Diagnostic role of SPP1 and collagen IV in a rat model of type 2 diabetes mellitus with MASLD.

Type 2 diabetes mellitus combined with metabolic dysfunction-associated steatotic liver disease (MASLD) leads to an increasing incidence of liver injury year by year, and patients are at a significantly higher risk of developing cirrhosis or even liver failure. No drugs have emerged to specifically treat this disease. The aim of this study is to investigate the mechanisms and causative hub genes of type 2 diabetes combined with MASLD. The data were obtained through the GEO platform for bioinformatics analysis and validated by in vitro experiments to find the causative targets of type 2 diabetes mellitus combined with MASLD, which will provide some theoretical basis for the development of future therapeutic drugs. GSE23343 and GSE49541 were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) in type 2 diabetes mellitus combined with MASLD for functional enrichment analysis. And STRING database and Cytoscape software were used to construct Protein-Protein Interaction (PPI) and hub gene networks. And GO (gene ontology, GO) analysis and KEGG (Kyoto encyclopedia of genes and genomes, KEGG) enrichment analysis were performed on target genes. A total of 185 co-expressed DEGs were obtained by differential analysis, and 20 key genes involved in the development and progression of type 2 diabetes were finally screened. These 20 key genes were involved in 529 GO enrichment results and 20 KEGG enrichment results, and were mainly associated with ECM-receptor interaction, Focal adhesion, Human papillomavirus infection, PI3K-Akt signaling pathway, and the Toll-like receptor signaling pathway. A total of two target genes (SPP1, collagen IV) were found to be highly correlated with type 2 diabetes mellitus combined with MASLD. Real time PCR results showed that there was a significant difference in SPP1 and collagen IV mRNA expression among the three groups (P < 0.05). SPP1 and Collagen IV may be candidate biomarkers for type 2 diabetes mellitus combined with MASLD, as verified by bioinformatics screening and in vitro experiments. Our findings provide new targets for the treatment of type 2 diabetes combined with MASLD.

Glucocorticoid-induced delayed fracture healing and impaired bone biomechanical properties in mice.

BACKGROUND: The objective of the study was to investigate the effects of glucocorticoid (GC) on the fracture healing process in a closed femur fracture mice model. MATERIALS AND METHODS: Forty 12-week-old female CD-1 mice were randomly allocated into four groups: healthy control and mice with prednisone exposure (oral gavage), 6 mg/kg/day (GC-L), 9 mg/kg/day (GC-M) and 12 mg/kg/day (GC-H). Three weeks after the initiation of prednisone dosing, closed femur fractures were created on prednisone-exposed mice and the healthy control. Prednisone administration was continued for 9 weeks post-fracture, and X-ray imaging was performed weekly to monitor the fracture healing process until the mice were euthanized. Necropsy was performed after 9 weeks and the fractured femurs were isolated and processed at necropsy for micro-CT and biomechanical property analysis. Another 20 mice (control and GC-H, 10 mice/group) were used for histology and micro-CT analysis at early time point (2-week post fracture) with continued prednisone exposure. RESULTS: The results showed that oral administration of prednisone for 3 months in this strain of mice could inhibit endochondral ossification and delay the healing process, especially hard callus formation (woven bone) and bone remodeling during healing. It also could significantly decrease bone biomechanical properties. CONCLUSION: Long-term GC administration leads to significantly delayed fracture healing and impaired bone biomechanical properties. This mouse model may be used to systematically study the cellular and molecular mechanisms underlying fracture healing with GC treatment background and may also be used to study the influence of different therapeutic interventions for bone fracture healing.

Radial Extracorporeal Shock Wave Therapy in a Person With Advanced Osteonecrosis of the Femoral Head.

This case report describes the first patient with avascular necrosis of the femoral head of Association Research Circulation Osseous stage IV, treated with radial extracorporeal shock wave therapy. By contrast, previous studies demonstrated the efficacy of a single treatment of focused extracorporeal shock wave therapy in improving pain and Harris Hip Scale in patients with avascular necrosis of the femoral head of Association Research Circulation Osseous stage I to III. The affected hip was treated with 6000 impulses of radial extracorporeal shock wave therapy at 10 Hz and an intensity ranging from 2.5 to 4.0 bar at 7-day intervals for 24 mos. The Harris Hip Scale values were 33, 43, 56, 77, 81, 88, and 92 at baseline and 1, 3, 6, 12, 18, and 24 mos, respectively. The radiographs showed that the subluxation of the right hip was slightly aggravated. Joint effusion was reduced, bone marrow edema disappeared, the density became more uniform, and the gluteal muscles were more developed based on magnetic resonance imaging. Increased tracer uptake was evident along the joint margin and superolateral aspect of the head both before and after radial extracorporeal shock wave therapy. This case report demonstrates the feasibility of long-term radial extracorporeal shock wave therapy in Association Research Circulation Osseous stage IV patients.

