The polymerase 1 and transcript release factor (PTRF)-cytoplasmic phospholipase A2 (cPLA2) phospholipid remodeling pathway facilitates tumor proliferation in glioma. Nevertheless, blockade of this pathway leads to the excessive activation of oncogenic receptors on the plasma membrane and subsequent drug resistance. Here, CD26/dipeptidyl peptidase 4 (DPP4) was identified through screening of CRISPR/Cas9 libraries. Suppressing PTRF-cPLA2 signaling resulted in the activation of the epidermal growth factor receptor (EGFR) pathway through phosphatidylcholine and lysophosphatidylcholine remodeling, which ultimately increased DPP4 transcription. In turn, DPP4 interacted with EGFR and prevented its ubiquitination. Linagliptin, a DPP4 inhibitor, facilitated the degradation of EGFR by blocking its interaction with DPP4. When combined with the cPLA2 inhibitor AACOCF3, it exhibited synergistic effects and led to a decrease in energy metabolism in glioblastoma cells. Subsequent in vivo investigations provided further evidence of a synergistic impact of linagliptin by augmenting the sensitivity of AACOCF3 and strengthening the efficacy of temozolomide. DPP4 serves as a novel target and establishes a constructive feedback loop with EGFR. Linagliptin is a potent inhibitor that promotes EGFR degradation by blocking the DPP4-EGFR interaction. This study presents innovative approaches for treating glioma by combining linagliptin with AACOCF3 and temozolomide.

Objective:To develop a nomogram based on the monocyte-to-lymphocyte ratio (MLR) for predicting the risk of aortic-related adverse events within 30 days in patients with acute uncomplicated type B aortic intramural hematoma.Methods:This single-center retrospective cohort study screened consecutive patients with acute uncomplicated type B aortic intramural hematoma treated at the Emergency and Cardiovascular Medicine Departments of the General Hospital of the Northern Theater Command from April 2018 to April 2024. Patients were divided into two groups based on the optimal MLR cut-off value for predicting aortic-related adverse events: low MLR and high MLR group. MLR was defined as the ratio of monocytes to lymphocytes. Aortic-related adverse events were defined as a composite of aortic-related death or aortic intramural hematoma progression (including aortic dissection and penetrating aortic ulcers) within 30 days. The receiver operating characteristic (ROC) curve identified the optimal MLR cut-off value. Multivariate logistic regression was used to identify independent predictors of aortic-related adverse events within 30 days, based on which nomogram models were constructed: the clinical characteristics model and the clinical characteristics-MLR model. The DeLong test was used to evaluate the diagnostic performance of different risk models. The additional predictive value of MLR was assessed using the net reclassification index (NRI) and integrated discrimination improvement (IDI).Results:A total of 332 patients were included, of whom 217 were male (65.4%), with an average age of (64.3±9.4) years. A total of 107 aortic-related adverse events occurred during the 30-day follow-up period. The optimal cut-off value for MLR was 0.529. There were 189 cases in the low MLR group (MLR<0.529) and 143 cases in the high MLR group (MLR≥0.529). The rate of aortic-related adverse events was higher in the high MLR group compared to the low MLR group (44.1% (63/143) vs. 23.3% (44/189), P<0.001), mainly due to a higher rate of progression to aortic dissection (9.8% (14/143) vs. 1.1% (2/189), P<0.001) and penetrating aortic ulcers (31.5% (45/143) vs. 20.6% (39/189), P=0.025). Multivariate analysis identified diabetes ( OR=0.25, 95% CI 0.08-0.78, P=0.017), anemia ( OR=3.45, 95% CI 1.28-9.27, P=0.014), maximum descending aorta diameter ( OR=1.08, 95% CI 1.02-1.15, P=0.007), ulcer-like projections ( OR=4.04, 95% CI 2.26-7.24, P<0.001), and MLR ( OR=6.61, 95% CI 2.50-17.46, P<0.001) as independent predictors of aortic-related adverse events during the 30-day follow-up period. The clinical characteristics model includes diabetes, anemia, ulcer-like projections and maximum diameter of the descending aorta, and the clinical characteristics-MLR model includes the above clinical characteristics and MLR. The results of the DeLong test showed that the clinical characteristic-MLR model demonstrated a higher area under the ROC curve compared to the clinical characteristic model alone (0.784 (95% CI 0.736-0.841) vs. 0.742 (95% CI 0.691-0.788), P=0.031). The continuous NRI was 0.461 (95% CI 0.237-0.685, P<0.001) and the IDI was 0.077 (95% CI 0.043-0.112, P<0.001), indicating that the inclusion of the MLR in the model significantly improved the predictive accuracy. Conclusion:The integration of MLR with other clinical characteristics improves the early identification of high-risk patients with acute uncomplicated type B aortic intramural hematoma, optimizing clinical decisions and improving patient outcomes.

