[Analysis of compliance with lung protective mechanical ventilation strategy in patients with acute respiratory distress syndrome].

Objective: To assess the compliance with a lung protective ventilation strategy and to evaluate the relationship with prognosis in patients with acute respiratory distress syndrome (ARDS). Methods: In the prospective multicenter cohort study (CHARDS), patients with ARDS undergoing invasive mechanical ventilation were enrolled to collect essential information, mechanical ventilation data, and prognostic data. Compliance was operationally defined as tidal volume ≤7 ml/kg predicted body weight (PBW) or plateau pressure ≤30 cmH2O or driving pressure≤15 cmH2O. Tidal volume data collected 7 days prior to ventilation after ARDS diagnosis were categorized into four groups: standard group (Group A, 100% compliance), non-standard group (Group B, 50%-99% compliance, Group C,1%-49% compliance,and Group D,totally non-compliant). Plateau pressure and drive pressure measurements were recorded on the first day. Stepwise regression, specifically Logistics regression, was used to identify the factors influencing ICU survival. Results: A total of 449 ARDS patients with invasive mechanical ventilation were included; the proportion of mild, moderate, and severe patients was 71 (15.8%), 198 (44.1%) and 180 (40.1%), respectively. During the first 7 days, a total of 2880 tidal volume measurements were recorded with an average tidal volume of (6.89±1.93) ml/kg PBW. Of these measurements, 53.2% were found to be≤7 ml/kg PBW. The rates of compliance with lung protective mechanical ventilation were 29.8% (134/449), 24.5% (110/449), 23.6% (106/449), and 22% (99/449) in groups A, B, C, and D, respectively. In the standard group, the tidal volume for mild ARDS patients was 18.3%(13/71), while it was 81.7%(58/71)in the non-standard group. Similarly, in patients with moderate ARDS, the tidal volume was 25.8% (51/198) in the standard group, while it was 74.2% (147/198) in the non-standard group. Finally, in patients with severe ARDS, the tidal volume was 38.9% (70/180) in the standard group, while it was 61.1% (110/180) in the non-standard group. Notably, the compliance rate was higher in patients with moderate and severe ARDS in group A compared to patients with mild and moderate ARDS (18.3% vs. 25.8% vs. 38.9%, χ2=13.124, P=0.001). Plateau pressure was recorded in 221 patients, 95.9% (212/221) patients with plateau pressure≤30 cmH2O, and driving pressure was recorded in 207 patients, 77.8% (161/207) patients with a driving pressure ≤15 cmH2O.During the first 7 days, the mortality rate in the intensive care unit (ICU) was lower in the tidal volume standard group compared to the non-standard group (34.6% vs. 51.3%, χ2=10.464, P=0.001). In addition, the in-hospital mortality rate was lower in the standard group compared to the non-standard group (39.8% vs. 57%, χ2=11.016, P=0.001).The results of the subgroup analysis showed that the mortality rates of moderate and severe ARDS patients in the standard group were significantly lower than those in the non-standard group, both in the ICU and in the hospital (all P<0.05). However, there was no statistically significant difference in mortality among mild ARDS patients (all P>0.05). Conclusions: There was high compliance with recommended lung protective mechanical ventilation strategies in ARDS patients, with slightly lower compliance in patients with mild ARDS, and high compliance rates for plateau and drive pressures. The tidal volume full compliance group had a lower mortality than the non-compliance group, and showed a similar trend in the moderate-to-severe ARDS subgroup, but there was no significant correlation between compliance and prognosis in patients with mild ARDS subgroup.

[Prognosis and related risk factors of acute respiratory distress syndrome in elder patients].

