The influence of coronavirus disease 2019 on emergency department visits in Nanjing, China: A multicentre cross-sectional study.

INTRODUCTION: Influenza has been linked to the crowding in emergency departments (ED) across the world. The impact of the Coronavirus Disease 2019 (COVID-19) pandemic on China EDs has been quite different from those during past influenza outbreaks. Our objective was to determine if COVID-19 changed ED visit disease severity during the pandemic. METHODS: This was a retrospective cross sectional study conducted in Nanjing, China. We captured ED visit data from 28 hospitals. We then compared visit numbers from October 2019 to February 2020 for a month-to-month analysis and every February from 2017 to 2020 for a year-to-year analysis. Inter-group chi-square test and time series trend tests were performed to compare visit numbers. The primary outcome was the proportion of severe disease visits in the EDs. RESULTS: Through February 29 th 2020, there were 93 laboratory-confirmed COVID-19 patients in Nanjing, of which 40 cases (43.01%) were first seen in the ED. The total number of ED visits in Nanjing in February 2020, were dramatically decreased (n = 99,949) in compared to January 2020 (n = 313,125) and February 2019 (n = 262,503). Except for poisoning, the severe diseases in EDs all decreased in absolute number, but increased in proportion both in year-to-year and month-to-month analyses. This increase in proportional ED disease severity was greater in higher-level referral hospitals when compared year by year. CONCLUSION: The COVID-19 outbreak has been associated with decreases in ED visits in Nanjing, China, but increases in the proportion of severe ED visits.

[A Meta analysis on the associations between air pollution and respiratory mortality in China].

OBJECTIVE: To analyze the associations between air pollution and adverse health outcomes on respiratory diseases and to estimate the short-term effects of air pollutions [Particulate matter with particle size below 10 microns (PM(10)), PM(10) particulate matter with particle size below 2.5 microns (PM(2.5)), nitrogen dioxide (NO2), sulphur dioxide (SO2) and ozone (O3)] on respiratory mortality in China. METHODS: Data related to the epidemiological studies on the associations between air pollution and adverse health outcomes of respiratory diseases that published from 1989 through 2014 in China, were collected by systematically searching databases of PubMed, SpringerLink, Embase, Medline, CNKI, CBM and VIP in different provinces of China. Short-term effects between (PM(10), PM(2.5), NO2, SO2, O3) and respiratory mortality were analyzed by Meta-analysis method, and estimations were pooled by random or fixed effect models, using the Stata 12.0 software. RESULTS: A total of 157 papers related to the associations between air pollution and adverse health outcomes of respiratory diseases in China were published, which covered 79.4% of all the provinces in China. Results from the Meta-analysis showed that a 10 µg/m³ increase in PM10, PM(2.5), NO2, SO2, and O3was associated with mortality rates as 0.50% (95% CI: 0-0.90%), 0.50% (95% CI: 0.30%-0.70%), 1.39% (95% CI: 0.90%-1.78%), 1.00% (95% CI: 0.40%-1.59%) and 0.10% (95% CI: -1.21%-1.39%) in respiratory tracts, respectively. No publication bias was found among these studies. CONCLUSION: There seemed positive associations existed between PM(10)/PM(2.5)/NO2/SO2and respiratory mortality in China that the relationship called for further attention on air pollution and adverse health outcomes of the respiratory diseases.

Connective tissue growth factor stimulates the proliferation, migration and differentiation of lung fibroblasts during paraquat-induced pulmonary fibrosis.

It is well established that paraquat (PQ) poisoning can cause severe lung injury during the early stages of exposure, finally leading to irreversible pulmonary fibrosis. Connective tissue growth factor (CTGF) is an essential growth factor that is involved in tissue repair and pulmonary fibrogenesis. In the present study, the role of CTGF was examined in a rat model of pulmonary fibrosis induced by PQ poisoning. Histological examination revealed interstitial edema and extensive cellular thickening of interalveolar septa at the early stages of poisoning. At 2 weeks after PQ administration, lung tissue sections exhibited a marked thickening of the alveolar walls with an accumulation of interstitial cells with a fibroblastic appearance. Masson's trichrome staining revealed a patchy distribution of collagen deposition, indicating pulmonary fibrogenesis. Western blot analysis and immunohistochemical staining of tissue samples demonstrated that CTGF expression was significantly upregulated in the PQ-treated group. Similarly, PQ treatment of MRC-5 human lung fibroblast cells caused an increase in CTGF in a dose-dependent manner. Furthermore, the addition of CTGF to MRC-5 cells triggered cellular proliferation and migration. In addition, CTGF induced the differentiation of fibroblasts to myofibroblasts, as was evident from increased expression of α-smooth muscle actin (α-SMA) and collagen. These findings demonstrate that PQ causes increased CTGF expression, which triggers proliferation, migration and differentiation of lung fibroblasts. Therefore, CTGF may be important in PQ-induced pulmonary fibrogenesis, rendering this growth factor a potential pharmacological target for reducing lung injury.