Calcitonin-negative medullary thyroid carcinoma(CNMTC)is a rare subtype of medullary thyroid carcinoma,characterized by normal serum calcitonin levels,which often leads to misdiagnosis or missed diagnosis.The pathogenesis of CNMTC remains unclear and may involve impaired secretion mechanisms or assay-related false negatives.Diagnostic approaches include ultrasound-guided fine needle aspiration cytology,serum CEA and ProGRP measurements,and RET gene testing.Surgical resection remains the mainstay of treatment,while neoadjuvant therapy may be considered in selected cases.This review summarizes recent advances in the understanding,diagnosis,treatment,and prognosis of CNMTC,aiming to provide clinical guidance for better management of this challenging condition.

Objective To investigate the application effect of high flow humidified oxygen therapy combined with tracheotomy in elderly patients with cerebral hemorrhage and analyze the risk factors of pulmonary infection.Methods A total of 140 elderly patients with cerebral hemorrhage who underwent tracheotomy in our hospital from 2019 to 2023 were selected as the study objects,of which 93 patients receiving high-flow humidified oxygen therapy were selected as the observation group,and 47 patients receiving conventional low-flow oxygen therapy were selected as the control group during the same period.The changes of PaO2,SpO2,heart rate and mean arterial pressure were compared,and patients in the observation group were divided into infected group(n=26)and non-infected group(n=67)according to whether pulmonary infection occurred during hospitalization.The risk factors affecting pulmonary infection during hospitalization in elderly patients with cerebral hemorrhage were analyzed,and a nematographic prediction model was built to predict the risk of pulmonary infection.Results The PaO2 and SpO2 levels in observation group were higher than those in control group at 24 h and 72 h,but the respiratory rate was lower than that in control group(P＜0.05).The improvement of sputum viscosity in the observation group(68 cases of grade Ⅰ sputum and 25 cases of grade Ⅱ sputum)was better than that in the control group(16 cases of grade Ⅰ sputum,17 cases of grade Ⅱ sputum and 14 cases of gradeⅢ sputum).The rate of phlegm scab formation(0)and the number of sputum aspiration(5.15±1.08)times were lower than those in the control group[14.87％,(8.17±1.82)times](P＜0.05).There were significant differences in tracheotomy time,smoking history,bed rest time,mechanical ventilation time and nasal feeding tube retention time between infected and non-infected groups(P＜0.05).Logistic regression analysis showed that tracheotomy time＞5 d,smoking history,bed time＞10 d,mechanical ventilation time ≥24 h,nasal feeding tube retention time≥10 d were the risk factors for pulmonary infection in elderly patients with cerebral hemorrhage during treatment(P＜0.05).The AUC,sensitivity and specificity were 0.696,0.565 and 0.889 in elderly patients with cerebral hemorrhage complicated by pulmonary infection during treatment.Conclusion High-flow humidification oxygen therapy combined with tracheotomy can improve the oxygenation status in elderly patients with cerebral hemorrhage,but the time of tracheotomy,smoking history,bed rest time,mechanical ventilation time,and nasal feeding tube retention time will affect the pulmonary infection during treatment.The construction of a nomogram model based on these risk factors has higher predictive efficacy in evaluating the pulmonary infection.

