Objective To evaluate the preventive effect of hydrocolloid dressings on mechanical phlebitis in patients with PICC (peripherally inserted central catheter).Method Articles of radomized or semi-radomized controlled clinical trial on hydrocolloid dressings on mechanical phlebitis in patients with PICC were retrieved across the databases of Pubmed, Google Scholar, CNKI and Wanfang and treated with the software of RevMan 5.0.Result Thirteen papers were included for the meta-analysis, which indicated that hydrocolloid dressings reduced the incidence of mechanical phlebitis in patients with PICC.Conclusion Early application of hydrocolloid dressings can effectively prevent mechanical phlebitis in the patients with PICC.

Objective To assess whether dynamic arterial elastance (Eadyn)can be used to predict the reduction of arterial pressure after decreasing norepinephrine (NE) dosage in patients with septic shock.Methods A prospective observational cohort study was conducted.Thirty-two patients with septic shock and mechanical ventilationwere enrolledfrom January 2014 to December 2015 in ICU of Wuxi People's Hospital of Nanjing Medical University.Hemodynamic parameters were recorded by pulse contour cardiac output(PiCCO) monitoring technology before and after decreasing norepinephrine dosage.Eadyn was defined as the ratio of pulse pressure variation (PPV) to stroke volume variation (SVV).Mean arterial pressure (MAP) variation was calculated after decreasing the dose of NE.Response was defined as a ≥ 15％decrease of MAP.AUC was plotted to assess the value of Eadyn in predicting MAP response.Results A total of 32 patients were enrolled in our study,with 13 responding to NE dose decrease where as the other 19 did not.Eadyn was lower in responders than in nonresponders (0.77 ± 0.13 vs 1.09 ± 0.31,P ＜ 0.05).Baseline Eadyn was positively correlated with systolic blood pressure variation,diastolic blood pressure variation,systemic vascular resistance variation and MAP variation (r =0.621,P =0.000;r =0.735,P =0.000;r =0.756,P =0.000;r =0.568,P =0.000 respectively).However,stoke volume variation,baseline level of systemic vascular resistance and NE baseline dose were not correlated with Eadyn baseline value (r =0.264,P =0.076;r =0.078,P =0.545;r =0.002,P =0.987 respectively).Eadyn ≤ 0.97 predicted a decrease of MAP when decreasing NE dose,with an area under the receiver-operating characteristic curve of 0.85.The sensitivity was 100.0％ and specificity was 73.7％.Conclusions In septic shock patients treated with NE,Eadyn is an index to predict the decrease of arterial pressure in response to NE dose reduction.

Objective To explore the effects of under-expression of large tumor suppressor 1 (LATS1) on activation of Hippo signaling pathway and differentiation, proliferation, migration of bone marrow mesenchymal stem cells (mMSCs) of micein vitro.Methods mMSCs of C57BL/6 mice were divided into normal control (MSC) group, empty vector control (MSC-GFP) group, LATS1-over-expressing (MSC-LATS1) group, empty vector without LATS1 shRNA control (MSC-shControl) group and LATS1-under-expressing (MSC-shLATS1) group. Lentiviral