Objective:To explore the effect of insulin-like growth factor 2 ( IGF2) mRNA binding protein 2 (IGF2BP2) inhibitor CWI1-2 on migration and invasion of glioma cells SHG-140 and LN229 as well as their resistance to temozolomide (TMZ). Methods:(1) SHG-140 and LN229 glioma cell lines were cultured in vitro; cell counting kit-8 (CCK-8) assay was used to detect the effects of 0.1, 0.2, 0.5, 1.0, 2, and 5 μmol/L CWI1-2 on survival rate of the two cell lines at 24 and 48 hours after treatment, and the best concentration and treatment time of CWI1-2 were screened. SHG-140 and LN229 cells were categorized into control group, 0.5 μmol/L CWI1-2 group, and 1.0 μmol/L CWI1-2 group, respectively, and equal amount of medium, 0.5 μmol/L CWI1-2 and 1.0 μmol/L CWI1-2 were added into the cells for 24 hours; Western blotting and immunofluorescent staining were used to detect the IGF2BP2 protein expression; cell scratch assay and Transwell assay were, respectively, used to detect the cell migration and invasion. (2) CCK-8 assay was employed to detect the effects of 100, 200, 400, 600, 800, and 1000 μmol/L TMZ on survival rate of SHG-140 and LN229 cells at 24 and 48 hours after treatment, and the best concentration and treatment time of TMZ were screened. SHG-140 and LN229 cells were categorized into control group, CWI1-2 group, TMZ group, and TMZ+CWI1-2 group, respectively, and equal amounts of culture medium, 0.5 μmol/L CWI1-2, 200 μmol/L TMZ, and 0.5 μmol/L CWI1-2+200 μmol/L TMZ were added into the 4 groups for 24 hours, respectively; colony formation assay was used to detect the colony formation rate and CCK-8 assay was utilized to determine the proliferation rate. Results:(1) CCK-8 results indicated that, compared with the 0.1 and 0.2 μmol/L CWI1-2 groups, SHG-140 and LN229 cells in the 0.5, 1.0, 2, and 5 μmol/L CWI1-2 groups had significantly lower survival rate at 24 and 48 hours after treatment ( P<0.05); furthermore, the survival rate in the SHG-140 and LN229 cells of the 0.5, 1.0, 2, and 5 μmol/L CWI1-2 groups decreased successively, with statistical differences ( P<0.05); therefore, 0.5 μmol/L and 1 μmol/L CWI1-2 for 24 hours with less effect on survival rate were selected for subsequent experiments. Western blotting results showed that, compared with the control group (1.27±0.05), the SHG-140 cells in 0.5 and 1.0 μmol/L CWI1-2 groups had significantly lower IGF2BP2 protein expression (0.91±0.09, 0.79±0.10; P<0.05); compared with the control group and 0.5 μmol/L CWI1-2 group (0.82±0.09, 0.82±0.04), the LN229 cells in 1.0 μmol/L CWI1-2 group had significantly lower IGF2BP2 protein expression (0.33±0.02, P<0.05). Immunofluorescent staining results showed that, compared with the control group, the 0.5 and 1.0 μmol/L CWI1-2 groups had obviously decreased IGF2BP2 protein immunofluorescent intensity. Cell scratch assay results showed that, compared with the control group, the SHG-140 cells in 0.5 and 1.0 μmol/L CWI1-2 groups had significantly lower migration rate ( P<0.05); the migration rate in LN229 cells of the control group, 0.5 μmol/L CWI1-2 group and 1.0 μmol/L CWI1-2 group decreased successively, with statistical differences ( P<0.05). Transwell assay results showed that the number of transmembrane SHG-140 and LN229 cells in the control group, 0.5 μmol/L CWI1-2 group and 1.0 μmol/L CWI1-2 group decreased successively, with significant differences ( P<0.05). (2) CCK-8 assay results showed that compared with the 100 and 200 μmol/L TMZ groups, SHG-140 and LN229 cells in the 400, 600, 800 and 1000 μmol/L TMZ groups had statistically lower survival rate at 24 and 48 hours after treatment ( P<0.05); therefore, concentration with less effect on cell survival rate (200 μmol/L TMZ) was selected for subsequent experiments. The cell colony formation rate of SHG-140 and LN229 cells in the control group, CWI1-2 group, TMZ group and TMZ+CWI1-2 group decreased successively, with significant differences ( P<0.05). Cell proliferation rate of LN229 cells in the control group, CWI1-2 group, TMZ group and TMZ+CWI1-2 group decreased successively, with significant differences ( P<0.05). Conclusion:CWI1-2 can inhibit the proliferation and invasion of glioma cells, and can also increase the killing effect of TMZ on glioma cells.

