Tumor cell-intrinsic programmed death-ligand 1 (PD-L1) signals mediate tumor initiation, progression and metastasis, but their effects in ameloblastoma (AM) have not been reported. In this comprehensive study, we observed marked upregulation of PD-L1 in AM tissues and revealed the robust correlation between elevated PD-L1 expression and increased tumor growth and recurrence rates. Notably, we found that PD-L1 overexpression markedly increased self-renewal capacity and promoted tumorigenic processes and invasion in hTERT⁺-AM cells, whereas genetic ablation of PD-L1 exerted opposing inhibitory effects. By performing high-resolution single-cell profiling and thorough immunohistochemical analyses in AM patients, we delineated the intricate cellular landscape and elucidated the mechanisms underlying the aggressive phenotype and unfavorable prognosis of these tumors. Our findings revealed that hTERT⁺-AM cells with upregulated PD-L1 expression exhibit increased proliferative potential and stem-like attributes and undergo partial epithelial‒mesenchymal transition. This phenotypic shift is induced by the activation of the PI3K-AKT-mTOR signaling axis; thus, this study revealed a crucial regulatory mechanism that fuels tumor growth and recurrence. Importantly, targeted inhibition of the PD-L1-PI3K-AKT-mTOR signaling axis significantly suppressed the growth of AM patient-derived tumor organoids, highlighting the potential of PD-L1 blockade as a promising therapeutic approach for AM.
Ameloblastoma/metabolism* ; Humans ; B7-H1 Antigen/metabolism* ; Neoplasm Recurrence, Local/pathology* ; Signal Transduction ; Cell Proliferation ; Up-Regulation ; TOR Serine-Threonine Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Telomerase/metabolism* ; Jaw Neoplasms/metabolism* ; Epithelial-Mesenchymal Transition ; Animals ; Cell Line, Tumor ; Female ; Male

Objective:To analyze the concentration of formic acid,propionic acid and butyric acid in gingival crevicular fluid(GCF)of patients with stages Ⅲ and Ⅳ periodontitis,and their relationship with periodontitis.Methods:The study enrolled 37 systemically healthy patients with periodontitis and 19 healthy controls who visited Department of Periodontology,Peking University School and Hospital of Sto-matology from February 2008 to May 2011.Their GCFs were collected from the mesial-buccal site of one molar or incisor in each quadrant.Periodontal clinical parameters,including plaque index(PLI),probing depth(PD),bleeding index(BI),and attachment loss(AL).Concentrations of formic acid,propionic acid and butyric acid in the supernatant of the GCFs were analyzed by high-performance capil-lary electrophoresis(HPCE).The prediction ability of formic acid,propionic acid and butyric acid with the risk of periodontitis and the differences between grade B and grade C periodontitis were analyzed.Results:In this study,32 patients with stage Ⅲ and 5 patients with stage Ⅳ were enrolled,including 9 patients with grade B and 28 patients with grade C.Clinical periodontal variables in the patients with pe-riodontitis were significantly higher than those in the control group(P＜0.001).Formic acid was signifi-cantly lower in periodontitis than that in the control group[5.37(3.39,8.49)mmol/L vs.12.29(8.35,16.57)mmol/L,P＜0.001].Propionic acid and butyric acid in periodontitis were significantly higher than those in the control group:Propionic acid,10.23(4.28,14.90)mmol/L vs.2.71(0.00,4.25)mmol/L,P＜0.001;butyric acid,2.63(0.47,3.81)mmol/L vs.0.00(0.00,0.24)mmol/L,P＜0.001.There was no significant difference in formic acid,propionic acid and butyric acid concentrations between grade B and grade C periodontitis(P＞0.05).Propionic acid and butyric acid in the deep pocket were significantly higher than in the shallow pocket,while the concentration of formic acid decreased with the increase of PD.Propionic acid(OR=1.51,95％CI:1.29-1.75)and butyric acid(OR=3.72,95％CI:1.93-7.17)were risk factors for periodontitis,while formic acid(OR=0.87,95％CI:0.81-0.93)might be a protective factor for periodontitis.Propionic acid(AUC=0.852,95％CI:0.805-0.900),butyric acid(AUC=0.889,95％CI:0.841-0.937),f(formic acid,AUC=0.844,95％CI:0.793-0.895)demonstrated a good predictive capacity for the risk of periodontitis.Conclusion:The concentration of formic acid decrease in the GCF of periodontitis patients,which is a protective factor for periodontitis,its reciprocal have good predictive capacity.However,propionic acid and butyric acid increase,which are risk factors for periodontitis and have good predictive capacity.The concentration of formic acid,propionic acid,and butyric acid vary with probing depth,but there is no significant difference between grade B and grade C periodontitis.

