[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.

Raspberry ketone glucoside suppresses melanin synthesis through IL6/JAK1/STAT3 signal pathway.

OBJECTIVE: This study aimed to evaluate the anti-melanogenic activity of raspberry ketone glucoside (RKG) and further explore the specific molecular mechanisms by which RKG affects melanogenesis. MATERIALS AND METHODS: The B16F10 cells model, the mushroom tyrosinase model and the zebrafish model were used to assess the whitening activity of RKG. We subsequently identified possible pathways related to RKG inhibition of melanogenesis by RNA-seq analysis and qRT-PCR on the zebrafish model, and further explored the effects of key genes on the pathway on the melanogenic effect of RKG by using related pathway inhibitors and Tg [mpeg: EGFP] transgenic zebrafish line. RESULTS: RKG could noticeably inhibit melanogenesis in B16F10 cells in vitro and on zebrafish in vivo. The RNA-Seq analysis and the qRT-PCR in zebrafish embryos indicated that the inhibition of melanogenesis by RKG could be achieved by activating JAK1/STAT3 signal pathway and inhibiting the expression levels of the MITFa, TYR, TYRP1a genes directly associated with melanogenesis. The inhibitor tests revealed that the inhibitory effect of the RKG on melanogenesis was restored by the IL6, JAK1/2, and STAT3 inhibitors, specifically STAT3 inhibitor. We further examine the relationship between the JAK1/STAT3 signal pathway and the MITFa. The achieved results indicate that the RKG could activate the zebrafish macrophages via the JAK1, but the inhibition of macrophage activation by loganin did not affect the anti-pigmentation effect of the RKG. CONCLUSIONS: RKG showed remarkable whitening activity on both B16F10 cells in vitro and zebrafish model in vivo. Furthermore, RKG could inhibit melanogenesis by activating the IL6/JAK1/STAT3 pathway, inhibiting the transcriptional activity of MITFa, and its downstream expression levels of the TYR and TYRP1a genes.

[Correlation between the pre-and post-operative sagittal parameters and the quality of life in patients with degenerative and isthmic spondylolisthesis].

Objective: To assess the relationship between health-related quality of life (HRQOL) and spinal sagittal parameters in patients with degenerative and isthmic spondylolisthesis before and after surgery, and to provide a biomechanical basis for improving the clinical prognosis of such patients. Methods: A retrospective analysis of 63 patients with lumbar spondylolisthesis who received lumbar fusion surgery in the Department of Spine Surgery, Tianjin Union Medical Center from December 2017 to June 2020 was carried out. There were 16 males and 47 females with a mean age of (59±8) years. Subgroup analyses were conducted based on disease type (degenerative lumbar spondylolisthesis (DS) and the isthmic spondylolisthesis (IS)) and HRQOL scores. Patients were evaluated post-operatively to observe the improvement of symptoms and quality of life. The relationship between operative related factors, HRQOL scores before and after surgery, and spino-pelvic sagittal parameters (including sagittal axis of the spine, lumbar lordosis angle, pelvic incidence angle, pelvic tilt angle (PT), sacral tilt angle, matching degree of pelvic incidence angle (PI) and lumbar lordosis angle (LL), lumbar 1 vertebra plumb line, upper lumbar curve, lower lumbar curve) in the two groups were analyzed. The correlation between the improvement of HRQOL scores and spino-pelvic sagittal parameters in the DS group and the IS group was analyzed and compared. Results: There were significant differences between postoperative HRQOL scores compared with those before the operation in both the DS and IS groups at three times of follow-up after the operation (all P<0.05). There was no difference in the last HRQOL score, the number of surgical segments, operation time and intraoperative blood loss between the two groups (all P>0.05). The parameters of PT and PI-LL in DS patients with VAS back pain score>3 and ≤3 were statistically different (13.7°±6.4° vs 26.6°±7.4°, 5.1°±8.2° vs 18.2°±13.1°, respectively, both P<0.05), similar results were obtained in IS patients (14.1°±6.9° vs 16.4°±8.7°, 2.9°±9.7° vs 6.8°±9.8°, respectively, both P<0.05). In addition, the parameters of PT and PI-LL between patients with ODI>20 and ≤20 were all statistically different in the two groups at the last follow-up after surgery (all P<0.05). The improvement of VAS back pain score in DS and IS groups was significantly related to the improvement of PT value, respectively (r=0.76, 0.78, both P<0.05). The PT, LL and PI-LL were significantly correlated with the ODI in the DS group (r=0.60, 0.62, 0.50, all P<0.05). There was also a correlation between the improvement of ODI and PT, LL and PI-LL in the IS group, respectively (r=0.22, 0.41, 0.76, all P<0.05). Conclusions: Certain correlation exists between the HRQOL and spinal sagittal parameters in patients with degenerative and isthmic spondylolisthesis before and after surgery. For the treatment of lumbar spondylolisthesis and improvement of quality of life, the primary goal is to reconstruct the matching degree of the lumbar lordosis angle and PI, and to reduce the PT value to the normal range by tilting the pelvis forward.

[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.

[Effect of esmolol in septic shock patients with tachycardia: a randomized clinical trial].

