ObjectiveTo investigate the therapeutic effect of Dayuanyin on acute lung injury induced by H1N1 infection and decipher the potential mechanism. MethodThe constituents in Dayuanyin were analyzed by ultra-high performance liquid chromatography-quadrupole-exactive orbitrap mass spectrometry （UHPLC-Q-Exactive Orbitrap MS）. Forty-eight female BALB/c mice were randomized into normal， model， oseltamivir （19.5 mg·kg^-1）， and low-， medium-， and high-dose （2.73， 5.46， 10.92 g·kg^-1） Dayuanyin groups. The normal and model groups were administrated with deionized water by gavage， and the other groups were administrated with the corresponding drugs by gavage. On day 3 of drug administration， the normal group received nasal inhalation of normal saline， and the other groups were inoculated intranasally with A/RP/8/34 （H1N1） for the modeling of influenza virus infection. Mice were administrated with drugs continuously for 7 days and weighed daily. Sampling was performed 12 h after the last administration， and the lung tissue was weighed to calculate the lung index. Hematoxylin-eosin staining was performed to observe the pathological and morphological changes of the lung tissue and bronchi. The cytometric bead array （CBA） was used to measure the serum levels of interferon-gamma （IFN-γ）， C-X-C motif ligand 1 （CXCL1）， tumor necrosis factor-alpha （TNF-α）， chemokine ligand 2 （CCL2）， interleukin-12p70 （IL-12p70）， chemokine ligand 5 （CCL5）， interleukin-1β （IL-1β）， chemokine （C-X-C motif） ligand 10 （CXCL10）， granulocyte-macrophage colony-stimulating factor （GM-CSF）， interleukin-10 （IL-10）， interferon-beta （IFN-β）， interferon-alpha （IFN-α）， and interleukin-6 （IL-6）. According to the results of mass spectrometry and network pharmacology， we analyzed the mechanism of Dayuanyin in treating acute lung injury caused by H1N1. The protein levels of extracellular signal-regulated kinase 1/2 （ERK1/2）， p38 mitogen-activated protein kinase （p38 MAPK）， nuclear factor-kappa B （NF-κB）， and their phosphorylated forms were determined by Western blot. The mRNA levels of myeloid differentiation factor 88 （MyD88）， Toll-like receptor 3 （TLR3）， Toll-like receptor 7 （TLR7）， and Toll-like receptor 8 （TLR8） in the lung tissue were measured by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultA total of 57 compounds， including paeoniflorin and baicalein， were detected in Dayuanyin. Compared with the normal group， the model group showed decreased body weight （P<0.01）， lung edema and hemorrhage， increased lung index （P<0.01）， and elevated levels of IFN-γ， IL-12p70， CCL5， IL-1β， CXCL10， GM-CSF， IFN-β， and IL-6 （P<0.01）. Compared with the model group， Dayuanyin attenuated alveolar wall thickening， capillary congestion， and immune cell infiltration， reduced the alterations in body weight and lung index （P<0.01）， and down-regulated the protein levels of IFN-γ， IL-12p70， CCL5， IL-1β， CXCL10， GM-CSF， IFN-β， and IL-6 （P<0.01）. A total of 57 key genes were predicted by network pharmacological analysis， of which the MAPK signaling pathway was the main target signaling pathway. Compared with the normal group， the model group showed up-regulation in the protein levels of phosphorylation （p）-ERK1/2， p-p38 MAPK， and p-NF-κB （P<0.01） and the mRNA levels of TLR7， TLR8， MyD88， and TLR3 （P<0.05， P<0.01）. Compared with the model group， Dayuanyin lowered the phosphorylation levels of ERK1/2， p38 MAPK， and NF-κB p65 in a dose-dependent manner （P<0.01） and down-regulated the mRNA levels of TLR3， TLR7， TLR8， and MyD88 （P<0.01）. ConclusionDayuanyin can prevent and control H1N1 infection-induced acute lung injury by inhibiting the TLR/MAPK/NF-κB signaling pathway.

Critical ultrasonography is widely used in ICU and has become an indispensable tool for clinicians. However, besides operator-dependency of critical ultrasonography, lack of standardized training mainly result in the physicians′ heterogenous ultrasonic skill. Therefore, standardized training as well as strict quality control plays the key role in the development of critical ultrasonography. We present this quality control standards to promote better development of critical ultrasonography.

