miR-106a Targets Anoctamin 1 (ANO1) to Regulate Lipopolysaccharide (LPS)-Induced Inflammatory Response in Macrophages.

BACKGROUND Sepsis is an organ dysfunction characterized by systemic inflammatory response. Micro(mi)ribonucleic acids take part in the regulation of the inflammatory response in many conditions. However, the role and mechanism of miR-106a and anoctamin 1 (ANO1) in the inflammatory response in sepsis remain largely unknown. MATERIAL AND METHODS The serum samples were collected from 31 sepsis patients and healthy volunteers. Lipopolysaccharide (LPS)-treated RAW264.7 cells were used for the study in vitro. The inflammatory response was investigated via interleukin-6 and tumor necrosis factor-alpha levels using quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay. The expression abundances of miR-106a and ANO1 were detected via qRT-PCR or western blot. The target association between miR-106a and ANO1 was explored using dual-luciferase reporter analysis. RESULTS The inflammatory response was trigged in sepsis and LPS-treated RAW264.7 cells. miR-106a expression was enhanced and ANO1 declined in sepsis and LPS-treated RAW264.7 cells. Overexpression of ANO1 suppressed the inflammatory response and knockdown of ANO1 promoted the inflammatory response in RAW264.7 cells. ANO1 was directly targeted via miR-106a, and miR-106a reversed ANO1-mediated inflammatory inhibition in LPS-treated RAW264.7 cells. CONCLUSIONS MiR-106a regulated LPS-induced inflammatory response by targeting ANO1 in RAW264.7 cells, indicating the potential value of miR-106a for treatment of inflammatory diseases, including sepsis.

[A multi-center survey on the therapeutic status of patients with acute myocardial infarction in Wuxi city of China].

OBJECTIVE: To explore the characteristics and therapies of patients with acute myocardial infarction (AMI) in Wuxi city, China. METHODS: A network was established to obtain information of patients with AMI who were admitted to 9 designated hospitals between 2011 and 2012. A total of 1 714 patients were enrolled (1 334 males, 754 smokers, 1 076 hypertension, 270 hyperlipidemia and 398 diabetes) including 1 410 patients with acute ST-segment elevation myocardial infarction (STEMI) and 304 patients with acute non ST-segment elevation myocardial infarction (NSTEMI). Patients' characteristics, therapies, the incidence of major adverse cardiovascular events (MACEs) and all-cause mortality were analyzed. RESULTS: (1) Medication therapy was as follows: antiplatelet therapy 98.3% (1 685 cases) , beta-blockers 59.1% (1 013 cases) , ACEI or ARB 67.6% (1 159 cases) , statins 98.1% (1 682 cases) , and nitrates 71.1% (1 218 cases) . Of the patients, 7.1% (132 cases) received temporary pacemakers, 34.0% (480 cases) with acute STEMI underwent reperfusion [direct PCI 18.4% (260 cases) and thrombolysis 15.6% (220 cases)]. (2) According to the hospital admission data, patients were divided into three groups: group A, transported to the hospital by ambulance (n = 361); group B, transported to the hospital by private vehicles (n = 1 318); and group C, AMI occurred in the hospital (n = 35). The median time of AMI onset to physician contact of the 3 groups was 178 min, 368 min, and 9 min, respectively. The median time from AMI onset to the first ECG was 181 min, 379 min, and 10 min, respectively. The median time from AMI onset to cardiology specialist consultation was 187 min, 431 min, and 69 min, respectively. AMI onset-to-physician contact, AMI onset-to-first ECG, and AMI onset-to-specialized treatment time was the shortest in group C, followed by group A and group B. For patients with STEMI underwent reperfusion therapy, the median AMI onset-to-reperfusion therapy time was significantly shorter in group A patients than group B patients [thrombolysis group: 224(171, 514) min vs. 378 (158, 785) min, PCI group: 318 (154, 674) min vs. 489 (143, 816) min, all P < 0.05]. (3) The total incidence of MACEs was 16.3% (279/1 714), the all-cause in-hospital mortality rate was 13.1% (224/1 714). According to the AMI onset-to-physician contact, patients were divided into 4 groups: <3 h, 3-6 h, 6-12 h, and >12 h. The incidence of MACEs [4.4% (23/517), 13.3% (60/451), 19.1% (77/404) and 34.8% (119/342),χ(2) = 114.36, P < 0.01] and all-cause in-hospital mortality rate [4.1% (21/517) , 10.4% (47/451), 18.6% (75/404), 23.7% (81/342), χ(2) = 84.36, P < 0.01] increased in proportion to the time of AMI onset-to-physician contact. Among STEMI patients, the incidence of MACEs [5.8% (15/260) , 12.3% (27/220) , 20.9% (194/930) ,χ(2) = 39.93, P < 0.01] and all-cause in-hospital mortality [1.5% (4/260) , 10.0% (22/220) , 18.2% (170/930) ,χ(2) = 50.90, P < 0.01] was the lowest in the primary PCI group, followed by thrombolysis group and was the highest in the early conservative treatment group. CONCLUSIONS: Guideline is well followed in terms of drug treatments of AMI in this cohort, but only a small proportion of AMI patients in Wuxi received reperfusion therapy. There is a considerable out-of-hospital time delay for AMI patients in this cohort which is shorter in group A than in group B. All-cause in-hospital mortality and MACEs is the lowest in AMI patients underwent primary PCI.