Protective effects of intestinal trefoil factor (ITF) on gastric mucosal epithelium through activation of extracellular signal-regulated kinase 1/2 (ERK1/2).

The rapid repair of gastric mucosa is critical upon exposure to injurious agents. Intestinal trefoil factor (ITF) is a member of the trefoil factor family domain peptides, which play an important role in the cytoprotection of gastric epithelium. However, the underlying molecular mechanisms that are responsible for ITF-induced gastric epithelial repair remain unclear. In the present study, we demonstrate that ITF enhances the proliferation and migration of GES-1 gastric endothelial cells in a dose- and time-dependent manner through the activation of extracellular signal-regulated kinase 1/2 (ERK1/2). Furthermore, the ITF-mediated protection of GES-1 cells from a NS398 (nonsteroidal anti-inflammatory drug) was dependent on the ERK1/2 signaling pathway. Taken together, the results provide a mechanistic explanation for ITF-mediated protection of gastric epithelial mucosa cells, suggesting that activation of the ERK1/2 signaling pathway may provide a new therapeutic strategy for repairing gastric injury.

[Logistic regression analysis on risk factors of cerebral hemorrhage complicated with stress ulcer].

OBJECTIVE: To explore the related risk factors of cerebral hemorrhage complicated with stress ulcer (SU). METHODS: The clinical data of 1 185 patients with cerebral hemorrhage admitted to Department of Emergency Medicine of Nanjing General Hospital from March 2006 to March 2014 were retrospectively analyzed. Patients were divided into two groups according to whether patients complicated with SU or not. Data was collected within 8 hours after admission in two groups including gender, age, amount of bleeding, the bleeding site (basal ganglia, thalamus, brainstem, brain lobe, ventricle, subarachnoid, and cerebellum), disturbance of consciousness, acute physiology and chronic health evaluation II (APACHEII) score, systolic blood pressure (SBP), history of hypertension, and history of cerebral hemorrhage. The statistically significant risk factors found using univariate analysis was selected and was analyzed to find independent risk factors with multivariate logistic regression analysis. The receiver operating characteristic curve (ROC curve) was plotted to analyze the independent risk factors and evaluate their power of test. RESULTS: 1 185 patients with cerebral hemorrhage were enrolled in the study, 293 cases occurred SU, accounting for 24.7%, and 892 cases without SU, which accounted for 75.3%. As shown by univariate analysis, risk factors for cerebral hemorrhage complicated with SU included age, amount of bleeding, the bleeding site, disturbance of consciousness, APACHEII score, SBP. As to the site of bleeding, brain, thalamus, brainstem hemorrhage complicated with SU were higher proportion, 45.3% (43/95), 39.1% (63/161), 36.9% (48/130), which were significantly higher than those of the lobes of the brain [26.2% (33/126)], cerebellum [18.8% (15/80)], basal ganglia [16.1% (78/485)], arachnoid the inferior vena cava [12.0% (13/108)]. Multivariate logistic regression analysis showed that amount of bleeding [odds ratio (OR)=3.305, P=0.001, 95% confidence interval (95%CI) 2.213-48.634], the bleeding site (OR=1.762, P=0.008, 95%CI 0.123-2.743), SBP (OR=1.223, P=0.034, 95%CI 0.245-2.812) were independent risk factors of cerebral hemorrhage complicated with SU. The area under the ROC curve (AUC) of amount of bleeding and SBP were 0.846 and 0.597, suggesting that amount of bleeding has moderate diagnostic value and SBP has low diagnostic value. CONCLUSIONS: Cerebral hemorrhage patients with large amount of bleeding, the bleeding site in the ventricle, thalamus or brainstem, high SBP are of great risk. We should lower blood pressure and give preventive treatment for SU as soon as possible.

Effects of different LAD-blocked sites on the development of acute myocardial infarction and malignant arrhythmia in a swine model.

