Adjuvants are an important part of vaccines. In order to overcome the weaknesses of traditional adjuvants, it is essential to develop new adjuvants. At present, CpG ODN has been used as vaccine adjuvants in clinical and preclinical studies of preventive antiviral, anti-parasitic and therapeutic tumor vaccines. Hepatitis B vaccine and COVID-19 vaccine with CpG ODN 1018 as adjuvant have been approved for marketing. In addition to single application, it is one of the most important research directions to develop new delivery systems of anti-tumor vaccines(such as nanoparticles and liposomes)with CpG ODN as adjuvant, and the delivery efficiency and targeting of CpG ODN need to be improved. In addition to the traditional subcutaneous and intramuscular immunization routes, CpG ODN is also being applied to the development of intranasal mucosal immune adjuvants, and its efficacy and mechanism as mucosal immune adjuvants have not been fully clarified.CpG ODN is an agonist of Toll-like receptor 9(TLR9), which can activate natural immunity and further mediate adaptive immune response. Its characteristic is that it can cause strong Th1 immune response. Although many clinical studies showed that CpG ODN adjuvants only cause slight and short-term adverse reactions, some studies also showed that CpG ODN may cause or aggravate autoimmune diseases and inflammatory syndrome by promoting Th1 response. How to overcome this shortcoming of CpG ODN adjuvants may be a challenge for the development of CpG ODN adjuvants in the future. In this paper,the latest research progress and challenges of CpG ODN adjuvants are reviewed.

Objective To explore the correlation of CPNE3 expression with long-term prognosis of patients with gastric cancer(GC)and the possible mechanism.Methods We retrospectively collected the data of 104 GC patients undergoing radical surgery in our hospital from February,2013 to October,2017.TCGA database and immunohistochemistry were used to analyze CPNE3 expression level in GC tissues and its effects on tumor progression and long-term prognosis of the patients.GO analysis was performed to predict the biological role of CPNE3 in GC.We also conducted cell experiments with MGC803 cells and observed the effects of CPNE3 knockdown,CPNE3 overexpression and LY294002(a PI3K/AKT inhibitor)treatment on cell apoptosis and cellular expressions of apoptotic proteins using flow cytometry and Western blotting.Results TCGA analysis and immunohistochemistry both showed high expressions of CPNE3 in GC(P<0.05).The patients with high CPNE3 expressions had a reduced 5-year survival(P<0.01),and a high CPNE3 expression,CEA level≥5 μg/L,CA19-9 level≥37 kU/L,T3-T4 stage,and N2-N3 stage were all independent risk factors for a lowered 5-year survival rate after surgery.The sensitivity and specificity of CPNE3 for predicting 5-year mortality was 79.59%and 74.55%,respectively(P<0.05).GO analysis predicted that CPNE3 negatively regulated GC cell apoptosis.In MGC803 cells,CPNE3 knockdown significantly increased cell apoptosis,enhanced Bax and Cleaved Caspase-3 expressions and decreased Bcl-2 expression,while CPNE3 overexpression produced the opposite results(P<0.05).The cellular expressions of p-PI3K and p-AKT were significantly decreased following CPNE3 knockdown and increased following CPNE3 overexpression(P<0.05).Treatment with LY294002 obviously attenuated the inhibitory effect of CPNE3 overexpression on apoptosis of MGC803 cells(P<0.05).Conclusion CPNE3 is highly expressed in GC tissues and affects the long-term prognosis of the patients possibly by inhibiting GC cell apoptosis through activation of PI3K/AKT signaling.

