Although cancer immunotherapy has made great strides in the clinic, it is still hindered by the tumor immunosuppressive microenvironment (TIME). The stimulator of interferon genes (STING) pathway which can modulate TIME effectively has emerged as a promising therapeutic recently. However, the delivery of most STING agonists, specifically cyclic dinucleotides (CDNs), is performed intratumorally due to their insufficient pharmacological properties, such as weak permeability across cell membranes and vulnerability to nuclease degradation. To expand the clinical applicability of CDNs, a novel pH-sensitive polycationic polymer-modified lipid nanoparticle (LNP-B) system was developed for intravenous delivery of CDNs. LNP-B significantly extended the circulation of CDNs and enhanced the accumulation of CDNs within the tumor, spleen, and tumor-draining lymph nodes compared with free CDNs thereby triggering the STING pathway of dendritic cells and repolarizing pro-tumor macrophages. These events subsequently gave rise to potent anti-tumor immune reactions and substantial inhibition of tumors in CT26 colon cancer-bearing mouse models. In addition, due to the acid-sensitive property of the polycationic polymer, the delivery system of LNP-B was more biocompatible and safer compared with lipid nanoparticles formulated with an indissociable cationic DOTAP (LNP-D). These findings suggest that LNP-B has great potential in the intravenous delivery of CDNs for tumor immunotherapy.

In the process of conducting implementation research on health service issues, stakeholders' preference for contents related to evidence-based practice (EBP) and implementation strategies is closely related to whether EBP can be effectively implemented.However, multiple preference assessment methods exist, each with their own strengths, weaknesses, and application scenarios, which makes it challenging for researchers to select appropriate and effective preference assessment methods. This paper aims to review the origins, characteristics, and application scenarios of commonly used preference assessment methods, with the hope of providing valuable reference and lessons for domestic scholars to select and apply appropriate preference assessment methods in implementation research.

In the process of conducting implementation research on health service issues, stakeholders' preference for contents related to evidence-based practice (EBP) and implementation strategies is closely related to whether EBP can be effectively implemented.However, multiple preference assessment methods exist, each with their own strengths, weaknesses, and application scenarios, which makes it challenging for researchers to select appropriate and effective preference assessment methods. This paper aims to review the origins, characteristics, and application scenarios of commonly used preference assessment methods, with the hope of providing valuable reference and lessons for domestic scholars to select and apply appropriate preference assessment methods in implementation research.

Objective To analyze the risk factors of nosocomial infection among the patients in neuro-surgical ICU,and to construct the risk prediction model to provide reference for the prediction of nosocomial infection in neurosurgical ICU patients.Methods The clinical data of 280 patients admitted and treated in the neurosurgery ICU of this hospital from January 2021 to December 2022 were retrospectively analyzed.The pa-tients were divided into the infection group and non-infection group based on whether or not nosocomial infec-tion occurring,140 cases in each group.A total of 196 patients were extracted as the training set by a ratio of 7︰3 for constructing the model,while the remaining 84 patients served as the validation set for conducting the internal verification.The logistic regression was used to analyze the risk factors of nosocomial infection in the neurosurgery ICU patients,and a predictive model was established.The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive effect of the model.Results The multivariate logistic re-gression analysis indicated that old age,long surgery time,catheter use and glucocorticoids use were screened as the main risk factors of nosocomial infection occurrence in neurosurgery ICU patients.The nomogram mod-el was constructed based on the results of multivariate analysis,the area under the curve of training set and validation set were 0.796 and 0.875,respectively.The correcting model reflected good consistency between actual diagnosis and predictive diagnosis.Conclusion The model constructed in this study has the high predic-tive value for the nosocomial infection occurrence risk in the patients of the neurosurgery ICU.