OBJECTIVE: To explore the effects of various left anterior descending (LAD) artery-blocked sites on the development of acute myocardial infarction (AMI) and malignant arrhythmia in a swine model. METHODS: Twenty-two pigs underwent occlusion of the coronary artery with balloon angioplasty were randomly divided into three groups according to the blocked site of the balloon: middle-site-blocked LAD group, bottom-third-blocked LAD group and control group. Then, the development of AMI and malignant arrhythmia, including ventricular tachycardia and ventricular fibrillation during the process of model creation, were recorded. Changes of the hemodynamics, blood gas analysis, electrocardiography, and myocardial enzymes were analyzed in each group before and after occlusion. RESULTS: Middle-site-LAD blockage resulted in a larger infarction size and the corresponding incidence of ventricular fibrillation was significantly higher than that of the bottom-third-blocked group (P<0.05). After the occlusion, the QTc interval of the Middle-site-blocked LAD group was significantly longer than that in the other groups (P<0.01). Moreover, mean arterial blood pressure (MAP), left ventricular ejection fraction (LVEF), and partial pressure of oxygen (PaO2) were significantly lower, but partial pressure of carbon dioxide (PaCO2) increased, in the Middle-site-blocked-LAD group compared with that in the bottom-third-blocked group (P<0.01). Compared with the control group, the two LAD-blocked groups showed significantly higher levels of Mb, CK-MB, LDH, AST and cTnT (P<0.01) four hours after the artery occlusion. However, these indexes were not significantly different between the two LAD-blocked groups (P>0.05). CONCLUSIONS: Location of LAD blockages in swine models may affect the development of AMI and malignant arrhythmia.

Intestinal trefoil factor activates the PI3K/Akt signaling pathway to protect gastric mucosal epithelium from damage.

Intestinal trefoil factor (ITF, also named as trefoil factor 3, TFF3) is a member of the TFF-domain peptide family, which plays an essential role in the regulation of cell survival, cell migration and maintains mucosal epithelial integrity in the gastrointestinal tract. However, the underlying mechanisms and associated molecules remain unclear. The aim of this study was to explore the protective effects of ITF on gastric mucosal epithelium injury and its possible molecular mechanisms of action. In the present study, we show that ITF was able to promote the proliferation and migration of GES-1 cells via a mechanism that involves the PI3K/Akt signaling pathway. Western blot results indicated that ITF induced a dose- and time-dependent increase in the Akt signaling pathway. ITF also plays an essential role in the restitution of GES-1 cell damage induced by lipopolysaccharide (LPS). LPS induced the apoptosis of GES-1 cells, decreased cell viability significantly (P<0.01) and led to epithelial tight junction damage, which is attenuated via ITF treatment. The protective effect of ITF on the integrity of GES-1 was abrogated by inhibition of the PI3K/Akt pathway. Taken together, our results demonstrate that ITF promotes the proliferation and migration of gastric mucosal epithelial cells and preserves gastric mucosal epithelial integrity after damage is mediated by activation of the PI3K/Akt signaling pathway. This study suggested that the PI3K/Akt pathway could act as a key intracellular pathway in the gastric mucosal epithelium that may serve as a therapeutic target to preserve epithelial integrity during injury.

Spontaneous type B aortic dissection in antepartum gemellary pregnancy and endovascular repair.

BACKGROUND: It has been found that 50% of all aortic dissections can be attributable to pregnancy in women younger than 45 years of age. An estimated 30% of cases are type B, with half occurring in the antepartum period. To date type B aortic dissection has rarely been reported in gemellary pregnancies. CASE: A 24-year-old primigravida at 36 weeks of gemellary gestation presented symptoms of severe and persistent chest pain for 1 day, before suffering the acute type B aortic dissection. The primigravida was treated with immediate cesarean section and endovacular stent graft placement. CONCLUSION: Aortic dissection is a rare complication of pregnancy, especially in gemellary pregnancies. Pregnancy is considered an independent risk factor for aortic dissection and endovascular repair may be an ideal option for the treatment of complicated type B aortic dissection during pregnancy, with reduced maternal and fetal mortality.

Establishment and evaluation of a swine model of acute myocardial infarction and reperfusion-ventricular fibrillation-cardiac arrest using the interventional technique.

BACKGROUND: Ventricular fibrillation is the main cause of sudden cardiac death among patients with acute myocardial infarction (AMI). Substantial benefits could be obtained by both researchers and practitioners if an AMI reperfusion-ventricular fibrillation-cardiac arrest model were established. METHODS: Twenty swine were anesthetized and underwent occlusion of the left anterior descending branch for 90 minutes prior to blood reperfusion. Throughout this process, continuous 12-lead electrocardiography (ECG) was used to monitor heart rate, rhythm, and electrocardiogram alteration. Thereafter, AMI was confirmed by ECG and left ventricular angiography. Heart tissue was collected for pathological analysis, and for evaluation of the establishment of a model of AMI reperfusion. RESULTS: Seven swine died during the model establishment, and the 13 surviving swine were proven to have myocardial infarction; nine of those survivors had ventricular fibrillation-cardiac arrest after reperfusion based on the electrocardiograph and pathological examination. CONCLUSION: Blocking the left anterior descending branch by inflation of an over-the-wire coronary balloon catheter in swine can result in successful establishment of a swine model of AMI and reperfusion-ventricular fibrillation-cardiac arrest, with good reproducibility and a high survival rate.