vectors with activated,inactivated LATS1 (the key molecule of Hippo signaling pathway) modifications and empty vectors were constructed and were used to infect mMSCsin vitro. The transduction efficiencies mediated by the lentiviral vectors were evaluated by fluorescence microscopy and flow cytometry. The mRNA expression of LATS1 was quantified by quantitative real-time polymerase chain reaction (qRT-PCR), and the protein expressions of LATS1, YAP (p-YAP), 14-3-3 were quantified by Western Blot to evaluate the activation of Hippo signaling pathway. Osteogenic and adipogenic differentiation of mMSCs were evaluated through measurement of Runx2, OSX and C/EBPα, PPAR-γ mRNA by qRT-PCR, as well as Alizarin Red S and Oil red O staining. Proliferation of mMSCs was evaluated using methy thiazdyl tetrazolium (MTT) assay. The scratch test and Transwell chamber test were used to analyze the horizontal and vertical migration ability of mMSCs.Results The transduction efficiencies mediated by the lentiviral vectors were 94.74%-96.10%. Compared with MSC-GFP group, the activation of Hippo signaling pathway was promoted in MSC-LATS1 group [LATS1 mRNA (2-ΔΔCT): 4.37±0.21 vs. 1.20±0.04, LATS1 protein (gray value): 2.21±0.06 vs. 1.09±0.10, p-YAP/YAP protein (gray value): 1.51±0.13 vs. 0.98±0.05, 14-3-3 protein (gray value): 1.92±0.18 vs. 1.10±0.09, allP < 0.05], osteogenic and adipogenic differentiation of mMSCs were decreased in MSC-LATS1 group [mineralization (A value):0.13±0.02 vs. 0.40±0.03, Runx2 mRNA (2-ΔΔCT): 0.51±0.02 vs. 0.98±0.09, OSX mRNA (2-ΔΔCT): 0.41±0.04 vs. 1.04±0.09, lipid accumulation (A value): 0.10±0.02 vs. 0.25±0.03, C/EBPα mRNA (2-ΔΔCT): 0.33±0.03 vs. 1.11±0.09, PPAR-γ mRNA (2-ΔΔCT): 0.29±0.02 vs. 1.04±0.10, allP < 0.05], the proliferation rate of mMSCs at 4-7 days was decreased in MSC-LATS1 group and so were the horizontal and vertical migration of mMSCs [wound healing rate: (18.65±3.53)% vs. (40.29±1.87)%, migrated cells (cells/MP): 35.99±6.18 vs. 103.67±17.77, bothP <0.05]. Compared with MSC-shControl group, the activation of Hippo signaling pathway was inhibited in MSC-shLATS1 group [LATS1 mRNA (2-ΔΔCT): 0.16±0.01 vs. 0.98±0.03, LATS1 protein (gray value): 0.38±0.03 vs. 1.04±0.07, p-YAP/YAP protein (gray value): 0.58±0.04 vs. 1.05±0.06, 14-3-3 protein (gray value): 0.14±0.02 vs. 1.02±0.09, allP < 0.05], osteogenic and adipogenic differentiation of mMSCs were increased in MSC-shLATS1 group [mineralization (A value): 0.93±0.13 vs. 0.44±0.05, Runx2 mRNA (2-ΔΔCT): 1.44±0.12 vs. 0.95±0.04, OSX mRNA (2-ΔΔCT):1.67±0.06 vs. 1.10±0.11, lipid accumulation (A value): 0.47±0.06 vs. 0.28±0.04, C/EBPα mRNA (2-ΔΔCT):3.98±0.61 vs. 0.99±0.10, PPAR-γ mRNA (2-ΔΔCT): 3.05±0.36 vs. 0.98±0.14, allP < 0.05], the proliferation rate of mMSCs at 3-7 days was increased in MSC-shLATS1 group and so were the horizontal and vertical migration of mMSCs [wound healing rate: (80.18±6.98)% vs. (46.18±1.01)%, migrated cells (cells/MP): 212.69±41.21 vs. 115.87±35.15, bothP < 0.05].Conclusions Under-expression of LATS1 promotes the differentiation, proliferation, migration of mMSCs by inhibition of Hippo signaling pathwayin vitro.