Objective:To describe the features of point-of-care cardiopulmonary ultrasound (POCUS) in the critically ill patients and analyze the independent factors associated with treatment changes after POCUS assessment.Methods:This was a prospective multicentric observational study from January to December 2018 in 13 intensive care units (ICU) in China. Consecutive patients admitted to the ICU were enrolled, POCUS were performed within the first 24 h of admission. The POCUS parameters included acute or chronic cardiac abnormality, diameter of inferior vena cava (IVC) at end-expiration, right ventricular systolic function, systolic and diastolic function of left ventricle (LV) and lung ultrasound score. The general features of patients and performers were recorded. Based on the treatment proposed by the performer before and after POCUS assessment, the patients were divided into treatment changed and unchanged groups. Factors associated with treatment changes were identified by multiple logistic regression analysis.Results:Totally 1 913 patients were enrolled including 322 (16.8%) patients with shock, 638 (33.3%) patients with respiratory failure, 139 (7.3%) patients with both shock and respiratory failure and 814 (42.6%) perioperative patients. POCUS had contributed to treatment changes in 1 204 (62.9%) patients, including 867 (72.0%) cases involved fluid management. Univariate analysis showed that there were significant differences in general characteristics of patients, performers and POCUS parameters between groups(all P<0.05). Logistic regression analysis showed that independent factors of treatment changes included ministry of education or university affiliated teaching hospitals (vs.general hospitals, OR=1.891, 95% CI=1.314-2.722, P<0.001 and OR=1.644, 95% CI=1.152-2.347, P=0.006 separately), middle and senior title performers (vs.primary title, OR=2.112, 95% CI=1.358-3.284, P=0.001, OR=3.271, 95% CI=2.129-5.025, P<0.001 separately), mechanical ventilation (vs.without, OR=0.488, 95% CI 0.381-0.626, P<0.001), IVC diameter ≤1 cm (vs.1-2 cm, OR=0.317, 95% CI 0.231-0.434, P<0.001), LV ejecting fraction <50% (vs.≥50%, OR=0.328, 95% CI=0.210-0.512, P<0.001), lung ultrasound score of 6-12 and >12 points(vs.score ≤ 6 points, OR=0.237, 95% CI=0.178-0.315, P<0.001 and OR=0.619, 95% CI=0.457-0.837, P=0.002 separately). Conclusions:POCUS assessment contributes to treatment changes, most of which involves fluid management strategy, in 62.9% critical patients. The independent influencing factors associated with POCUS parameters includes IVC diameter at end-expiratory, LV systolic function and lung ultrasound score. The performers′ title and hospital grade also have a noticeable effect.

Nephrotic syndrome (NS) is one of the most common primary kidney diseases during childhood.Acute kidney injury (AKI) is a common complication of NS, caused by severe hypovolemia, nephrotoxic medications, and infections, etc.It has been proved that the incidence of AKI complicated by NS was increased during these years.Early identification, correct diagnosis and treatment are very important to improve the prognosis.Hence, this study reviewed the recent data on epidemiology, mechanism of AKI in NS, early identification, diagnosis and management of this increasingly common complication.

Severe patients with coronaviras disease 2019 (COVID-19) are characterized by persistent lung damage, causing respiratory failure, secondary circulatory changes and multiple organ dysfunction after virus invasion. Because of its dynamic, real-time, non-invasive, repeatable and other advantages, critical ultrasonography can be widely used in the diagnosis, assessment and guidance of treatment for severe patients. Based on the recommendations of critical care experts from all over the country who fight against the epidemic in Wuhan, this article summarizes the guidelines for the treatment of COVID-19 based on critical ultrasonography, hoping to provide help for the treatment of severe patients. The recommendations mainly cover the following aspects: (1) lung ultrasound in patients with COVID-19 is mainly manifested by thickened and irregular pleural lines, different types of B-lines, shred signs, and other consolidation like dynamic air bronchogram; (2) Echocardiography may show right heart dysfunction, diffuse cardiac function enhancement, stress cardiomyopathy, diffuse cardiac depression and other multiple abnormalities; (3) Critical ultrasonography helps with initiating early treatment in the suspect patient, screening confirmed patients after intensive care unit admission, early assessment of sudden critical events, rapid grading assessment and treatment based on it; (4) Critical ultrasonography helps to quickly screen for the etiology of respiratory failure in patients with COVID-19, make oxygen therapeutic strategy, guide the implementation of lung protective ventilation, graded management and precise off-ventilator; (5) Critical ultrasonography is helpful for assessing the circulatory status of patients with COVID-19, finding chronic cardiopulmonary diseases and guiding extracorporeal membrane oxygenation management; (6) Critical ultrasonography contributes to the management of organs besides based on cardiopulmonary oxygen transport; (7) Critical ultrasonography can help to improve the success of operation; (8) Critical ultrasonography can help to improve the safety and quality of nursing; (9) When performing critical ultrasonography for patients with COVID-19, it needs to implement three-level protection standard, pay attention to disinfect the machine and strictly obey the rules from nosocomial infection. (10) Telemedicine and artificial intelligence centered on critical ultrasonography may help to improve the efficiency of treatment for the patients with COVID-19. In the face of the global spread of the epidemic, all we can do is to share experience, build a defense line, We hope this recommendations can help COVID-19 patients therapy.

