Intensivists' response to hyperoxemia in mechanical ventilation patients: The status quo and related factors.

BACKGROUND: Due to the still sparse literature in China, the investigation of hyperoxemia management is required. Thus, we aim to conduct a retrospective study to provide more information about hyperoxemia management in intensive care unit (ICU) patients. METHODS: We retrospectively screened the medical records of adult patients (age ≥18 years) who required mechanical ventilation (MV) ≥24 hours from January 1, 2018, to December 31, 2018. All arterial blood gas (ABG) tested during MV was retrieved, and MV settings were recorded. The median arterial partial pressure of oxygen (PaO2) >120 mmHg (1 mmHg=0.133 kPa) was defined as mild to moderate hyperoxemia, and PaO2 >300 mmHg as extreme hyperoxemia. Intensivists' response to hyperoxemia was assessed based on the reduction of fraction of inspired oxygen (FiO2) within one hour after hyperoxemia was recorded. Multivariable logistic regression analysis was performed to determine the independent factors associated with the intensivists' response to hyperoxemia. RESULTS: A total of 592 patients were finally analyzed. The median Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 21 (15-26). The PaO2, arterial oxygen saturation (SaO2), FiO2, and positive end expiratory pressure (PEEP) were 96.4 (74.0-126.0) mmHg, 97.8% (95.2%-99.1%), 0.4 (0.4-0.5), and 5 (3-6) cmH2O, respectively. Totally 174 (29.39%) patients had PaO2 >120 mmHg, and 19 (3.21%) patients had extreme hyperoxemia at PaO2 >300 mmHg. In cases of mild to moderate hyperoxemia with FiO2 ≤0.4, only 13 (2.20%) patients had a decrease in FiO2 within one hour. The multivariable logistic regression analysis showed that a positive response was independently associated with FiO2 (odds ratio [OR] 1.09, 95% confidence interval [CI] 1.06-1.12, P<0.001), PaO2 (OR 1.01, 95% CI 1.00-1.01, P=0.002), and working shifts (OR 5.09, 95% CI 1.87-13.80, P=0.001). CONCLUSIONS: Hyperoxemia occurs frequently and is neglected in most cases, particularly when mild to moderate hyperoxemia, hyperoxemia with lower FiO2, hyperoxemia during night and middle-night shifts, or FiO2 less likely to be decreased. Patients may be at a risk of oxygen toxicity because of the liberal oxygen strategy. Therefore, further research is needed to improve oxygen management for patients with MV in the ICUs.

A novel mutation of p.F32I in GJA8 in human dominant congenital cataracts.

AIM: To identify a causative mutation in a three-generation family with autosomal dominant congenital total cataract and dissect the molecular consequence of the identified mutation. METHODS: Clinical and ophthalmological examinations were performed on the affected and unaffected family members. Mutation were screened in recruited family members by polymerase chain reaction (PCR) of the two reported genes (CRYAA and GJA8) which were linked to human total cataracts and direct sequencing of the PCR product. The molecular consequences of the identified mutation was dissected. The plasmids carrying wild-type and mutant mouse ORF of Gja8, coding for connexin 50 (Cx50), were generated and ectopic expressed in 293 cells. Recombinant protein expression and cellular localization of recombinated Cx50 were assessed by confocal microscopy. RESULTS: Clinical and ophthalmological examinations were performed on the affected and unaffected family members. Mutation were screened in recruited family members by PCR of the two reported genes (CRYAA and GJA8) which were linked to human total cataracts and direct sequencing of the PCR product. The molecular consequences of the identified mutation was dissected. The plasmids carrying wild-type and mutant mouse ORF of Gja8, coding for Cx50, were generated and ectopic expressed in 293 cells. Recombinant protein expression and cellular localization of recombinated Cx50 were assessed by confocal microscopy. CONCLUSION: This study has identified a novel cataract mutation in GJA8, which adds a novel mutation to the existing spectrum of Cx50 mutations with cataract. The molecular consequences of p.F32I mutation in GJA8 exclude instability and the mislocalization of mutant Cx50 protein.

Genomic analysis of snub-nosed monkeys (Rhinopithecus) identifies genes and processes related to high-altitude adaptation.

The snub-nosed monkey genus Rhinopithecus includes five closely related species distributed across altitudinal gradients from 800 to 4,500 m. Rhinopithecus bieti, Rhinopithecus roxellana, and Rhinopithecus strykeri inhabit high-altitude habitats, whereas Rhinopithecus brelichi and Rhinopithecus avunculus inhabit lowland regions. We report the de novo whole-genome sequence of R. bieti and genomic sequences for the four other species. Eight shared substitutions were found in six genes related to lung function, DNA repair, and angiogenesis in the high-altitude snub-nosed monkeys. Functional assays showed that the high-altitude variant of CDT1 (Ala537Val) renders cells more resistant to UV irradiation, and the high-altitude variants of RNASE4 (Asn89Lys and Thr128Ile) confer enhanced ability to induce endothelial tube formation in vitro. Genomic scans in the R. bieti and R. roxellana populations identified signatures of selection between and within populations at genes involved in functions relevant to high-altitude adaptation. These results provide valuable insights into the adaptation to high altitude in the snub-nosed monkeys.