Impact of polygenic risk score for triglyceride trajectory and diabetic complications in subjects with type 2 diabetes based on large electronic medical record data from Taiwan: a case control study.

BACKGROUND: The prevalence of diabetic dyslipidemia has gradually increased worldwide and individuals with hypertriglyceridemia often have a high polygenic burden of triglyceride (TG)-increasing variants. However, the contribution of genetic variants to dyslipidemia in patients with type 2 diabetes (T2D) remains limited. Therefore, in this study, we aimed to investigate the genetic characteristics of longitudinal changes in TG levels among patients with T2D and summarize the genetic effects of polygenic risk score (PRS) on TG trajectory and risk of diabetic complications. METHODS: We conducted a case-control study. A total of 11,312 patients with T2D with longitudinal TG and genetic data were identified from a large hospital database in Taiwan. We then performed a genome-wide association study and calculated the relative PRS. RESULTS: In total, 21 single-nucleotide polymorphisms (SNPs) related to TG trajectory were identified and yielded an area under the receiver operating characteristic curve (ROC) of 0.712 for high TG trajectory risk among Taiwanese patients with T2D. A cumulative genetic effect was observed for high TG trajectory, even when considering the adherence of a lipid-lowering agent in stratified analysis. An increased PRS increases high TG trajectory risk in a logistic regression model (odds ratio = 1.55; 95% confidence interval [CI] = 1.31-1.83 in the validation cohort). The TG-specific PRS was associated with the risk of diabetic microvascular complications, including diabetic retinopathy and nephropathy (with hazard ratios of 1.11 [95% CI = 1.01-1.21, P = 0.027] and 1.05 [95% CI = 1.01-1.1, P = 0.018], respectively). CONCLUSIONS: This study may contribute to the identification of patients with T2D who are at risk of abnormal TG levels and diabetic microvascular complications using polygenic information.

[Chronic myeloid leukemia with e6a2 fusion gene: a case report and literature review].

Chronic myeloid leukemia (CML) with e6a2 transcript type is very rare in clinic,which is usually related to disease aggressiveness. Its clinical characteristics and relationship with tyrosine kinase inhibitor efficacy are still unclear. In this paper, the clinical characteristics and related laboratory tests of a patient with e6a2 fusion gene positive CML characterized by multiple osteolytic bone destruction throughout the body and eosinophil infiltration in gastrointestinal tract, lymph nodes and other organs were retrospectively analyzed, and the relevant literature was reviewed. The patient was Ph chromosome positive with chromosome +8, and the common BCR::ABL1 transcript of CML was negative, but e6a2 transcript was positive detected by RT-PCR. The patient was treated with dasatinib 100 mg/d. Three months later, the patients achieved CHR, CCyR and MR4.0. However, the e6a2 transcript is very rare in clinical practice, and more cases of e6a2 transcript need to be studied to clarify its clinical characteristics and improve the treatment effect of these rare cases.

[Application effects of rehabilitation care decision-making scheme based on case management model in severe burn patients].

