[Molecular mechanism analysis of a family with hereditary coagulation F â ª deficiency caused by compound heterozygous mutations].

A 34 year old female patient was scheduled to undergo surgical resection due to a "breast nodule". Preoperative examination revealed an activated partial thromboplastin time (APTT) of 66.2 seconds, coagulation factor Ⅺ activity (FⅪ: C) of 2%, and FⅪ antigen (FⅪ: Ag) of 40.3%. The patient and family members showed no abnormal bleeding symptoms. Diagnosed as hereditary coagulation factor Ⅺ deficiency. Genetic testing revealed that the F11 gene had a heterozygous nonsense mutation in exon 10, c.1107C>A (p.Tyr351stop), and a heterozygous missense mutation in exon 13, c.1562A>G (p.Tyr503Cys). The father and son were p Heterozygous carriers of Tyr351stop mutation, while the mother and daughter are p Heterozygous carriers of Tyr503Cys mutations. The in vitro expression results showed that p The Tyr351stop mutation resulted in a significant decrease in the transcription level of F11 gene, while p The Tyr503Cys mutation has no effect on the transcription level and protein expression level of F11 gene, but it leads to a significant decrease in the level of FⅪ:C in the cell culture supernatant.

MiR-133a alleviates renal injury caused by sepsis by targeting BNIP3L.

OBJECTIVE: Sepsis is an important cause of acute kidney injury (AKI), seriously jeopardizing the health of patients. This paper's aim was to investigate whether microRNA-133a had a protective effect on sepsis-induced kidney injury. MATERIALS AND METHODS: We established a kidney injury model with lipopolysaccharide (LPS) and divided TCMK-1 cells into 4 groups: control group (con); LPS treatment group; LPS + negative control (NC) treatment group; LPS + miR-133a mimic (mim) group. The expressions of miR-133a, TNF-α mRNA, IL-6 mRNA, Bax mRNA, Bcl-2 mRNA, BNIP3L mRNA, IκKα Mrna and IκB-α mRNA were detected by PCR. Western blot was used to detect the protein expression of TNF-α, IL-6, Bax, Bcl-2, BNIP3L, IκKα and IκB-α. Cell viability was measured by cell counting kit-8 (CCK-8). Flow cytometry was utilized to detect apoptosis rate. IL-1ß immunofluorescence and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining were used to observe the inflammation and apoptosis in TCMK-1 cells. RESULTS: The miR-133a expression was decreased in TCMK-1 cells treated with LPS. In the LPS treatment group, the expression of TNF-α, IL-6, Bax, BNIP3L and IκKα increased, and the expression of Bcl-2 and IκB-α decreased. When overexpressing miR-133a, the protein and mRNA expression of TNF-α, IL-6, Bax, BNIP3L and IκKα decreased markedly, while the expression of Bcl-2 and IκB-α increased markedly. Compared with the LPS-treated group, the apoptotic rate, the number of TUNEL-positive cells, and the immunofluorescence intensity of IL-1ß in LPS+mim group were greatly decreased. CONCLUSIONS: The miR-133a expression was decreased in TCMK-1 cells treated by LPS and miR-133a can inhibit inflammation and apoptosis of TCMK-1 cells induced by LPS by targeting BNIP3L via inhibiting NF-κB pathway.

Association between Serum Uric Acid Level and Carotid Atherosclerosis in Chinese Individuals Aged 75 Years or Older: A Hospital-Based Case-Control Study.

OBJECTIVES: To investigate the association between serum uric acid level and the presence and progression of carotid atherosclerosis in Chinese individuals aged 75 years or older. DESIGN: Case-control study. SETTING: In a teaching hospital. PARTICIPANTS: Five hundred and sixty-four elderlies (75 years or above) who underwent general health screening in our hospital were enrolled. MEASUREMENTS: The detailed carotid ultrasound results, physical examination information, medical history, and laboratory test results including serum uric acid level were recorded, these data were used to analyze the relationship between serum uric acid level and carotid atherosclerosis. Then, subjects who underwent the second carotid ultrasound 1.5-2 years later were further identified to analyzed the relationship between serum uric acid and the progression of carotid atherosclerosis. RESULTS: A total of 564 subjects were included, carotid plaque was found in 482 (85.5%) individuals. Logistic regression showed that subjects with elevated serum uric acid (expressed per 1 standard deviation change) had significantly higher incidence of carotid plaque (odds ratio, 1.37; 95% confidence interval, 1.07-1.75; P= 0.012) after controlling for other factors. A total of 236 subjects underwent the follow-up carotid ultrasound. Linear regression showed that serum uric acid level (expressed per 1 standard deviation change; 1 standard deviation = 95.5 µmol/L) was significantly associated with percentage of change of plaque score (P = 0.008). Multivariable linear regression showed that 1 standard deviation increase in serum uric acid levels was expected to increase 0.448% of plaque score (P = 0.023). CONCLUSION: The elevated serum uric acid level may be independently and significantly associated with the presence and progression of carotid atherosclerosis in Chinese individuals aged 75 years or older.