Objective To explore the influence of transcutaneous oximetry on septic shock-associated acute kidney injury (AKI) in intensive care unit (ICU).Methods Forty-nine patients with septic shock admitted in the ICU of Wuxi People's Hospital Affiliated to Nanjing Medical University were enrolled from January 2013 to December 2015.The 10 min oxygen challenge test was conducted using transcutaneous oximetry just before (0 h) and 6 h after initiation of fluid resuscitation,and 10 min oxygen challenge test data (10 min OCT) at 0 h and 6 h were then calculated,respectively.The enrolled patients were divided into low 10 min OCT group (10 min OCT ＜ 66 mmHg,L group) or high 10 min OCT group (10 min OCT ≥66 mmHg,H group) according to the 10 min OCT value at 6 h.The hemodynamic variables [mean arterial pressure (MAP),central venous pressure (CVP)],oxygen metabolism indexes [central venous oxygen saturation (ScvO2),arterial lactate (Lac)],dose of vasoactive agents,10 min OCT at 0 h and 6 h were recorded.APACHE Ⅱ score,incidence and severity of septic shock-associated AKI,frequency of CRRT,ICU mortality and 28 d mortality were compared between groups using SPSS 22.0 software,risk factors associated with prognosis were analyzed using COX regression model.Results There were 27 cases in L group and 22 cases in H group.The MAP,CVP,ScvO2,lactate level and dose of vasoactive agents were comparable between groups at 0 h or 6 h (P ＞ 0.05),while 10 min OCT at 6 h was higher in H group than that inLgroup [(77.6±18.5) mmHgvs.(51.3 ±21.6) mmHg,P＜0.05].The incidence of septic shock-associated AKI (77.8％ vs.50.0％,P ＜ 0.05),proportion of phase 3 AKI (44.4％vs.22.7％,P ＜0.05) and frequency of CRRT (48.1％ vs.22.7％,P ＜0.05) was higher in L group than those in H group,and similarly were the ICU mortality (51.8％ vs.22.7％,P ＜0.05) and 28 d mortality (63.0％ vs.31.8％,P ＜ 0.05).Therefore,the 6 h 10 min OCT ≥66 mmHg was a protective factor to improve the ICU mortality (RR =0.01,95％ CI:0.001-0.39,P ＜ 0.05) and 28 d mortality (RR =0.01,95％CI:0.001-0.27,P＜0.05) in patients with septic shock-associated AKI.Conclusions 10 min OCT imposes substantial influence on the incidence,severity and prognosis of patients with septic shockassociated AKI,oxygen challenge test could improve the treatment of septic shock-associated AKI.

Objective To determine the association between plasma concentrations of brain derived neurotrophic factor (BDNF), neuron-specific enolase (NSE), and S100β, and the occurrence of delirium in critically ill patients. Methods Totally 65 patients in Intensive Care Unit (ICU) of Wuxi People's Hospital of Nanjing Medical University between June 2015 and February 2016 were included in the present study. Delirium diagnosis was used by confusion assessment method for the ICU (CAM-ICU). Plasma BDNF, NSE, and S100β concentrations were determined on day 1(T1), 3(T3), and 10(T10) after ICU admission. The day of ICU admission was defined as T0. Results Compared with the plasma BDNF level on T1 (0.23±0.22) μg/L, the plasma BDNF level on T3 (0.59±0.34) μg/L and T10 (0.24±0.21) μg/L were higher, especially for that on T3 with a significant difference (F=21.58, P=0.018). Plasma NSE level on T3 (1.68±0.25) μg/L was significantly higher than that on T1 (1.22±0.32) μg/L (F=10.24, P=0.042). Compared with those without delirium, the delirious patients had lower BDNF, higher NSE and S100β on T1, T3 and T10, of which the difference of BDNF [T1: (0.23±0.22) μg/L vs. (1.02±0.24) μg/L, F=116.25,P<0.01; T3: (0.59±0.34) μg/L vs. (1.55±0.36) μg/L, F=82.39, P<0.01; T10: (0.24±0.21) μg/L vs. (1.09±0.55)μg/L, F=50.93, P=0.003, and NSE (T1: (1.22±0.32) μg/L vs. (0.47±0.23) μg/L, F=94.30, P<0.01;T3:(1.68±0.25) μg/L vs. (0.79±0.28) μg/L, F=78.63, P=0.017; T10: (0.98±0.37) μg/L vs. (0.51±0.22) μg/L, F=70.95, P=0.026) reached significant differences. Conclusions Plasma BDNF and NSE are closely related to the occurrence of delirium in critically ill patients, especially for BDNF. Clinical monitoring of plasma levels of BDNF can help to predict the outcome of brain function in critically ill patients.

