Aluminum adjuvants (Alum), approved by the US Food and Drug Administration, have been extensively used in vaccines containing recombinant antigens, subunits of pathogens, or toxins for almost a century. While Alums typically elicit strong humoral immune responses, their ability to induce cellular and mucosal immunity is limited. As an alternative, layered double hydroxide (LDH), a widely used antacid, has emerged as a novel class of potent nano-aluminum adjuvants (NanoAlum), demonstrating advantageous physicochemical properties, biocompatibility and adjuvanticity in both humoral and cellular immune responses. In this review, we summarize and compare the advantages and disadvantages of Alum and NanoAlum in these properties and their performance as adjuvants. Moreover, we propose the key features for ideal adjuvants and demonstrate that LDH NanoAlum is a promising candidate by summarizing its current progress in immunotherapeutic cancer treatments. Finally, we conclude the review by offering our integrated perspectives about the remaining challenges and future directions for NanoAlum's application in preclinical/clinical settings.

Anesthesia, General/adverse effects* ; Hypertension/etiology* ; Humans

Background: The onset and progression of type 1 diabetes mellitus (T1DM) is closely related to autoimmunity. Effective monitoring of the immune system and developing targeted therapies are frontier fields in T1DM treatment. Currently, the most available tissue that reflects the immune system is peripheral blood mononuclear cells (PBMCs). Thus, the aim of this study was to identify key PBMC biomarkers of T1DM. Methods: Common differentially expressed genes (DEGs) were screened from the Gene Expression Omnibus (GEO) datasets GSE9006, GSE72377, and GSE55098, and PBMC mRNA expression in T1DM patients was compared with that in healthy participants by GEO2R. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein-protein interaction (PPI) network analyses of DEGs were performed using the Cytoscape, DAVID, and STRING databases. The vital hub genes were validated by reverse transcription-polymerase chain reaction using clinical samples. The disease-gene-drug interaction network was built using the Comparative Toxicogenomics Database (CTD) and Drug Gene Interaction Database (DGIdb). Results: We found that various biological functions or pathways related to the immune system and glucose metabolism changed in PBMCs from T1DM patients. In the PPI network, the DEGs of module 1 were significantly enriched in processes including inflammatory and immune responses and in pathways of proteoglycans in cancer. Moreover, we focused on four vital hub genes, namely, chitinase-3-like protein 1 (CHI3L1), C-X-C motif chemokine ligand 1 (CXCL1), matrix metallopeptidase 9 (MMP9), and granzyme B (GZMB), and confirmed them in clinical PBMC samples. Furthermore, the disease-gene-drug interaction network revealed the potential of key genes as reference markers in T1DM. Conclusion These results provide new insight into T1DM pathogenesis and novel biomarkers that could be widely representative reference indicators or potential therapeutic targets for clinical applications.

ObjectiveThe effect of ghrelin on glucose metabolism is still controversial. This study aims to investigate the effects of long-term application of acyl ghrelin (AG) and des-acyl ghrelin (DAG) on insulin resistance and serum inflammatory factor levels by establishing a mouse model of obesity, induced by a high-fat diet.MethodsThirty two male C57BL/6 mice were randomly divided into 4 groups, 8 in each group. Except for the control group, the high fat diet group (HFD), HFD+AG group and HFD+DAG group were given a high-fat diet to induce obesity in mice. Control group: standard feed and an intraperitoneal injection of 10mL isotonic saline were given every day. HFD: high-fat feed and an intraperitoneal injection of 10mL isotonic saline were given every day. HFD+AG group: high-fat diet was fed with 0.8mg AG; HFD+DAG group: high-fat diet was fed with 0.8mg DAG. Intraperitoneal glucose tolerance test (IPGTT) was performed 16 weeks later. The blood glucose was collected from the tail veins at 0min, 30min, 60min and 120min after injection, respectively, the fluctuation curve was drawn, the area under the curve was calculated, and then the epididymal fat index was weighted. Fasting insulin, interleukin 6 (IL6) and TNFα levels were measured by enzyme-linked immunosorbent assay (ELISA). Then the insulin resistance index (HOMA IR) was compared.ResultsAfter 6 weeks of feeding, the weight of the mice in HFD was significantly higher than that of the control group (P<0.05). After 14 and 12 weeks of administration, the mice in the HFD+AG group and the HFD+DAG group had a significant weight loss (P<0.05). The fat mass of the epididymis in the HFD+DAG group [(0.92±0.32)g] was significantly lower than that of the HFD group [(1.08±0.11)g] (P<0.05); the fasting insulin level was significantly lower, too (P<0.05). The insulin resistance index (4.94±1.27, 4.08±1.35), IL6 [(34.82±6.23), (36.90±5.27)pg/mL] and TNFα levels [(73.01±7.75), (69.39±8.43)pg/mL] in the HFD+AG group and HFD+DAG group were significantly lower than those in the HFD group [(81.70±7.53), (45.85±6.41) pg/mL, (81.70±7.53)pg/mL], with statistically significant differences (P<0.05). The serum levels of IL 6 and TNFα in the HFD group were significantly lower than those in the control group (P<0.05).ConclusionLong-term application of AG and DAG could improve the insulin resistance and reduce the inflammation level of the mice induced by a high-fat diet. DAG can also decrease the visceral fat in mice.