Objective: To study the risk factors associated with the hospital survival rate of elder patients with acute respiratory distress syndrome (ARDS) in Medical/Respiratory Intensive Care Units (MICUs/RICUs) by evaluating the prognosis, and therefore to provide insight into patient treatment strategy. Methods: Twenty MICUs/RICUs of 19 general hospitals in mainland China participated in the multicenter prospective cohort study carried out from Mar 1st, 2016 to Feb 28th, 2018. Patients who met the criteria of Berlin ARDS and older than 65 years were recruited. Baseline data, risk factors of ARDS, ventilator setup and prognosis data were collected from all patients. Univariant and multivariant regression analysis were conducted to analyze the factors associated with the prognosis. Results: 170 elder ARDS patients (age≥65 years) met the Berlin ARDS criteria, among whom 8.8% (15/170), 42.9% (73/170) and 48.2% (82/170) patients had mild, moderate and severe ARDS, respectively. The most common predisposing factor for elder ARDS was pneumonia, which was present in 134 patients (78.8%). 37.6% (64/170) patients were treated with noninvasive mechanical ventilation (NIV), but 43.8% (28/64) cases experienced treatment failure. 76.5% (130/170) patients were treated with invasive mechanical ventilation. All patients 80 years or older were given invasive mechanical ventilation. 51.8% (88/170) cases had complications of non-pulmonary organ failure. 61.8% (105/170) patients deceased during hospital stay. Multivariant logistic analysis showed that the independent risk factors for hospital survival rate in elder patients with ARDS were SOFA score (P=0.030, RR=0.725, 95% CI 0.543-0.969), oxygen index after 24 hours of ARDS diagnosis (P=0.030, RR=0.196, 95% CI 0.045-0.853), accumulated fluid balance within 7 days after diagnosis of ARDS (P=0.026, RR=1.000, 95% CI 1.000-1.000) and shock (P=0.034, RR=0.140, 95% CI 0.023-0.863). Conclusion: Among 20 ICUs, the high mortality rate of elder patients with ARDS was correlated with higher 24 hour SOFA score, lower 24 hour oxygen index after ARDS diagnosis, more positive fluid balance within 7 days and concomitant shock. The conservative fluid strategy within 7 days of ARDS diagnosis may benefit the elder ARDS patients.

Combination of mRNA of Repair-related Genes in Rat Skeletal Muscles for Wound Age Estimation.

ABSTRACT: Objective To investigate the estimation of early and mid-term wound age by a combination of four mRNAs, the DNA polymerase delta-interacting protein 3 （POLDIP3） mRNA, regulator of chromosome condensation 1 like （RCC1L） mRNA, proline-rich 5 （PRR5） mRNA, and ribonucleic acid export 1 （RAE1） mRNA in rats skeletal muscles. Methods The model of rat skeletal muscle contusion was established, and then contusion area muscle tissue was extracted 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 h after injury. Histomorphological changes during the repair process after rat skeletal muscle contusion were observed. The relative expressions of Poldip3, Rcc1l, Prr5 and Rae1 mRNAs were detected by reverse transcription real-time quantitative polymerase chain reaction （RT-qPCR）. Different stages of wound age were classified by using the expression patterns of four genes at various time points after injury. The accuracy of the results was verified by Fisher discriminant analysis. Results Histomorphological results showed that the repair process after skeletal muscle contusion occurred with the prolonging of time. Through combination of the expression trends of the four kinds of mRNAs, the 48 h after injury could be divided into three periods, 4-12 h, 16-28 h and 32-48 h. The Fisher discrimination method showed that the classification accuracy rates of the three periods were 83.3%, 75.0% and 73.3%, respectively. Conclusion The classification discrimination based on the relative expression of every gene has a higher accuracy, and the accuracy of wound age estimation with combination of mRNA relative expressions is higher than that with a single indicator. By combining with Fisher discrimination method, this method can be used for early and mid-term wound age estimation.

MiR-216a-3p promotes differentiation of BMMSCs into ACE II cells via Wnt/ß-catenin pathway.