Objective:To investigate the value of plasma syndecan-1 (SDC-1) combined with lung ultrasonography in evaluating the degree of extravascular lung water in patients with acute respiratory distress syndrome (ARDS).Methods:From July 2018 to July 2019, 50 patients with ARDS admitted to the department of intensive care unit of Wuxi People's Hospital Affiliated to Nanjing Medical University were enrolled. After admission, pulse indicator continuous cardiac output (PiCCO) catheter was established for all patients. PiCCO indexes, including extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI) were monitored by one doctor. Another doctor performed lung ultrasound examination, and calculated the sum of the number of B-lines under 10 ultrasound sections of upper blue point, lower blue point, diaphragm point, Plaps point and rear blue point of both lungs. Then the level of plasma SDC-1 was detected by enzyme linked immunosorbent assay (ELISA). Pearson correlation method was used to analyze the correlation between the number of ultrasonic B-lines, plasma SDC-1 level and EVLWI and PVPI. Taking 10 mL/kg EVLWI as the boundary value, the degree of pulmonary edema in patients with ARDS was divided into mild pulmonary edema and severe pulmonary edema. The receiver operator characteristic curve (ROC curve) was drawn, and the number of B-lines, SDC-1 and the predictive value of the combination of the above two indicators on the severity of pulmonary edema in patients with ARDS were analyzed.Results:The cardiac index (CI) and central venous pressure (CVP) of 50 patients with ARDS were (46.84±6.00) mL·s -1·m -2 and (8.12±1.80) mmHg (1 mmHg = 0.133 kPa), cardiogenic pulmonary edema was excluded. In 50 patients with ARDS, EVLWI was (10.82±2.92) mL/kg, PVPI was 3.02±0.69, the number of ultrasound B-lines was 40.90±13.05, and plasma SDC-1 was (568.25±118.14) μg/L. Pearson correlation analysis showed that the number of ultrasound B-lines in patients with ARDS was significantly positively correlated with EVLWI and PVPI ( r1 = 0.802, r2 = 0.799, both P < 0.01). Plasma SDC-1 was also positively correlated with EVLWI and PVPI ( r1 = 0.732, r2 = 0.576, both P < 0.01). ROC curve analysis showed that the number of B-lines and SDC-1 had good predictive value for the severity of pulmonary edema in patients with ARDS. The area under ROC curve (AUC) and 95% confidence interval (95% CI) were 0.891 (0.803-0.979) and 0.875 (0.772-0.978), respectively. When the cut-off of B-lines was 40.50, the sensitivity and specificity were 82.1% and 86.4%, respectively. When the cut-off of SDC-1 was 559.37 μg/L, the sensitivity and specificity were 85.7% and 81.8%, respectively. Combining the number of B-lines with SDC-1 could further improve the predictive value of pulmonary water in patients with ARDS. The AUC (95% CI) was 0.958 (0.890-1.000), and the sensitivity and specificity were 92.9% and 91.8%, respectively. Conclusions:The level of plasma SDC-1 and the number of pulmonary ultrasonic B-lines have a good correlation with the degree of extravascular lung water in patients with ARDS. The combined application of the two noninvasive indexes can be used to evaluate the degree of extravascular lung water in patients with ARDS.

