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 observe the effectiveness of extracorporeal counterpulsation therapy in patients with heart failure in ischaemic cardiomyopathy.Methods:A total of 112 patients with ischemic cardiomyopathy and heart failure admitted to the Second Affiliated Hospital of Xingtai Medical College from August 2020 to June 2023 were prospectively selected and divided into two groups by random number table method. The control group was treated with conventional drugs and conventional cardiac rehabilitation program, and the observation group was combined with external counterbeating therapy on the basis of the control group. The levels of N-terminal B-type brain natriuretic peptide (NTproBNP), soluble growth stimulation-expression gene-2 protein (sST2), neutrophil gelatinase-associated lipid carrier protein (NGAL), galactin-3 (Gal-3), cardiopulmonary exercise test (CPET) parameters and cardiac ultrasound indexes were compared between the two groups before and after treatment. The curative effect and the rate of re-hospitalization within 6 months were compared between the two groups.Results:After treatment, the levels of NTproBNP, sST2, NGAL and Gal-3 in the observation group were lower than those in the control group: (1941.36 ± 312.59) ng/L vs. (2674.22 ± 404.64) ng/L, (44.78 ± 3.97) ng/L vs. (52.45 ± 4.13) ng/L, (22.63 ± 3.65) μg/L vs. (26.41 ± 3.77) μg/L, (4.63 ± 1.29) ng/L vs. (6.11 ± 1.78) ng/L, there were statistical differences ( P<0.05); the maximum kilogram oxygen uptake (VO 2max/kg), maximum kilogram oxygen uptake as a percentage of predicted value (VO 2max/kg%pred), maximum minute ventilation as a percentage of predicted value (VEmax%pred) in the observation group were higher than those in the control group: (22.41 ± 2.23) ml/(min·kg) vs. (21.35 ± 2.09) ml/(min·kg), (83.79 ± 11.04)% vs. (78.74 ± 10.14)%, (88.95 ± 12.74)% vs. (75.45 ± 11.14)%, there were statistical differences ( P<0.05 or <0.01); the left ventricular ejection fraction (LVEF) in the observation group was higher than that in the control group and the left ventricular posterior wall thickness (LVPWT) and left ventricular posterior wall end-systolic thickness (PWS) were lower than those in the control group: (50.12 ± 3.87)% vs. (48.63 ± 3.74)%, (8.77 ± 1.58) mm vs. (9.63 ± 1.97) mm, (9.34 ± 1.54) mm vs. (10.14 ± 1.79) mm, there were statistical differences ( P<0.05). There was no statistical difference in the total effective rate between the two groups ( P>0.05). The patient readmission rate within 6 months of follow-up in the observation group was lower than that in the control group: 5.45%(3/55) vs. 20.00%(11/55), there was statistical difference( χ2 = 5.24, P<0.05). Conclusions:Extracorporeal counterpulsation therapy for the treatment of heart failure in ischaemic cardiomyopathy can improve the cardiorespiratory function, reduce the expression of NTproBNP, sST2, NGAL and Gal-3, and decrease the patient readmission rate.

Objective To evaluate the application of high-resolution magnetic resonance vessel wall imaging(HRMR-VWI)in identifying high-risk features of intracranial atherosclerotic plaques,and to analyze the correlation between plaque characteristics and stroke recurrence under varying degrees of stenosis.Methods The data from 368 patients with intracranial atherosclerotic stenosis(ICAS)across two centers were retrospectively analyzed.Based on the degree of stenosis,all patients were categorized into mild-to-moderate stenosis group(luminal stenosis<70%,n=155)and severe stenosis group(luminal stenosis≥70%,n=213).HRMR-VWI images and clinical information of the patients were collected and analyzed,and the culprit plaques were quantitatively analyzed.Univariate and multivariate logistic regression analyses were employed to identify the risk factors for stroke recurrence,and the predictive performance was evaluated using the area under the curve(AUC)of the receiver operating characteristic(ROC)curve.Results Higher normalized wall index(NWI)[odds ratio(OR)=1.082,95%confidence interval(CI)1.050-1.118,P<0.05]and the presence of intraplaque hemorrhage(IPH)(OR=1.843,95%CI 1.120-3.036,P<0.05)were risk factors for stroke recurrence in all patients.And these two factors were also significant in the mild-to-moderate stenosis group(NWI:OR=1.088,95%CI 1.009-1.186,P<0.05;IPH:OR=4.049,95%CI 1.227-16.065,P<0.05).A predictive model for stroke recurrence was constructed using the combination of IPH and NWI,with the best performance in the mild-to-moderate stenosis group(AUC=0.813,95%CI 0.723-0.906).Conclusion In patients with luminal stenosis<70%,the increase of NWI and the presence of IPH have been validated as significant and effective indicators for predicting stroke recurrence,demonstrating notable predictive performance.In contrast,among patients with luminal stenosis≥70%,the utility of plaque characteristics in predicting stroke recurrence is relatively lower,indicating that the correlation between plaque characteristics and stroke recurrence varies across different degrees of stenosis.