Objective:To investigate the clinical predictive value of Ki67 proliferation index combined with preoperative serum Ctn for postoperative biochemical cure of medullary thyroid carcinoma (MTC) .Methods:Clinical data were collected from Dec. 2008 to Dec. 2024 from 90 patients with surgically confirmed MTC at China-Japan Union Hospital of Jilin University. The optimal cut-off value for preoperative Ctn prediction of biochemical cure (171.18pg/mL) was determined by the ROC curve; the Ki67 proliferation index cut-off value was adopted from the international MTC grading system standard (5%). Patients were divided into three groups based on the above cutoff values: double-low group (Ki67 <5% and Ctn <171.18pg/mL, n=23), single-high group (Ki67 ≥5% and Ctn <171.18pg/mL or Ki67 <5% and Ctn ≥171.18pg/mL, n=49), and double-high group (Ki67 ≥5% and Ctn ≥171.18pg/mL, n=18). The Kaplan-Meier method (Log-Rank and Trend test) was used to compare the differences in biochemical cure rates between groups, and the Cox proportional risk model was used to analyze the risk factors affecting biochemical cure. Results:The correlation between preoperative Ctn and Ki67 proliferation index was not significant. The three groups differed significantly in gender, tumor distribution, tumor size, vascular invasion, N stage, TNM stage, and biochemical cure ( P<0.05), with the double-high group being significantly associated with larger tumors, later N stage and TNM stage, and lower biochemical cure ( P<0.001). Kaplan-Meier analysis showed that the biochemical cure rate in the double-high, single-high, and double-low groups showed a stepwise improvement.Cox univariate analysis showed that tumor size, N stage, TNM stage, preoperative Ctn, and Ki67 combined with Ctn were risk factors for failure to biochemically cure; multivariate analysis confirmed that the double-high group was an independent risk factor ( P<0.05). In the single-high group, the biochemical cure rate of patients in the low Ki67-high Ctn group was lower than that of the high Ki67-low Ctn group and more malignant. Ki67 had less effect on biochemical cure and disease-free survival at the low Ctn level, and Ki67 was an independent risk factor for failure to biochemically cure at the high Ctn level ( P=0.023) and was significantly associated with disease-free survival ( P=0.004) . Conclusions:Serum Ctn is more sensitive than Ki67 index in predicting biochemical cure after MTC, and the correlation between the two was weak. Ki67 proliferation index alone has limited prognostic value, but combines with preoperative Ctn significantly optimize the prognostic assessment of patients.The role of Ki67 index varied at different Ctn levels.

Objective:To analyze the prognostic influencing factors in patients with isocitrate dehydrogenase (IDH) wild-type glioma, and further evaluate the value of surgical resection in prognosis.Methods:The clinical data and molecular pathological information of 647 patients with IDH wild-type glioma were retrieved from the Chinese Glioma Genome Atlas (CGGA) database (from 2006 to 2019). The clinical characteristics were recorded, including gender, age, initial symptoms, preoperative Karnofsky performance status (KPS) score, tumor location, tumor laterality, extent of resection, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status and postoperative treatment. Kaplan-Meier survival curve was plotted to calculate overall survival (OS) and progression-free survival (PFS), and comparisons were performed using the log-rank test. Multivariate Cox regression analysis was used to identify the independent influencing factors of prognosis in patients with IDH wild-type glioma.Results:Among the 647 patients with IDH wild-type glioma, there were 120 cases of WHO grade Ⅱ, 115 cases of grade Ⅲ, and 412 cases of grade Ⅳ; the median OS was 20.3 months. There were statistical differences in age, initial symptoms, tumor location, preoperative KPS score, extent of resection, MGMT promoter methylation status and postoperative treatment among patients with different WHO grades (P<0.01), but there were no statistical difference in gender and tumor laterality (P>0.05). The median OS and PFS in patients with WHO grade Ⅱ were significantly longer than those in patients with WHO grade Ⅲ and WHO grade Ⅳ (169.9 months vs. 24.7 and 14.4 months, 138.8 months vs. 17.7 and 11.4 months), the indexes in patients with WHO grade Ⅲ were significantly longer than patients with WHO grade Ⅳ, and there were statistical differences (P<0.05). The median OS and PFS in patients with total resection were significantly longer than those in patients with subtotal resection and partial resection (37.2 months vs. 20.3 and 8.5 months, 29.5 months vs. 17.6 and 6.0 months), the indexes in patients with subtotal resection were significantly longer than patients with partial resection, and there were statistical differences (P<0.05). Among 153 patients with MGMT promoter methylation who received postoperative chemoradiotherapy, the median OS and PFS in patients with total resection (67 cases) were significantly longer than those in patients with subtotal resection (64 cases) and partial resection (22 cases): 28.8 months vs. 18.4 and 9.0 months, 25.6 months vs. 16.6 and 6.5 months), the indexes in patients with subtotal resection were significantly longer than patients with partial resection, and there were statistical differences (P<0.05). Among 202 patients with MGMT promoter non-methylation who received postoperative chemoradiotherapy, the median OS and PFS in patients with total resection (81 cases) were significantly longer than those in subtotal resection (81 cases) and partial resection (40 cases): 31.3 months vs. 21.9 and 14.0 months, 22.7 months vs. 16.8 and 9.7 months, and there were statistical differences (P<0.05), but there were no statistical difference in the indexes between patients with subtotal and patients with partial resection (P>0.05). Multivariate Cox regression analysis result showed that age, extent of resection, WHO grade (grade Ⅲ/grade Ⅳ) and postoperative treatment were independent OS and PFS influencing factors in patients with IDH wild-type glioma (OS: HR = 1.327, 3.295, 3.406/7.964 and 1.597; 95% CI 1.079 to 1.633, 2.627 to 4.132, 2.225 to 5.216/5.339 to 11.880 and 1.288 to 1.981; P<0.01. PFS: HR = 1.282, 2.655, 3.143/6.511 and 1.477; 95% CI 1.039 to 1.583, 2.123 to 3.322, 2.049 to 4.819/4.376 to 9.690 and 1.181 to 1.849; P<0.05 or <0.01).Conclusions:The age, extent of resection, WHO grade and postoperative treatment are independent prognosis influencing factors in patients with IDH wild-type glioma. Treatment strategies should fully consider the clinical and molecular pathological characteristics to achieve maximal safe tumor resection and optimal survival benefit.