Objective To investigate the long-term incidence of in-stent stenosis(ISS)in patients with intracranial aneurysms receiving pipeline embolization device(PED)who showed no ISS at short-to-medium term follow-up examination.Methods The clinical data of patients,who received PED treatment at the Department of Neurointervention,First Affiliated Hospital of Zhengzhou University of China between April 2015 and June 2022,were retrospectively collected.The patients with intracranial aneurysms,who showed no ISS at the initial follow-up with DS A and completed＞12 months long-term follow-up check after treatment at the same hospital,were screened out,and their relevant clinical data and imaging materials were collected.The incidence of ISS occurring in postoperative＞12 months long-term follow-up was calculated.The ISS was defined as a＞25％lumen loss of the parent artery when compared with its lumen size measured immediately after PED implantation.Results A total of 57 patients with 61 aneurysms were enrolled in this study,and a total of 68 PEDs were implanted.Forty-one(67.21％)aneurysms were treated by PED implantation only,and 20(32.79％)aneurysms by PED plus spring coils.The median initial follow-up time was 184.0 days(119.0,212.5).At postoperative＞12 months long-term follow-up visit,DSA was employed for 35(57.38％)aneurysms,CTA was adopted for 22(36.07％)aneurysms,and 3D-SPACE sequence MR scan was performed in 4(6.56％)aneurysms.The median follow-up time was 538.0 days(407.5,678.0),and the incidence of ISS was 0％.No ISS-related neurological symptoms occurred in all patients.Conclusion In treating intracranial aneurysms with PED,the postoperative incidence of ISS is low.No ISS is found during the short-term follow-up period,and long-term follow-up results tend to indicate that no ISS events have occurred.

Objective To explore the correlation of CPNE3 expression with long-term prognosis of patients with gastric cancer(GC)and the possible mechanism.Methods We retrospectively collected the data of 104 GC patients undergoing radical surgery in our hospital from February,2013 to October,2017.TCGA database and immunohistochemistry were used to analyze CPNE3 expression level in GC tissues and its effects on tumor progression and long-term prognosis of the patients.GO analysis was performed to predict the biological role of CPNE3 in GC.We also conducted cell experiments with MGC803 cells and observed the effects of CPNE3 knockdown,CPNE3 overexpression and LY294002(a PI3K/AKT inhibitor)treatment on cell apoptosis and cellular expressions of apoptotic proteins using flow cytometry and Western blotting.Results TCGA analysis and immunohistochemistry both showed high expressions of CPNE3 in GC(P<0.05).The patients with high CPNE3 expressions had a reduced 5-year survival(P<0.01),and a high CPNE3 expression,CEA level≥5 μg/L,CA19-9 level≥37 kU/L,T3-T4 stage,and N2-N3 stage were all independent risk factors for a lowered 5-year survival rate after surgery.The sensitivity and specificity of CPNE3 for predicting 5-year mortality was 79.59%and 74.55%,respectively(P<0.05).GO analysis predicted that CPNE3 negatively regulated GC cell apoptosis.In MGC803 cells,CPNE3 knockdown significantly increased cell apoptosis,enhanced Bax and Cleaved Caspase-3 expressions and decreased Bcl-2 expression,while CPNE3 overexpression produced the opposite results(P<0.05).The cellular expressions of p-PI3K and p-AKT were significantly decreased following CPNE3 knockdown and increased following CPNE3 overexpression(P<0.05).Treatment with LY294002 obviously attenuated the inhibitory effect of CPNE3 overexpression on apoptosis of MGC803 cells(P<0.05).Conclusion CPNE3 is highly expressed in GC tissues and affects the long-term prognosis of the patients possibly by inhibiting GC cell apoptosis through activation of PI3K/AKT signaling.

Objective:To study the expression levels and clinical significance of thyroid transcription factor-1(TTF-1) and galectin-3 in pleural fluid sediment embedded tissues of lung adenocarcinoma patients.Methods:A study was conducted on the clinical data of 82 lung cancer patients who received treatment at the First People′s Hospital of Anqing City from March 2020 to December 2022. According to the type of lung adenocarcinoma, they were divided into metastatic lung adenocarcinoma group (16 cases) and primary lung adenocarcinoma group (66 cases). The expression of levels TTF-1 and galectin-3 were compared between the two groups. Immunohistochemical method was used to detect the expression levels of TTF-1 and galectin-3 in pleural fluid sediment embedded tissues and their clinical significance was analyzed.Results:The positive rate of TTF-1 in primary lung adenocarcinoma group was higher than that in metastatic lung adenocarcinoma group: 77.27%(51/66) vs. 2/16, there was statistical difference ( χ2 = 23.64, P<0.01). The positive rate of galectin-3 in primary adenocarcinoma group was lower than that in metastatic adenocarcinoma group: 31.82%(21/66) vs. 13/16, there was statistical difference ( χ2 = 12.96, P<0.01). Galectin-3 and TTF-1 positive expressions were not correlated with the degree of tissue differentiation, lymph node metastasis and clinical stage of lung adenocarcinoma ( P>0.05). Conclusions:The expression level of TTF-1 increases and the expression level of galectin-3 decreases in the pleural fluid sediment embedded tissues of lung adenocarcinoma patients, the combined detection of TTF-1 and galectin-3 has important clinical application value in the diagnosis of primary lung adenocarcinoma cells and differential diagnosis of metastatic cancer.