Objective: To explore the application effects of application of rehabilitation care decision-making scheme based on case management model in severe burn patients. Methods: The study was a non-randomized historical control study. Thirty patients who met the inclusion criteria and received routine rehabilitation nursing in the First Affiliated Hospital of Army Medical University (the Third Military Medical University, hereinafter referred to as the hospital) from April 2021 to March 2022 were included in routine rehabilitation nursing group (26 males and 4 females, aged 48.50 (31.75, 56.25) years), and 30 patients who met the inclusion criteria and received case management rehabilitation nursing in the hospital from April 2022 to March 2023 were included in case management rehabilitation nursing group (22 males and 8 females, aged 46.00 (36.75, 55.25) years). The length of intensive care unit (ICU) stay, total hospitalization day, and total hospitalization cost of the patients in two groups were recorded. At admission, convalescence, discharge, and 6 months after injury, the patients' life quality was evaluated by the concise burn specific health scale, the sleep quality was evaluated by the Pittsburgh sleep quality index, and the functional independence was evaluated by the functional independence rating scale. At convalescence, discharge, and 6 months after injury, the patients' scar status was evaluated by the Vancouver scar scale. At 6 months after injury, a third-party satisfaction questionnaire was used to investigate the efficacy satisfaction of patients. Results: The length of ICU stay and total hospitalization day of patients in case management rehabilitation nursing group were both significantly shorter than those in routine rehabilitation nursing group (with Z values of -1.97 and -1.99, respectively, P<0.05), and the total hospitalization cost was less than that in routine rehabilitation nursing group (Z=-1.99, P<0.05). At discharge and 6 months after injury, the life quality scores of patients in case management rehabilitation nursing group were significantly higher than those in routine rehabilitation nursing group (with t values of -3.19 and -4.43, respectively, P<0.05), while the sleep quality scores were significantly lower than those in routine rehabilitation nursing group (with Z values of -2.18 and -3.33, respectively, P<0.05). There were no statistically significant differences in cognitive function scores of functional independence of patients between the 2 groups at admission, convalescence, discharge, and 6 months after injury (P>0.05). The exercise function scores and total scores of functional independence of patients in case management rehabilitation nursing group at convalescence, discharge, and 6 months after injury were significantly higher than those in routine rehabilitation nursing group (with Z values of -4.37, -2.73, -4.10, -4.37, -2.64, and -4.06, respectively, P<0.05). The scar pigmentation scores of patients in case management rehabilitation nursing group at 6 months after injury were significantly lower than those in routine rehabilitation nursing group (Z=-2.05, P<0.05), and the scar vascularity scores of patients in case management rehabilitation nursing group at discharge and 6 months after injury in case management rehabilitation nursing group were significantly lower than those in routine rehabilitation nursing group (with Z values of -3.16 and -2.07, respectively, P<0.05). The scar pliability scores (with Z values of -3.16, -2.45, and -4.38, respectively, P<0.05), thickness scores (with Z values of -2.56, -2.35, and -4.70, respectively, P<0.05), and total scores (with Z values of -3.77, -3.04, and -3.13, respectively, P<0.05) of patients in case management rehabilitation nursing group at convalescence, discharge, and 6 months after injury were significantly lower than those in routine rehabilitation nursing group. At 6 months after injury, the efficacy satisfaction scores of patients in case management rehabilitation nursing group were 4.00 (3.00, 4.25), which were significantly higher than 3.00 (2.00, 4.00) in routine rehabilitation nursing group (Z=-2.72, P<0.05). Conclusions: The implementation of rehabilitation care decision-making scheme based on case management model can optimize the cost efficiency, improve the effectiveness of clinical treatment, and enhance the life quality and satisfaction of the curative effect of severe burn patients.

[Phenotype and genotype analyses of two pedigrees with inherited fibrinogen deficiency].

Objective: To analyze the phenotype and genotype of two pedigrees with inherited fibrinogen (Fg) deficiency caused by two heterozygous mutations. We also preliminarily probed the molecular pathogenesis. Methods: The prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and plasma fibrinogen activity (Fg∶C) of all family members (nine people across three generations and three people across two generations) were measured by the clotting method. Fibrinogen antigen (Fg:Ag) was measured by immunoturbidimetry. Direct DNA sequencing was performed to analyze all exons, flanking sequences, and mutated sites of FGA, FGB, and FGG for all members. Thrombin-catalyzed fibrinogen polymerization was performed. ClustalX 2.1 software was used to analyze the conservatism of the mutated sites. MutationTaster, PolyPhen-2, PROVEAN, SIFT, and LRT online bioinformatics software were applied to predict pathogenicity. Swiss PDB Viewer 4.0.1 was used to analyze the changes in protein spatial structure and molecular forces before and after mutation. Results: The Fg∶C of two probands decreased (1.28 g/L and 0.98 g/L, respectively). The Fg∶Ag of proband 1 was in the normal range of 2.20 g/L, while it was decreased to 1.01 g/L in proband 2. Through genetic analysis, we identified a heterozygous missense mutation (c.293C>A; p.BßAla98Asp) in exon 2 of proband 1 and a heterozygous nonsense mutation (c.1418C>G; p.BßSer473*) in exon 8 of proband 2. The conservatism analysis revealed that Ala98 and Ser473 presented different conservative states among homologous species. Online bioinformatics software predicted that p.BßAla98Asp and p.BßSer473* were pathogenic. Protein models demonstrated that the p.BßAla98Asp mutation influenced hydrogen bonds between amino acids, and the p.BßSer473* mutation resulted in protein truncation. Conclusion: The dysfibrinogenemia of proband 1 and the hypofibrinogenemia of proband 2 appeared to be related to the p.BßAla98Asp heterozygous missense mutation and the p.BßSer473* heterozygous nonsense mutation, respectively. This is the first ever report of these mutations.