Objective:To explore the prognostic effect and safety of neurally adjusted ventilatory assist (NAVA) mode on the patients with severe neurological cerebrovascular disease undergoing mechanical ventilation.Methods:A prospective study was conducted. Fifty-four patients with cerebrovascular disease undergoing mechanical ventilation admitted to the neurosurgery intensive care unit (NSICU) of the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital) from December 2020 to May 2022 were enrolled. They were divided into NAVA group and pressure support ventilation (PSV) group by computer random number generator with 27 patients in each group. The ventilation time of the two groups was ≥72 hours. The general basic data of the two groups were recorded. The time without mechanical ventilation 28 days after enrollment, total length of mechanical ventilation, survival rate of 90 days after enrollment, length of NSICU stay, total length of hospital stay, NSICU mortality, in-hospital mortality, Glasgow outcome score (GOS), complications related to mechanical ventilation, and changes of respiratory mechanics indexes, arterial blood gases, vital signs, and diaphragm function indexes were observed.Results:The time without mechanical ventilation 28 days after enrollment in the NAVA group was significantly longer than that in the PSV group [days: 22 (15, 26) vs. 6 (0, 23), P < 0.05]. However, there were no significant differences in the total length of mechanical ventilation, 90-day survival rate, length of NSICU stay, total length of hospital stay, NSICU mortality, in-hospital mortality, GOS score, and incidence of mechanical ventilator-related complications between the two groups. In terms of respiratory mechanics parameters, the expiratory tidal volume (VTe) on 3 days after mechanical ventilation of patients in the NAVA group was significantly lower than that on 1 day and 2 days, and significantly lower than that in the PSV group [mL: 411.0 (385.2, 492.6) vs. 489.0 (451.8, 529.4), P < 0.01]. Minute ventilation (MV) at 2 days and 3 days in the NAVA group was significantly higher than that at 1 day, and significantly higher than that in the PSV group at 2 days [L/min: 9.8 (8.4, 10.9) vs. 7.8 (6.5, 9.8), P < 0.01], while there was no significant change of MV in the PSV group. At 1 day, peak airway pressure (Ppeak) and mean airway pressure (Pmean) in the NAVA group were significantly lower than those in the PSV group [Ppeak (cmH 2O, 1 cmH 2O≈0.098 kPa): 14.0 (12.2, 17.0) vs. 16.6 (15.0, 17.4), Pmean (cmH 2O): 7.0 (6.2, 7.9) vs. 8.0 (7.0, 8.2), both P < 0.05]. However, there was no significant difference in the Ppeak or Pmean at 2 days and 3 days between the two groups. In terms of arterial blood gas, there was no significant difference in pH value between the two groups, but with the extension of mechanical ventilation time, the pH value at 3 days of the two groups was significantly higher than that at 1 day. Arterial partial pressure of oxygen (PaO 2) at 1 day in the NAVA group was significantly lower than that in the PSV group [mmHg (1 mmHg≈0.133 kPa): 122.01±37.77 vs. 144.10±40.39, P < 0.05], but there was no significant difference in PaO 2 at 2 days and 3 days between the two groups. There was no significant difference in arterial partial pressure of carbon dioxide (PaCO 2) or oxygenation index (PaO 2/FiO 2) between the two groups. In terms of vital signs, the respiratory rate (RR) at 1, 2, and 3 days of the NAVA group was significantly higher than that of the PSV group [times/min: 19.2 (16.0, 25.2) vs. 15.0 (14.4, 17.0) at 1 day, 21.4 (16.4, 26.0) vs. 15.8 (14.0, 18.6) at 2 days, 20.6 (17.0, 23.0) vs. 16.7 (15.0, 19.0) at 3 days, all P < 0.01]. In terms of diaphragm function, end-inspiratory diaphragm thickness (DTei) at 3 days in the NAVA group was significantly higher than that in the PSV group [cm: 0.26 (0.22, 0.29) vs. 0.22 (0.19, 0.26), P < 0.05]. There was no significant difference in end-expiratory diaphragm thickness (DTee) between the two groups. The diaphragm thickening fraction (DTF) at 2 days and 3 days in the NAVA group was significantly higher than that in the PSV group [(35.18±12.09)% vs. (26.88±8.33)% at 2 days, (35.54±13.40)% vs. (24.39±9.16)% at 3 days, both P < 0.05]. Conclusions:NAVA mode can be applied in patients with neuro-severe cerebrovascular disease, which can prolong the time without mechanical ventilation support and make patients obtain better lung protective ventilation. At the same time, it has certain advantages in avoiding ventilator-associated diaphragm dysfunction and improving diaphragm function.

After implantation, complex and highly specialized molecular events render functionally distinct organ formation, whereas how the epigenome shapes organ-specific development remains to be fully elucidated. Here, nano-hmC-Seal, RNA bisulfite sequencing (RNA-BisSeq), and RNA sequencing (RNA-Seq) were performed, and the first multilayer landscapes of DNA 5-hydroxymethylcytosine (5hmC) and RNA 5-methylcytosine (m⁵C) epigenomes were obtained in the heart, kidney, liver, and lung of the human foetuses at 13-28 weeks with 123 samples in total. We identified 70,091 and 503 organ- and stage-specific differentially hydroxymethylated regions (DhMRs) and m⁵C-modified mRNAs, respectively. The key transcription factors (TFs), T-box transcription factor 20 (TBX20), paired box 8 (PAX8), krueppel-like factor 1 (KLF1), transcription factor 21 (TCF21), and CCAAT enhancer binding protein beta (CEBPB), specifically contribute to the formation of distinct organs at different stages. Additionally, 5hmC-enriched Alu elements may participate in the regulation of expression of TF-targeted genes. Our integrated studies reveal a putative essential link between DNA modification and RNA methylation, and illustrate the epigenetic maps during human foetal organogenesis, which provide a foundation for for an in-depth understanding of the epigenetic mechanisms underlying early development and birth defects.
Humans ; DNA Methylation ; RNA ; Epigenesis, Genetic ; DNA/genetics* ; Basic Helix-Loop-Helix Transcription Factors/genetics*

The DNA fragments of ag85b、esat-6、hsp65、mpb64 and ag85b-esat-6、hsp65-esat-6、mpb64-esat-6 were amplified by PCR and SOE technique.These seven fragments were inserted into pCDNA3.1(+)vector to construct recombinant plasmids pCA、pCE6、pCH、pCM、pCAE、pCHE and pCME.The seven plasmids were transfected into SP2/0 cell in vitro to detect the expression of target genes.BALB/c mice were intramuscularly vaccinated with the seven plasmids and the control vector pCDNA3.1(+)and PBS respectively.The serum antibodies and the spleen lymphocyte proliferation(SLP)and secreted IFN～? of spleen were tested.The results of indirect ELISA showed the levels of antibodies in all recombinant plasmids groups were significantly higher than the two control groups(P