SZ168 treats LPS-induced acute lung injury by inhibiting the activation of NF-κB and MAPKs pathways.

BACKGROUND: This study aimed to elucidate the effect and underlying molecular mechanisms of SZ168 (Podoplanin (PDPN) monoclonal antibody) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) mice and LPS-induced MH-S cells. METHODS: The survival rate was calculated by recording the death of mice in each group. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of interleukin (IL)- 6 and tumor necrosis factor-alpha (TNF-α) in blood and bronchoalveolar lavage fluid (BALF) of mice. Hematoxylin-eosin (H&E) staining were performed to evaluate the pathological changes in pulmonary tissues. Additionally, the phagocytosis of cells was tested by flow cytometry, and the expression levels of caveolin-1 (CAV-1) and Occludin proteins in lung tissue and the expression of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathway-related proteins in MH-S cells were determined by western blot. RESULTS: SZ168 significantly improved the survival rate of ALI mice. Briefly speaking, SZ168 protected pulmonary vascular permeability, reduced the level of pro-inflammatory cytokines, improved the pathological changes of lung tissue, reduced the infiltration of inflammatory cells, increased CAV-1 and Occludin protein expression, and then effectively relieved lung injury. In addition, SZ168 could significantly reduce the phagocytic ability of LPS-induced MH-S cells and inhibit the expression of hospho-extracellular regulated protein kinases (p-ERK), Phospho-Jun N-terminal kinase (p-JNK), Phospho-NF-κB p65 (p-p65) and Phospho-IkappaB-alpha (p-IκBα). CONCLUSION: SZ168 can treat ALI by inhibiting the activation of NF-κB and MAPK signaling pathways and restoring tight junction protein expression.

A ZSG-DEA model with factor constraint cone-based decoupling analysis for household CO2 emissions: a case study on Sichuan province.

This study employed an input-output approach to measure household CO2 emissions (HCEs) in Sichuan province, China from 2010 to 2017. A ZSG-DEA model with a factor constraint cone was built, to allocate such emission allowances to provincial subordinate cities and investigate their spatiotemporal heterogeneity. Using Tapio decoupling analysis, this study further examined the nexus between regional economic performance and HCEs. The results indicated that HCEs in Sichuan province initially increased and then decreased, peaking at 69.60 million tons in 2015. The structure of the HCEs changed from coal- to petroleum-dominated from 2010 to 2017. Indirect emissions from consumption-related sectors accounted for 60% of the total HCEs, including food, transportation, communication, and accommodation. The capital city of Chengdu, with the largest economic scale, overwhelmingly dominated the total household CO2 emissions, whereas Panzhihua, a heavy-industry-dominated city, had the highest HCEs  per capita. The Tapio decoupling results suggested that seven cities, led by Chengdu, had strong decoupling statuses, indicating that these cities performed well in the trade-off between economic growth and HCEs reduction. These results indicated that HCEs had a head effect centered on cities with advanced urbanization, but there was a virtuous cycle between CO2 emissions reduction and economic development. Given the spatial and temporal heterogeneity of HCEs, differentiated policymaking on emissions reduction is the key to facilitating green transformations.

[Evaluation of extravascular lung water in patients with acute respiratory distress syndrome by syndecan-1 combined with lung ultrasonography].

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.

Analysis of the lymphocyte count in type 2 diabetic patients with coronavirus disease (COVID-19): A retrospective study in a centralized treatment center.

