ROUGE-1/2 (0.368/0.157), and METEOR (0.218), demonstrating a balanced and superior normalized performance profile of 0.900 across the dimensions of accuracy, coverage, and consistency. Although its ROUGE-L score (0.299) was lower than that of HuatuoGPT-II (7B) (0.351), it significantly outperformed domain-specific models in expert-validated win rates for professionalism (86%) and safety (73%). Qualitative analysis confirmed that the model strictly adheres to the “symptom-syndrome-pathogenesis-treatment” reasoning chain, though occasional misclassifications and hallucinations persisted when dealing with rare medicinal materials and uncommon syndromes. Conclusion Combining domain-specific corpus construction with parameter-efficient prompt tuning enhances the reasoning behavior and domain adaptation of LLMs for TCM-related tasks. This work provides a technical framework for the digital organization and intelligent utilization of TCM knowledge, with potential value for supporting diagnostic reasoning and medical education.

Objective To explore the feasibility of magnetic compression technique (MCR) in the treatment of severe single mid-ureteral stricture in a rabbit model. Methods After 10 female New Zealand rabbits were selected, the distal end of the right ureter was ligated with silk thread. Two weeks after the operation, when the right ureter was dilated, the mid-ureter was ligated again with silk thread to create a severe single mid-ureteral stricture animal model. Longitudinal incisions were made at the upper and lower ends of the ligation site, and cylindrical NdFeB magnets with central holes (sub-magnets and main magnets) were placed to anastomose and recanalize the mid-ureteral stricture. The magnets were adjusted to the appropriate position to automatically align and attract each other. The longitudinal incision sites of the ureter were sutured with 6-0 Prolene thread, and the abdominal cavity was closed layer by layer. The operation time was recorded. X-ray films were taken every two days to confirm the position of the magnets and record the time of magnet detachment. Three weeks after the operation, the anastomotic specimens were obtained, and the formation of the anastomosis was evaluated with gross observation and histological staining. Results Two weeks after ligation, all experimental rabbits showed obvious dilation of the right ureter. The mid-ureteral ligation and placement of the male and female magnets were successfully completed in all 10 experimental rabbits, with an operation time of (24.00±5.15)minutes. The male and female magnets attracted each other well. X-ray examination showed that the magnets detached and entered the distal ureter (14.0±1.9) days after magnetic compression. The recanalization of the severe single mid-ureteral stricture was successfully achieved. The gross specimens and histological examination of the anastomosis showed that the anastomosis remained patent and the mucosal healing was good. All experimental rabbits survived well after the operation without serious complications. Conclusion MCT provides a new idea and novel method for the treatment of mid-ureteral stricture. This study confirmed the feasibility of this technique in treating severe single mid-ureteral stricture in a rabbit model. The operation is relatively simple and has potential for clinical application.

BACKGROUND: The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. METHODS: We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. RESULTS: The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. CONCLUSIONS 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.
Transplantation, Heterologous/methods* ; Kidney Transplantation/methods* ; Heterografts/pathology* ; Immunoglobulins, Intravenous/administration & dosage* ; Graft Survival/immunology* ; Humans ; Animals ; Sus scrofa ; Graft Rejection/prevention & control* ; Kidney/pathology* ; Gene Editing ; Species Specificity ; Immunosuppression Therapy/methods* ; Plasma Exchange ; Brain Death ; Biopsy ; Male ; Aged

