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 explore the clinical features of IgG4-related urinary diseases so as to provide reference for the diagnosis and treatment of such diseases. [Methods] The clinical data of 4 cases of IgG4-related urinary system diseases diagnosed and treated in Xijing Hospital of Air Force Medical University during Aug.2019 and Dec.2023 were retrospectively collected.Here, we report on the diagnosis and treatment of these patients, analysing their symptoms, serology, imaging and pathology as well as their treatment and outcomes. [Results] The patients included 2 male and 2 female.The lesions were involved with the retroperitoneum and urinary system.Three patients had symptoms of lumbar pain.The imaging manifestations were complex, including retroperitoneal mass involving urinary system organs in 2 cases, tabdense shadow of the right kidney in 1 case, and simple cystic mass of kidney in 1 case.Serum IgG4 value was not detected before surgery.All patients underwent radical surgical treatment.Postoperative pathology showed fibrous tissue hyperplasia with a large number of plasma cells, lymphocytes, a few neutrophil infiltrates, and lymphoid follicles and obliterated vasculitis in some specimens.The number of IgG4⁺ plasma cells was more than 10 in all tissues under high power microscope.After surgery, 3 patients had symptoms improved, and serum IgG4 value was within the normal range; 1 patient (patem 3) had elevated IgG4 value during follow-up, received subsequent hormone therapy, and the serum IgG 4 level remained stable. [Conclusion] The symptoms of IgG4-related diseases involving the urinary system are non-specific, and the imaging findings are various, easily confused with other diseases.Early detection of serum IgG4 and biopsy pathology can help clinicians make correct diagnosis in the early stage.

Objective To investigate the factors affecting the distribution of Pomacea and project the trends in the spread of suitable distribution areas of Pomacea in 2050 and 2070 in Dali Bai Autonomous Prefecture, so as to provide insights into Pomacea control in the prefecture. Methods The longitudes and latitudes of Pomacea sampling sites were captured based on Pomacea field survey data in 12 cities (counties) of Dali Bai Autonomous Prefecture from 2023 to 2024. A total of 19 climatic factors (annual mean temperature, mean diurnal range, isothermality, temperature seasonality, maximum temperature of the warmest month, minimum temperature of the coldest month, temperature annual range, mean temperature of the wettest quarter, mean temperature of the driest quarter, mean temperature of the warmest month, mean temperature of the coldest month, annual precipitation, precipitation of the wettest month, precipitation of the driest month, precipitation seasonality, precipitation of the wettest quarter, precipitation of the driest quarter, mean temperature of the warmest quarter, and mean temperature of the coldest quarter) and representative concentration pathways (RCPs) were retrieved from the world climate database (www.worldclim.org). All climatic variables were employed to create a maximum entropy (MaxEnt) model. The predictive accuracy of the model was assessed with the area under the receiver operating characteristic (ROC) curve (AUC), and the contributions of these 19 climatic factors to the distribution of Pomacea were analyzed in Dali Bai Autonomous Prefecture using Jackknife test. In addition, the suitable distribution areas of Pomacea were predicted with the MaxEnt model in Dali Bai Autonomous Prefecture in 2024 and in 2050 and 2070 under RCP4.5. Results Data pertaining to 91 Pomacea sampling sites were captured. ROC analysis revealed the MaxEnt model had an AUC value of 0.885 ± 0.088 for predicting the suitable distribution areas of Pomacea in Dali Bai Autonomous Prefecture. Of the 19 climatic factors, the maximum temperature of the warmest month had the highest contribution to the distribution of Pomacea in Dali Bai Autonomous Prefecture, followed by mean temperature of the driest quarter, mean temperature of the wettest quarter and minimum temperature of the coldest month. The suitable distribution area of Pomacea was predicted to be 14 555.69 km² in Dali Bai Autonomous Prefecture in 2024, and would expand gradually to the southeastern part of the prefecture in the future due to climatic factors. The suitable distribution areas of Pomacea were projected to expand to 21 475.61 km² in 2050 and 25 782.52 km² in 2070 in Dali Bai Autonomous Prefecture, respectively. Conclusions Temperature is an important contributor to the distribution of Pomacea in Dali Bai Autonomous Prefecture, and the suitable distribution area of Pomacea will gradually expand to the southeastern part of the prefecture in 2050 and 2070.