TNF-α promoter single nucleotide polymorphisms and haplotypes associate with susceptibility of immune thrombocytopenia in Chinese adults.

OBJECTIVE: Tumor necrosis factor-alpha (TNF-α) participates as a candidate susceptibility factor for immune thrombocytopenia (ITP). This study attempted to investigate the association between five single nucleotide polymorphisms (SNPs) spanning the TNF-α promoter and the susceptibility of primary ITP in Chinese Han adults. METHODS: In 215 adult primary ITP patients and 206 healthy controls, SNPs were detected by PCR-RFLP and PCR-SSP. The χ(2) test or fisher's exact test was used to compare frequencies of genotypes and alleles between patients and controls. Haplotypes were analyzed with the SHEsis online program. TNF-α, IFN-γ and Galectin-9 mRNA of 35 newly diagnosed adult ITP patients and 35 healthy controls were detected by qRT-PCR. RESULTS: The haplotype GGC (-238G/-308G/-857C) of TNF-α promoter was significantly associated with a decreased susceptibility of primary ITP, especially in males. The relative levels of mRNA expression of TNF-α, IFN-γ and Gal-9 in adult active primary ITP patients was significantly up-regulated compared with patients in remission and controls. CONCLUSIONS: This study represented the first report that the haplotype GGC of TNF-α was differentially associated with the susceptibility of primary ITP in Chinese Han adults. The up-regulation of TNF-α, IFN-γ and Galectin-9 was significantly correlated with active primary ITP in adult patients.

A novel approach to improve hand hygiene compliance of student nurses.

BACKGROUND: The National University Hospital, Singapore routinely undertakes standardized Hand Hygiene auditing with results produced by ward and by staff type. In 2010 concern was raised over consistently low compliance by nursing students averaging 45% (95% CI 42%-48%) prompting us to explore novel approaches to educating our next generation of nurses to improve their hand hygiene practice.We introduced an experiential learning assignment to final year student nurses on attachment to NUH inclusive of hand hygiene auditor training followed by a period of hand hygiene observation. The training was based on the World Health Organisation (WHO) "My 5 moments for hand hygiene" approach. Upon completion students completed an anonymous questionnaire to evaluate their learning experience. FINDINGS: By 2012, nursing students were 40% (RR: 1.4, 95% CI 1.3-1.5, p<0.001) more likely to comply with hand hygiene practices. 97.5% (359/368) of nursing students felt that the experience would enhance their own hand hygiene practice and would recommend participating in audits as a learning instrument. CONCLUSIONS: With consideration of all stakeholders a sustainable, flexible, programme was implemented. Experiential learning of hand hygiene was a highly valued educational tool and in our project was directly associated with improved hand hygiene compliance. Feedback demonstrated popularity amongst participants and success in achieving its program objectives. While this does not guarantee long term behavioural change it is intuitive that instilling good habits and messages at the early stages of a career will potentially have significant long-term impact.

Polymorphisms of the T-cell immunoglobulin and mucin domain molecule-3 are not associated with autoimmune Graves' disease in a Chinese Han Population.

OBJECTIVES: This study aimed to investigate the association between polymorphisms of T-cell immunoglobulin and mucin domain molecule-3 (TIM-3) and Graves' disease (GD) in a Chinese population. DESIGN AND METHODS: Genomic DNA was extracted from peripheral blood cells of the 182 GD patients and 150 control subjects. The TIM-3 gene polymorphic sites were genotyped. We also analyzed the relationships between the genotypes of each SNP and serum specific clinical variables. To detect whether the variants were associated with the TIM-3 expression, we further studied 40 patients by using the method of real-time quantitative reverse-transcription polymerase chain reaction (real-time RT-PCR). RESULTS: The genotype and allele frequency of each polymorphic site were not significantly different between GD and control individuals. Furthermore, it also showed no relationship between the variants and TIM-3 mRNA expression. CONCLUSIONS: Our results demonstrated that the polymorphisms of TIM-3 gene may not contribute to GD susceptibility in the Chinese Han population.

[Correlation between gene polymorphism of endothelial protein C receptor and cerebral infarction in Chinese Han population of Hubei province].

