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.

Objective:To investigate the clinical value of abdominal adipose volume in predicting early tumor recurrence after resection of hepatocellular carcinoma (HCC).Methods:The retrospective case-control study was conducted. The clinicopathological data of 132 HCC patients with tumor diameter ≤5 cm who were admitted to The First Affiliated Hospital of Army Medical University from December 2017 to October 2019 were collected. There were 110 males and 22 females, aged (51±4)years. All patients underwent resection of HCC. Preoperative computer tomography scanning was performed and the visceral and subcutaneous fats of patients were quantified using the Mimics Research 21.0 software. Based on time to postoperative tumor recurrence patients were divided to two categories: early recurrence and non-early recurrence. Observation indicators: (1) consistency analy-sis; (2) analysis of factors influencing early tumor recurrence after resection of HCC and construction of prediction model. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribu-tion were represented as M( Q1,Q3) or M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Consistency analysis was conducted using the intragroup correlation coefficient (ICC) test. Multivariate analysis was performed using the binary Logistic regression model forward method. Independent risk factors influencing early tumor recurrence after resection of HCC were screened. The area under curve (AUC) of receiver operating characteristic (ROC) curve was applied to select the optimal cut-off value to classify high and low risks of recurrence. The Kaplan-Meier method was used to draw survival curve and calculate survival time. The Log-Rank test was used for survival analysis. Results:(1) Consistency analysis. The consistency ICC of abdominal fat parameters of visceral fat volume (VFV), subcutaneous fat volume, visceral fat area, and subcutaneous fat area measured by 2 radiologists were 0.84, 1.00, 0.86, and 0.94, respectively. (2) Analysis of factors influencing early tumor recurr-ence after resection of HCC and construction of prediction model. All 132 patients were followed up after surgery for 662(range, 292-1 111)days. During the follow-up, there were 52 patients with non-early recurrence and 80 patients with early recurrence. Results of multivariate analysis showed that VFV was an independent factor influencing early tumor recurrence after resection of HCC ( odds ratio=4.07, 95% confidence interval as 2.27-7.27, P<0.05). The AUC of ROC curve based on VFV was 0.78 (95% confidence interval as 0.70-0.85), and the sensitivity and specificity were 72.2 % and 77.4 %, respectively. The optimal cut-off value of VFV was 1.255 dm 3, and all 132 patients were divided into the high-risk early postoperative recurrence group of 69 cases with VFV >1.255 dm 3, and the low-risk early postoperative recurrence group of 63 cases with VFV ≤1.255 dm 3. The disease-free survival time of the high-risk early postoperative recurrence group and the low-risk early post-operative recurrence group were 414(193,702)days and 1 047(620,1 219)days, showing a significant difference between them ( χ2=31.17, P<0.05). Conclusions:VFV is an independent factor influen-cing early tumor recurrence of HCC after resection. As a quantitative indicator of abdominal fat, it can predict the prognosis of HCC patients.

ObjectiveTo explore the prevalence rate and related risk factors of anxiety， depression and insomnia symptoms in close contacts of COVID-19 patients undergoing centralized quarantine and observation， so as to provide references for follow-up targeted psychological crisis intervention. MethodsFrom February 6 to 8， 2020， a total of 136 close contacts at designated quarantine sites in four districts and counties of Ya'an city were enrolled， and assessed using the general information questionnaire， Hospital Anxiety and Depression Scale （HAD） and Insomnia Severity Index （ISI）. ResultsA total of 26 quarantined individuals （19.12%） had various degrees of anxiety， depression or insomnia， including 16 cases （11.76%） with anxiety， 9 cases （6.62%） with depression and 16 cases （11.76%） with insomnia. Correlation analysis showed that HAD （A） score was positively correlated with HAD （D） score （r=0.642， P<0.01）. HAD （A） score was positively correlated with ISI score （r=0.590， P<0.01）. HAD （D） score was positively correlated with ISI score （r=0.329， P<0.01）. Multivariate Logistic regression analysis showed that the risk factor of anxiety was the first week of isolation （OR=3.290， P<0.05）， meantime， the risk factors of insomnia included the old age （OR=7.990， P<0.05） and the first week of isolation （OR=4.659， P<0.05）. ConclusionThe close contacts of COVID-19 infections undergoing centralized quarantine and observation in Ya’an have high prevalence rate of anxiety and insomnia， and the symptoms are most severe during the first week of quarantine.

Objective To investigate the correlations among homocysteine(Hcy)level,serum cystatin C (Cys-c)and diabetic peripheral neuropathy(DPN).Methods Two hundred and three diagnosed cases of type 2 diabetes were enrolled,including 123 DPN patients(DPN+)and 80 non-DPN(DPN-)patients.Levels of serum Hcy,Cys-c,high-sensitivity C-reactive protein(hs-CRP)and fiber fibrinogen(Fg)were detected.The above indi-cators and the baseline data such as sex,age,duration,BMI,WHR,HOMA-IR(CP),HOMA-islet(CP)were statistically analyzed. Results Hcy,Cys-c,and the duration of the DPN+ group were significantly higher than those in the DPN-group(P<0.05,respectively).HOMA-islet(CP)in the DPN-group was markedly higher than that in the DPN+group(P<0.01).The prevalence of DPN in the high level of Hcy group was much higher than that in the low and the normal level of Hcy group.Hcy was still significantly correlated with the Cys-c after taking the controlled procedure such as duration and fibrinogen. Conclusion High levels of Hcy and Cys-c are the criti-cal risk factors of DPN,collaborative determination of Hcy and Cys-c level might be of quitevaluable in early diag-nosis of DPN.

[ ABSTRACT] AIM:To investigate whether the increase in PTEN expression is related to apoptosis, and whether it is regulated by reactive oxygen species( ROS) .METHODS: The rat islet cells were divided into constant low glucose group ( group L) , constant high glucose group ( group H) , glucose fluctuation group ( group F) , low glucose after high glucose group (group HL) and low glucose after fluctuation group (group FL).The ROS level, apoptotic rate, intracellu-lar calcium, insulin release and PTEN protein expression were analyzed.RESULTS:Compared with groups H and L, the insulin secretion decreased, and intracellular calcium, ROS level, PTEN protein expression and apoptotic rate increased in group F ( P<0.05) .Compared with group H, the intracellular calcium, ROS level, PTEN protein expression and apoptot-ic rate in group HL decreased, but were still higher than those in group L (P<0.05).Compared with group F, the intra-cellular calcium, ROS level, PTEN protein expression and apoptotic rate in group FL decreased, but were still higher than those in group L (P<0.05).CONCLUSION:Glucose fluctuation can cause the apoptosis of islet cells more easily than constant high glucose.This may be related to the change of intracellular calcium and increase in oxidative stress which pro-motes PTEN expression.The recovery of glucose level to some extent relieves oxidative stress, decrease PTEN expression and reduce cell damage.