Berberine,an isoquinoline alkaloid,is abundant in plants such as Coptis and Phellodendri.It exhibits a wide range of pharmacological activities and has been effectively applied in the clinical treatment of metabolic diseases,infectious diseases,and inflammation.In recent years,berberine's anti-tumor effects have garnered significant attention.Research has demonstrated that berberine can inhibit tumor progression via multiple pathways,including inducing tumor cell apoptosis,regulating the tumor microbiome,arresting the cell cycle,inhibiting tumor angiogenesis,and enhancing the efficacy of tumor immunotherapy.Additionally,berberine can synergistically increase the sensitivity of chemotherapeutic drugs and reduce drug resistance by modulating key signaling pathways such as PI3K/Akt,MAPK,and NF-κB.The antioxidant and immunomodulatory properties of berberine further expand its potential for anti-tumor applications.Based on the findings from basic and clinical research,this review systematically summarizes the latest advances in berberine's anti-tumor mechanisms and clinical applications.It also discusses the challenges and potential solutions in the clinical translation of berberine for cancer therapy,providing a theoretical basis for its development as a novel anti-tumor drug.

Objective:To investigate the clinical predictive value of Ki67 proliferation index combined with preoperative serum Ctn for postoperative biochemical cure of medullary thyroid carcinoma (MTC) .Methods:Clinical data were collected from Dec. 2008 to Dec. 2024 from 90 patients with surgically confirmed MTC at China-Japan Union Hospital of Jilin University. The optimal cut-off value for preoperative Ctn prediction of biochemical cure (171.18pg/mL) was determined by the ROC curve; the Ki67 proliferation index cut-off value was adopted from the international MTC grading system standard (5%). Patients were divided into three groups based on the above cutoff values: double-low group (Ki67 <5% and Ctn <171.18pg/mL, n=23), single-high group (Ki67 ≥5% and Ctn <171.18pg/mL or Ki67 <5% and Ctn ≥171.18pg/mL, n=49), and double-high group (Ki67 ≥5% and Ctn ≥171.18pg/mL, n=18). The Kaplan-Meier method (Log-Rank and Trend test) was used to compare the differences in biochemical cure rates between groups, and the Cox proportional risk model was used to analyze the risk factors affecting biochemical cure. Results:The correlation between preoperative Ctn and Ki67 proliferation index was not significant. The three groups differed significantly in gender, tumor distribution, tumor size, vascular invasion, N stage, TNM stage, and biochemical cure ( P<0.05), with the double-high group being significantly associated with larger tumors, later N stage and TNM stage, and lower biochemical cure ( P<0.001). Kaplan-Meier analysis showed that the biochemical cure rate in the double-high, single-high, and double-low groups showed a stepwise improvement.Cox univariate analysis showed that tumor size, N stage, TNM stage, preoperative Ctn, and Ki67 combined with Ctn were risk factors for failure to biochemically cure; multivariate analysis confirmed that the double-high group was an independent risk factor ( P<0.05). In the single-high group, the biochemical cure rate of patients in the low Ki67-high Ctn group was lower than that of the high Ki67-low Ctn group and more malignant. Ki67 had less effect on biochemical cure and disease-free survival at the low Ctn level, and Ki67 was an independent risk factor for failure to biochemically cure at the high Ctn level ( P=0.023) and was significantly associated with disease-free survival ( P=0.004) . Conclusions:Serum Ctn is more sensitive than Ki67 index in predicting biochemical cure after MTC, and the correlation between the two was weak. Ki67 proliferation index alone has limited prognostic value, but combines with preoperative Ctn significantly optimize the prognostic assessment of patients.The role of Ki67 index varied at different Ctn levels.