Pancreatic cancer is currently recognized as one of the most malignant solid tumors， with a 5-year survival rate of 13% over a long period of time， and 80% of the patients have lost the opportunity for surgery at the time of confirmed diagnosis. In addition， the efficacy of conventional radiochemotherapy and targeted therapy is limited by high tumor heterogeneity and the complex immunosuppressive microenvironment. In recent years， mRNA vaccines have become a new focus of tumor immunotherapy due to their unique technical advantages. Based on non-integrating mRNA templates， mRNA vaccines enable precise encoding of tumor neoantigens， which are efficiently expressed in the host and can induce multifaceted immune responses. As for pancreatic cancer， current studies mainly focus on the development and optimization of tumor-associated antigen vaccines and tumor-specific antigen vaccines， as well as next-generation sequencing-guided neoantigen epitope optimization， innovative targeted delivery systems， and artificial intelligence-powered predictive models for immune response， thereby promoting the application of mRNA vaccines in the precise treatment of pancreatic cancer. Further studies should make breakthroughs in the targeted blockade of critical immunosuppressive molecules within the tumor microenvironment， the precise identification of tumor-specific antigenic epitopes， and the development of highly efficient vaccines， so as to bring new hopes for patients with pancreatic cancer.

The Solomon four-group design， a critical method for improving internal validity in clinical research， can reduce bias and control the interference of Hawthorne effects and pretest sensitization on research results， which offers unique advantages in evaluating complex intervention outcomes. This paper systematically outlined the core framework and key points of statistical analysis of the Solomon four-group design， summarized its applications in clinical research at home and abroad， explored its advantages and limitations， and discussed the potential value in traditional Chinese medicine （TCM） clinical trials. It is believed that the Solomon four-group design can help distinguish between testing effects and intervention effects in TCM clinical studies， and reduce the bias in the evaluation of subjective indicators. Meanwhile， given the complexity of the Solomon four-group design and the particularity of TCM clinical research， it is proposed that future TCM clinical studies should focus on using psychological scales， know-ledge， attitude， and behavior measurements， and other similat evaluations as endpoints. It also advocates strengthening interdisciplinary collaboration to provide new methodological paths for TCM clinical research.

Objective To observe the effect of comorbidity for patients with non-small cell lung cancer (NSCLC) on exercise tolerance and cardiopulmonary function. Methods NSCLC patients who underwent cardiopulmonary exercise testing (CPET) before surgery were retrospectively included. According to the Charlson comorbidity index (CCI) score, patients were divided into two groups: a CCI≥3 group and a CCI＜3 group. The patients were matched with a ratio of 1 : 1 by propensity score matching according to the age, body mass index, sex, smoking history, exercise habits, pathological stage and type of surgery. After matching, CPET indexes were compared between the two groups to explore the differences in exercise tolerance and cardiopulmonary function. Results A total of 276 patients were included before matching. After matching, 56 patients were enrolled with 28 patients in each group, including 38 (67.9%) males and 18 (32.1%) females with an average age of (70.7±6.8) years. Compared with the CCI＜3 group, work rate at peak (WR peak), WR peak/predicted value (WR peak%), kilogram oxygen uptake at anaerobic threshold (VO2/kg AT), VO2/kg peak, VO2/kg peak%, peak carbon dioxide output, the minute ventilation to carbon dioxide production slope, O2 pulse peak and O2 pulse peak% of CCI≥3 group were statistically different (P＜0.05). Among them, the rate of postoperative pulmonary complication in the CCI≥3 group was higher than that in the CCI＜3 group (60.7% vs. 32.1%, P=0.032). Conclusion In the NSCLC patients, exercise tolerance and cardiopulmonary function decreased in patients with CCI≥3 compared with those with CCI<3. CPET can provide an objective basis for risk assessment in patients with comorbidity scored by CCI for pulmonary resection.