In order to explore the distribution frequency of endothelial protein C receptor (EPCR) gene A6936G variant and to study the correlation between this mutation and cerebral infarction in Chinese Han population of Hubei province district. The genotype and allele frequencies of EPCR A6936G were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 380 cerebral infarction patients and 380 healthy Chinese Han persons. The results indicated that the frequencies of A/A, A/G and G/G genotypes in cerebral infarction group were 77.1%, 22.1% and 0.8% respectively. While the frequencies of A/A and A/G genotypes in control group were 88.2% and 11.8%, and without G/G genotype. It is concluded that A6936G polymorphism of EPCR can be detected in Chinese Han population of Hubei province district, which may be correlated with the increasing risk of thrombosis in cerebral infarction patients.

[Clinical value of D-dimer in diagnosis and treatment of thrombotic diseases].

OBJECTIVE: To investigate the clinical significance of D-dimer detection in the diagnosis and treatment of thrombotic diseases. METHODS: Peripheral blood samples were collected from 156 patients with acute cerebral infarction (ACI), 38 patients with deep venous thrombosis (DVT), and 148 patients with acute myocardial infarction (AMI), all under relevant treatment, and 170 healthy examinees. The level of plasma D-dimer was detected by ELISA before and after the treatment. RESULTS: The positive rates of plasma D-dimer of the ACI, DVT, and AMI patients before treatment were 59.3%, 100.0%, and 61.7% respectively, all significantly higher than that of the health examinees (4.3%, all P < 0.01). And the positive rates of plasma D-dimer decreased rapidly after treatment in the patients of these 3 groups who responded magnificently to thrombolysis treatment (all P < 0.01). CONCLUSION: Increased in most thrombotic patients, the plasma D-dimer level helps diagnose thrombotic diseases early and reflect the efficacy of thrombolysis treatment.

Impact of trisomy 8 on cytobiological and clinical features of acute myelomonocytic and monocytic leukemia.

To evaluate the impact of trisomy 8 on cytobiological and clinical features of acute myelomonocytic and monocytic leukemia (M(4), M(5)), a total of 56 cases of acute myelomonocytic and monocytic leukemia were investigated. Karyotypes were analyzed by G-banding or R-banding. The immunotypes in all cases were detected by flow cytometry. And the clinical characteristics at the first visit were analyzed retrospectively. The results showed that thirty-four of 56 (60.7%) patients had normal cytogenetics; 10 (17.9%) patients had trisomy 8 in their karyotypes, including 3 (5.4%) patients with trisomy 8 as the sole aberration; and 12 (21.4%) patents had other cytogenetic abnormalities (except trisomy 8). All trisomy 8 cases demonstrated a increased expression frequency of surface markers of myeloid progenitor cells CD34 (P < 0.01) and CD117 (P < 0.05) and a decreased expression frequency of surface markers of mature monocytes CD11c (P < 0.01) and CD14 (P < 0.05), compared with normal cytogenetics cases. Patients with trisomy 8 were slightly older (P < 0.05), which had lower percentages of peripheral blasts (P < 0.05) and lower WBC (P < 0.05) than the patients without trisomy 8. Patients with trisomy 8 had a shorter disease-free survival time than that of patients with normal cytogenetics (P < 0.05). It is concluded that trisomy 8 may play an important role in the pathogenesis and progression of acute myelomonocytic/monocytic leukemia (M(4)/M(5)), whic seems to be related with a block in differentiation of monocytes. Therefore, trisomy 8 may be an adverse prognostic factor for patients with M(4) or M(5).

Cytobiological and clinicobiological features of AML with 11q23 chromosome abnormalities.

To investigate the interrelationship among morphology, immunology and clinical features in adult acute myeloid leukemia cases with 11q23 chromosome abnormalities, 210 newly diagnosed AML patients were retrospectively analyzed by cell morphology, immunophenotyping, G-banding or R-bamding analysis and clinical features. The results showed that 13 cases were found with 11q23 rearrangements or deletion (the incidence rate was 6.19%.), totally 84.6% showed the involvement with the monocytic lineage. Immunophenotyping tests indicated that AML cases with 11q23 abnormalities usually expressed the marker molecules of hematopoietic stem or progenitor cells, monocytic lineage cells, such as CD34, CD117, CD14, CD15 and CD11b. The complete remission rate of the cases with 11q23 abnormalities was comparable to that of the cases with normal karyotype (P = 0.075), but the median disease-free survival in the former was significantly lower than that in the latter (P < 0.001). It is concluded that the category AML with 11q23 abnormalities accounts for 6.19% of all the newly diagnosed AML cases, that seems to be closely associated with monocytic differentiation blocking with a dismal prognosis.