Calcitonin-negative medullary thyroid carcinoma(CNMTC)is a rare subtype of medullary thyroid carcinoma,characterized by normal serum calcitonin levels,which often leads to misdiagnosis or missed diagnosis.The pathogenesis of CNMTC remains unclear and may involve impaired secretion mechanisms or assay-related false negatives.Diagnostic approaches include ultrasound-guided fine needle aspiration cytology,serum CEA and ProGRP measurements,and RET gene testing.Surgical resection remains the mainstay of treatment,while neoadjuvant therapy may be considered in selected cases.This review summarizes recent advances in the understanding,diagnosis,treatment,and prognosis of CNMTC,aiming to provide clinical guidance for better management of this challenging condition.

Objective To investigate the application effect of high flow humidified oxygen therapy combined with tracheotomy in elderly patients with cerebral hemorrhage and analyze the risk factors of pulmonary infection.Methods A total of 140 elderly patients with cerebral hemorrhage who underwent tracheotomy in our hospital from 2019 to 2023 were selected as the study objects,of which 93 patients receiving high-flow humidified oxygen therapy were selected as the observation group,and 47 patients receiving conventional low-flow oxygen therapy were selected as the control group during the same period.The changes of PaO2,SpO2,heart rate and mean arterial pressure were compared,and patients in the observation group were divided into infected group(n=26)and non-infected group(n=67)according to whether pulmonary infection occurred during hospitalization.The risk factors affecting pulmonary infection during hospitalization in elderly patients with cerebral hemorrhage were analyzed,and a nematographic prediction model was built to predict the risk of pulmonary infection.Results The PaO2 and SpO2 levels in observation group were higher than those in control group at 24 h and 72 h,but the respiratory rate was lower than that in control group(P＜0.05).The improvement of sputum viscosity in the observation group(68 cases of grade Ⅰ sputum and 25 cases of grade Ⅱ sputum)was better than that in the control group(16 cases of grade Ⅰ sputum,17 cases of grade Ⅱ sputum and 14 cases of gradeⅢ sputum).The rate of phlegm scab formation(0)and the number of sputum aspiration(5.15±1.08)times were lower than those in the control group[14.87％,(8.17±1.82)times](P＜0.05).There were significant differences in tracheotomy time,smoking history,bed rest time,mechanical ventilation time and nasal feeding tube retention time between infected and non-infected groups(P＜0.05).Logistic regression analysis showed that tracheotomy time＞5 d,smoking history,bed time＞10 d,mechanical ventilation time ≥24 h,nasal feeding tube retention time≥10 d were the risk factors for pulmonary infection in elderly patients with cerebral hemorrhage during treatment(P＜0.05).The AUC,sensitivity and specificity were 0.696,0.565 and 0.889 in elderly patients with cerebral hemorrhage complicated by pulmonary infection during treatment.Conclusion High-flow humidification oxygen therapy combined with tracheotomy can improve the oxygenation status in elderly patients with cerebral hemorrhage,but the time of tracheotomy,smoking history,bed rest time,mechanical ventilation time,and nasal feeding tube retention time will affect the pulmonary infection during treatment.The construction of a nomogram model based on these risk factors has higher predictive efficacy in evaluating the pulmonary infection.