Objective: To explore the laboratory testing methods and clinical management strategies for immune hemolytic anemia induced by Ceftizoxime sodium drug-dependent antibodies. Methods: Patient blood samples were subjected to blood typing, direct antiglobulin test, and unexpected antibody identification. Ceftizoxime sodium drug-dependent antibodies were detected using the immune complex method and drug-sensitized red cell method. The properties and titers of the drug antibodies were further assessed. Flow cytometry was used to assess the complement activation capacity of the drug antibodies in vitro. Results: Direct antiglobulin tests (IgG and C3d) were positive. Ceftizoxime sodium drug-dependent antibodies were identified using both the immune complex method and the sensitized red cell method, their titers significantly increased following the addition of the drug. Flow cytometry confirmed the complement activation capability of these antibodies and identified 30 minutes as the optimal time for activation in vitro. The patient's condition improved rapidly after drug withdrawal and supportive transfusion, resulting in a favorable outcome. Conclusion: Ceftizoxime sodium can cause drug-induced immune hemolytic anemia via complement activation mediated by drug-dependent antibodies. Serological testing is essential for diagnosing drug-induced hemolytic anemia. Clinicians should be vigilant for this adverse reaction. The offending drug must be promptly discontinued, and supportive care should be initiated upon the onset of symptoms.

OBJECTIVE: To observe the effect of electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) on hippocampal neuronal ferritinophagy mediated by the nuclear receptor coactivator 4 (NCOA4)/ferritin heavy chain 1 (FTH1) signaling pathway in vascular dementia (VD) rats, and to explore the potential mechanisms of electroacupuncture for VD. METHODS: A total of 60 male rats of SPF grade were randomly divided into a blank group (12 rats), a sham surgery group (12 rats) and a modeling group (36 rats). In the modeling group, the modified 4-vessel occlusion method was used to establish the VD model. The 24 successfully modeled rats were randomly divided into a model group and an electroacupuncture group, with 12 rats in each group. In the electroacupuncture group, electroacupuncture was applied at left and right "Sishencong" (EX-HN1), and bilateral "Fengchi" (GB20), with continuous wave, in frequency of 2 Hz and current intensity of 1 mA, 30 min a time, once daily for 21 consecutive days. The learning and memory abilities were assessed using the Morris water maze test before modeling, after modeling and after intervention, as well as the novel object recognition test after intervention. After intervention, the neuronal morphology in the hippocampus was observed by Nissl staining; the iron deposition was observed by Prussian blue staining; the reactive oxygen species (ROS) level was detected by dihydroethidium (DHE) fluorescence staining; the levels of iron, malondialdehyde (MDA) and superoxide dismutase (SOD) in the hippocampal tissue were measured by the colorimetric assay, TBA method, and WST-1 method, respectively; the positive expression of NCOA4, FTH1 and glutathione peroxidase 4 (GPX4) was detected by immunohistochemistry; the protein expression of NCOA4, FTH1, GPX4, and the ratio of microtubule-associated protein 1 light chain 3B (LC3B) Ⅱ/Ⅰ in the hippocampus were detected by Western blot. RESULTS: Compared with the sham surgery group, in the model group, the escape latency was prolonged, and the number of platform crossings reduced (P<0.01), the recognition index (RI) was decreased (P<0.01); the hippocampal neurons displayed a blurred laminar structure, disorganized cellular arrangement, and the number of Nissl bodies was decreased (P<0.01); the percentage of iron deposition area in the hippocampus was increased (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were increased (P<0.01), the SOD level, and the protein expression of FTH1 and GPX4 were decreased (P<0.01). Compared with the model group, in the electroacupuncture group, the escape latency was shortened and the number of platform crossings was increased (P<0.01), the RI was increased (P<0.01); the hippocampal neurons exhibited more regular morphology, better-organized cellular structure, and the number of Nissl bodies was increased (P<0.05); the percentage of iron deposition area in the hippocampus reduced (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were decreased (P<0.01, P<0.05), the SOD level, and the protein expression of FTH1 and GPX4 were increased (P<0.01). CONCLUSION Electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) can improve learning and memory abilities in VD rats, and its mechanism may be associated with the regulation of the hippocampal NCOA4/FTH1 signaling pathway, inhibition of ferritinophagy, and alleviation of oxidative stress damage.
Animals ; Electroacupuncture ; Dementia, Vascular/genetics* ; Male ; Rats ; Signal Transduction ; Humans ; Memory ; Rats, Sprague-Dawley ; Nuclear Receptor Coactivators/genetics* ; Ferritins/genetics* ; Learning ; Hippocampus/metabolism* ; Acupuncture Points

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

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