Objective:This study aimed to investigate the characteristic expression of programmed death-ligand 2(PD-L2)and epithelial-mesenchymal transition(EMT)-related biomarkers in head and neck squamous cell carcinoma(HNSCC)and their mechanism of action in HNSCC metastasis.Methods:Tumor tissue samples from 94 patients with HNSCC were collected from Tianjin Medical University Cancer Hos-pital from January 2018 to July 2023,and their correlation with clinicopathological parameters,including lymph node metastasis,was statist-ically assessed.Western blot was used to detect PD-L2 expression in HNSCC tumor tissues.PD-L2 overexpression and knockdown stably-transfected monoclonal cell lines were generated using lentiviral vectors.Transwell assays were performed to explore the effect of PD-L2 on the invasive migration of the HNSCC cell lines.Additionally,RNA sequencing was used to identify downstream target genes regulated by PD-L2.The expression levels of key EMT markers,including E-cadherin,N-cadherin,and Vimentin,were examined by Western blot to elucidate the molecular mechanism by which PD-L2 promotes tumor cell metastasis through EMT pathway activation.Additionally,RNA sequencing was employed to identify downstream target genes regulated by PD-L2.The expression levels of key EMT markers,including E-cadherin,N-cadherin,and Vimentin,were examined with Western blot analysis to elucidate the molecular mechanism by which PD-L2 promotes tumor cell metastasis through the EMT pathway activation.Results:High expression of PD-L2 is positively correlated with N staging(P<0.05),and elevated PD-L2 expression predicts a poor prognosis in HNSCC patients.Conclusions:PD-L2 regulates the EMT pathway to promote HNSCC metastasis.Targeting PD-L2 is expected to provide a new strategy for the treatment of metastatic HNSCC.

Objective:This study aimed to investigate the characteristic expression of programmed death-ligand 2(PD-L2)and epithelial-mesenchymal transition(EMT)-related biomarkers in head and neck squamous cell carcinoma(HNSCC)and their mechanism of action in HNSCC metastasis.Methods:Tumor tissue samples from 94 patients with HNSCC were collected from Tianjin Medical University Cancer Hos-pital from January 2018 to July 2023,and their correlation with clinicopathological parameters,including lymph node metastasis,was statist-ically assessed.Western blot was used to detect PD-L2 expression in HNSCC tumor tissues.PD-L2 overexpression and knockdown stably-transfected monoclonal cell lines were generated using lentiviral vectors.Transwell assays were performed to explore the effect of PD-L2 on the invasive migration of the HNSCC cell lines.Additionally,RNA sequencing was used to identify downstream target genes regulated by PD-L2.The expression levels of key EMT markers,including E-cadherin,N-cadherin,and Vimentin,were examined by Western blot to elucidate the molecular mechanism by which PD-L2 promotes tumor cell metastasis through EMT pathway activation.Additionally,RNA sequencing was employed to identify downstream target genes regulated by PD-L2.The expression levels of key EMT markers,including E-cadherin,N-cadherin,and Vimentin,were examined with Western blot analysis to elucidate the molecular mechanism by which PD-L2 promotes tumor cell metastasis through the EMT pathway activation.Results:High expression of PD-L2 is positively correlated with N staging(P<0.05),and elevated PD-L2 expression predicts a poor prognosis in HNSCC patients.Conclusions:PD-L2 regulates the EMT pathway to promote HNSCC metastasis.Targeting PD-L2 is expected to provide a new strategy for the treatment of metastatic HNSCC.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

This study was designed to investigate the effect of graphene far-infrared irradiation on the relevant immune indexes of Lewis lung cancer tumor bearing mice after cisplatin chemotherapy.A lung cancer tumor-bearing mouse immune damage model was established in Lewis mice,and the model mice were divided into a model control group(CTL),a chemotherapy group(DDP),a low-power graphene group(G-Low,30℃),and a high-power graphene group(G-High,35℃).Mice in all groups were subjected to detect the tumor volume growth rate,thymus index and spleen index,spleen lymphocyte proliferation activity and NK cell killing activity,the number of white blood cells in the peripheral blood and the ratio of CD4+T/CD8+T in the peripheral blood.Compared with the CTL group,the thymus index and spleen index of the DDP group were significantly lower(P＜0.01);compared with the DDP group,the tumor inhibition rate of the G-Low group was significantly improved(P＜0.05),and the tumor inhibition rate of the G-High group was extremely significantly improved(P＜0.01).The thymus index,white blood cell count,peripheral blood CD4+T/CD8+T ratio,and NK cell killing activity of the spleen in the G-High group were significantly higher than those in the DDP group(P＜0.05).Taken together,Graphene far-infrared irradiation has a good repair effect on the immune damage caused by cisplatin chemotherapy in Lewis lung cancer tumor-bearing mice,and can significantly inhibit tumor growth.

