Immunotherapy has emerged as a revolutionary approach to treat immune-related diseases. Dendritic cells (DCs) play a pivotal role in orchestrating immune responses, making them an attractive target for immunotherapeutic interventions. Modulation of gene expression in DCs using genome editing techniques, such as the CRISPR-Cas system, is important for regulating DC functions. However, the precise delivery of CRISPR-based therapies to DCs has posed a significant challenge. While lipid nanoparticles (LNPs) have been extensively studied for gene editing in tumor cells, their potential application in DCs has remained relatively unexplored. This study investigates the important role of cholesterol in regulating the efficiency of BAMEA-O16B lipid-assisted nanoparticles (BLANs) as carriers of CRISPR/Cas9 for gene editing in DCs. Remarkably, BLANs with low cholesterol density exhibit exceptional mRNA uptake, improved endosomal escape, and efficient single-guide RNA release capabilities. Administration of BLAN_mCas9/gPD-L1 results in substantial PD-L1 gene knockout in conventional dendritic cells (cDCs), accompanied by heightened cDC1 activation, T cell stimulation, and significant suppression of tumor growth. The study underscores the pivotal role of cholesterol density within LNPs, revealing potent influence on gene editing efficacy within DCs. This strategy holds immense promise for the field of cancer immunotherapy, offering a novel avenue for treating immune-related diseases.

The fluid status and rate of blood flow through the arteriovenous fistula (AVF) are two important factors affecting hemodynamic in hemodialysis patients; however, their effects on pulmonary hypertension have rarely been studied. Hence, we aimed to evaluate the effects of these factors in hemodialysis patients with pulmonary hypertension. Methods: This single-center cross-sectional survey included 219 maintenance hemodialysis patients (139 [63.5%] male). The prevalence of pulmonary hypertension was 13.6% (30 of 219). Pulmonary artery pressure was measured by echocardiography, fluid status was measured objectively using bioimpedance spectroscopy, and blood flow rate in the AVF (Qa) was determined using Doppler ultrasound. Results: The overall mean overhydration before hemodialysis was 1.5 L (range, 0.6–2.8 L). The mean overhydration in patients with and without pulmonary hypertension was 3.6 L (range, 2.3–4.6 L) and 1.4 L (range, 0.6–2.4 L), respectively (p < 0.001). The overall mean Qa was 780 mL/min (range, 570–1,015.5 mL/min). The mean Qa of patients with and without pulmonary hypertension was 672 mL/min (range, 505.7–982.2 mL/min) and 790 mL/min (range, 591–1,026 mL/min), respectively (p = 0.27). Overhydration (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.08–1.97; p = 0.01), N-terminal prohormone of brain natriuretic peptide (NT-proBNP; OR, 1.36; 95% CI, 1.09–1.71; p = 0.007), and left atrial diameter (OR, 1.14; 95% CI, 1.01–1.28; p = 0.03) were risk factors. Conclusion: Pulmonary hypertension is strongly associated with overhydration, NT-proBNP, and left atrial diameter in hemodialysis patients

BACKGROUND:Previous studies have reported inconsistent results with positive,negative,and J-shaped associations between alcohol consumption and the hazard of aortic aneurysm and dissection(AAD).This study aimed to examine the connections between weekly alcohol consumption and the subsequent risk of AAD. METHODS:The UK Biobank study is a population-based cohort study.Weekly alcohol consumption was assessed using self-reported questionnaires and the congenital risk of alcohol consumption was also evaluated using genetic risk score(GRS).Cox proportional hazards models were used to estimate hazard ratios(HRs)with 95%confidence intervals(CIs)for the associations between alcohol consumption and AAD.Several sensitivity analyses were performed to assess the robustness of the results. RESULTS:Among the 388,955 participants(mean age:57.1 years,47.4%male),2,895 incident AAD cases were documented during a median follow-up of 12.5 years.Compared with never-drinkers,moderate drinkers(adjusted HR:0.797,95%CI:0.646-0.984,P<0.05)and moderate-heavy drinkers(adjusted HR:0.794,95%CI:0.635-0.992,P<0.05)were significantly associated with a decreased risk of incident AAD.Interaction-based subgroup analysis revealed that the protective effect of moderate drinking was reflected mainly in participants younger than 65 years and women. CONCLUSION:Our findings support a protective effect of moderate alcohol consumption on AAD,but are limited to participants younger than 65 years and women.