BACKGROUND: Treatment with chimeric antigen receptor-T (CAR-T) cells has shown promising effectiveness in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), although the process of preparing for this therapy usually takes a long time. We have recently created CD19 Fast-CAR-T (F-CAR-T) cells, which can be produced within a single day. The objective of this study was to evaluate and contrast the effectiveness and safety of CD19 F-CAR-T cells with those of CD19 conventional CAR-T cells in the management of R/R B-ALL. METHODS: A multicenter, retrospective analysis of the clinical data of 44 patients with R/R B-ALL was conducted. Overall, 23 patients were administered with innovative CD19 F-CAR-T cells (F-CAR-T group), whereas 21 patients were given CD19 conventional CAR-T cells (C-CAR-T group). We compared the rates of complete remission (CR), minimal residual disease (MRD)-negative CR, leukemia-free survival (LFS), overall survival (OS), and the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) between the two groups. RESULTS: Compared with the C-CAR-T group, the F-CAR-T group had significantly higher CR and MRD-negative rates (95.7% and 91.3%, respectively; 71.4% and 66.7%, respectively; P = 0.036 and P = 0.044). No significant differences were observed in the 1-year or 2-year LFS or OS rates between the two groups: the 1-year and 2-year LFS for the F-CAR-T group vs.C-CAR-T group were 47.8% and 43.5% vs. 38.1% and 23.8% (P = 0.384 and P = 0.216), while the 1-year and 2-year OS rates were 65.2% and 56.5% vs. 52.4% and 47.6% (P = 0.395 and P = 0.540). Additionally, among CR patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CAR-T-cell therapy, there were no significant differences in the 1-year or 2-year LFS or OS rates: 57.1% and 50.0% vs. 47.8% and 34.8% (P = 0.506 and P = 0.356), 64.3% and 57.1% vs. 65.2% and 56.5% (P = 0.985 and P = 0.883), respectively. The incidence of CRS was greater in the F-CAR-T group (91.3%) than in the C-CAR-T group (66.7%) (P = 0.044). The incidence of ICANS was also greater in the F-CAR-T group (30.4%) than in the C-CAR-T group (9.5%) (P = 0.085), but no treatment-related deaths occurred in the two groups. CONCLUSION Compared with C-CAR-T-cell therapy, F-CAR-T-cell therapy has a superior remission rate but also leads to a tolerably increased incidence of CRS/ICANS. Further research is needed to explore the function of allo-HSCT as an intermediary therapy after CAR-T-cell therapy.

OBJECTIVES: To assess the preliminary efficacy and safety of a dose-intensified C5VD regimen (cisplatin, 5-fluorouracil, vincristine, and doxorubicin) in children with locally advanced hepatoblastoma. METHODS: This prospective study enrolled 24 children with newly diagnosed, locally advanced hepatoblastoma who received the dose-intensified C5VD regimen at Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, and Shanghai Children's Hospital between January 2020 and December 2023. Clinical characteristics, treatment outcomes, and chemotherapy-related toxicities were analyzed. RESULTS: Of the 24 patients, 13 were male and 11 were female, with a median age at diagnosis of 18.7 months (range: 3.5-79.4 months). All patients achieved complete macroscopic resection of hepatic lesions without liver transplantation. Serum alpha-fetoprotein levels decreased significantly after two chemotherapy cycles. During a median follow-up of 38.4 months (range: 15.8-50.7 months), all patients maintained continuous complete remission, with 3-year event-free survival and overall survival rates of 100%. Across 144 chemotherapy cycles, the incidence rates of grade 3-4 neutropenia, thrombocytopenia, and infections were 97%, 77%, and 71%, respectively; no treatment-related deaths occurred. Notably, 5 patients (21%) developed Brock grade ≥3 hearing loss, of whom 1 required a hearing aid. CONCLUSIONS The dose-intensified C5VD regimen demonstrates significant efficacy with an overall favorable safety profile in the treatment of newly diagnosed, locally advanced pediatric hepatoblastoma. Grade 3-4 myelosuppression and infection are the predominant toxicities. However, high‑dose cisplatin-induced ototoxicity remains a concern, highlighting the need for improved otoprotective strategies.
Humans ; Hepatoblastoma/pathology* ; Male ; Female ; Infant ; Liver Neoplasms/pathology* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Child, Preschool ; Prospective Studies ; Doxorubicin/adverse effects* ; Child ; Cisplatin/adverse effects* ; Vincristine/adverse effects* ; Fluorouracil/adverse effects*

The European Association for Cardio-Thoracic Surgery (EACTS) has recently updated and published the "2024 EACTS guidelines on perioperative medication in adult cardiac surgery". Based on the latest evidence, the guidelines have been updated in multiple aspects including underlying disease management, antithrombotic medication, arrhythmia treatment and other supportive care, etc. This paper aims to summarize and interpret the guidelines, in order to promote clinicians’ understanding and optimize perioperative medical treatment in adult cardiac surgery.