Objective: To investigate the effect of esmolol in septic shock patients with tachycardia. Methods: A prospective randomized controlled trial was conducted. Screening septic shock patients that admitted to Department of General Intensive Care Unit of the First Affiliated Hospital of Zhengzhou University from June 2016 to August 2017. After 24 h resuscitation therapy, 100 cases of septic shock patients with tachycardia (heart rate>100 bpm) were divided into esmolol group (n=50) and control group (n=50) with random number table. Patients in esmolol group accepted standard treatment plus esmolol injection with an initial dose of 25 mg/h. Heart rate target is 80 to 100 bpm. Patients in esmolol group continued to use esmolol for 7 days or to the day the patient left the ICU when the heart rate didn't achieve the target. Patients in control group were given standard treatment. Primary outcome was 28 d mortality. Secondary outcomes included heart rate, norepinephrine dosages, lactate level, inflammatory markers in per day during the trial; acute physiology and chronic health evaluation (APACHE Ⅱ) and sequential organ failure assessment (SOFA) on day 1, 3, 5, 7; length of hospital stay, length of mechanical ventilation, medication time of vasoactive agent. The data were compared with t test or rank sum test between the two groups. Results: The 28 d mortality of esmolol group and control group was 62%, 68%, respectively(χ(2)=0.529, P=0.529). Logistic regression analysis showed that primary heart rate (increase of 10 bpm, OR=1.568, 95%CI: 1.039-1.238, P=0.027), primary APACHEⅡ (OR=1.134, 95%CI: 1.026-1.239, P=0.005), integral heart rate (per 10 bpm, OR=2.207, 95%CI: 1.400-3.479, P=0.001) were independent risk factors for 28 d mortality. Compared with control group, the esmolol group had a lower heart rate on day 1-7; but over all, there was no statistically significant difference in heart rate between the two groups (P>0.05). There was no significant difference in total does of norepinephrine, lactate level, inflammatory markers, APACHE Ⅱ, SOFA, length of hospital stay between the two groups (all P>0.05). Conclusion: Tachycardia significantly increases the risk of death in patients with septic shock, esmolol may decrease the mortality by controlling heart rate.

[Effects of ß-blockers in patients with septic shock: a meta analysis].

OBJECTIVE: To evaluate the effect of ß-blockers in patients with septic shock. METHODS: PubMed, EMBASE, Cochrane central registration of controlled trials, CNKI and Wanfang Data were searched to identify relevant studies from inception to October 2015.Statistical analysis was performed using STATA 12.0.The random effects model was used due to wide clinical variability across the trials. RESULTS: After application of the inclusion criteria, 7 trials with 392 patients were included, involving 3 randomized controlled trials (RCT) and 4 quasi-experiments.The results of the meta-analysis for the quasi-experiments showed that compared with baseline, heart rates (standardized mean difference (SMD)=-2.51, 95%CI: -4.32--0.70, P=0.007) and lactate levels (SMD=-0.34, 95%CI: -0.67--0.02, P=0.039) significantly decreased, while no significant differences were seen for mean arterial pressure (SMD=0.01, 95%CI: -0.42-0.44, P=0.969), cardiac index (SMD=-0.35, 95%CI: -1.15-0.44, P=0.385) or norepinephrine requirements (SMD=-0.06, 95%CI: -0.38-0.27, P=0.726) after 24-hour therapy. Among randomized controlled trials, ß-blockers, compared with standard care, was associated with reductions in heart rates (P<0.001) , 28-day mortality (RR=0.60, 95%CI: 0.48-0.75, P<0.001) and troponin I levels (P<0.001). While no differences were found between the two groups in other hemodynamic and cardiac function variables, such as mean arterial pressure, cardiac index or stroke volume index (P>0.05). CONCLUSIONS: The currently available evidence indicates that the use of ß-blockers is associated with a significant decrease in heart rate, troponin I levels and 28-day mortality in patients with septic shock, while mean arterial pressure, cardiac index and stroke volume index might remain unchanged.Large scale, muti-center RCTs need to be carried out to confirm the effects of ß-blockers in patients with septic shock.

Beta-CTX and ICTP act as indicators of skeletal metastasis status in male patients with non-small cell lung cancer.

Bone metastasis is common in lung cancer patients and associated with reduced quality of life and reduced overall and median survival, so the early detection of bone metastasis and monitoring of its status is very important for clinicians. Serum bone-specific alkaline phosphatase (BAP), osteocalcin (OC), beta isomer of C-terminal telopeptide of type I collagen (beta-CTX) and cross-linked C-terminal telopeptide of type I collagen (ICTP) were compared with regard to their usefulness as indicators of bone metastasis in lung cancer. The serum concentrations of the 4 markers were measured by commercially available tests in 96 male patients with non-small cell lung cancer and 30 male patients with other pulmonary diseases. The levels of both â-CTX and ICTP were significantly higher in 61 lung cancer patients with bone metastases than in 35 lung cancer patients without bone metastases (both p<0.001), and significantly correlated with the extent of bone disease. Although ICTP had a better sensitivity and accuracy than beta-CTX (75.4% vs 65.6% and 72.9% vs 68.8%, respectively), they had a similar area under the receiver operating characteristic curve (0.85 vs 0.83). These results support the use of beta-CTX and ICTP as an adjunct tool for the diagnosis and screening of bone metastasis in lung cancer.