Objective:We examined the levels of Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling in head and neck squamous cell carcinoma(HNSCC)and their influence on chemotherapy sensitization.Methods:Sixty patients with HNSCC who were treated at Tianjin Medical University Cancer Institute&Hospital,between January 2018 and December 2022,were included in the study.Levels of expressed JAK2,p-STAT3Y705,c-Myc,and Ki-67 in HNSCC tissues were evaluated using immunohistochemical staining,and correlation analysis was performed.The viability of UM-SCC1 cells treated with fedratinib,a JAK2 inhibitor,combined with cisplatin(DDP)and paclitaxel(PTX)was determined using the CCK8 assay.Western blot was performed to detect p-STAT3Y705 expression in tumor tissues and HNSCC cell lines.SCC15 and UM-SCC1 cell lines stably transfected with JAK2 or STAT3 vectors were constructed and verified.Cell activity and cell proliferation capacity were measured to evaluate the detrimental impact of STAT3 overexpression on chemotherapy with fedratinib using Western blot,CCK8,and plate cloning assays.Results:JAK2 expression in HNSCC positively correlated with p-STAT3Y705(r=0.43,P<0.000 1)and c-Myc(r=0.48,P<0.01)expression.High p-STAT3Y705 expression positively correlated with AJCC stage(P<0.000 1)and Ki-67 expression(P<0.05).High STAT3 and p-STAT3 levels were associated with poor prognosis in patients with HNSCC.In vitro,the JAK2 inhibitor fedratinib inhibited HNSCC cell proliferation and enhanced tumor cell sensitivity to DDP and PTX.JAK2 activation promotes STAT3 phosphorylation,and STAT3 overexpression reverses the effects of fedratinib on HNSCC sensitivity to chemotherapy.Conclusions:JAK2/STAT3 signaling is elev-ated in patients with HNSCC.Targeting the JAK2/STAT3 pathway is a potential method for increasing the sensitivity of HNSCC to chemotherapy.

This study was designed to investigate the effect of graphene far-infrared irradiation on the relevant immune indexes of Lewis lung cancer tumor bearing mice after cisplatin chemotherapy.A lung cancer tumor-bearing mouse immune damage model was established in Lewis mice,and the model mice were divided into a model control group(CTL),a chemotherapy group(DDP),a low-power graphene group(G-Low,30℃),and a high-power graphene group(G-High,35℃).Mice in all groups were subjected to detect the tumor volume growth rate,thymus index and spleen index,spleen lymphocyte proliferation activity and NK cell killing activity,the number of white blood cells in the peripheral blood and the ratio of CD4+T/CD8+T in the peripheral blood.Compared with the CTL group,the thymus index and spleen index of the DDP group were significantly lower(P＜0.01);compared with the DDP group,the tumor inhibition rate of the G-Low group was significantly improved(P＜0.05),and the tumor inhibition rate of the G-High group was extremely significantly improved(P＜0.01).The thymus index,white blood cell count,peripheral blood CD4+T/CD8+T ratio,and NK cell killing activity of the spleen in the G-High group were significantly higher than those in the DDP group(P＜0.05).Taken together,Graphene far-infrared irradiation has a good repair effect on the immune damage caused by cisplatin chemotherapy in Lewis lung cancer tumor-bearing mice,and can significantly inhibit tumor growth.

Hypervirulent Klebsiella pneumoniae, short for hvKP, is a hypervirulent variant of classical Klebsiella pneumoniae, which accounts for serious infection in healthy people, exhibits strong pathogenicity, high mortality and poor prognosis. At present, hvkp is of high prevalence all over the world, and the infection rate shows a continuous upward trend, which brings great challenges to public health security and clinical treatment. This paper summarized the research progress on virulence factors of hvkp, such as capsular polysaccharides, siderophore, lipopolysaccharide, adhesins and recently discovered Type Ⅵ secreting system, and aimed to deepen the understanding and recognition of hvKP.

Hypervirulent Klebsiella pneumoniae, short for hvKP, is a hypervirulent variant of classical Klebsiella pneumoniae, which accounts for serious infection in healthy people, exhibits strong pathogenicity, high mortality and poor prognosis. At present, hvkp is of high prevalence all over the world, and the infection rate shows a continuous upward trend, which brings great challenges to public health security and clinical treatment. This paper summarized the research progress on virulence factors of hvkp, such as capsular polysaccharides, siderophore, lipopolysaccharide, adhesins and recently discovered Type Ⅵ secreting system, and aimed to deepen the understanding and recognition of hvKP.