Purpose: Knowing the distinction between benign and borderline/malignant phyllodes tumors (PTs) can help in the surgical treatment course. Herein, we investigated the value of magnetic resonance imaging-based texture analysis (MRI-TA) in differentiating between benign and borderline/malignant PTs. Methods: Forty-three women with 44 histologically proven PTs underwent breast MRI before surgery and were classified into benign (n = 26) and borderline/malignant groups (n = 18 [15 borderline, 3 malignant]). Clinical and routine MRI parameters (CRMP) and MRI-TA were used to distinguish benign from borderline/malignant PT. In total, 298 texture parameters were extracted from fat-suppression (FS) T2-weighted, FS unenhanced T1-weighted, and FS first-enhanced T1-weighted sequences. To evaluate the diagnostic performance, receiver operating characteristic curve analysis was performed for the K-nearest neighbor classifier trained with significantly different parameters of CRMP, MRI sequence-based TA, and the combination strategy. Results: Compared with benign PTs, borderline/malignant ones presented a higher local recurrence (p = 0.045); larger size (p < 0.001); different time-intensity curve pattern (p = 0.010); and higher frequency of strong lobulation (p = 0.024), septation enhancement (p = 0.048), cystic component (p = 0.023), and irregular cystic wall (p = 0.045). TA of FS T2-weighted images (0.86) showed a significantly higher area under the curve (AUC) than that of FS unenhanced T1-weighted (0.65, p = 0.010) or first-enhanced phase (0.72, p = 0.049) images. The texture parameters of FS T2-weighted sequences tended to have a higher AUC than CRMP (0.79, p = 0.404). Additionally, the combination strategy exhibited a similar AUC (0.89, p = 0.622) in comparison with the texture parameters of FS T2-weighted sequences. Conclusion MRI-TA demonstrated good predictive performance for breast PT pathological grading and could provide surgical planning guidance. Clinical data and routine MRI features were also valuable for grading PTs.

Purpose: Temozolomide is used in first-line treatment for glioblastoma. However, chemoresistance to temozolomide is common in glioma patients. In addition, mechanisms for the anti-tumor effects of temozolomide are largely unknown. Ferroptosis is a form of programmed cell death triggered by disturbed redox homeostasis, overloaded iron, and increased lipid peroxidation. The present study was performed to elucidate the involvement of ferroptosis in the anti-tumor mechanisms of temozolomide. Materials and Methods: We utilized the CCK8 assay to evaluate cytotoxicity. Levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), iron, and glutathione (GSH) were measured. Flow cytometry and fluorescence microscope were used to detect the production of reactive oxygen species (ROS). Western blotting, RT-PCR and siRNA transfection were used to investigate molecular mechanisms. Results: Temozolomide increased the levels of LDH, MDA, and iron and reduced GSH levels in TG905 cells. Furthermore, we found that ROS levels and DMT1 expression were elevated in TG905 cells treated with temozolomide and were accompanied by a decrease in the expression of glutathione peroxidase 4, indicating an iron-dependent cell death, ferroptosis. Our results also showed that temozolomide-induced ferroptosis is associated with regulation of the Nrf2/HO-1 pathway. Conversely, DMT1 knockdown by siRNA evidently blocked temozolomide-induced ferroptosis in TG905 cells. Conclusion Taken together, our findings indicate that temozolomide may suppress cell growth partly by inducing ferroptosis by targeting DMT1 expression in glioblastoma cells.

Purpose: Temozolomide is used in first-line treatment for glioblastoma. However, chemoresistance to temozolomide is common in glioma patients. In addition, mechanisms for the anti-tumor effects of temozolomide are largely unknown. Ferroptosis is a form of programmed cell death triggered by disturbed redox homeostasis, overloaded iron, and increased lipid peroxidation. The present study was performed to elucidate the involvement of ferroptosis in the anti-tumor mechanisms of temozolomide. Materials and Methods: We utilized the CCK8 assay to evaluate cytotoxicity. Levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), iron, and glutathione (GSH) were measured. Flow cytometry and fluorescence microscope were used to detect the production of reactive oxygen species (ROS). Western blotting, RT-PCR and siRNA transfection were used to investigate molecular mechanisms. Results: Temozolomide increased the levels of LDH, MDA, and iron and reduced GSH levels in TG905 cells. Furthermore, we found that ROS levels and DMT1 expression were elevated in TG905 cells treated with temozolomide and were accompanied by a decrease in the expression of glutathione peroxidase 4, indicating an iron-dependent cell death, ferroptosis. Our results also showed that temozolomide-induced ferroptosis is associated with regulation of the Nrf2/HO-1 pathway. Conversely, DMT1 knockdown by siRNA evidently blocked temozolomide-induced ferroptosis in TG905 cells. Conclusion Taken together, our findings indicate that temozolomide may suppress cell growth partly by inducing ferroptosis by targeting DMT1 expression in glioblastoma cells.