Objective To evaluate the application of high-resolution magnetic resonance vessel wall imaging(HRMR-VWI)in identifying high-risk features of intracranial atherosclerotic plaques,and to analyze the correlation between plaque characteristics and stroke recurrence under varying degrees of stenosis.Methods The data from 368 patients with intracranial atherosclerotic stenosis(ICAS)across two centers were retrospectively analyzed.Based on the degree of stenosis,all patients were categorized into mild-to-moderate stenosis group(luminal stenosis<70%,n=155)and severe stenosis group(luminal stenosis≥70%,n=213).HRMR-VWI images and clinical information of the patients were collected and analyzed,and the culprit plaques were quantitatively analyzed.Univariate and multivariate logistic regression analyses were employed to identify the risk factors for stroke recurrence,and the predictive performance was evaluated using the area under the curve(AUC)of the receiver operating characteristic(ROC)curve.Results Higher normalized wall index(NWI)[odds ratio(OR)=1.082,95%confidence interval(CI)1.050-1.118,P<0.05]and the presence of intraplaque hemorrhage(IPH)(OR=1.843,95%CI 1.120-3.036,P<0.05)were risk factors for stroke recurrence in all patients.And these two factors were also significant in the mild-to-moderate stenosis group(NWI:OR=1.088,95%CI 1.009-1.186,P<0.05;IPH:OR=4.049,95%CI 1.227-16.065,P<0.05).A predictive model for stroke recurrence was constructed using the combination of IPH and NWI,with the best performance in the mild-to-moderate stenosis group(AUC=0.813,95%CI 0.723-0.906).Conclusion In patients with luminal stenosis<70%,the increase of NWI and the presence of IPH have been validated as significant and effective indicators for predicting stroke recurrence,demonstrating notable predictive performance.In contrast,among patients with luminal stenosis≥70%,the utility of plaque characteristics in predicting stroke recurrence is relatively lower,indicating that the correlation between plaque characteristics and stroke recurrence varies across different degrees of stenosis.

Objective To observe the value of the integrated model of MR high-resolution vascular wall imaging(HR-VWI)and attention mechanism for predicting stroke recurrence in symptomatic intracranial atherosclerotic stenosis(sICAS)patients.Methods A total of 363 patients with sICAS who underwent HR-VWI were enrolled and stratified into training set(n=254)and validation set(n=109)according to their origins.Employing a radiomics model that utilized HR-VWI T1 and contrast-enhanced sequences for feature extraction,image data were captured from relevant plaques.Subsequently,a Trans model was developed by integrating the Transformer attention mechanism.The predictive performance and clinical utility of conventional radiomics models and Trans models for forecasting stroke recurrence among patients with sICAS were evaluated.Results In training set and validation set,the area under the curve of Trans model for predicting stroke recurrence in sICAS patients was 0.992 and 0.988,respectively,both superior to that of T1 model,T1 enhanced model and dual sequence model(all P＜0.05).The calibration curve and decision curve analysis showed that Trans model had good predictive probability and clinical practicality.Conclusion The obtained integrated model of HR-VWI radiomics combined with attention mechanism had certain value for predicting stroke recurrence in patients with sICAS.