Objective:To construct a risk prediction score for the needs of coronary care unit (CCU) care in stable condition acute ST-segment elevation myocardial infarction (STEMI) patients who receive percutaneous coronary intervention (PCI) treatment.Methods:The clinical data of 805 STEMI patients who accepted PCI in the First Hospital of Jilin University from November 2017 to October 2018 were retrospectively analyzed. Among the patients, 654 patients from November 2017 to July 2018 were served as the modeling group, the patients with needs of CCU had 125 cases, and the patients without needs of CCU had 529 cases; 151 patients from August 2018 to October 2018 were served as the validation group, the patients with needs of CCU had 28 cases, and the patients without needs of CCU had 123 cases. Binary Logistic regression analysis was used to establish the risk prediction model and determine the score standards. The critical value was determined according to the best Youden index of receiver operating characteristic (ROC) curve.Results:Among 805 patients with STEMI, 153 cases (19.01%) had the needs of CCU, and the most common reason was pump failure (heart failure and cardiogenic shock, 113 cases). In the modeling group, age (60 to 74 years old, OR = 1.513, 95% CI 0.945 to 2.424, P = 0.085; ≥75 years old, OR = 2.740, 95% CI 1.371 to 5.478, P = 0.004), total ischemic time>4 h ( OR = 1.701, 95% CI 1.022 to 2.831, P = 0.041), admission shock index ≥0.8 ( OR = 1.910, 95% CI 1.178 to 3.099, P = 0.009), multi-vessel disease ( OR = 2.090, 95% CI 1.272 to 3.432, P = 0.004), preoperative diseased vessels thrombolysis in myocardial ischemia (TIMI) blood flow grade 0 ( OR = 2.099, 95% CI 1.313 to 3.353, P = 0.002), acute anterior myocardial infarction ( OR = 3.696, 95% CI 2.347 to 5.819, P<0.001) and previous history of stroke ( OR = 3.927, 95% CI 2.057 to 7.500, P<0.001) were independent risk factors for CCU needs in STEMI patients undergoing PCI. The scoring criteria were as followings: age<60 years old was given 0 score, 60 to 74 years old 1 score, ≥75 years old 2 score; total ischemic time>4 h in 1 score, admission shock index ≥0.8 2 scores, multi-vessel disease 2 scores, preoperative diseased vessels TIMI blood flow grade 0 2 scores, acute anterior myocardial infarction 3 scores, previous history of stroke 3 scores, and the total score was 15 scores. The patients with 0 to 6 scores were low-risk, and the patients with 7 to 15 scores were high-risk. ROC curve analysis result showed that, in modeling group, the area under curve (AUC) of risk prediction score for predicting the needs of CCU in STEMI patients was 0.740 (95% CI 0.692 to 0.788, P = 0.580); in validation group, the AUC of risk prediction score for predicting the needs of CCU in STEMI patients was 0.755 (95% CI 0.658 to 0.853, P = 0.755). Conclusions:A predictive risk score based on seven risk factors such as age, total ischemic time, admission shock index, multi-vessel disease, preoperative diseased vessels TIMI blood flow grade, acute anterior myocardial infarction and previous history of stroke is constructed in order to predict the needs of CCU in STEMI patients with stable condition who receive PCI treatment. It can be used to help doctors to identify high-risk patients before the admission to CCU, thus providing simple and practical clinical tool for rational allocation of limited CCU resources.

Objective:To explore the predictive value of the recurrence risk estimator at 90-days(RRE-90) score combined with lipoprotein-associated phospholipase A2 (Lp-PLA2) and high sensitivity C-reactive protein(hs-CRP) in the recurrence risk of acute atherosclerotic cerebral infarction.Methods:Totally 400 patients with acute atherosclerotic cerebral infarction who were hospitalized for the first time in neurology department were followed up for 90 days.However, 8 cases were lost and 392 cases were included finally.According to recurrence or not, 64 cases were divided into recurrence group and 328 cases into non-recurrence group.The RRE-90 score was applied to all the participants and the levels of Lp-PLA2 was detected by enzyme-linked immunosorbent assay, the levels of hs-CRP was detected by immunoturbidimetry.The ROC curve was used to analyze the predictive value of RRE-90 score combined with Lp-PLA2 and hs-CRP for the recurrence risk of acute cerebral infarction.Results:Compared with the non-recurrence group(RRE-90: (3.07±1.01)score, Lp-PLA2: (103.53±8.11)μg/L, hs-CRP: (4.07±1.48)mg/L), the levels of (RRE-90 score: (4.11±0.78)score, Lp-PLA2: (121.52±13.95)μg/L, hs-CRP: (12.40±2.46) mg/L)in the recurrence group of cerebral infarction were significantly higher ( P<0.05, P<0.01). Compared with RRE-90 score (0.705), Lp-PLA2 (0.697), hs-CRP (0.622), RRE-90 score combined with Lp-PLA2 (0.752), RRE-90 score combined with hs-CRP (0.746), RRE-90 score combined with Lp-PLA2 and hs-CRP (0.782) had the largest area under the curve for predicting recurrence of cerebral infarction within 90 days, with statistical significance( P<0.05), sensitivity was 87.8%, specificity was 89.6%. Conclusion:RRE-90 score combined with Lp-PLA2 and hs-CRP detection can further improve the accuracy of predicting recurrence within 90 days in patients with cerebral atherosclerotic infarction, and the predictive value is high.