OBJECTIVE: To explore whether miR-216a-3p could promote differentiation of bone marrow mesenchymal stem cells (BMMSCs) into type II alveolar epithelial cells (ACE II) via Wnt/ß-catenin pathway, thereby alleviating neonatal respiratory distress syndrome (NRDS). MATERIALS AND METHODS: BMMSCs were directionally differentiated into ACE II cells. Expressions of ACE II cell-specific transcription factors Occludin, KGF, CK18, SpA, SpB, and SpC were detected at the different time points after cell differentiation. Enzyme-linked immunosorbent assay (ELISA) was applied to detect inflammatory factors in the culture medium, including interleukin-1 (IL-1), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and Interferon-α (INF-α). After overexpression or knockdown of miR-216a-3p in BMMSCs, expressions of ACE II cell-specific transcription factors and inflammatory factors were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot. Rescue experiments were carried out after DKK-1 treatment in BMMSCs. RESULTS: Expressions of ACE II cell-specific transcription factors Occludin, KGF, CK18, SpA, SpB, and SpC were elevated with the prolongation of cell differentiation. Overexpression of miR-216a-3p elevated levels of pro-inflammatory factors (IL-1, TNF-α, and INF-α) and reduced anti-inflammatory factor (IL-10). Expressions of ACE II cell-specific transcription factors Occludin, KGF, CK18, SpA, SpB, and SpC were remarkably increased at 7 d and 14 d compared to those detected at 1 d. Overexpression of miR-216a-3p in BMMSCs downregulated Wnt3a expression. The regulatory effect of miR-216a-3p on BMMSCs differentiation was partially reversed by DKK-1 treatment. CONCLUSIONS: Knockdown of miR-216a-3p induces differentiation of BMMSCs into ACE II cells through Wnt/ß-catenin pathway, thereby alleviating NRDS.

Probing the influence of carboxyalkyl groups on the molecular flexibility and the charge density of apigenin derivatives.

Apigenin is an important flavonoids due to its antidiabetic bioactivity. It was reported experimentally that the 7-substituent derivative of apigenin has higher biological activity than 4'- and 5-substituted derivatives while introducing sole carboxyalkyl group -(CH2)7COOH into the parent structure. Molecular docking studies indicated that the other two derivatives have lower binding affinities than the 7-substituent derivative (-7.52 kcal mol-1), which is considered to be a better inhibitor than the parent molecule. Almost all of the carbon atoms and oxygen atoms are coplaner for all three molecules in solution phase, however, all carboxyalkyl groups bend inside into the parent molecules in the active site, and the jagged geometries of the carbon chains are destroyed correspondingly. In addition, most of the electron densities of the chemical bonds for all molecules are decreased, especially the 7-substituent derivative. In contrast, most of the Laplacian values for three molecules are increased in the active site, which suggests that the charge densities at the bond critical point (bcp) are much more depleted than the solution phase. Dipole moments of derivatives are all increased in the active site, suggesting strong intermolecular interactions. After interacting with the S. cerevisiae α-glucosidase, only the 7-substituent derivative has the lowest energy gap ΔE HOMO-LUMO, which indicates the lowest stability and the highest inhibition activity. Graphical abstract Probing the influence of carboxyalkyl groups on the molecular flexibility and the charge density of apigenin derivatives.

Comparison of the molecular interactions of 7'-carboxyalkyl apigenin derivatives with S. cerevisiae α-glucosidase.

As one of the most investigated flavonoids, apigenin, is considered to be a strong α-glucosidase inhibitor. However, the clinical utility of apigenin is limited due to its low solubility. It was reported that the solubility and biological activity can be improved by introducing sole carboxyalkyl group into apigenin, especially the 7'-substitution. With the increase of length of the alkyl chain in carboxyalkyl group, B ring of the apigenin derivative is embedded much more deeply into the binding cavity while the carboxyalkyl stretches to the neighboring cavity. All of the terminal carboxyl groups form hydrogen bonding interactions easily with the surrounding polar amino acids, such as His239, Ser244, Arg312 and Asp349. Thus, the electron density values of the carbonyl in the carboxyl group become higher than the solution status due to the strong molecular interactions. In fact, electron densities of most of the chemical bonds are decreased after molecular docking procedure. On compared with the solution phase, however, dipole moments of most of these molecules are increased, and their vectors are reoriented distinctly in the active sites. It is noticed that all of the Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO) are distributed throughout the whole parent apigenin ring in solution phase, whereas the disappeared situation happened on the B rings of some molecules (II-IV) in the active site, leading to higher energy gaps.

[The influence of condensate in the piezometric tube on patient ventilator interaction during noninvasive positive pressure ventilation].