OBJECTIVE To explore the effect of Zi Zhu Ointment combined with herbal fumigation on wound heal-ing,oxidative stress and microribonucleic acid(miR)-200b of the patients with diabetic foot infection.METHODS A total of 102 patients with diabetic foot infection who were treated in Heping Hospital Affiliated to Changzhi Medical College from Sep.2020 to Sep.2023 were enrolled in the study and were divided into the control group with 48 cases and the study group with 54 cases according to the treatment program.The control group was trea-ted with conventional therapy and herbal fumigation,the study group was given additional Zi Zhu Ointment on ba-sis of the treatment of the control group,and both groups were persistently treated for 1 month.The clinical cura-tive effect,wound healing status,hemodynamics indexes of dorsal foot,pain score,oxidative stress indexes and miR-200b expression levels were observed and compared between the two groups of patients.RESULTS The effec-tive rate of clinical treatment of the study group was higher than that of the control group after the treatment(Z=2.138,P=0.033).The wound area of the study group was(0.42±0.05)cm2 after the treatment,smaller than that of the control group;the cover area of neoplastic granulation tissue of the study group was(16.87±3.21)cm2,larger than that of the control group;the coverage fraction of the neoplastic granulation tissue of the study group was(55.23±6.17)％,greater than that of the control group;there were significant differences between the two groups(P＜0.05).The blood vessel diameter of dorsal foot of the study group was greater than that of the control group after the treatment,the blood flow velocity of the study group was greater than that of the control group,and the visual analogue scale(VAS)score of the study group was lower than that of the control group(P＜0.05).There were no significant differences in the expression levels of advanced oxidative protein product(AOPP),superoxide dismutase(SOD),malondialdehyde(MDA)and miR-200b between the two groups of pa-tients before the treatment;the expression levels of AOPP,MDA and miR-200b of the study group were lower than those of the control group after the treatment,while the SOD level of the study group was higher than that of the control group(P＜0.05).CONCLUSIONS Zi Zhu Ointment combined with herbal fumigation can remarkably improve the clinical curative effect on the patients with diabetic foot infection,promote the wound healing,im-prove the arterial hemodynamics of dorsal foot,and relieve the pain.The mechanism may be associated with the improvement of oxidative stress response and downregulated expression level of miR-200b.

Objective:To observe the effectiveness of extracorporeal counterpulsation therapy in patients with heart failure in ischaemic cardiomyopathy.Methods:A total of 112 patients with ischemic cardiomyopathy and heart failure admitted to the Second Affiliated Hospital of Xingtai Medical College from August 2020 to June 2023 were prospectively selected and divided into two groups by random number table method. The control group was treated with conventional drugs and conventional cardiac rehabilitation program, and the observation group was combined with external counterbeating therapy on the basis of the control group. The levels of N-terminal B-type brain natriuretic peptide (NTproBNP), soluble growth stimulation-expression gene-2 protein (sST2), neutrophil gelatinase-associated lipid carrier protein (NGAL), galactin-3 (Gal-3), cardiopulmonary exercise test (CPET) parameters and cardiac ultrasound indexes were compared between the two groups before and after treatment. The curative effect and the rate of re-hospitalization within 6 months were compared between the two groups.Results:After treatment, the levels of NTproBNP, sST2, NGAL and Gal-3 in the observation group were lower than those in the control group: (1941.36 ± 312.59) ng/L vs. (2674.22 ± 404.64) ng/L, (44.78 ± 3.97) ng/L vs. (52.45 ± 4.13) ng/L, (22.63 ± 3.65) μg/L vs. (26.41 ± 3.77) μg/L, (4.63 ± 1.29) ng/L vs. (6.11 ± 1.78) ng/L, there were statistical differences ( P<0.05); the maximum kilogram oxygen uptake (VO 2max/kg), maximum kilogram oxygen uptake as a percentage of predicted value (VO 2max/kg%pred), maximum minute ventilation as a percentage of predicted value (VEmax%pred) in the observation group were higher than those in the control group: (22.41 ± 2.23) ml/(min·kg) vs. (21.35 ± 2.09) ml/(min·kg), (83.79 ± 11.04)% vs. (78.74 ± 10.14)%, (88.95 ± 12.74)% vs. (75.45 ± 11.14)%, there were statistical differences ( P<0.05 or <0.01); the left ventricular ejection fraction (LVEF) in the observation group was higher than that in the control group and the left ventricular posterior wall thickness (LVPWT) and left ventricular posterior wall end-systolic thickness (PWS) were lower than those in the control group: (50.12 ± 3.87)% vs. (48.63 ± 3.74)%, (8.77 ± 1.58) mm vs. (9.63 ± 1.97) mm, (9.34 ± 1.54) mm vs. (10.14 ± 1.79) mm, there were statistical differences ( P<0.05). There was no statistical difference in the total effective rate between the two groups ( P>0.05). The patient readmission rate within 6 months of follow-up in the observation group was lower than that in the control group: 5.45%(3/55) vs. 20.00%(11/55), there was statistical difference( χ2 = 5.24, P<0.05). Conclusions:Extracorporeal counterpulsation therapy for the treatment of heart failure in ischaemic cardiomyopathy can improve the cardiorespiratory function, reduce the expression of NTproBNP, sST2, NGAL and Gal-3, and decrease the patient readmission rate.

