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.

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization

Objective:To observe the clinical effect of tracheal tube with an attached laryngeal pillow cushion(LPC)in the patients under general anesthesia,and to provide new methods for the preventing arytenoid dislocation during tracheal intubation.Methods:Forty-eight patients scheduled for elective oral tracheal intubation under general anesthesia and meeting the inclusion criteria were selected.Based on the head and neck positions,the patients were divided into supine without pillow(SWOP)group,supine with pillow(SWP)group,trendelenburg position(TP)group,and head side position(HSP)group,each group consisted of 12 patients.The patient in the following groups underwent two sequential treatments after tracheal intubation:intervention group(LPC-inflated)and control group(LPC uninflated,representing the current method of tracheal tube use).One patient in TP group and two patients in HSP group rminated the experiment,so a total of 45 patients were successfully included in this study.Electronic fiber laryngoscopy was used to observe and record the positional relationship between the endotracheal tube LPC and the posterior commissure arytenoid joint area under different head and neck positions after two treatments.The evaluation indicators were whether the tracheal tube was lifted from the posterior commissure arytenoid joint area and the degree of compression of the tracheal tube on the arytenoid joint.The incidence of tracheal tube lift-off and the percentage of compression degree on cricoarytenoid joint of the patients in various groups were calculated.Results:Within the same head and neck position group,compared with control group,the incidence of endotracheal tube lift-off of the patients in intervention group was significantly increased(P<0.05),and the percentage of compression degree of endotracheal tube on the arytenoid joint was significantly decreased(P<0.05).In control and intervention groups,there were no statistically significant differences in the incidence of endotracheal tube lift-off and the percentage of compression degree on arytenoid joint of the patients in various head and neck positions groups(P>0.05).Conclusion:Under the four head and neck positions,inflating the LPC of the tracheal tube can lift the tracheal tube from the posterior commissure arytenoid joint area,effectively relieving or reducing the compression and mechanical friction injuries to the arytenoid joint.

Objective To identify the enhancer landscape marked by histone H3K27ac modifications in diffuse-type gastric cancer(DGC)tissues,and to elucidate the epigenetic remodeling mechanisms by which active enhancers regulate cachexia-related genes.Methods Gastric mucosal tissue samples were collected from Department of Gastroenterology of Army Medical Center of PLA during January 2022 to March 2023,including 10 normal gastric mucosa tissues(Normal group),10 DGC tissues diagnosed with cachexia(DGC group),and 10 organoids derived from DGC tissues(Organoid group).Using H3K27ac chromatin targeting cleavage and tagmentation(CUT&Tag)technology,genomic modification regions were captured to screen specific active enhancers and their potential target genes in DGC tissues.CRISPR-dCas9 gene editing technology was used to intervene with the enhancers,and the expression of target genes was detected with Western blotting and qRT-PCR.Sixteen female SPF-grade BALB/c Nude mice(6～8 weeks old,weighing 18～21 g)were utilized to establish an orthotopic xenograft tumor model using the human diffuse-type gastric cancer cell line MKN45.Cachexia-related phenotypes were evaluated in 3 groups:normal group(n=4),silencing group(n=6),and control group(n=6).Results Significant differential enhancer regions were identified between DGC and normal gastric mucosa tissues.DGC tissues exhibited a marked increase in enhancer abundance(P<0.05)and signal intensity when compared with the normal counterparts.Integrated analysis of transcriptome data revealed that some of these active enhancers up-regulated the expression of GDF15,a cachexia-associated target gene in DGC.Targeted silencing of the active enhancer of GDF15 using CRISPR/dCas9-KRAB plasmid technology resulted in a significant reduction in GDF15 expression at both mRNA levels(P<0.05)and protein.Results from orthotopic transplantation experiments of DGC demonstrated that silencing of active enhancers alleviated the cachexia phenotype in nude mice(P<0.05).Conclusion DGC exhibits enhancer remodeling,which regulates the expression of the cachexia-associated gene GDF15,and thereby contributes to the pathogenesis and progression of cancer cachexia.

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 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 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 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 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 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.