Objective:To explore the effect of insulin-like growth factor 2 ( IGF2) mRNA binding protein 2 (IGF2BP2) inhibitor CWI1-2 on migration and invasion of glioma cells SHG-140 and LN229 as well as their resistance to temozolomide (TMZ). Methods:(1) SHG-140 and LN229 glioma cell lines were cultured in vitro; cell counting kit-8 (CCK-8) assay was used to detect the effects of 0.1, 0.2, 0.5, 1.0, 2, and 5 μmol/L CWI1-2 on survival rate of the two cell lines at 24 and 48 hours after treatment, and the best concentration and treatment time of CWI1-2 were screened. SHG-140 and LN229 cells were categorized into control group, 0.5 μmol/L CWI1-2 group, and 1.0 μmol/L CWI1-2 group, respectively, and equal amount of medium, 0.5 μmol/L CWI1-2 and 1.0 μmol/L CWI1-2 were added into the cells for 24 hours; Western blotting and immunofluorescent staining were used to detect the IGF2BP2 protein expression; cell scratch assay and Transwell assay were, respectively, used to detect the cell migration and invasion. (2) CCK-8 assay was employed to detect the effects of 100, 200, 400, 600, 800, and 1000 μmol/L TMZ on survival rate of SHG-140 and LN229 cells at 24 and 48 hours after treatment, and the best concentration and treatment time of TMZ were screened. SHG-140 and LN229 cells were categorized into control group, CWI1-2 group, TMZ group, and TMZ+CWI1-2 group, respectively, and equal amounts of culture medium, 0.5 μmol/L CWI1-2, 200 μmol/L TMZ, and 0.5 μmol/L CWI1-2+200 μmol/L TMZ were added into the 4 groups for 24 hours, respectively; colony formation assay was used to detect the colony formation rate and CCK-8 assay was utilized to determine the proliferation rate. Results:(1) CCK-8 results indicated that, compared with the 0.1 and 0.2 μmol/L CWI1-2 groups, SHG-140 and LN229 cells in the 0.5, 1.0, 2, and 5 μmol/L CWI1-2 groups had significantly lower survival rate at 24 and 48 hours after treatment ( P<0.05); furthermore, the survival rate in the SHG-140 and LN229 cells of the 0.5, 1.0, 2, and 5 μmol/L CWI1-2 groups decreased successively, with statistical differences ( P<0.05); therefore, 0.5 μmol/L and 1 μmol/L CWI1-2 for 24 hours with less effect on survival rate were selected for subsequent experiments. Western blotting results showed that, compared with the control group (1.27±0.05), the SHG-140 cells in 0.5 and 1.0 μmol/L CWI1-2 groups had significantly lower IGF2BP2 protein expression (0.91±0.09, 0.79±0.10; P<0.05); compared with the control group and 0.5 μmol/L CWI1-2 group (0.82±0.09, 0.82±0.04), the LN229 cells in 1.0 μmol/L CWI1-2 group had significantly lower IGF2BP2 protein expression (0.33±0.02, P<0.05). Immunofluorescent staining results showed that, compared with the control group, the 0.5 and 1.0 μmol/L CWI1-2 groups had obviously decreased IGF2BP2 protein immunofluorescent intensity. Cell scratch assay results showed that, compared with the control group, the SHG-140 cells in 0.5 and 1.0 μmol/L CWI1-2 groups had significantly lower migration rate ( P<0.05); the migration rate in LN229 cells of the control group, 0.5 μmol/L CWI1-2 group and 1.0 μmol/L CWI1-2 group decreased successively, with statistical differences ( P<0.05). Transwell assay results showed that the number of transmembrane SHG-140 and LN229 cells in the control group, 0.5 μmol/L CWI1-2 group and 1.0 μmol/L CWI1-2 group decreased successively, with significant differences ( P<0.05). (2) CCK-8 assay results showed that compared with the 100 and 200 μmol/L TMZ groups, SHG-140 and LN229 cells in the 400, 600, 800 and 1000 μmol/L TMZ groups had statistically lower survival rate at 24 and 48 hours after treatment ( P<0.05); therefore, concentration with less effect on cell survival rate (200 μmol/L TMZ) was selected for subsequent experiments. The cell colony formation rate of SHG-140 and LN229 cells in the control group, CWI1-2 group, TMZ group and TMZ+CWI1-2 group decreased successively, with significant differences ( P<0.05). Cell proliferation rate of LN229 cells in the control group, CWI1-2 group, TMZ group and TMZ+CWI1-2 group decreased successively, with significant differences ( P<0.05). Conclusion:CWI1-2 can inhibit the proliferation and invasion of glioma cells, and can also increase the killing effect of TMZ on glioma cells.

Objective:To summarize the best evidence for the prevention and management of oral mucosal pressure injury (OMPI) in severe neurological patients with tracheal intubation.Methods:The clinical decisions, guidelines, expert consensus, evidence summary, systematic reviews, and clinical practice regarding the prevention and management of OMPI in severe neurological patients with tracheal intubation were searched in domestic and foreign databases, guideline websites, and professional association websites. The search period was from database establishment to May 30, 2023. Four researchers who undergone systematic evidence-based training conducted literature quality evaluation and evidence extraction.Results:A total of 15 articles were included, including three evidence summaries, three systematic reviews, two guidelines, three clinical practices, three expert consensus, and one clinical decision. A total of 27 pieces of best evidence were summarized from six aspects of risk assessment, oral mucosal assessment, oral nursing, tracheal intubation management, nutritional support, and organizational training.Conclusions:The best evidence for the prevention and management of OMPI in severe neurological patients with tracheal intubation summarized provides evidence-based evidence for medical and nursing staff to prevent and manage OMPI in severe neurological patients with tracheal intubation.