Objective To observe the value of the integrated model of MR high-resolution vascular wall imaging(HR-VWI)and attention mechanism for predicting stroke recurrence in symptomatic intracranial atherosclerotic stenosis(sICAS)patients.Methods A total of 363 patients with sICAS who underwent HR-VWI were enrolled and stratified into training set(n=254)and validation set(n=109)according to their origins.Employing a radiomics model that utilized HR-VWI T1 and contrast-enhanced sequences for feature extraction,image data were captured from relevant plaques.Subsequently,a Trans model was developed by integrating the Transformer attention mechanism.The predictive performance and clinical utility of conventional radiomics models and Trans models for forecasting stroke recurrence among patients with sICAS were evaluated.Results In training set and validation set,the area under the curve of Trans model for predicting stroke recurrence in sICAS patients was 0.992 and 0.988,respectively,both superior to that of T1 model,T1 enhanced model and dual sequence model(all P＜0.05).The calibration curve and decision curve analysis showed that Trans model had good predictive probability and clinical practicality.Conclusion The obtained integrated model of HR-VWI radiomics combined with attention mechanism had certain value for predicting stroke recurrence in patients with sICAS.

OBJECTIVE To explore the effect of Zi Zhu Ointment combined with herbal fumigation on wound heal-ing,oxidative stress and microribonucleic acid(miR)-200b of the patients with diabetic foot infection.METHODS A total of 102 patients with diabetic foot infection who were treated in Heping Hospital Affiliated to Changzhi Medical College from Sep.2020 to Sep.2023 were enrolled in the study and were divided into the control group with 48 cases and the study group with 54 cases according to the treatment program.The control group was trea-ted with conventional therapy and herbal fumigation,the study group was given additional Zi Zhu Ointment on ba-sis of the treatment of the control group,and both groups were persistently treated for 1 month.The clinical cura-tive effect,wound healing status,hemodynamics indexes of dorsal foot,pain score,oxidative stress indexes and miR-200b expression levels were observed and compared between the two groups of patients.RESULTS The effec-tive rate of clinical treatment of the study group was higher than that of the control group after the treatment(Z=2.138,P=0.033).The wound area of the study group was(0.42±0.05)cm2 after the treatment,smaller than that of the control group;the cover area of neoplastic granulation tissue of the study group was(16.87±3.21)cm2,larger than that of the control group;the coverage fraction of the neoplastic granulation tissue of the study group was(55.23±6.17)％,greater than that of the control group;there were significant differences between the two groups(P＜0.05).The blood vessel diameter of dorsal foot of the study group was greater than that of the control group after the treatment,the blood flow velocity of the study group was greater than that of the control group,and the visual analogue scale(VAS)score of the study group was lower than that of the control group(P＜0.05).There were no significant differences in the expression levels of advanced oxidative protein product(AOPP),superoxide dismutase(SOD),malondialdehyde(MDA)and miR-200b between the two groups of pa-tients before the treatment;the expression levels of AOPP,MDA and miR-200b of the study group were lower than those of the control group after the treatment,while the SOD level of the study group was higher than that of the control group(P＜0.05).CONCLUSIONS Zi Zhu Ointment combined with herbal fumigation can remarkably improve the clinical curative effect on the patients with diabetic foot infection,promote the wound healing,im-prove the arterial hemodynamics of dorsal foot,and relieve the pain.The mechanism may be associated with the improvement of oxidative stress response and downregulated expression level of miR-200b.

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.