Objective To observe the value of ultrasound-guided percutaneous ethanol injection(PEI)combined with microwave ablation(MWA)for treating thyroid benign partially cystic masses.Methods A total of 100 patients with single benign partially cystic mass who would undergo ultrasound-guided ablation treatment were prospectively enrolled.The patients were randomly assigned into PEI group(received PEI combined with MWA sequential ablation)or control group(received simple MWA),each n=50.Data before and after treatments were compared within groups,the therapeutic efficacy were compared between groups after treatments,and the value of sequential ablation was analyzed.Results Ultrasound-guided ablation was successfully performed for all 100 masses.During follow-up,5 cases in PEI group and 3 cases in control group were lost.The operation time of MWA,total MWA energy and patients'pain level during treatments in PEI group were all lower than those in control group(all P＜0.05).Significant difference of thyroid mass volumes were found before and 3,6 and 12 months after treatments in both groups(all P＜0.05).The volume reduction rate(VRR)in PEI group before and 1,3,6 and 12 months after treatments were all higher than that in control group(all P＜0.05).The success rate was 95.56％(43/45)in PEI group and 89.36％(42/47)in control group 12 months after treatments,respectively,without significant difference(P=0.451).There were significant differences of neck aesthetics scores and symptom scores before and 3,6 and 12 months after treatments in both groups(all P＜0.05).The incidence of complications in PEI group was 6.67％(3/45),while in control group was 14.89％(7/47),the former was lower than the latter(P＜0.05).Conclusion Ultrasound-guided PEI combined with MWA sequential ablation had better effect for treating thyroid benign partially cystic masses than single MWA.

Objective:To construct a competency evaluation indicator system for infection prevention and control nurses in Operating Rooms (hereinafter referred to as "IPC") and provide an objective basis for the management of IPC nurses.Methods:From June to November 2022, an initial competency evaluation indicator system for IPC nurses was developed through literature review and semi-structured interviews. The Delphi method was employed to consult 20 experts from 11 provinces and municipalities across the country. Analytical Hierarchy Process (AHP) and mean distribution method were applied to quantify and determine the weight of each level of indicators within the system.Results:Nineteen experts were finally included, with two rounds of questionnaire recovery rates of 95.00% (19/20) and 100.00% (19/19), respectively. The authority coefficients of the experts were 0.858 and 0.861, familiarity coefficients were 0.850 and 0.853, and coefficients of judgment basis were 0.865 and 0.868, respectively. The Kendall's W coefficient of concordance for the two rounds of inquiries were 0.139 and 0.202 ( P<0.05), respectively. The final IPC nurse competency evaluation indicator system included six primary indicators, 22 secondary indicators, and 66 tertiary indicators. Conclusions:The constructed IPC nurse competency evaluation indicator system is scientific, reasonable, objective, and comprehensive, providing a valuable reference for the capability training, assessment, entry standards, and qualification certification of IPC nurses.

Purpose To study the safety and clinical value of adenosine stress myocardial perfusion imaging(MPI)in evaluating myocardial ischemia in children with Kawasaki disease.Materials and Methods A total of 78 children with a history of Kawasaki disease and coronary artery aneurysm confirmed by echocardiography and coronary angiography were prospectively studied in Children's Hospital of Fudan University from August 2019 to February 2021.Adenosine stress MPIs were performed to analyze the safety of adenosine stress test and its sensitivity and specificity in detecting significant coronary artery stenosis(≥75%),and the positive rate of adenosine stress MPIs in different groups of coronary artery stenosis were further compared.Results All 78 children completed adenosine stress test without serious side effects.Among 78 children with adenosine stress imaging,44 patients with negative adenosine stress imaging did not undergo rest imaging,which reduced radiation exposure by 56.4%(44/78).The sensitivity and specificity of adenosine stress MPIs in detecting significant coronary artery stenosis were 66.7%and 60.6%(40/66),respectively.Adenosine stress MPIs were positive in 21 cases(21/52,40.3%)in non-stenosis group,5 cases(35.7%)in mild to moderate stenosis group,and 8 cases(66.7%)in significant stenosis group.There was no significant difference in the positive rate among the three groups(χ2=3.169,P=0.205).Conclusion Adenosine stress test is safe and feasible in children.The stress-first imaging strategy can reduce radiation exposure.Adenosine stress MPI has important clinical value in evaluating and monitoring myocardial ischemia in children with Kawasaki disease complicated with coronary aneurysm.