Objective:To explore the diagnosis and treatment of HIV infection complicated with acute lymphoblastic leukemia.Methods:The diagnosis and treatment of a patient with HIV infection and ALL who was admitted to Tianjin People's Hospital on February 13, 2021 were retrospectively analyzed, and the experience was summarized and the literature was reviewed.Results:The patient had a history of HIV infection for more than 3 years, and was diagnosed as acute lymphoblastic leukemia, and was treated with VCP (Vindesine 2 mg on days 1, 8, 15, 22, cyclophosphamide 600 mg on days 1-2, 15-16, dexamethasone 9 mg on days 1-14, 5 mg. 15-28 days) and died on the 8th day of chemotherapy. The cause of death was infection.Conclusion:Combined chemotherapy and hematopoietic stem cell transplantation on the basis of highly active antiretroviral therapy can improve the prognosis and survival rate of HIV-infected patients with acute lymphoblastic leukemia.

Objective To investigate the changes and clinical significance of γδT cells and their major functional subsets γδT1 and γδT17 cells in the peripheral blood of patients with systemic lupus erythematosus (SLE). Methods Ratios and absolute numbers of γδT cells, γδT1 cells and γδT17 cells in peripheral blood were detected by flow cytometry in 21 SLE patients (SLE) group and 16 healthy controls (HC group). Correlations of γδT cells, γδT1 cells and γδT17 cells in the peripheral blood with clinical indicators were analyzed by Pearson correlation analysis. Results In SLE patients, the percentage of γδT cells to lymphocytes in the peripheral blood was (2.30±1.10)%, which was significantly lower than (3.30±1.51)% in the HC group (P < 0.05); the percentage of γδT1 cells to lymphocytes in peripheral blood was (0.93±0.67)%, which was significantly lower than (2.09±1.21)% in the HC group (P < 0.001); the ratio of γδT17 cells to lymphocytes in the peripheral blood was (1.53±2.82)‰, which showed an increasing trend when compared to (0.18±0.12)‰ in the HC group (P>0.05). The absolute number of γδT cells in the peripheral blood in SLE patients was (2.88±2.18)×10⁴/mL, which was significantly lower than (7.96±3.96)×10⁴/mL in the HC group (P < 0.000 1); the absolute number of γδT1 cells in the peripheral blood in SLE patients was (1.20±1.17)×10⁴/mL, which was significantly lower than (5.05±3.04)×10⁴/mL in the HC group (P < 0.000 1); the absolute number of γδT17 cells in the peripheral blood in SLE patients was (1.03±1.08)×10³/mL, which was significantly higher than (0.40±0.24)×10³/mL in the HC group (P < 0.05). The proportion of γδT17 cells in the peripheral blood of SLE patients was positively correlated with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) (r=0.59, P < 0.01) and erythrocyte sedimentation rate (r=0.65, P < 0.01), while the absolute number of γδT17 cells was positively correlated with the SLEDAI score (r=0.59, P < 0.01) and negatively correlated with the complement C3 level (r=-0.53, P < 0.05). Conclusion The significant decrease in the number of γδT cells in the peripheral blood of SLE patients is mainly due to the reduction of its γδT1 cell subset; γδT17 cells play an important role in the pathogenesis and activity of SLE.

