BACKGROUND:The cervical pedicle screws provide ideal three-column stability for cervical vertebra, but there is stil no a standard with the choice of pedicle screw place methods in cervical vertebra. Here, we try to seek a simpler, safer and accurate pedicle screw place method.OBJECTIVE:To evaluate the accuracy and security of transpedicular screw placement assisted by rapid prototyping individual navigation template. METHODS:Eight cadaver cervical specimens (C3-6) were selected to take CT-scan and data were saved in DICOM format. Three-dimensional (3D) software MIMICS was used to establish the C3~6 3D model, and designed the best pedicle screw channel. According to the morphological feature of the posterior cervical spine elements, the reverse template was designed. Then, the best pedicle screw channels were fused into bilateral navigation template. The navigation template was manufactured by rapid prototyping, and saved in STL format. Rapid prototyping technology was used to print out the navigation template. Cervical pedicle screws were inserted with the assistance of navigation templates fitted with the posterior structure of the vertebral body. Postoperative X-ray and CT scan were used to evaluate the accuracy of screw placement. RESULTS AND CONCLUSION:(1) Total y 64 screws were inserted with the assistance of individual navigation templates. Of them, 62 screws were completely in the pedicle;1 screw perforated the medial cortex of pedicle;1 screw perforated the lateral cortex of pedicle. Accuracy of screw placement was 97%. (2) The individual navigation template with a high accuracy rate is a feasible and safe method for cervical pedicle screw placement, which has great prospects for clinical application.

Objective To analyze the influence of intraoperative blood glucose fluctuation and postoperative insulin resistance(IR)on postoperative cognitive dyfunction(POCD)in elderly patients undergoing thoracoscopic radical resection of lung cancer under general anesthesia.Methods A total of 352 elderly patients undergoing thoracoscopic radical resection of lung cancer under general anesthesia were collected and divided into the POCD group(n=84)and the non-POCD group(n=268).The covariates between the two groups were balanced by propensity score matching method(PSM).Eighty-four cases in each group were successfully matched.The data between the two groups before and after PSM were compared.After PSM,receiver operating characteristic(ROC)curve of blood glucose fluctuation amplitude for predicting POCD was drawn,and patients were divided into the low-level blood glucose fluctuation group(n=97)and the high-level blood glucose fluctuation group(n=71)according to the cut-off value.According to the existence of postoperative IR,patients were divided into the IR group(n=53)and the non-IR group(n=115).Then,incidences of POCD between groups were compared.Logistic regression was used to analyze the influencing factors of POCD.Results Before PSM,the POCD group had older age,higher blood glucose fluctuation amplitude,IR ratio,operation time,anesthesia time,propofol dosage,remifentanil dosage and sufentanil dosage in anesthesia maintenance period than those in the non-POCD group(P＜0.05).The POCD group had higher blood glucose fluctuation amplitude and IR ratio than those in the non-POCD group after PSM(P＜0.05).After PSM,the incidences of POCD in the high-level blood glucose fluctuation group and the IR group were higher than those in the low-level blood glucose fluctuation group and the non-IR group(P＜0.05).Logistic regression analysis showed that higher intraoperative blood glucose fluctuation(OR=9.140,95%CI:4.338-19.257)and postoperative IR(OR=4.034,95%CI:1.163-13.991)were risk factors of POCD.Conclusion The risk of POCD in elderly patients undergoing thoracoscopic radical lung cancer surgery under general anesthesia is increased in patients with higher intraoperative blood glucose fluctuation and postoperative IR.