OBJECTIVE: To investigate the correlation between soluble receptor for advanced glycation end products (sRAGE) level in the follicular fluid and ovarian responsiveness in non-PCOS patients undergoing controlled ovarian hyperstimulation. METHODS: Ninety non-PCOS patients underwent IVF/ICSI using a short-acting long protocol for ovarian stimulation with a GnRH agonist. For each patient, the level of sRAGE in the follicular fluid was measured by enzyme linked immunosorbent assay (ELISA), and the data including the clinical baseline state, hormone level, number of oocytes obtained and the fertilization rate were collected. RESULTS: Follicular fluid sRAGE level showed significant negative correlations with basal FSH level (=0.0036) and Gn dose ( < 0.0001) and positive correlations with AFC ( < 0.0001), number of oocytes obtained ( < 0.0001), and the fertilization rate (=0.0047). Follicular fluid sRAGE level was positively correlated with the number of oocytes obtained, and was significantly higher in cases with oocytes obtained above the target number (> 15) than in cases with oocytes obtained within the range of the target numbers (7-15) and below the target number (< 7) ( < 0.0001 and =0.0012, respectively). CONCLUSIONS Follicular fluid sRAGE level can reflect ovarian reserve function in non-PCOS patients, the number of oocytes obtained and the fertilization rate, and can thus predict ovarian responsiveness during controlled hyperstimulation in nonPCOS patients.
Female ; Fertilization in Vitro ; Follicular Fluid ; Humans ; Ovarian Hyperstimulation Syndrome ; Receptor for Advanced Glycation End Products

Objective: To investigate the relationship between dietary polyunsaturated fatty acid (PUFA) intake and blood lipid, C-reactive protein (CRP) and homocysteine (Hcy) in patients with acute ischemic stroke or transient ischemic attack (TIA). Methods: Patients with acute ischemic stroke or TIA were enrolled consecutively from Nanjing Stroke Registry Program. The total dietary PUFA intake level was assessed by the food semi-quantitative frequency questionnaire. Venous blood samples were collected in the morning of the day after admission to the hospital to detect the levels of serum total cholesterol, triacylglycerol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, Hcy, and CRP. According to the median level of total PUFA intake, the patients were divided into low PUFA group and high PUFA group. The relationship between PUFA intake and blood lipid, CRP and Hcy was analyzed by Spearman correlation analysis, and multiple linear regression analysis was used to determine the independent correlation. Results: A total of 170 patients (85.1%) with acute ischemic stroke and 31 patients with TIA (14.9%) were enrolled. Their age was 62.9±14.1 years, 143 were males (71.1%), and the median PUFA daily intake was 12.8 g (interquartile range: 8.05-17.5 g). Compared with the high PUFA group (n=100), patients in the low PUFA group (n=101) were older, serum high-density lipoprotein cholesterol levels were lower, and CRP and Hcy levels were higher. The above differences were statistically significant (all P<0.05). Spearman correlation analysis showed that total dietary PUFA intake was significantly negatively correlated with the serum CRP (r=-0.24, P=0.001) and Hcy (r=-0.17, P=0.013) levels, and there was no significant correlation with the blood lipid levels. Multiple linear regression analysis showed that CRP was significantly negatively correlated with PUFA intake after adjusting for confounding factors (B=-0.28, P=0.012). Conclusions Dietary PUFA intake in patients with acute ischemic stroke or TIA may affect blood metabolism index and oxidative stress index. It is necessary to adjust the dietary structure of patients with low PUFA intake to reduce the risk of stroke recurrence.

