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 compare the contents of alkaloid in Aconiti Kusnezoffii Radix with different degrees of processing and their effects on electrocardiogram and vagus nerve action potential in SD rats;To establish a toxicity evaluation method for Aconiti Kusnezoffii Radix and its processed products.Methods HPLC was used to determine the contents of six alkaloid components,including benzoyl neoaconitine,benzoyl aconitine,benzoyl subeaconitine,neoaconitine,subeaconitine and aconitine in Aconiti Kusnezoffii Radix and Aconiti Kusnezoffii Radix Cocta of soaking and boiled for 30 minutes,boiled for 4 h without soaking,soaking and boiled for 4 h,and soaking and boiled for 8 h.SD rats were subjected to sublingual drainage with Aconiti Kusnezoffii Radix and four types of processed products.The vagus nerve action potential and electrocardiogram of rats before and after administration were recorded,and the correlation analysis between alkaloid content and vagus nerve action potential and heart rate was conducted.Results The contents of alkaloid of the four processed products showed that the content of diester alkaloids was soaking and boiled for 30 min>boiled for 4 h without soaking>soaking and boiled for 4 h>soaking and boiled for 8 h;monoester alkaloid content:boiled for 4 h without soaking>soaking and boiled for 30 min>soaking and boiled for 4 h>soaking and boiled for 8 h.After the administration of each sample,compared with the basal discharge,the vagus nerve discharge of rats with different processed products was changed by sublingual administration,heart rate increased,the degree of arrhythmia increased,and it varied with the degree of processing;the results of correlation analysis showed that there was a significant correlation between the nerve discharge area and the contents of diester alkaloids and total alkaloids.Conclusion The action potential of the vagus nerve and electrocardiogram of rats after sublingual drainage administration can reflect the degree of numbness in the tongue,which can provide reference for the study of tongue sensation of Aconiti Kusnezoffii Radix.

Background::Hypothermia therapy has been suggested to attenuate myocardial necrosis; however, the clinical implementation as a valid therapeutic strategy has failed, and new approaches are needed to translate into clinical applications. This study aimed to assess the feasibility, safety, and efficacy of a novel selective intracoronary hypothermia (SICH) device in mitigating myocardial reperfusion injury.Methods::This study comprised two phases. The first phase of the SICH was performed in a normal porcine model for 30 minutes ( n = 5) to evaluate its feasibility. The second phase was conducted in a porcine myocardial infarction (MI) model of myocardial ischemia/reperfusion which was performed by balloon occlusion of the left anterior descending coronary artery for 60 minutes and maintained for 42 days. Pigs in the hypothermia group ( n = 8) received hypothermia intervention onset reperfusion for 30 minutes and controls ( n = 8) received no intervention. All animals were followed for 42 days. Cardiac magnetic resonance analysis (five and 42 days post-MI) and a series of biomarkers/histological studies were performed. Results::The average time to lower temperatures to a steady state was 4.8 ± 0.8 s. SICH had no impact on blood pressure or heart rate and was safely performed without complications by using a 3.9 F catheter. Interleukin-6 (IL-6), tumor necrosis factor-α, C-reactive protein (CRP), and brain natriuretic peptide (BNP) were lower at 60 min post perfusion in pigs that underwent SICH as compared with the control group. On day 5 post MI/R, edema, intramyocardial hemorrhage, and microvascular obstruction were reduced in the hypothermia group. On day 42 post MI/R, the infarct size, IL-6, CRP, BNP, and matrix metalloproteinase-9 were reduced, and the ejection fraction was improved in pigs that underwent SICH.Conclusions::The SICH device safely and effectively reduced the infarct size and improved heart function in a pig model of MI/R. These beneficial effects indicate the clinical potential of SICH for treatment of myocardial reperfusion injury.

Objective To investigate the expression of OTU deubiquitinase 3(OTUD3)and interleukin en-hancer binding factor 2(ILF2)in esophageal squamous cell cancer and their correlation with clinicopathologi-cal characteristics and prognosis.Methods A total of 102 patients with esophageal squamous cell cancer who underwent radical resection in Huai'an Fifth People's Hospital between January 2019 and July 2020 were in-cluded in this study.Immunohistochemistry was used to detect OTUD3 and ILF2 expression.Spearman rank correlation analysis was conducted to assess the relationship between OTUD3 and ILF2.Kaplan-Meier surviv-al curves were used to analyze the impact of OTUD3 and ILF2 expression on patient survival prognosis.COX regression analysis was employed to identify prognostic factors.Results Compared with adjacent tissues,the positive rate of OTUD3 was lower and the positive rate of ILF2 was higher in esophageal squamous cell cancer tissues,and the differences were statistically significant(P＜0.05).A significant negative correlation was ob-served between the expression of OTUD3 and ILF2 in esophageal squamous cell cancer(r=-0.712,P＜0.001).Furthermore,patients with TNM stage Ⅲ,low differentiation,and lymph node metastasis exhibited a lower positive rate of OTUD3 and a higher positive rate of ILF2 compared to patients with TNM stage Ⅰ-Ⅱ,medium-high differentiation,and no lymph node metastasis(P＜0.05).The 3-year survival rate for the OTUD3-positive group was significantly higher than that of the OTUD3-negative group(Log-rank x2=5.869,P=0.015).The 3-year survival rate for the ILF2-positive group was significantly lower than that of the ILF2-negative group(Log-rank x2=16.257,P＜0.001).TNM staging,lymph node metastasis,degree of differentiation,OTUD3,and ILF2 were independent factors affecting the prognosis of esophageal squamous cell cancer patients.Conclusion Decreased expression of OTUD3 and increased expression of ILF2 in esopha-geal squamous cell cancer tissues are implicated in the malignant progression of esophageal squamous cell cancer and serve as independent factors affecting patient outcomes.