OBJECTIVE To conduct the pharmacoeconomic evaluation of empagliflozin in the treatment of heart failure with reduced ejection fraction （HFrEF），and to provide evidence-based reference for rational drug use and medical and healthy decision-making. METHODS A Markov model was used to perform a cost-effectiveness analysis of the regimen of empagliflozin in the treatment of HFrEF ，and to evaluate the cost and effectiveness of standard treatment plan plus empagliflozin （empagliflozin group）vs. standard treatment plan （standard treatment group ）. Clinical parameters were obtained from the EMPEROR-Reduced study；cost and utility data came from the published literatures. The cycle of the model was 1 month and the simulation time was 20 years. Single-factor sensitivity analysis and probability sensitivity analysis were performed to validate the results of cost-effectiveness analysis. RESULTS Compared with the standard treatment group ，each additional quality-adjusted life year in the empagliflozin group cost 37 995.94 yuan more ，which was less than China ’s 1 time GDP per capita in 2020（72 447 yuan）. The results of single factor sensitivity analysis showed that steady-state hospitalization rate of 2 groups was the most important factor affecting the incremental cost-effectiveness ratio . The results of probability sensitivity analysis showed that when the willingness-to-pay threshold （WTP）was 1 time GDP per capita in 2020（72 447 yuan），the probability of empagliflozin group with cost-effectiveness advantage was 58.8％；when the WTP was 3 times GDP per capita in 2020（217 341 yuan），the probability of empagliflozin group with cost-effectiveness advantage was 63.8％. CONCLUSIONS Compared with standard treatment plan alone，standard treatment plan plus empagliflozin is more cost-effective in the treatment of HFrEF. However ，the economic probability is not high.

Central nervous system (CNS) injuries, including stroke, traumatic brain injury, and spinal cord injury, are essential causes of death and long-term disability and are difficult to cure, mainly due to the limited neuron regeneration and the glial scar formation. Herein, we apply extracellular vesicles (EVs) secreted by M2 microglia to improve the differentiation of neural stem cells (NSCs) at the injured site, and simultaneously modify them with the injured vascular targeting peptide (DA7R) and the stem cell recruiting factor (SDF-1) on their surface via copper-free click chemistry to recruit NSCs, inducing their neuronal differentiation, and serving as the nanocarriers at the injured site (Dual-EV). Results prove that the Dual-EV could target human umbilical vascular endothelial cells (HUVECs), recruit NSCs, and promote the neuronal differentiation of NSCs in vitro. Furthermore, 10 miRNAs are found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via bioinformatic analysis, and further NSC differentiation experiment by flow cytometry reveals that among these miRNAs, miR30b-3p, miR-222-3p, miR-129-5p, and miR-155-5p may exert effect of inducing NSC to differentiate into neurons. In vivo experiments show that Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice, potentiate NSCs recruitment, and increase neurogenesis. This work provides new insights for the treatment of neuronal regeneration after CNS injuries as well as endogenous stem cells, and the click chemistry EV/peptide/chemokine and related nanocarriers for improving human health.

Anti-CD19 chimeric antigen receptor (CAR)-T cell therapy has achieved 40%-50% long-term complete response in relapsed or refractory diffuse large B-cell lymphoma (DLBCL) patients. However, the underlying mechanism of alterations in the tumor microenvironments resulting in CAR-T cell therapy failure needs further investigation. A multi-center phase I/II trial of anti-CD19 CD28z CAR-T (FKC876, ChiCTR1800019661) was conducted. Among 22 evaluable DLBCL patients, seven achieved complete remission, 10 experienced partial remissions, while four had stable disease by day 29. Single-cell RNA sequencing results were obtained from core needle biopsy tumor samples collected from long-term complete remission and early-progressed patients, and compared at different stages of treatment. M2-subtype macrophages were significantly involved in both in vivo and in vitro anti-tumor functions of CAR-T cells, leading to CAR-T cell therapy failure and disease progression in DLBCL. Immunosuppressive tumor microenvironments persisted before CAR-T cell therapy, during both cell expansion and disease progression, which could not be altered by infiltrating CAR-T cells. Aberrant metabolism profile of M2-subtype macrophages and those of dysfunctional T cells also contributed to the immunosuppressive tumor microenvironments. Thus, our findings provided a clinical rationale for targeting tumor microenvironments and reprogramming immune cell metabolism as effective therapeutic strategies to prevent lymphoma relapse in future designs of CAR-T cell therapy.