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 investigate the efficacy and prognosis of different surgical approaches in sporadic medullary thyroid carcinoma.Methods:A retrospective analysis was conducted on 101 patients with sporadic medullary thyroid carcinoma (MTC) who underwent surgical treatment at the Department of Thyroid Surgery, China-Japan Union Hospital of Jilin University, from Feb. 2009 to Nov. 2023. The patients included 36 males and 75 females, with a male-to-female ratio of 1:2.1. The median age of the patients was 47 years old, with an age range of 21 to 72 years old. The study divided participants into two groups based on their surgical methods: an observation group (78 cases) and a control group (23 cases). The observation group received surgical methods in accordance with expert consensus, while the control group did not. The study compared the efficacy and prognosis of the two groups.Results:Statistical differences were found between the two groups in terms of stage II and III in TNM staging, intraoperative frozen pathological findings, number of lymph node resections in the central group, number of lymph node metastases in the central group, number of lymph node resections in the lateral cervical region, postoperative follow-up time, and five-year postoperative serum procalcitonin (Ctn) levels ( P<0.05) .Both groups of patients obtained a significant decrease in Ctn after surgical treatment. In the observation group, Ctn was at the remission level in 57 cases (73.1%), at the stable level in 13 cases (16.7%), and at the progression level in 8 cases (10.2%), while in the control group, Ctn was at the remission level in 20 cases (86.9%), at the progression level in 3 cases (13.1%), and there were no patients at the stable level after the operation.One patient (1.3 per cent) in the observation group had a recurrence after surgery; Two patients (8.7 per cent) in the control group had a recurrence. Conclusions:Standardised and thorough surgery can maximise the clearance of metastatic lymph nodes, effectively reduce the recurrence rate, achieve better efficacy, and improve the long-term prognosis of patients without increasing the risk of surgery and postoperative complications.

Posterior lumbar interbody fusion (PLIF) is currently well accepted and considered as safe and effective spinal surgical technique for the treatment of degenerative lumbar spondylolisthesis, and is widely used in clinical practice. But there are still some cases with poor overall postoperative efficacy. In order to discuss the relevant factors and mechanisms affecting the clinical outcomes of PLIF surgery, many scholars have conducted a large number of clinical studies over the years. However, due to the different methods and the factors among included studies, the conclusions reached were also different or even completely opposed. This article reviews the research results of various influencing factors of the postoperative efficacy of PLIF in recent years, and analyzes age, gender, body mass index, bone mineral density, duration of preoperative symptoms, whether the sliding vertebral body is reduced, spine-pelvic sagittal parameters (including lumbar lordosis, sacral slope, pelvic tilt, pelvic incidence, pelvic incidence-lumbar lordosis and Roussouly classification) and other factors (underlying diseases and poor lifestyle habits) on the clinical effects of PLIF, in order to provide a reference for further improving the postoperative quality of life and functional recovery of patients with degenerative lumbar spondylolisthesis.

Carcinoma-associated fibroblasts (CAFs) are the main cellular components of the tumor microenvironment and promote cancer progression by modifying the extracellular matrix (ECM). The tumor-associated ECM is characterized by collagen crosslinking catalyzed by lysyl oxidase (LOX). Small extracellular vesicles (sEVs) mediate cell-cell communication. However, the interactions between sEVs and the ECM remain unclear. Here, we demonstrated that sEVs released from oral squamous cell carcinoma (OSCC)-derived CAFs induce collagen crosslinking, thereby promoting epithelial-mesenchymal transition (EMT). CAF sEVs preferably bound to the ECM rather than being taken up by fibroblasts and induced collagen crosslinking, and a LOX inhibitor or blocking antibody suppressed this effect. Active LOX (αLOX), but not the LOX precursor, was enriched in CAF sEVs and interacted with periostin, fibronectin, and bone morphogenetic protein-1 on the surface of sEVs. CAF sEV-associated integrin α2β1 mediated the binding of CAF sEVs to collagen I, and blocking integrin α2β1 inhibited collagen crosslinking by interfering with CAF sEV binding to collagen I. CAF sEV-induced collagen crosslinking promoted the EMT of OSCC through FAK/paxillin/YAP pathway. Taken together, these findings reveal a novel role of CAF sEVs in tumor ECM remodeling, suggesting a critical mechanism for CAF-induced EMT of cancer cells.
Humans ; Paxillin/metabolism* ; Protein-Lysine 6-Oxidase/metabolism* ; Carcinoma, Squamous Cell/pathology* ; Epithelial-Mesenchymal Transition ; Integrin alpha2beta1/metabolism* ; Mouth Neoplasms/pathology* ; Collagen/metabolism* ; Fibroblasts ; Extracellular Vesicles/metabolism* ; Cell Line, Tumor ; Tumor Microenvironment