Objective To investigate the changes in the expression of complement C3,high mobility group protein B1(HMGB1),and glutathione peroxidase 4(GPX4)in brain tissue at different time points after cerebral ischemia-reperfusion injury in rats.Methods A total 72 SPF male SD rats were randomly divided into a sham operation group(36 rats)and a model group(36 rats).A rat model of middle cerebral artery occlusion was established using thread occlusion,and then the rats from the model group were further assigned into 4 subgroups with reperfusion time for 3,6 and 24 h and 3 d,respectively,with 9 rats in each subgroup.Zea Longa scoring was used to assess neu-rological function.R2StarMap imaging,diffusion-weighted imaging(DWI),T1 weighted imaging,and T2 weighted imaging were performed on all the rats.The volume of abnormal DWI signals were detected and the volume of cerebral infarction was measured.The original R2StarMap images were post-processed to generate R2*pseudo color images,and then the R2*values of the areas with blood supply from bilateral middle cerebral artery were measured to detect iron deposition in the brain.The protein expression of C3,HMGB1,and GPX4 was detected by Western blotting.Results The sham operation group showed no neurological damage,while the model group had a significant increase in neurological function scores at 3,6 and 24 h and 3 d after modeling when compared to the sham surgery group(P＜0.05).While the size of right cerebral infarct was in-creased significantly at 3,6 and 24 h and 3 d in the rats of the model group(P＜0.05).The R2*value of the area with blood supply from the right middle cerebral artery in the model group was significantly higher than that in the left side at 3,6 and 24 h and 3 d(P＜0.05,P＜0.01),and it was also obviously higher than that in the right side of the sham operation group at these time points(P＜0.05,P＜0.01).The R2*ratio of the right and left blood supply areas in the model group at 3,6 and 24 h and 3 d was also statistically higher than that in the sham operation group at corresponding time points(1.82±0.82 vs 1.12±0.31,P＜0.05;1.31±0.26 vs 1.04±0.14,P＜0.05;1.94±0.74 vs 1.06±0.10,P＜0.01;1.99±0.39 vs 1.02±0.11,P＜0.01).Compared with the sham operation group,the expression levels of C3 and HMGB1 was significantly increased in the model group at 3,6 and 24 h and 3 d,while that of GPX4 was notably reduced(P＜0.01).Conclu-sion Cerebral ischemia-reperfusion injury impairs the neurological function of rats and signifi-cantly affects the cerebral expression of complement C3,HMGB1,and GPX4.

Objective: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. Methods: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. Results: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). Conclusion QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.

Objective: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. Methods: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. Results: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). Conclusion QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.

Objective: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. Methods: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. Results: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). Conclusion QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.

Blau syndrome is a rare genetic disorder characterized by the a mix of granulomatous arthritis, uveitis, and dermatitis. Patients typically manifest multisystem involvement, including ocular, skin, and skeletal abnormalities. Blau syndrome is extremely rare, with a global incidence of less than one in a million among children. In this multidisciplinary consultation, we present a case of a 21-year-old young female patient having multisystemic involvement since early childhood. She was presented with multiple joint swelling, skin lesions, increased eye discharge, and accompanied by hypertension and arterial abnormalities, and received a diagnosis of uveitis. The patient had been receiving steroid treatment since the age of 6 and has tried various medications, with some improvement in joint swelling and ocular symptoms. Through this rare disease multidisciplinary consultation, we aim to provide guidance in the molecular diagnosis of the patient, multisystem assessment, and the selection and formulation of treatment plans. Additionally, we hope that by reporting this case, clinical physicians can gain a better understanding of the diagnosis and comprehensive treatment strategies for Blau syndrome, thereby improving the management and treatment of rare diseases.