Objective To investigate the current status of application of the Confusion assessment method for the Intensive Care Unit (Cam-ICU),and to explore its influencing factors.Methods A total of 300 patients admitted to were enrolled.The researchers and nurses used Cam-ICU to assess patients' delirium,respectively,and the differences in deliriun assessment were analyzed.Results For delirium assessment,the Kappa value was 0.546 between the researchers and nurses.The consensus rate was 17.6％ for hypoactive delirium,and 77.8％ for hyperactive delirium in 44 delirium patients.Logistic regression analysis showed that APACHE Ⅱ score,RASS score and delirium type were influencing factors of accurate assessment of delirium.Conclusion The consistence of assessment of delirium by ICU nurses is generally good,but the accuracy of assessment of hypoactive delirium is the worst.

Objective To investigate the regulating mechanism of Notch1 signaling pathway on the invasion and migration ofglioma initiating cells (GICs).Methods (1) Box-plotting was conducted to analyze the mRNA expression of Notch1 in normal brain tissue and glioblastoma tissue using Bredel Brain,Sun Brain and TCGA databases;Kaplan-Meier survival analysis was conducted to analyze the association between the prognosis of glioma patients with the expression of Hes1 in TCGA database;Heatmap was conducted to analyze the expression of Notch1 and CXCR4 in GICs and common cell line in GEO database.(2) Magnetic activated cell sorting was adopted to establish cell lines of U87 GICs and U251 GICs;immunofluorescence staining was used to detect expression of CXCR4 and Notch1.After the cell lines of U87 GICs and U251 GICs were divided into DMSO,shNC,MK0752 and shNotchl groups,the shNotch1 and shNC groups were transfected respectively with recombinant lentivirus of Notch1-shRNA and its control sequence while the MK0752 and DMSO groups were added respectively with MK-0752 of 80 nmol/mL and the same amount of DMSO.The protein expression of Notch1,CXCR4 and p-mTOR was detected by Westem blotting in the 4 groups.The capabilities of invasion and migration of the GICs were detected by Transwell assay in the shNotch1 and shNC groups.Results (1) The box-plotting showed the mRNA expression of Notch 1 in the glioblastoma tissue was significantly higher than in the normal brain tissue (P＜0.05).The Kaplan-Meier survival analysis showed that the life span ofglioma patients with high expression of Hes1 was significantly shorter than that of those with low expression of Hes1 (P＜0.05).Heatmaps showed that the expression levels of Notch1 and CXCR4 in GICs were higher than in the common cell line.(2) The immunofluorescence staining showed that Notch1 and CXCR4 were highly expressed and colocalized in cell lines of U87 GICs and U251 GICs.The Western blotting showed that the protein expression of Notch1,CXCR4 and p-mTOR in the cell lines of U87GICs and U251 GICs in the MK0752 and shNotch1 groups was lower than that in the DMSO and shNC groups.Transwell assay showed that the penetrating-membrane cells per visual field in the shNotch1group were significantly fewer than those in the shNC group (P＜0.05).Conclusion Notch1 signaling pathway can promote invasion and migration of GICs through regulating CXCR4 expression.

Tumor immunotherapy refers to the application of immunological principles and methods to stimulate and enhance the body's antitumor immune response as well as assist the immune system to kill tumors and inhibit tumor growth.These methods in-volve injecting immune cells and effector molecules into the host.Immunotherapy,especially immunoprecipitation treatment,has ex-erted a strong antitumor effect on melanoma,renal cell carcinoma,non-small cell lung cancer,and hematological malignancies.This method has also received widespread attention.However,in malignant glioma,immunotherapy is still in its infancy.Numerous clinical trials have shown that immunotherapy for glioma is feasible and safe.This paper reviews the latest advances in immunization strate-gies,such as immunological checkpoints,adoptive immunotherapy,and tumor vaccines,to provide new ideas for glioma treatment.

One of the primary purposes of the innovative development of ethnomedicines is to use their excellent safety and significant efficacy to serve a broader population.To achieve this purpose,modern scientific and technological means should be referenced,and relevant national laws and regulations as well as technical guides should be strictly followed to develop standards and to perform systemic research in producing ethnomedicines.Finally,ethnomedicines,which are applied to a limited extent in ethnic areas,can be transformed into safe,effective,and quality-controllable medical products to relieve the pain of more patients.The innovative development path of ethnomedicines includes the following three primary stages:resource study,standardized development research,and industrialization of the achievements and efforts for internationalization.The implementation of this path is always guaranteed by the research and development platform and the talent team.This article is based on the accumulation of long-term practice and is combined with the relevant disciplines,laws and regulations,and technical guidance from the research and development of ethnomedicines.The intention is to perform an in-depth analysis and explanation of the major research thinking,methods,contents,and technical paths involved in all stages of the innovative development path of ethnomedicines to provide useful references for the development of proper ethnomedicine use.