A Compound Heterozygosis of Two Novel Mutations Causes Factor X Deficiency in a Chinese Pedigree.

BACKGROUND: Mutations in the F10-coding gene can cause factor X (FX) deficiency, leading to abnormal coagulation activity and severe tendency for hemorrhage. Therefore, identifying mutations in F10 is important for diagnosing congenital FX deficiency. METHODS: We studied a 63-year-old male patient with FX deficiency and 10 of his family members. Clotting and immunological methods were used to determine activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time (TT), fibrinogen levels, FX activity, and FX antigen levels. The platelet count was determined. A mixing study was performed to eliminate the presence of coagulation factor inhibitors and lupus anticoagulant. Mutations were searched using whole-exome sequencing and certified by Sanger sequencing. RESULTS: Genetic analysis of the proband identified two single-base substitutions: c.1085G>A (p.Ser362Asn) and c.1152C>A (p.Tyr384Ter, termination codon, caused by the DNA sequence TAA). His FX activity and antigen levels were 1.7% and 408.53 pg/mL, respectively; aPTT and PT were 52.3 and 48.0 s, respectively. One brother had the same compound heterozygous mutations, and his FX activity and antigen levels were 1.3% and 465.47 pg/mL, respectively; his aPTT and PT were 65.2 and 54.5 s, respectively. His mother, another brother, and one sister were heterozygous for c.1085G>A (p.Ser362Asn), and his daughter and grandson (6 years old) were heterozygous for c.1152C>A (p.Tyr384Ter). CONCLUSION: The heterozygous variants p.Ser362Asn or p.Tyr384Ter indicate mild FX deficiency, but the compound heterozygous mutation of the two causes severe congenital FX deficiency and bleeding. Genetic analysis of these two mutations may help characterize the bleeding tendency and confirm congenital FX deficiency.

[Characteristics and failure risk factors of sequential high-flow nasal cannula oxygen therapy after weaning from invasive ventilation in patients of surgical intensive care unit].

OBJECTIVE: To investigate the characteristics and failure risk factors of sequential high-flow nasal cannula oxygen therapy (HFNC) after weaning from invasive ventilation. METHODS: The patients who received sequential HFNC after weaning from invasive ventilation admitted to surgical intensive care unit (ICU) of Peking University People's Hospital from June 1st 2016 to May 31st 2018 were retrospectively analyzed. Clinical variables, respiratory therapy parameters, respiratory variables, cardiac variables and outcomes were reviewed and analyzed. Treatment characteristics of HFNC after weaning was analyzed. Patients were divided into HFNC success group and HFNC failure group according to the failure of HFNC, and the differences between the two groups were compared. The independent risk factors of HFNC treatment failure were analyzed by Logistic regression analysis. The value of predictive treatment failure of risk factors and regression models were analyzed by receiver operating characteristic (ROC) curve. RESULTS: A total of 99 patients were included, 61 men, and the median age was 67.0 (57.0, 76.0) years old. The medianinitial HFNC flow was 50 (50, 60) L/min, and inspired oxygen concentration (FiO2) was 0.50 (0.40, 0.60). Eighteen patients experienced HFNC failure (18.2%). Compared with the HFNC success group, the sequential organ failure assessment (SOFA) score in the HFNC failure group was higher [4 (3, 5) vs. 2 (1, 3), P < 0.01], B type natriuretic peptide (BNP) before HFNC therapy were significant higher [ng/L: 647.2 (399.2, 1 331.3) vs. 127.2 (55.2, 369.5), P < 0.01], and respiratory frequency (RR) and heart rate (HR) were significant faster, mean arterial pressure (MAP) was significant higher, oxygen index (PaO2/FiO2) was significant lower after 30 minutes HFNC treatment [RR (times/min): 26 (22, 28) vs. 19 (17, 21), HR (bpm): 105 (97, 107) vs. 85 (77, 90), MAP (mmHg, 1 mmHg = 0.133 kPa): 104.3 (101.7, 110.7) vs. 92.3 (88.3, 97.7), PaO2/FiO2 (mmHg): 207.3 (185.8, 402.8) vs. 320.2 (226.2, 361.5), all P < 0.05]. It was shown by multiple Logistic regression analysis that the SOFA score [odds ratio (OR) = 2.818, P = 0.022, ß = 1.036], BNP before HFNC treatment (OR = 1.002, P = 0.033, ß = 0.002) and HR after HFNC treatment 30 minutes (OR = 1.140, P = 0.032, ß = 0.131) were independent risk factors for HFNC treatment failure. It was shown by ROC curve that the area under the ROC curve (AUC) for the prediction of HFNC failure was 0.840, 0.859, 0.860 and 0.962 for SOFA, BNP before HFNC treatment, HR after HFNC treatment 30 minutes, and regression model, all had good forecast values (all P < 0.01). CONCLUSIONS: HFNC is one of the commonly used oxygen therapy methods in the ICU, but not all patients who are treated as a sequential therapy after invasive mechanical ventilation weaning can benefit from it. SOFA score, BNP before HFNC treatment and HR after 30 minutes HFNC treatment were independent risk factors of HFNC failure. Each independent risk factor and regression model can predict the success of HFNC treatment.

[Promoting patient- and family-centered care services in intensive care unit].

OBJECTIVE: In recent years, more and more people have recognized the importance of patients' family in the intensive care unit (ICU) in medical care, and advocated the use of patient- and family-centered care (PFCC) in the ICU. This article explains the content (family presence, family support, communication with family members, consultations and ICU team members, environmental issues) and significance of PFCC in the ICU, and provides guidance for the practice of PFCC in China.

Transcriptome analysis of phycocyanin inhibitory effects on SKOV-3 cell proliferation.

Phycocyanin (PC) from Spirulina platensis has inhibitory effects on tumor cell growth. In this research, the transcriptome study was designed to investigate the underlying molecular mechanisms of PC inhibition on human ovarian cancer cell SKOV-3 proliferation. The PC IC50 was 216.6µM and 163.8µM for 24h and 48h exposure, respectively, as determined by CCK-8 assay. The morphological changes of SKOV-3 cells after PC exposure were recorded using HE staining. Cells arrested in G2/M stages as determined by flow cytometry. The transcriptome analysis showed that 2031 genes (with > three-fold differences) were differentially expressed between the untreated and the PC-treated cells, including 1065 up-regulated and 966 down-regulated genes. Gene ontology and KEGG pathway analysis identified 18 classical pathways that were remarkably enriched, such as neurotrophin signaling pathway, VEGF signaling pathway and P53 signaling pathway. qPCR results further showed that PTPN12, S100A2, RPL26, and LAMA3 increased while HNRNPA1P10 decreased in PC-treated cells. Molecules and genes in those pathways may be potential targets to develop treatments for ovarian cancer.