Objective To explore the effects of Hippo signaling on anti-oxidative stress of mouse marrow mesenchymal stem cells (mMSCs) in vitro. Methods mMSCs derived from C57BL/6 mice were identified using fluorescence-activated cell sorting analysis and the capabilities of osteogenic, chondrogenic and adipogenic differentiation were evaluated. 2-deoxy-D-glucose (2-DG) or XMU-MP-1 was used to modulate Hippo signaling. Oxidative stress was induced by H2O2treatment and the effect of oxidative stress induced by H2O2on survival of mMSCs was evaluated using methyl thiazolyl tetrazolium (MTT) assay. The effect of oxidative stress induced by H2O2on Hippo signaling and the effect of Hippo signaling on capability of anti-oxidative stress of mMSCs were analyzed through apoptosis-regulated proteins (Bcl-2 and Bax) using Western Blot. Results Hippo signaling was activated by 2-DG in a concentration-dependent manner and the effect was most prominent by 5 mmol/L of 2-DG [compared with the blank control group, large tumor suppressor 1 (LATS1) protein (grey value): 2.33±0.25 vs. 0.98±0.03, phosphorylated Yes-associated protein (p-YAP)/YAP protein ratio (grey value): 2.30±0.35 vs. 1.01±0.05, 14-3-3 protein (grey value):2.19±0.40 vs. 0.99±0.04, all P < 0.05]; Hippo signaling was inhibited by 100 nmol/L of XMU-MP-1 [compared with the blank control group, LATS1 protein (grey value): 0.69±0.10 vs. 0.98±0.03, p-YAP/YAP protein ratio (grey value):0.65±0.06 vs. 1.01±0.05, 14-3-3 protein (grey value): 0.75±0.11 vs. 0.99±0.04, all P < 0.05]. Death of mMSCs was induced by H2O2in a concentration-dependent manner and the minimal effective concentration was 0.1 mmol/L [compared with the blank control group, survival rate of mMSCs: (81.25±11.85)% vs. (100.44±12.39)%, P < 0.05]. Inhibition of Hippo signaling was induced by H2O2in a concentration-dependent manner and the minimal effective concentration was also 0.1 mmol/L [compared with the blank control group, LATS1 protein (grey value): 0.75±0.06 vs. 1.01±0.09, p-YAP/YAP protein ratio (grey value): 0.69±0.05 vs. 0.98±0.05, both P < 0.05], those effects might associate with reduction of Bcl-2/Bax ratio (grey value: 0.48±0.18 vs. 1.06±0.09, P < 0.05). Compared with the treatment of 0.1 mmol/L of H2O2, activation of Hippo signaling by 5 mmol/L of 2-DG [ LATS1 protein (grey value):0.95±0.05 vs. 0.64±0.06, p-YAP/YAP protein ratio (grey value): 0.87±0.03 vs. 0.45±0.16, both P < 0.05] improved survival of mMSCs [(92.80±9.43)% vs. (75.47±9.43)%, P < 0.05] through an increase of Bcl-2/Bax ratio (grey value:1.14±0.16 vs. 0.77±0.12, P < 0.05); however, inhibition of Hippo signaling by 100 nmol/L of XMU-MP-1 [ LATS1 protein (grey value): 0.39±0.03 vs. 0.64±0.06, p-YAP/YAP protein ratio (grey value): 0.28±0.04 vs. 0.45±0.16, both P < 0.05] decreased survival of mMSCs [(57.54±4.59)% vs. (75.47±9.43)%, P < 0.05] through an decrease of Bcl-2/Bax ratio (grey value: 0.63±0.20 vs. 0.77±0.12, P < 0.05). Compared with normal lung tissue, acute respiratory distress syndrome (ARDS) lung tissue markedly activate Hippo signaling in mMSCs [LATS1 protein (grey value): 1.71± 0.08 vs. 1.00±0.10, p-YAP/YAP protein ratio (grey value): 2.46±0.39 vs. 1.01±0.04, 14-3-3 protein (grey value):2.27±0.52 vs. 1.01±0.08, all P < 0.05]. Conclusion Hippo signaling could affect survival and capability of anti-oxidative stress of mMSCs via modulation of Bcl-2/Bax ratio in vitro.