To establish the experts consensus on the management of delirium in critically ill patients.A special committee was set up by 15 experts from the Chinese Critical Hypothermia-Sedation Therapy Study Group.Each statement was assessed based on the GRADE (Grading of Recommendations Assessment,Development,and Evaluation) principle.Then the Delphi method was adopted by 36 experts to reassess all the statements.(1) Delirium is not only a mental change,but also a clinical syndrome with multiple pathophysiological changes.(2) Delirium is a form of disturbance of consciousness and a manifestation of abnormal brain function.(3) Pain is a common cause of delirium in critically ill patients.Analgesia can reduce the occurrence and development of delirium.(4) Anxiety or depression are important factors for delirium in critically ill patients.(5) The correlation between sedative and analgesic drugs and delirium is uncertain.(6) Pay attention to the relationship between delirium and withdrawal reactions.(7) Pay attention to the relationship between delirium and drug dependence/ withdrawal reactions.(8) Sleep disruption can induce delirium.(9) We should be vigilant against potential risk factors for persistent or recurrent delirium.(10) Critically illness related delirium can affect the diagnosis and treatment of primary diseases,and can also be alleviated with the improvement of primary diseases.(11) Acute change of consciousness and attention deficit are necessary for delirium diagnosis.(12) The combined assessment of confusion assessment method for the intensive care unit and intensive care delirium screening checklist can improve the sensitivity of delirium,especially subclinical delirium.(13) Early identification and intervention of subclinical delirium can reduce its risk of clinical delirium.(14) Daily assessment is helpful for early detection of delirium.(15) Hopoactive delirium and mixed delirium are common and should be emphasized.(16) Delirium may be accompanied by changes in electroencephalogram.Bedside electroencephalogram monitoring should be used in the ICU if conditions warrant.(17) Pay attention to differential diagnosis of delirium and dementia/depression.(18) Pay attention to the role of rapid delirium screening method in delirium management.(19) Assessment of the severity of delirium is an essential part of the diagnosis of delirium.(20) The key to the management of delirium is etiological treatment.(21) Improving environmental factors and making patient comfort can help reduce delirium.(22) Early exercise can reduce the incidence of delirium and shorten the duration of delirium.(23) Communication with patients should be emphasized and strengthened.Family members participation can help reduce the incidence of delirium and promote the recovery of delirium.(24) Pay attention to the role of sleep management in the prevention and treatment of delirium.(25) Dexmedetomidine can shorten the duration of hyperactive delirium or prevent delirium.(26) When using antipsychotics to treat delirium,we should be alert to its effect on the heart rhythm.(27) Delirium management should pay attention to brain functional exercise.(28) Compared with non-critically illness related delirium,the relief of critically illness related delirium will not accomplished at one stroke.(29) Multiple management strategies such as ABCDEF,eCASH and ESCAPE are helpful to prevent and treat delirium and improve the prognosis of critically ill patients.(30) Shortening the duration of delirium can reduce the occurrence of long-term cognitive impairment.(31) Multidisciplinary cooperation and continuous quality improvement can improve delirium management.Consensus can promote delirium management in critically ill patients,optimize analgesia and sedation therapy,and even affect prognosis.