Objective:A machine learning algorithm was used to develop a predictive model of self-injury among college students and to explore the high-risk factors for self-injury among college students.Methods:From November to December 2022, a convenience sample of 791 college students from a university in Hebei Province was selected.Whether the self-injurious behavior occurred or not was regarded as an outcome variable.The basic demographics data were collected for statistical analysis.The adolescent self-harm questionnaire, the acquired helplessness scale, the Chinese version of the interpersonal needs questionnaire, the adolescent life events scale, and the childhood traumatic experiences questionnaire were used for assessment.The predictor variables were statistically analyzed by SPSS 26.0 software, and the performance of the model was evaluated by random forest, support vector machine and logistic regression so as to predict the self-injury behavior of college students.The model performance was evaluated by the accuracy, F1 score, sensitivity, specificity, and AUC value of the model, and the optimal model was selected.Finally, the optimal model was used to analyze the high-risk factors of college students' self-injury behaviors.Results:(1) The results of one-way ANOVA showed that the detection rate of self-injury behavior among college students was 42.4%(335/791), and the detection rate of male students was significantly higher than that of female students ( χ2=14.139, P<0.05). Individuals with lower-middle monthly household income(RMB 3 000-5 999) had a significantly higher detection rate of self-injury behavior than those with other monthly household income( P<0.05). (2) The accuracy of random forest, support vector machine, and logistic regression models were 85.53%, 85.96%, and 68.86%, F1 scores were 0.853, 0.864, and 0.676, and sensitivities were 83.91%, 89.04%, and 64.91%, respectively.The AUCs of support vector machine, logistic regression models and random forest were 0.89, 0.73 and 0.92.(3) The top ten characteristic variables of high risk factors for college students' self-injury behaviors based on the random forest algorithm with better predictive efficacy were emotional abuse, frustration of belonging, helplessness, interpersonal relationship factor, despair, emotional neglect, academic stress factor, monthly family income, perception of tiredness, and health adaptation factor, in that order. Conclusions:Random forest is optimal for predicting self-injury behavior among college students compared to support vector machine and logistic regression.Factors influencing self-injury behavior among college students originate from environmental factors, individual factors and interpersonal factors.

Objective To systematically evaluate the qualitative studies on the care experience of caregivers for primary malignant bone tumors patients,in order to provide references for the construction of bone tumor support care system.Methods The Cochrane Library,PubMed,Embase,CNKI,Wanfang Database,VIP database,and China Biomedical Literature Database were searched by computer to collect qualitative studies on the care experience of caregivers of malignant bone tumors patients from the establishment of the databases to November 2022.The quality of the literature was evaluated using the Joanna Briggs Institute(JBI)Quality Evaluation Criteria for Quality Research in Evidence-Based Health Care Centers(2016),and the results were integrated by a pooled integration approach.Results A total of 12 studies were included;48 themes were extracted and summarized into 9 categories,which were combined into 3 integrated results.Integration result 1 is obvious physical and mental disturbance.Integration result 2 is multiple role maladaptation.Integration result 3 is positive growth after adjustment.Conclusion Caregivers of patients with malignant bone tumors have serious physical and mental burden and are eager for multiple support.It is suggested that medical staff pay attention to the multi-dimensional needs of patients,formulate personalized support strategies,help caregivers adapt and transform their roles,and promote the post-traumatic growth of caregivers.

Objective:To investigate the association between metabolic syndrome and the risk of early renal function injury in chronic kidney disease(CKD) in the elderly.Methods:A retrospective cohort was established based on health check-up data of 4 495 elderly residents in Mengzi City, Yunnan Province from January 2016 to December 2018. The medial history, living habits, and related physical examination information were collected. Cox hazard regression model was used to explore the association between metabolic syndrome, along with its components, and the early renal function injury in CKD. Results:The median age of the elderly was 71.00(67.00, 75.00) years, with metabolic syndrome detection rate of 21.98%. Early renal function injury of CKD developed in 1 300(28.92%) subjects during the follow-up. Univariate Cox regression showed that the number of metabolic syndrome components was associated with the risk of early kidney development in CKD. The HRs were 1.23 (95% CI 1.03-1.47, P=0.022) with 1 component, 1.54 (95% CI 1.28-1.84, P<0.001) with 2, and 1.38 (95% CI 1.14-1.67, P<0.001) with 3 or more. Multivariate Cox regression showed that elevated fasting triglycerides( HR=1.20, 95% CI 1.07-1.36, P=0.003) and lower high density lipoprotein-cholesterol(HDL-C; HR=1.25, 95% CI 1.09-1.43, P=0.002) were risk factors for early kidney injury in CKD, while doing some physical activity( HR=0.57, 95% CI 0.33-0.98, P=0.042), or on daily basis( HR=0.57, 95% CI 0.49-0.66, P<0.001) was a protective factor for early kidney injury in CKD. Conclusion:The abnormality of one or more metabolic components can significantly increase the risk of early kidney injury in the elderly with CKD. Elevated triglyceride and decreased HDL-C may be the risk factors.