OBJECTIVE: To investigate the characteristics of lymphocytes in type 2 diabetic patients with coronavirus disease (COVID-19). METHODS: Patients with COVID-19 admitted to hospital in Wuxi, China from January 29 to March 15 were included in the study. Lymphocytes were measured and recorded at admission and during treatment. Hospitalization days, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid positive days, minimal lymphocyte count, and occurrence time were collected and comparatively analyzed. Correlations between minimal lymphocyte count and hospitalization days as well as SARS-CoV-2 nucleic acid positive days were analyzed. RESULTS: A total of 63 patients were included in the study, with 16 in the diabetic group and 47 in the non-diabetic group. After adjusting for potential confounding factors, we observed lower minimal lymphocyte count (0.67 ± 0.36 * 109/L vs. 1.30 ± 0.54 * 109/L, adjusted P = 0.001), earlier occurrence of the minimal lymphocyte count (2.68 ± 2.33 days vs. 5.29 ± 4.95 days, adjusted P = 0.042), and longer hospitalization time (20.44 ± 5.24 days vs. 17.11 ± 4.78 days, adjusted P = 0.047) in the diabetic group than in the non-diabetic group. There was a negative correlation between minimal lymphocyte count and hospitalization days (R = -0.600, P < 0.05) as well as SARS-CoV-2 nucleic acid positive days (R = -0.420, P < 0.05). CONCLUSIONS: The diabetic group with COVID-19 had lower lymphocyte count, reached the minimal count faster, and had longer hospital stays than the non-diabetic group. Hospitalization days and SARS-CoV-2 nucleic acid positive days were negatively correlated with the minimal lymphocyte count.

The Effects of Abnormal Body Temperature on the Prognosis of Patients with Septic Shock.

We aimed to use temperature and the area under temperature curve to represent the severity of abnormal body temperature of patients with septic shock and to observe their impact on the prognosis. Five hundred twenty-eight adult patients with septic shock admitted to intensive care unit (ICU) were analyzed. Within the first 24 hours and throughout the period in ICU, the maximum temperature (24hTmax, Tmax), lowest temperature (24hTmin, Tmin), and the temperature range (24hTmax-min, Tmax-min) were aggregated. Patients were divided into the survival group and the death group. Binary logistic regression was used to assess the relationship between body temperature aberrations and survival. The following risk factors of death in 21 days were identified: Tmax (odds ratio [OR] 2.967, 95% confidence interval [CI] 1.626-5.414, p < 0.001), Tmin (OR 0.337, 95% CI 0.143-0.794, p = 0.013), and Tmax-min (OR 3.259, 95% CI 1.847-5.749, p < 0.001). This is an observational study, so one can infer association but not causation. Therefore, we infer that abnormal body temperature is associated with an adverse prognosis in patients with septic shock.

[Effects of body temperature on the prognosis of patients with septic shock].

OBJECTIVE: To observe the effects of abnormal body temperature and the area under temperature curve on the prognosis of patients with septic shock. METHODS: A retrospective cohort study was conducted. Patients with septic shock admitted to intensive care unit (ICU) of Wuxi People's Hospital Affiliated to Nanjing Medical University from September 2013 to June 2019 were enrolled. Data were obtained from the hospital case database, including the gender, age, infection source, the length of ICU stay, sequential organ failure assessment (SOFA) score, 21-day prognosis; within the first 24 hours and throughout the period in ICU, the maximum temperature (24 h Tmax, Tmax), lowest temperature (24 h Tmin, Tmin), and the temperature range (24 h Tmax-min, Tmax-min) were aggregated. The area under temperature curve when body temperature was higher than T (A> T), or lower than T (A< T), and area section between T1 and T2 (AT1-T2) was calculated respectively. Patients were divided into survival group and death group according to 21-day prognosis. Binary Logistic regression was used to analyze the effect of the above temperature indices on the prognosis. RESULTS: 635 septic shock patients were enrolled in the study. 476 patients were survived and 159 died within 21 days. Compared with the survival group, the age, SOFA score were higher in the death group, while the length of ICU stay was shorter. There was no significant difference in gender or infection source between two groups. After adjusting for gender, age, the length of ICU stay and SOFA score, binary Logistic regression analysis showed that the increase of Tmax, decrease of Tmin, and increase of Tmax-min were risk factors for 21-day mortality [Tmax: odds ratio (OR) = 2.959, 95% confidence interval (95%CI) was 1.620-5.398, P > 0.001; Tmin: OR = 0.329, 95%CI was 0.140-0.790, P = 0.012; Tmax-min: OR = 3.258, 95%CI was 1.840-5.471, P > 0.001], while 24 h Tmax, 24 h Tmin and 24 h Tmax-min were not related to prognosis. A< 36.0 centigrade (OR = 1.335, 95%CI was 1.102-1.745, P = 0.014), and A> 38.0 centigrade (OR = 1.041, 95%CI was 1.019-1.077, P = 0.001) showed positive correlation with 21-day mortality. When the T level was set at 38.0-40.0 centigrade, for every 1 centigrade×hour increase in A> T, the 21-day relative risk of death increased by 4.1%-83.2%. CONCLUSIONS: When the body temperature of patients with septic shock is lower than 36.0 centigrade, or higher than 38.0 centigrade, the 21-day relative risk of death rose with the increase of the magnitude and duration of abnormal body temperature.