Pneumomediastinum from acute inhalation of chlorine gas in 2 young patients.

Trichloroisocyanuric acid is a high-efficiency and-low toxicity fungicide and bleach. It is commonly used as disinfectant for industrial circulating water, swimming pools, restaurants, and other public places in China. When trichloroisocyanuric acid is put into water, chlorine gas is produced. Chlorine gas is a potent pulmonary irritant that causes acute damage in both the upper and lower respiratory tracts (J Toxicol Clin Toxicol. 1998;36(1-2):87-93). Pneumomediastinum is a rare complication in patients with acute chlorine gas poisoning. A small amount of gas can be asymptomatic, but a large amount of gas entering the mediastinum suddenly will lead to respiratory and circulatory disorder, mediastinal swing, or even cardiopulmonary arrest. Severe chlorine gas poisoning patients usually need mechanical ventilation; if the pneumomediastinum is not found on time, threat to life would be greatly increased. It requires a high index of suspicion for diagnosis and rapid treatment. The proper use of ventilator, timely and effective treatment of original disease, and multiple system organ support had significant impact on the prognosis. The pneumomediastinum case secondary to inhalation of chlorine gas that we report here should remind all emergency department physicians to maintain a high index of suspicion for this disease and seek immediate and proper intervention when treating patients with acute chlorine gas poisoning, once diagnosed, especially in younger patients.

Effect of penehyclidine hydrochloride on patients with acute lung injury and its mechanisms.

OBJECTIVE: To assess the effects of penehyclidine hydrochloride on patients with acute lung injury (ALI), to observe the expression of Toll-like receptor 4 (TLR4) on the peripheral monocytes of ALI patients and changes of inflammatory and anti-inflammatory cytokines and to investigate the mechanism of TLR4 in ALI. METHODS: Forty-five patients with ALI were randomly divided into penehyclidine hydrochloride treatment group (P group, n equal to 21) and conventional treatment group (control group, C group, n equal to 24). Patients in both groups received conventional treatment, including active treatment of the primary disease, respiratory support, nutritional support and fluid management therapy, while those in P group were given penehyclidine hydrochloride (1 mg, im, q. 12 h) in addition. The TLR4 expression of 20 healthy volunteers were detected. The clinical effect, average length of stay in ICU and hospital, values of PaO2 and PaO2/FiO2, expression of TLR4 on the surface of peripheral blood mononuclear cells and some serum cytokines were evaluated for 48 h. RESULTS: The general conditions of the two groups were improved gradually and PaO2 increased progressively. Compared with 0 h, PaO2 and PaO2/FiO2 at 6, 12, 24 and 48 h after treatment were significantly increased (P less than 0.05). The improvement in P group was obviously greater than that in C group (P less than 0.05). The average length of hospitalization showed no difference between the two groups, but penehyclidine hydrochloride significantly decreased the average length of stay in ICU (t equal to 3.485, P less than 0.01). The expression of TLR4 in two groups were both obviously higher than that of healthy volunteers (P less than 0.01). It decreased significantly at 24 h (t equal to 2.032, P less than 0.05) and 48 h (t equal to 3.620, P less than 0.01) and was lower in P group than in C group. The patients who showed a higher level of TLR4 expression in early stage had a worse prognosis and most of them developed acute respiratory distress syndrome (ARDS). The incidence of ARDS was 23.8% in P group and 29.17% in C group at 24 h. Untill 48 h, there were other two patients developing ARDS in control group. Serum IL-1, IL-8 and TNF-alpha expressions reduced after 24 h in both groups. The reduction in P group was more obvious than that in C group (P less than 0.05). IL-13 increased gradually from 0 h to 24 h, and decreased slightly at 48 h, which showed no difference between two groups (t equal to 1.028, P larger than 0.05). CONCLUSIONS: Penehyclidine hydrochloride improves the arterial oxygen pressure, down-regulates the expression of TLR4 and restrains the inflammatory cytokines in the downstream of TLR4 signaling pathway. It prevents the development of ALI and can be considered as an important drug in ALI treatment.

Effects of ketamine on levels of cytokines, NF-kappaB and TLRs in rat intestine during CLP-induced sepsis.