BACKGROUND:Previous studies have reported inconsistent results with positive,negative,and J-shaped associations between alcohol consumption and the hazard of aortic aneurysm and dissection(AAD).This study aimed to examine the connections between weekly alcohol consumption and the subsequent risk of AAD. METHODS:The UK Biobank study is a population-based cohort study.Weekly alcohol consumption was assessed using self-reported questionnaires and the congenital risk of alcohol consumption was also evaluated using genetic risk score(GRS).Cox proportional hazards models were used to estimate hazard ratios(HRs)with 95%confidence intervals(CIs)for the associations between alcohol consumption and AAD.Several sensitivity analyses were performed to assess the robustness of the results. RESULTS:Among the 388,955 participants(mean age:57.1 years,47.4%male),2,895 incident AAD cases were documented during a median follow-up of 12.5 years.Compared with never-drinkers,moderate drinkers(adjusted HR:0.797,95%CI:0.646-0.984,P<0.05)and moderate-heavy drinkers(adjusted HR:0.794,95%CI:0.635-0.992,P<0.05)were significantly associated with a decreased risk of incident AAD.Interaction-based subgroup analysis revealed that the protective effect of moderate drinking was reflected mainly in participants younger than 65 years and women. CONCLUSION:Our findings support a protective effect of moderate alcohol consumption on AAD,but are limited to participants younger than 65 years and women.

BACKGROUND:Previous studies have reported inconsistent results with positive,negative,and J-shaped associations between alcohol consumption and the hazard of aortic aneurysm and dissection(AAD).This study aimed to examine the connections between weekly alcohol consumption and the subsequent risk of AAD. METHODS:The UK Biobank study is a population-based cohort study.Weekly alcohol consumption was assessed using self-reported questionnaires and the congenital risk of alcohol consumption was also evaluated using genetic risk score(GRS).Cox proportional hazards models were used to estimate hazard ratios(HRs)with 95%confidence intervals(CIs)for the associations between alcohol consumption and AAD.Several sensitivity analyses were performed to assess the robustness of the results. RESULTS:Among the 388,955 participants(mean age:57.1 years,47.4%male),2,895 incident AAD cases were documented during a median follow-up of 12.5 years.Compared with never-drinkers,moderate drinkers(adjusted HR:0.797,95%CI:0.646-0.984,P<0.05)and moderate-heavy drinkers(adjusted HR:0.794,95%CI:0.635-0.992,P<0.05)were significantly associated with a decreased risk of incident AAD.Interaction-based subgroup analysis revealed that the protective effect of moderate drinking was reflected mainly in participants younger than 65 years and women. CONCLUSION:Our findings support a protective effect of moderate alcohol consumption on AAD,but are limited to participants younger than 65 years and women.

Objective:To investigate the effects of selinexor,a inhibitor of nuclear export protein 1(XPO1)on the proliferation inhibition and apoptosis of Kasumi-1 cells in acute myeloid leukemia(AML).Methods:MTS method was used to detect the inhibitory effect of different concentrations of selinexor on the proliferation of Kasumi-1 cells at different time points.The apoptosis rate and cell cycle changes after treatment with different concentration of selinexor were detected by flow cytometry.Results:Selinexor inhibited the growth of Kasumi-1 cells at different time points in a concentration-dependent manner(r24 h=0.7592,r48 h=0.9456,and r72 h=0.9425).Selinexor inhibited Kasumi-1 cells growth in a time-dependent manner(r=0.9057 in 2.5 μmol/L group,r=0.9897 in 5 μmol/L group and r=0.9994 in 10 μmol/L group).Selinexor could induce apoptosis of Kasumi-1 cells in a dose-dependent manner(r=0.9732),and the apoptosis of Kasumi-1 cells was more obvious with the increase of drug concentration.The proportion of G0/G1 phase was significantly increased and the proportion of S phase was significantly decreased after the treatment of Kasumi-1 cells by selinexor.With the increase of drug concentration,the proportion of Kasumi-1 cells cycle arrest in G0/G1 phase was increased and the cell synthesis was decreased.Conclusion:Selinexor can promote the death of tumor cells by inhibiting Kasumi-1 cells proliferation,inducing apoptosis and blocking cell cycle.

Objective To explore the value of 11C-methionine(MET)PET/CT radiomics model for evaluating isocitrate dehydrogenase1(IDH1)status of glioblastoma.Methods Data of 157 patients with glioblastoma who underwent 11C-MET PET/CT examination,including 68 cases of IDH1 mutation and 89 cases of IDH1 wild-type were retrospectively analyzed.The patients were divided into training set(n=125)and validation set(n=32)at the ratio of 8:2.Based on PET/CT images,lesions ROI were delineated and radiomics features were extracted and screened to establish radiomics models with logistic regression(LR),support vector machine(SVM)and decision trees(DT),respectively.Meanwhile,the nomogram based on patients'age and radiomics features was drawn.The efficacy of radiomics models and clinical-radiomics nomogram for evaluating IDH1 status were comparatively observed.Results The area under the curve(AUC)of DT radiomics model for evaluating IDH1 status of glioblastoma in training set was 0.910,higher than that of LR(0.697)and SVM(0.698)models(both P＜0.05).In validation set,the AUC of DT model for evaluating IDH1 status of glioblastoma was 0.805,which was higher than that of LR model(0.740)and clinical-radiomics nomogram(0.704)(both P＜0.05).Conclusion 11C-MET PET/CT radiomics model based on DT was helpful for evaluating IDH1 status of glioblastoma.