Objective To compare the clinical effects between laparoscopic radical resection combined with radiofrequency ablation (RFA) and open radical resection for colorectal liver metastases.Methods The retrospective cohort study was conducted.The clinicopathological data of 120 colorectal liver metastases patients who were admitted to the Mengchao Hepatobiliary Hospital of Fujian Medical University (80 patients) and the Third Mfiliated Hospital of Chongqing Medical University (40 patients) between September 2012 and April 2017 were collected.Sixty patients undergoing laparoscopic radical resection of colorectal cancer combined with RFA of liver metastases were allocated into the laparoscopy with RFA group,and 60 undergoing open radical resection of colorectal liver metastases were allocated into the open group.Observation indicators:(1) surgical and postoperative situations;(2) follow-up and survival situations.Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival up to May 2017.Measurement data with normal distribution were represented as x±s,and comparisons between groups were analyzed using independent-sample t test.Measurement data with skewed distribution were described as M (range).Comparisons of count data were analyzed using chi-square test or Fisher exact probability.The repeated measures data were analyzed using the repeated measures ANOVA.The survival curve and rate were respectively drawn and calculated by the Kaplan-Meier method,and the Log-rank test was used for survival analysis.Results (1) Surgical and postoperative situations:① All the patients underwent successful surgery,without conversion to open surgery in the laparoscopy with RFA group.Operation time,volume of intraoperative blood loss,cases with overall complications,death,abdominal pain,nausea and vomiting,liver dysfunction,pleural effusion,non-calculus cholecystitis and peptic ulcer and duration of postoperative hospital stay were respectively (135±34)minutes,(451±197)mL,31,0,18,6,6,4,3,2,(13±4)days in the laparoscopy with RFA group and (165±49)minutes,(794±204)mL,42,1,15,9,10,11,5,5,(19±4)days in the open group,with statistically significant differences in operation time,volume of intraoperative blood loss,cases with overall complications and duration of postoperative hospital stay between groups (t =3.983,9.394,x2 =4.232,t =9.148,P＜0.05),and no statistically significant differences in cases with death,abdominal pain,nausea and vomiting,liver dysfunction,pleural effusion,non-calculus cholecystitis and peptic ulcer between groups x2 =0.376,0.686,1.154,3.733,0.134,0.607,P＞0.05).() Levels of alanine aminotransferase (ALT),total bilirubin (TBil) and prothronbin time (PT) before operation,at day 1 and 3 postoperatively were respectively (70±9)U/L,(399±36)U/L,(231±19) U/L,(21±3) μmol/L,(26±3) μmol/L,(23±5) μmol/L,(17.3±2.4) seconds,(20.2-±4.4) seconds,(18.9±2.8) seconds in the laparoscopy with RFA group and (68± 8) U/L,(412±39)U/L,(253±22)U/L,(21±4)μmol/L,(28±4)μmol/L,(27±8)μmol/L,(16.6±3.0)seconds,(22.1±5.2) seconds,(20.1± 4.4)seconds in the open group,with statistically significant differences in the levels of ALT,TBil and PT before operation,at day 1 and 3 postoperatively between groups (F=16.727,13.115,4.194,P＜0.05).(2) Follow-up and survival situations:120 patients were followed up for 7-24 months,with a median time of 20 months.The postoperative 1-and 2-year tumor-free survival rates,1-and 2-year overall survival rates were respectively 23.3％,11.9％,85.0％,40.0％ in the laparoscopy with RFA group and 20.0％,12.8％,83.3％,38.3％ in the open group,with no statistically significant difference in above indicators between groups (x2 =0.145,0.069,0.012,0.196,P＞0.05).Further analysis showed that postoperative 2-year overall survival rate of patients with 1,2,3 and ＞3 liver metastasis lesions were respectively 53.3％,38.2％,40.0％,16.7％ in the laparoscopy with RFA group and 50.0％,35.7％,40.0％,15.4％ in the open group,with a statistically significant difference in 2-year survival rate of patients with different liver metastasis lesions in the laparoscopy with RFA group (x2 =20.949,P＜0.05) and in the open group (x2 ＝ 21.349,P＜0.05).Conclusion There are some advantages of fewer traumas,less complications,faster postoperative recovery and minimally invasive in laparoscopic radical resection combined with RFA for colorectal liver metastases,meanwhile,less liver metastasis lesions and better prognosis are found.