This study was designed to investigate the effects of ketamine on levels of inflammatory cytokines, nuclear factor-kappa B (NF-kappaB) and Toll-like receptors (TLRs) in rat intestine during polymicrobial sepsis, induced by cecal ligation and puncture (CLP). After the induction of sepsis or sham-operation, the rats were treated with ketamine (2.5, 5 or 10 mg/kg) or saline (10 ml/kg). At 2, 4 or 6 h post-operation, the intestinal concentrations of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6, were determined by enzyme-linked immunosorbent assay (ELISA). Activity of NF-kappaB in rat intestine was assessed by electrophoretic mobility shift assay (EMSA). And expressions of Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) of rat intestine were examined by reverse transcription-polymerase chain reaction (RT-PCR). We found that TNF-alpha and IL-6 concentrations, NF-kappaB activity, TLR2 and TLR4 expressions in rat intestine were increased after CLP. At the doses of 5 and 10 mg/kg, ketamine suppressed CLP-induced elevation of IL-6. Ketamine 2.5, 5 and 10 mg/kg after CLP decreased intestinal TNF-alpha level and NF-kappaB activity, and inhibited TLR2 and TLR4 expressions as well. These results suggest that ketamine may have anti-inflammatory effects, such as suppressing the levels of inflammatory cytokines and attenuating NF-kappaB activity, during polymicrobial sepsis. And these anti-inflammatory effects possibly correlate with the inhibitory influence of ketamine on TLR2 and TLR4 expressions.

Effects of ketamine on pulmonary inflammatory responses and survival in rats exposed to polymicrobial sepsis.

PURPOSE: Ketamine is reported to suppress production of proinflammatory cytokines and activity of nuclear factor-kappa B (NF-kappaB) after lipopolysaccharide (LPS) stimulation. Our study was designed to investigate the effects of ketamine on pulmonary inflammatory responses and survival in a clinically relevant model of polymicrobial sepsis, induced by cecal ligation and puncture (CLP). METHODS: After the induction of sepsis or sham-operation, animals were treated with ketamine (0.5, 5 or 10 mg/kg) or saline (10 ml/kg) at 3h after operation. At 6 h post-operation, the levels of tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-6, activity of NF-kappaB, expression of Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) of the lungs were measured. And the mortality was recorded for 7 days. RESULTS: TNF-alpha and IL-6 production, NF-kappaB activity, TLR2 and TLR4 expression in rat lungs were increased after CLP. Ketamine at the doses of 5 mg/kg and 10 mg/kg suppressed CLP-induced elevation of TNF-alpha and IL-6 production, NF-kappaB activity and TLR2 expression. Ketamine 0.5, 5 and 10 mg/kg inhibited TLR4 expression in sepsis. Ketamine 5mg/kg and 10 mg/kg after CLP improved the survival of rats. CONCLUSIONS: Ketamine at sub-anesthetic doses could suppress the production of inflammatory cytokines such as TNF-alpha and IL-6, attenuate NF-kappaB activity, and inhibit TLR2 and TLR4 expression in polymicrobial sepsis. These anti-inflammatory effects of ketamine may correlate with improved survival in sepsis.

Ketamine suppresses intestinal TLR4 expression and NF-kappaB activity in lipopolysaccharide-treated rats.

AIM: To investigate whether ketamine suppresses lipopolysaccharide (LPS)-induced increase in Toll-like receptor 4 (TLR4) expression and nuclear factor-kappa B (NF-kappaB) activity in the intestines of rats. METHODS: Six groups of rats received one of the following: normal saline control, LPS (5 mg/kg) plus saline, LPS (5 mg/kg) plus ketamine (0.5 mg/kg), LPS (5 mg/kg) plus ketamine (2.5 mg/kg), LPS (5 mg/kg) plus ketamine (10 mg/kg), or ketamine (10 mg/kg) alone. Intestinal TLR4 mRNA expression was analyzed by reverse transcription polymerase chain reaction (RT-PCR), and NF-kappaB activity was tested by electrophoretic mobility shift assay (EMSA) 1, 3, or 5 hours after the LPS injection. RESULTS: Lipopolysaccharide increased TLR4 expression and NF-kappaB activity in the intestines of rats. Ketamine at the dosage of 0.5, 2.5, and 10 mg/kg suppressed the LPS-induced increase in TLR4 expression and NF-kappaB activity. Ketamine alone had no effect. CONCLUSION: The study demonstrated that ketamine inhibits NF-kappaB activation in the intestines of LPS-treated rats, possibly by suppressing TLR4 expression.