Objective To explore the acupoint selection rules of acupuncture for the treatment of lower limb spasm after stroke based on data mining technology.Methods Through the computer retrieval of CNKI,Wanfang,VIP,PubMed,EMbase,web of science databases and other databases,the literature that meets the inclusion criteria was selected to establish a database.Descriptive analysis,cluster analysis and association rule analysis were performed on the data through Microsoft Excel 2016,IBM SPSS Statistics 21 and IBM SPSS Modeler 18.0 software.Results(1)A total of 68 acupuncture prescriptions were included,involving 100 acupoints and a total frequency of 536 uses;(2)the top five in terms of frequency of use of acupoints were Yanglingquan(GB34),Zusanli(ST36),Xuanzhong(GB39),Qiuxu(GB40),Sanyinjiao(SP6);(3)the core acupoint pairing was Yanglingquan(GB34)-Xuanzhong(GB39),and five valid clustering clusters were obtained,which were Shenmai(BL62)-Zhaohai(KI6),Weizhong(BL40)-Kunlun(BL60),Xuehai(SP10)-Huantiao(GB30)-Fenglong(ST40)-Zusanli(ST36),Taixi(KI3)-Yinlingquan(SP9)-Sanyinjiao(SP6),Jiexi(ST41)-Taichong(LR3)-Xuanzhong(GB39)-Qiuxu(GB40)-Yanglingquan(GB34).Conclusion Through data mining,it is found that acupuncture treatment of lower limb spasm after stroke is mostly based on Yanglingquan,Zusanli,Xuanzhong,Qiuxu and Xuanzhong.Priority should be given to the application of three yang channels of the foot and five shu acupoint,syndrome differentiation and treatment,and modification should be adjusted according to the syndromes,so as to provide reference for clinical treatment of lower limb spasm after stroke.

Objective:To assess the usage of the robot-assisted core-needle biopsy for the bone tumors, moreover to compare its outcomes with the manual technique.Methods:A retrospective study was conducted from February 2019 to February 2021, the medical records of the patients with bone lesions that had received core-needle biopsy were collected. There were 57 males and 45 females, the age was 45.9 (10~79) years. Eight patients received robot-assisted biopsy, whereas 94 patients underwent C-arm/ CT guided biopsy, the recorded data included operational duration, aspirational direction adjustment, etc. The pathological diagnosis reports of the biopsy specimens and the operational specimens were compared.Results:The diagnosis outcomes included metastases (33 cases), osteosarcoma (12 cases), chondrosarcoma (12 cases), giant cell tumor of bone (12 cases), fibrous dysplasia (7 cases), chronic osteomyelitis (7 cases), lymphoma (4 cases), multiple myeloma (4 cases), chronic fracture (3 cases), chondroblastoma (2 cases), pleomorphic undifferentiated sarcoma (2 cases), leiomyosarcoma (1 case), and Langerhans cell histiocytosis (1 case). Eighty-seven cases (85.29 %) lesions were found in the limbs, whereas 15 cases (14.71%) were in the axial locations. Compared with the manual group, the robot-assisted group had more axial locations: 7/8 vs. 11.70%(11/94), P<0.01; fewer aspirational direction adjustment: (0.4 ± 0.1) times vs. (3.1 ± 1.5) times, P<0.01 ; longer operational duration: (48.8 ± 8.8) min vs. (29.6 ± 6.0) min, P<0.01. There were no statistical differences between the two groups regarding the sex, age, pathological fracture, diagnostic accuracy, open biopsy rate and complications ( P>0.05). Conclusions:The robot-assisted core-needle biopsy is a reliable technique, it helps decrease the operational difficulty. The usage of this technique is recommendable for the bone lesions with great difficulty for biopsy, such as the minimal bone tumors and the lesions in the spine and the pelvis.

BACKGROUND:Previous studies have reported inconsistent results with positive,negative,and J-shaped associations between alcohol consumption and the hazard of aortic aneurysm and dissection(AAD).This study aimed to examine the connections between weekly alcohol consumption and the subsequent risk of AAD. METHODS:The UK Biobank study is a population-based cohort study.Weekly alcohol consumption was assessed using self-reported questionnaires and the congenital risk of alcohol consumption was also evaluated using genetic risk score(GRS).Cox proportional hazards models were used to estimate hazard ratios(HRs)with 95%confidence intervals(CIs)for the associations between alcohol consumption and AAD.Several sensitivity analyses were performed to assess the robustness of the results. RESULTS:Among the 388,955 participants(mean age:57.1 years,47.4%male),2,895 incident AAD cases were documented during a median follow-up of 12.5 years.Compared with never-drinkers,moderate drinkers(adjusted HR:0.797,95%CI:0.646-0.984,P<0.05)and moderate-heavy drinkers(adjusted HR:0.794,95%CI:0.635-0.992,P<0.05)were significantly associated with a decreased risk of incident AAD.Interaction-based subgroup analysis revealed that the protective effect of moderate drinking was reflected mainly in participants younger than 65 years and women. CONCLUSION:Our findings support a protective effect of moderate alcohol consumption on AAD,but are limited to participants younger than 65 years and women.