With the advent of Twenty-First century, more and more genome-wide association studies (GWAS) showed that idiosyncratic adverse drug reactions (ADRs) were closely related with human leukocyte antigen (HLA) alleles, such as the associations of abacavir-HLA-B*5701, allopurinol-HLA-B*5801, and carbamazepine-HLA-B*1502, etc. To explore the mechanisms of these idiosyncratic drug reactions, hapten hypothesis, danger signal hypothesis, pharmacological interaction (P-I) concept and autoimmune mechanism are proposed. In this paper, recent GWAS studies on the HLA-mediated adverse drug reactions and underlying mechanism are reviewed in detail.

Objective To analyze the metabolic profile in serum between normal and orthotopic xenograft nude mice burdened with three human pancreatic cancer cell lines,which were differentiated differently.Methods Human pancreatic cancer lines SW1990,BxPC-3 and Panc-1 were subcutaneously injected into the nude mice,respectively.When the tumor volume reached 1.0 cm3,the nude mice were euthanized and the tumor tissues were removed and implanted to the pancreas to establish the orthotopic xenograft mice model.The serum from three orthotopic xenograft tumor nude mice and the normal controls were collected and then analyzed by 1H nuclear magnetic resonance spectroscopy.Results The three orthotopic xenograft nude mice models were successfully established.In SW1990,BxPC-3 and Panc-1 group,the orthotopic xenograft tumor formation rate was 79％ (11/14),93％ (13/14) and 86％ (12/14),while the mortality was 7％ (1/14),0 and 7％ (1/14),respectively.Compared with control group,the content of metabolites in the serum of orthotopic xenograft tumor nude mice was increased including creatine,alanine,glutamine,1-methylhistidine,isoleucine,lactate,phenylalanine,tryptophan and valine,but the glycerolphosphocholine (GPC) and glucose levels were reduced.As the tumors progressed to be more malignant,the content of valine and isoleucine tended to increase.Conclusions The establishment of the orthotopic implantation tumor nude mice model was stable and reliable with high tumor formation rate.Obvious metabolic differences of glucose,lipid and amino acids were observed between normal and human pancreatic cancer tumor burdening nude mice models.The common metabolic features identified in all three nude mice models burdened with human pancreatic cancer could be used as the potential markers for diagnosing human pancreatic cancer.

Objective:To investigate the correlation between soluble growth stimulating gene protein 2 (sST2) and the severity of traumatic brain injury (TBI) and its value in the diagnosis of traumatic brain injury.Methods:The clinical data of 110 patients with traumatic brain injury who were treated in The First Affiliated Hospital of University of Science and Technology of China (Anhui Province Hospital) from July 2022 to December 2022 were retrospectively analyzed. These 110 patients were included in the observation group. An additional 62 patients without traumatic brain injury who concurrently received treatment in the same hospital were included in the control group. In the observation group, patients were divided into a severe group [Glasgow Coma Scale (GCS) score 3-8 points), a moderate group (GCS score 9-12 points), and a mild group (GCS score 13-15 points) according to the GCS score. Serum sST2 levels were measured using enzyme-linked immunosorbent assay (ELISA) within 24 hours after injury in each group. Serum sST2 levels were compared between the observation group and the control group. Serum sST2 levels were compared among patients with severe, moderate, and mild TBI in the observation group to analyze the correlation between serum sST2 levels and the GCS score. The efficacy of serum sST2 levels in the diagnosis of TBI was evaluated using the receiver operating characteristic curve (ROC curve).Results:Serum sST2 levels in the observation group were 96.25 (48.05, 200.00) μg/L, which were significantly higher than 25.45 (19.78, 40.46) μg/L in the control group ( Z = -8.19, P < 0.05). Serum sST2 levels in pastients with severe TBI were slightly, but not significantly, higher than those in patients with moderate TBI ( P > 0.05), and serum sST2 levels in patients with severe and moderate TBI were significantly higher than those in patients with mild TBI ( Z = -5.20, Z = -4.40, both P < 0.05). There was a significant difference in sST2 levels among patients with mild, moderate and severe TBI ( H = 36.88, P < 0.05). In the observation group, serum sST2 levels within 24 hours after surgery were significantly negatively correlated with GCS score within 24 hours after admission ( rs = -0.561, 95% CI: -0.680~-0.413, P < 0.001). As serum sST2 levels increased, GCS scores showed a decreasing trend. Serum sST2 levels can be used as a prognostic indicator for TBI. Serum sST2 levels within 24 hours after injury can serve as a risk factor for TBI ( β = 0.042, OR = 1.043, 95% CI: 1.026-1.061, P < 0.001). The serum sST2 levels within 24 hours after injury have good diagnostic efficacy for TBI (area under the curve = 87.5%, 95% CI: 0.825-0.926, P < 0.001). Conclusion:The measurement of serum sST2 levels has a high value in the evaluation of the severity of TBI and prognosis, which is crucial for developing personalized treatment strategies for TBI.