OBJECTIVE: To investigate the effects of Hippo signaling pathway on lung injury repair of mesenchymal stem cells (MSC) in acute respiratory distress syndrome (ARDS) and its mechanism. METHODS: Mouse bone marrow-derived MSC (mMSCs) cell lines with low expression of large tumor suppressor 2 (LATS2) were constructed by lentiviral vector transfection. Male C57BL/6 mice aging 6-8 weeks old were divided into four groups according to random number table (n = 36). The ARDS animal model (ARDS group) was reproduced by intratracheally injection of 2 g/L lipopolysaccharide (LPS) 50 μL, the normal saline (NS) control group was injected with an equal volume of NS. After 4 hours of model reproduction, 5×10⁴ mMSCs transfected with blank lentivirus vector (MSC-shcontrol group) or shLATS2 lentivirus vector (MSC-shLATS2 group) were transplanted intratracheally, while NS control group and ARDS group were injected with equal volume of phosphate buffered saline (PBS). Mice were sacrificed at 3, 7, and 14 days after modeling, and lung tissue and bronchoalveolar lavage fluid (BALF) were harvested. Near-infrared fluorescence imaging, immunofluorescence staining and Western Blot were used to track mMSCs in lung tissue. Retension and proportion of mMSC differentiation into type II alveolar epithelial cells (AEC II) were evaluated. Lung tissue wet weight/body weight ratio (LWW/BW) and total protein (TP) and albumin (ALB) in BALF were determined to reflect pulmonary edema. The expression of Occludin protein in lung epithelium was tested by Western Blot to reflect permeability of epithelium. The levels of interleukins (IL-1β, IL-6, IL-10) in BALF were assessed by enzyme-linked immunosorbent assay (ELISA) to reflect lung inflammation. Hematoxylin-eosin (HE) staining and modified Masson staining were carried out, and the scores were assessed to reflect lung injury and evaluate pulmonary fibrosis. RESULTS: The signal intensity of isolated lung fluorescence images at 3 days in the MSC-shLATS2 group was significantly higher than that in the MSC-shcontrol group (fluorescence intensity: 0.039±0.005 vs. 0.017±0.002, P < 0.05), the number of green fluorescent protein (GFP)-positive cells in lung tissue was also significantly higher than that in the MSC-shcontrol group (cells/HP: 29.65±6.98 vs. 17.50±4.58, P < 0.05), but they all decreased with time; and the proportion of mMSCs differentiated into AEC II was significantly increased [(64.12±15.29)% vs. (19.64±3.71)%, P < 0.05]. Compared with the NS control group, the levels of surface active protein C (SPC) and Occludin protein in the ARDS group were significantly decreased, LWW/BW ratio and TP, ALB and inflammatory factors levels in BALF were significantly increased; extensive alveolar and interstitial edema, hemorrhage and diffuse inflammatory cell infiltration were found in lung tissue, and the lung injury score was significantly increased; collagen fibers were deposited in alveolar septum and alveolar cavity, and pulmonary fibrosis score was also increased significantly. Compared with the ARDS group, the expression levels of SPC and Occludin at 14 days in the MSC-shcontrol group and the MSC-shLATS2 group were significantly increased (SPC/β-actin: 0.51±0.12, 0.68±0.10 vs. 0.27±0.08, Occludin/β-actin: 0.49±0.19, 0.79±0.11 vs. 0.25±0.08, all P < 0.05), TP, ALB, IL-1β, IL-6 levels in BALF at 3 days were significantly decreased [TP (g/L): 8.08±1.72, 5.12±0.87 vs. 12.55±2.09; ALB (g/L): 0.71±0.21, 0.44±0.18 vs. 1.18±0.29, IL-1β (ng/L): 99.26±14.32, 60.11±8.58 vs. 161.86±25.17, IL-6 (ng/L): 145.54±13.29, 101.74±11.55 vs. 258.79±27.88, all P < 0.05], and IL-10 was significantly increased (ng/L: 190.83±22.61, 316.65±37.88, both P < 0.05). Furthermore, all the above parameters in the MSC-shLATS2 group were significantly improved as compared with those in the MSC-shcontrol group (all P < 0.05). LWW/BW ratio in the MSC-shLATS2 group was significantly lower than that in the ARDS group and the MSC-shcontrol group (mg/g: 9.85±1.51 vs. 16.78±1.92, 14.88±1.74, both P < 0.05). CONCLUSIONS Inhibiting Hippo signaling pathway by low expression of LATS2 could promote the retention of mMSCs in lung tissue and differentiation into AEC II cells of ARDS mice, improve pulmonary edema and alveolar epithelial permeability, regulate pulmonary inflammatory response, and alleviate pathological damage and fibrosis of lung tissue.
Animals ; Hippo Signaling Pathway ; Lung Injury/prevention & control* ; Male ; Mesenchymal Stem Cells/metabolism* ; Mice ; Mice, Inbred C57BL ; Protein Serine-Threonine Kinases/metabolism* ; Respiratory Distress Syndrome/metabolism* ; Signal Transduction