Objective To observe the degradation time and the intimal hyperplasia of biodegradable magnesium alloy stent (MPM) implanted in the abdominal aorta of experimental rabbits.Methods A total of 24 New Zealand white rabbits were randomly divided into four groups (30 d,60 d,90 d and 180 d) with 6 rabbits in each group.In cach rabbit one MPM stent was implanted in the abdominal aorta at the level of one cm below the left renal artery.Reexamination of abdominal aortography with DSA was separately performed at 30,60,90 and 180 d after stent implantation to check the stent condition.The rabbits of each group were sacrificed at the corresponding scheduled day,the stenting segment of aorta of each rabbit was removed and the specimen was sent for microscopic examination.The experimental results were analyzed with SPSS20.0 software.Results All the 24 experimental rabbits survived.During the follow-up period the stent showed gradual degradation changes,and basically complete degradation was not observed until to 180 days.Meanwhile,the intimal hyperplasia reached its peak at 90 days after implantation.The abdominal aorta remained unobstructed during the whole process of degradation.Conclusion The time of complete degradation for MPM stent is 182 days,which is long enough to meet the needs of vascular positive remodeling.

Objective To discuss the application of different types of bronchial arteriography catheter in performing bronchial artery embolization (BAE) for the treatment of hemoptysis.Methods The clinical data of a total of 97 patients with hemoptysis,who received BAE during the period from January 2013 to May 2016,were collected.According to angiographic findings in aspect of the opening and running direction of the arteries causing bleeding,the responsible arteries were divided into 4 types:upward opening,horizontal opening and running upwards,horizontal opening and running downwards,and downward opening.For each responsible artery,appropriate angiography catheter was selected from the following catheters:MIK catheter,left gastric artery catheter,Cobra catheter,Simmon-1 catheter and Simmon-2 catheter.With super-selective catheterization technique the selected suitable catheter was inserted into the responsible artery and angiography was subsequently performed.The effect of the selection of bronchial arteriography catheter in performing BAE for hemoptysis was analyzed.Results A total of 180 responsible arteries were detected in 97 patients.Of the 180 responsible arteries,artery with upward opening was seen in 42,artery with horizontal opening and running upwards was found in 54,artery with horizontal opening and running downwards was observed in 46,and artery with downward opening was detected in 38.The success rates of super-selective catheterization for MIK catheter,left gastric artery catheter,Cobra catheter and Simmon catheter were 83.3％ (35/42),92.6％ (50/54),87.0％ (40/46) and 89.5％ (34/38,including 30 Simmon-1 catheters and 4 Simmon-2 catheters) respectively.After BAE,the responsible arteries were occluded in all patients,and hemoptysis stopped immediately.The recurrence rate at 6 months after BAE was 7.2％ (7/97).Conclusion For the treatment of hemoptysis,BAE is safe and effective.The key point to ensure a successful BAE is that the selection of appropriate catheter should be based on the opening and running direction of the artery causing bleeding.