Antibiotics are playing an increasingly important role in clinical antibacterial applications. However, their abuse has also brought toxic and side effects, drug-resistant pathogens, decreased immunity and other problems. New antibacterial schemes in clinic are urgently needed. In recent years, nano-metals and their oxides have attracted wide attention due to their broad-spectrum antibacterial activity. Nano-silver, nano-copper, nano-zinc and their oxides are gradually applied in biomedical field. In this study, the classification and basic properties of nano-metallic materials such as conductivity, superplasticity, catalysis, and antibacterial activities were firstly introduced. Secondly, the common preparation techniques, including physical, chemical and biological methods, were summarized. Subsequently, four main antibacterial mechanisms, such as cell membrane, oxidative stress, DNA destruction and cell respiration reduction, were summarized. Finally, the effect of size, shape, concentration and surface chemical characteristics of nano-metals and their oxides on antibacterial effectiveness and the research status of biological safety such as cytotoxicity, genotoxicity and reproductive toxicity were reviewed. At present, although nano-metals and their oxides have been applied in medical antibacterial, cancer treatment and other clinical fields, some issues such as the development of green preparation technology, the understanding of antibacterial mechanism, the improvement of biosafety, and the expansion of application fields, require further exploration.
Oxides/chemistry* ; Metal Nanoparticles/chemistry* ; Anti-Bacterial Agents/chemistry* ; Zinc ; Copper

In recent years， the increasing scale and scope of public health emergencies have brought serious challenges to China's health emergency system. It is in urgent need to develop the existing health emergency system toward the goal of multi-industry， multi-discipline， multi-professional and multi-regional， while the concept of standardization is essential to achieve this goal. This article describes the construction process of health emergency standardization system by the World Health Organization， the International Organization for Standardization， the United States， and China； analyzes the problems of China's health emergency standardization system by comparing the system between China and the United States， proposes the construction dimensions of China's health emergency standard system， and suggests development strategies targeting the shortcomings of China's health emergency standardization.

Objective:To explore the effects of LncRNA HCG18 on endoplasmic reticulum stress and autophagy via regulating miR-185-5p/AGER axis in diabetic nephropathy (DN) .Methods:The kidney tissues of patients with DN were collected and the podocyte injury model induced by high glucose (HG) was established. The expression of HCG18 in renal tissue in DN patients and cell model was detected. The localization and expression of HCG18 in cells were determined. The regulatory relationship between HCG18 and miR-185-5p, miR-185-5p and AGER was testified. QRT-PCR and western blot were used to detect the expression of endoplasmic reticulum stress related factors (CHOP, XBP1) and autophagy related factors (Beclin-1, p62) .Results:Compared with non-DN patients, HCG18 was overexpressed in renal tissue of DN patients ( P<0.05) . Compared with normal glucose (NG) group, mRNA and protein expression of endoplasmic reticulum stress related factors (CHOP, XBP1) were overexpressed but mRNA and protein expression of autophagy related factors Beclin-1 were inhibited, p62 mRNA and protein expression were increased (all P<0.05) . HCG18 regulated the miR-185-5p/AGER axis and played a biological role. Knocking down of HCG18 reduced endoplasmic reticulum stress, activated autophagy and reduced podocyte injury, but this effect can be partially reversed by miR-185-5p inhibitors. Conclusion:HCG18 regulates the miR-185-5p/AGER signal axis and promotes DN progression through regulating endoplasmic reticulum stress and autophagy.

Objective:To explore how to enhance the strength of science and technology of research-oriented hospital using goal management, thereby effectively promoting the construction and development of research hospitals.Methods:This paper studies the goal management measures and their effectiveness through data analysis, analyzes the problems of scientific research, goal management measures and changes in scientific research before and after the implementation measures over the years.Results:The goal management significantly enhances the scientific and technological strength. Total amount of research funding kept increasing year by year. Goal accountability management effectively improve the participation in individual scientific research activities. The implementation of high-quality papers goal management has a significant role in promoting the researchers to publish their achievements in domestic journals with international influence.Conclusions:Goal management plays an important role in the improvement of the scientific and technological strength of the hospital, which can effectively promote the construction and development of the research-oriented hospitals connotation. Goal management can serve as a powerful grasper for the research-oriented hospital to improve the scientific research capacity.

Objective:To explore the feasibility and preliminary effect of improving the comprehensive quality of medical students by introducing the teaching model of cleft lip and palate treatment platform in medical education.Methods:A total of 40 grade two undergraduates of Shantou University medical college were randomly divided into experimental group ( n=20) and control group ( n=20). The students in the experimental group were the volunteers of Cleft lip and palate treatment center, receiving the characteristic idea and methods in clinical teaching. The control group received conventional teaching. The evaluation indicators, including the intellectual quality (60 points), moral quality (15 points), humanistic quality (5 points), physical and mental quality (10 points), social practice (10 points), were quantified by fuzzy evaluation method and a professional evaluation team was set up to evaluate the effect of teaching. SPSS 19.0 was used to perform t test for comparison between the two groups. Results:The average scores of the above items in the experimental group were respectively (51.477±2.381), (10.613±0.169), (4.228±0.124), (8.677±0.296), and (8.565±0.421), and the average total score was (83.559±2.333); the average scores of above items in the control group were respectively (49.746±3.176), (10.268±0.266), (4.008±0.195), (8.207±0.354), and (7.575±0.321), and the average total score was (79.804±3.510). Statistical difference was found in all scores except the intellectual quality score between the two group ( P<0.05). Conclusion:Though no significant difference was found in the intellectual quality, the other qualities have played important roles in improving medical students' comprehensive quality. It is significant to improve the medical students' comprehensive quality by the method of cleft lip and palate treatment platform.