OBJECTIVE: To study the effects of condensate in the piezometric tube on patient ventilator interaction during noninvasive positive pressure ventilation. METHODS: Eleven healthy adults volunteered to receive noninvasive positive pressure ventilation. Different capacity of physiological saline was injected gradually into the piezometric tube until the volunteers could not trigger the ventilator or the total volume of the water reached 1.5 ml. The dynamic changes of the pressure of mask(Pmask), piezometric tube near mask (Ppro), piezometric tube near breathing machine(Pdis), and the flow were observed. RESULTS: With increasing volume of saline injected, the trigger time TItri(Pmask) increased from 0.09(0.07-0.11) to 0.31(0.22-0.39)s, the trigger pressure TPtri(Pmask) increased from 0.26(0.15-0.33) to 2.29(1.76-3.09)cmH2O, and the pressure-time product PTP (Pmask) increased from 0.02(0.01-0.03) to 0.55(0.41-0.68) cmH2O·s. Ineffective triggering rate increased from 0 up to 9 times/min, and spurious triggering rate increased from 0 up to 33 times/min. The plateau pressure of Pmask and Ppro exceeded the preset parameters, increased significantly as compared with 0 ml, from (9.74±0.34)to (15.79±3.10) cmH2O and from(9.80±0.31) to(15.44±3.47) cmH2O. The change of plateau pressure of Pdis was not significant [from (9.85±0.29)to (12.58±2.64)cmH2O]. The baseline pressure of Pmask, Ppro and Pdis changed from (3.67±0.36) to (8.40±3.22) cmH2O, from (3.71±0.32) to (8.13±3.55) cmH2O and from( 3.77±0.32) to (5.36±1.25) cmH2O, respectively. The pressure fluctuation of platform of Pmask increased significantly compare with 0 ml, from 0.60(0.48-0.71) to 7.94(7.11-8.63)cmH2O. The frequency of fluctuation of platform increased as many as 7 times during a single respiratory period. The time when the pressure of the Pdis began to change was delayed to Pmask and Ppro, 0.11(0.08-0.12)s compared with 0 ml. CONCLUSION: Condensate in the piezometric tube during noninvasive positive pressure ventilation could influence patient-ventilator synchrony. To improve patient ventilator interaction in noninvasive positive pressure ventilation, condensate in the piezometric tube should be avoided.

Association between polymorphisms of the swine MHC-DQA gene and diarrhoea in three Chinese native piglets.

Swine leucocyte antigen (SLA) is a highly polymorphic multigene family that plays a crucial role in swine immune response and disease resistance. Here, we identified polymorphisms and gene variations of SLA-DQA exon 2 using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and DNA sequencing analysis, and further investigated the correlation between the polymorphisms and piglet diarrhoea in three Chinese native pig breeds (Bamei, Juema and Gansu Black pigs). Consequently, 12 genotypes and 8 alleles including two novel alleles were detected. Nucleotide polymorphism was compared with the actual functional polymorphism in the peptide-binding region (PBR), binding pockets P1, P6 and P9, and the antigen-binding groove, variations in the antigen-binding groove of alleles DQA*01xa01, DQA*01xa03, DQA*01xb01, DQA*We02, DQA*03xb03 and DQA*wy06 were higher than alleles DQA*03xa01 and DQA*03xa03, while amino acid variations in peptide-binding pockets of allele DQA*03xa03 were most abundant among all alleles. The results of association analysis showed the diarrhoea score of Gansu Black pigs (-0.08 ± 0.78) was significantly higher than Bamei and Juema pigs (P < 0.01), and genotype DQA*03xa0103xa01 (0.39 ± 0.54) was significantly higher relative to other genotypes (P < 0.01), while that of genotype DQA*03xa0303xa03 (-1.31 ± 0.88) was markedly lower than scores obtained with genotypes DQA*03xa0103xa01 and DQA*03xa0101xa01 (P < 0.01), as well as DQA*01xa0101xa01 (P < 0.05), indicating that amino acid variations in the peptide-binding pockets play a more important role than the antigen-binding groove in piglet diarrhoea resistance. Further studies on other SLA molecules of native pigs are required to validate the link between this gene complex and diarrhoea.