This study was aimed to investigate the association between dyslipidemia and thyroid associated ophthalmopathy (TAO). We evaluated the relationship between dyslipidemia and TAO in 218 patients with Graves′ disease (GD) and found that the serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) in the GD subjects with TAO (n=110) were significantly increased [(5.32±1.39) mmol/L vs. (3.18±2.12) mmol/L, (2.98±0.75) mmol/L vs. (1.25±0.98) mmol/L] than those in the GD subjects without TAO (n=108). TC and LDL-C were positively correlated with the Clinical disease activity score (CAS) [TC (r=0.7, P=0.03),LDL-C (r=0.82, P=0.03)], and the levels of TC (OR=2.56, P=0.02) and LDL-C(OR=2.01, P=0.015) were positively associated with TAO. These suggested that high serum cholesterol level is a novel risk factor for TAO, and management of blood lipids should be included in the treatment of TAO.

Vacuum sealing drainage (VSD) is frequently used in abdominal surgeries. However, relevant guidelines are rare. Chinese Trauma Surgeon Association organized a committee composed of 28 experts across China in July 2017, aiming to provide an evidence-based recommendation for the application of VSD in abdominal surgeries. Eleven questions regarding the use of VSD in abdominal surgeries were addressed: (1) which type of materials should be respectively chosen for the intraperitoneal cavity, retroperitoneal cavity and superficial incisions? (2) Can VSD be preventively used for a high-risk abdominal incision with primary suture? (3) Can VSD be used in severely contaminated/infected abdominal surgical sites? (4) Can VSD be used for temporary abdominal cavity closure under some special conditions such as severe abdominal trauma, infection, liver transplantation and intra-abdominal volume increment in abdominal compartment syndrome? (5) Can VSD be used in abdominal organ inflammation, injury, or postoperative drainage? (6) Can VSD be used in the treatment of intestinal fistula and pancreatic fistula? (7) Can VSD be used in the treatment of intra-abdominal and extra-peritoneal abscess? (8) Can VSD be used in the treatment of abdominal wall wounds, wound cavity, and defects? (9) Does VSD increase the risk of bleeding? (10) Does VSD increase the risk of intestinal wall injury? (11) Does VSD increase the risk of peritoneal adhesion? Focusing on these questions, evidence-based recommendations were given accordingly. VSD was strongly recommended regarding the questions 2-4. Weak recommendations were made regarding questions 1 and 5-11. Proper use of VSD in abdominal surgeries can lower the risk of infection in abdominal incisions with primary suture, treat severely contaminated/infected surgical sites and facilitate temporary abdominal cavity closure.
Abdomen ; surgery ; China ; Drainage ; methods ; Evidence-Based Medicine ; Humans ; Practice Guidelines as Topic ; Societies, Medical ; organization & administration ; Surgical Wound Infection ; prevention & control ; Traumatology ; organization & administration ; Vacuum

Vitamin B12 (VitB12) is one of the essential vitamins in humans and is involved in DNA synthesis and cellular metabolism. Many studies have shown that the lack of VitB12 is closely related to the occurrence and development of diabetes and its complications. Therefore, regular testing and reasonable supplementation of VitB12 can help prevent diabetes complications. The article reviews the relationship between VitB12 and diabetes as well as the application of VitB12 in diabetic patients.

Objective Recent studies have shown that rhein could improve glucose metabolism,while the specific mechanism is not yet clear，the aim of this study is to explore the effects of rhein on the insulin signaling pathway in C2C12 cells.Methods To measure the optimum substrate and optimum enzyme concentrations of rhein and the protein tyrosine phosphatase-1B(PTP1B)and calculate the half maximal inhibitory concentration of rhein on PTP1B(IC50). Differentiated and maturated C2C12 myotubes were divided into two groups, the rhein group and the control group. The rhein groups were treated with different rhein concentrations(0.1,1, 10,100 μmol/L) , the positive control group was given 10 nmol/L insulin stimulation for 0.5 hours and the blank control group was treated with equal volume solvent. Related proteins in the insulin signaling pathway were detected by Western blotting and PTP-1B activity was measured by immunoprecipitation.Results The IC50 of rhein to PTP1B was 80.5 μmol/L,and when C2C12 myotubes were treated with 100 μmol/L rhein, the activity of PTP1B decreased significantly. Compared with the blank control group, the rhein groups' phosphorylation levels in insulin receptor and insulin receptor substrates were enhanced and the levels of GLUT4 were obviously improved in C2C12 cells. Moreover, the protein levels of insulin receptor and insulin receptor substrates were not affected significantly.Conclusion Rhein could reduce the activity of PTP1B and enhance insulin signaling transduction. Therefore，we speculated that the enhancement of insulin signaling may be related to the decrease of PTP1B activity in skeletal muscle cells.