ObjectiveTo achieve high-dimensional prediction of class imbalanced of adverse drug reaction（ADR） of traditional Chinese medicine（TCM） and to classify and identify risk factors affecting the occurrence of ADR based on the post-marketing safety data of TCM monitored centrally in real world hospitals. MethodThe ensemble clustering resampling combined with regularized Group Lasso regression was used to perform high-dimensional balancing of ADR class-imbalanced data， and then to integrate the balanced datasets to achieve ADR prediction and the risk factor identification by category. ResultA practical example study of the proposed method on a monitoring data of TCM injection performed that the accuracy of the ADR prediction， the prediction sensitivity， the prediction specificity and the area under receiver operating characteristic curve（AUC） were all above 0.8 on the test set. Meanwhile， 40 risk factors affecting the occurrence of ADR were screened out from total 600 high-dimensional variables. And the effect of risk factors on the occurrence of ADR was identified by classification weighting. The important risk factors were classified as follows：past history， medication information， name of combined drugs， disease status， number of combined drugs and personal data. ConclusionIn the real world data of rare ADR with a large amount of clinical variables， this paper realized accurate ADR prediction on high-dimensional and class imbalanced condition， and classified and identified the key risk factors and their clinical significance of categories， so as to provide risk early warning for clinical rational drug use and combined drug use， as well as scientific basis for reevaluation of safety of post-marketing TCM.

Objective : To study the expression and clinical significance of Wnt signal secretory protein DKK1 in cervical cancer. Methods : Reverse transcription polymerase chain reaction (RT⁃PCR) was used to detect the expression of DKK1 mRNA in 30 pairs of cervical cancer tissues and adjacent normal tissues. The expression of DKK1 protein was detected by immunohistochemistry in 60 cases of cervical cancer and 30 cases of normal cervical tissue , and the relationship between the expression and clinicopathological characteristics of cervical cancer was analyzed. Results : The expression of DKK1 in cervical cancer tissues was lower than that in adjacent tissues and normal cervical tissues (P < 0. 05) . The expression of DKK1 was closely related to clinicopathological stage , tissue differentiation , lymph node metastasis and depth of invasion (P < 0. 05) . Conclusion The expression of DKK1 is low in cervical cancer and plays an important role in the occurrence and development of cervical cancer.

Objective:To investigate the significance of ventricular intracranial pressure monitoring in the treatment of traumatic multiple intracranial hematoma (TMIH).Methods:The clinical data of 14 TMIH patients treated with ventricular intracranial pressure monitoring from January 2016 to August 2021 in Beijing Luhe Hospital, Capital Medical University were analyzed retrospectively. The patients were followed up 6 months after injury, and the Glasgow outcome score (GOS) was assessed.Results:All the 14 patients successfully completed ventricular intracranial pressure probe placement. Among them, 8 patients recovered well after continuous monitoring of ventricular intracranial pressure and continuous cerebrospinal fluid drainage. Their ventricular intracranial pressure probe was placed for 5 to 10 (7.3 ± 2.2) d, with no intracranial infection occurred; and their GOS was 5 scores 6-month follow-up after injury. Six cases underwent craniotomy for hematoma removal due to the expansion of intracranial hematoma or aggravation of edema, and decompressive craniectomy was performed during the operation; 6-month follow-up after injury, GOS of 5 scores was in 3 cases, 4 scores in 2 cases, 3 scores in 1 case.Conclusions:The condition of TMIH patients is complex and changeable, and ventricular intracranial pressure monitoring can improve the prognosis of TMIH patients.

Sesamin, a lipid-soluble lignin originally isolated from sesame seeds, which induces cancer cell apoptosis and autophagy. In the present study, has been reported that sesamin induces apoptosis via several pathways in human lung cancer cells. However, whether mitophagy is involved in sesamin induced lung cancer cell apotosis remains unclear. This study, the anticancer activity of sesamin in lung cancer was studied by reactive oxygen species (ROS) and mitophagy. A549 cells were treated with sesamin, and cell viability, migration ability, and cell cycle were assessed using the CCK8 assay, scratch-wound test, and flow cytometry, respectively. ROS levels, mitochondrial membrane potential, and apoptosis were examined by flow cytometric detection of DCFH-DA fluorescence and by using JC-1 and TUNEL assays. The results indicated that sesamin treatment inhibited the cell viability and migration ability of A549 cells and induced G0/G1 phase arrest. Furthermore, sesamin induced an increase in ROS levels, a reduction in mitochondrial membrane potential, and apoptosis accompanied by an increase in cleaved caspase-3 and cleaved caspase-9. Additionally, sesamin triggered mitophagy and increased the expression of PINK1 and translocation of Parkin from the cytoplasm to the mitochondria. However, the antioxidant N-acetyl-L-cysteine clearly reduced the oxidative stress and mitophagy induced by sesamin. Furthermore, we found that cyclosporine A (an inhibitor of mitophagy) decreased the inhibitory effect of sesamin on A549 cell viability. Collectively, our data indicate that sesamin exerts lethal effects on lung cancer cells through the induction of ROS-mediated mitophagy and mitochondrial apoptosis.

Sesamin, a lipid-soluble lignin originally isolated from sesame seeds, which induces cancer cell apoptosis and autophagy. In the present study, has been reported that sesamin induces apoptosis via several pathways in human lung cancer cells. However, whether mitophagy is involved in sesamin induced lung cancer cell apotosis remains unclear. This study, the anticancer activity of sesamin in lung cancer was studied by reactive oxygen species (ROS) and mitophagy. A549 cells were treated with sesamin, and cell viability, migration ability, and cell cycle were assessed using the CCK8 assay, scratch-wound test, and flow cytometry, respectively. ROS levels, mitochondrial membrane potential, and apoptosis were examined by flow cytometric detection of DCFH-DA fluorescence and by using JC-1 and TUNEL assays. The results indicated that sesamin treatment inhibited the cell viability and migration ability of A549 cells and induced G0/G1 phase arrest. Furthermore, sesamin induced an increase in ROS levels, a reduction in mitochondrial membrane potential, and apoptosis accompanied by an increase in cleaved caspase-3 and cleaved caspase-9. Additionally, sesamin triggered mitophagy and increased the expression of PINK1 and translocation of Parkin from the cytoplasm to the mitochondria. However, the antioxidant N-acetyl-L-cysteine clearly reduced the oxidative stress and mitophagy induced by sesamin. Furthermore, we found that cyclosporine A (an inhibitor of mitophagy) decreased the inhibitory effect of sesamin on A549 cell viability. Collectively, our data indicate that sesamin exerts lethal effects on lung cancer cells through the induction of ROS-mediated mitophagy and mitochondrial apoptosis.

Objective To explore the effect of cerebrospinal fluid release combined with controlled decompression under intracranial pressure monitoring on prevention of intraoperative intracranial swelling in patients with acute severe craniocerebral injury. Methods According to the inclusion and exclusion criteria, 90 patients with acute severe craniocerebral injury were randomly divided into study group (48 cases) and control group (42 cases). Patients in the study group underwent ventricular intracranial pressure probe placement, and then the standard decompressive craniectomy. During the operation, cerebrospinal fluid release combined with controlled decompression under intracranial pressure monitoring was applied to prevent brain swelling. Patients in the control group underwent standard decompressive craniectomy combined with controlled decompression to prevent brain swelling. The incidence of intraoperative brain swelling and cerebral infarction within 3 d after surgery, and the mortality within 1 month after surgery were evaluated. Prognosis was evaluated by GOS score after 3 months of follow-up. Results The brain swelling rate, cerebral infarction rate, mortality within 1 month, and Glasgow Coma Scale (GOS) score at 3 months after operation in the study group were better than those in the control group with statistical significance:10.4％(5/48) vs. 28.6％(12/42), 29.2％(14/48) vs. 64.3％(27/42), 18.8％(9/48) vs. 35.7％(15/42)], (2.83 ± 1.08) scores vs.(1.83 ± 0.76) scores, P<0.05. Conclusions Cerebrospinal fluid release combined with controlled decompression under intracranial pressure monitoring can reduce the incidence of intraoperative brain swelling and improve the prognosis of patients with acute severe craniocerebral injury.