Objective: To investigate the changes of B cell-activating factor (BAFF) and a proliferation- inducing ligand (APRIL) in serum of children with Henöch- Schönlein purpura nephritis (HSPN), and to explore their role in the pathogenesis of children HSPN. Methods: A total of 28 children with HSPN who were before treatment were selected in Department of Pediatrics Nephrology and Rheumatology, Shengjing Hospital of China Medical University from November 2017 to August 2018.Sixteen children with Henöch-Schönlein purpura were selected as HSP group, and 20 healthy children were selected as healthy control group.Followed the HSPN guideline to cure the patients for 6-8 weeks.The clinical data were collected.Serum levels of BAFF and APRIL were measured by adopting enzyme-linked immunosorbent assay (ELISA). Results: (1)Changes of serum BAFF level: the serum levels of BAFF in HSPN children were significantly lower than those in the HSP group and the healthy control group[ HSPN group (0.652±0.360) μg/L, HSP group (1.276±0.459) μg/L, healthy control group (1.285±0.299) μg/L, F=17.519, P=0.000]. Moreover, the serum levels of BAFF in before treatment were significantly lower than those in after treatment [before treatment (0.652±0.360) μg/L, after treatment (0.860±0.262) μg/L, P<0.05). However, there were no significant di-fferences in the serum levels of BAFF between HSP group and healthy control group (P>0.05). (2)Changes of serum APRIL level: the serum levels of APRIL in HSPN and HSP children were both significantly higher than those in healthy control group, but there were no marked differences between the 2 groups [HSPN group (2.285±1.015) μg/L, HSP group (2.609±1.264) μg/L, healthy control group (1.677±0.118) μg/L, F=3.647, P=0.016]. There were no significant differences in the serum levels of APRIL between before treatment and after treatment [ before treatment (2.285±1.015) μg/L, after treatment (2.042±0.695) μg/L, P>0.05]. (3)Pearson correlation analysis results showed that the serum levels of BAFF were negatively correlated with 24 h urinary protein, urinary microalbumin, and urine red blood cell count (r=-0.587, -0.608, -0.515, all P<0.05). The serum levels of APRIL were positively correlated with serum IgA(r=0.588, P<0.05). Conclusions The level of serum BAFF decreased and APRIL increased in children with HSPN, which was related to the degree of renal involvement.It suggests that BAFF and APRIL may be related to the pathogenesis of HSPN in children.

Objective: To analyze the influencing factors for bladder cancer in Taizhou,and to provide evidence for strengthening the prevention and treatment of bladder cancer in Taizhou. Methods : A total of 500 cases of bladder cancer diagnosed in Taizhou Hospital from 2012 to 2017 were selected as a case group,and 504 patients without tumor or urinary system diseases during the same period were selected as a control group. A structured questionnaire was used to retrospectively investigate the demographic information,occupational exposure（whether they were exposed to aromatic amine,polycyclic aromatic hydrocarbons,tobacco,tobacco smoke or heavy metals at work）,healthy behaviors and diets of the two groups one year before admission. A Logistic regression model was used to analyze the influencing factors for bladder cancer. Results : There was no significant differences in sex,age,ethnicity,education and marital status between the case group and the control group（P > 0.05）. Patients with occupational exposure history accounting for 31.60% in the case group and 24.60% in the control group,for overweight/obesity were 37.60% and 31.74%,for smoking were 55.80% and 46.23%,for high vegetable intake frequency were 43.80% and 52.58%,for high fruit intake frequency were 55.40% and 62.70%,for physical activity were 24.60% and 31.75%,respectively. The results of multivariate logistic regression analysis showed that occupational exposure（OR=1.861,95%CI：1.229-2.836）,overweight/obesity（OR=1.374,95%CI：1.021-1.863）,current smoking（OR=1.664,95%CI：1.101-2.503）and previous smoking（OR=1.454,95%CI：1.016-2.066）were the risk factors for bladder cancer. High vegetable intake frequency（OR=0.731,95%CI：0.566-0.947）,high fruit intake frequency（OR=0.659,95%CI：0.463-0.927）and vigorous physical activity（OR=0.566,95%CI：0.403-0.798）were the protective factors for bladder cancer. Conclusion Occupational exposure,overweight/obesity,current smoking,previous smoking were the risk factors for bladder cancer. High vegetables intake frequency,high fruit intake frequency and vigorous physical activity were the protective factors for bladder cancer.

Transesophageal echocardiography(TEE) is valuable in intensive care unit (ICU) because its application meets the requirements of diagnosis and treatment of critically ill patients.However, the current application has not fully adapted to the specialty of critical care. TEE could be more valuablein ICU when used with a new way that under the guidance of the theory of critical care and embedded into the treatment workflow. We have expanded and improved the application of traditional TEE and integrated the concept of critical care, established the concept of transesophageal echocardiography for critical care (TEECC). Chinese Critical Ultrasound Study Group (CCUSG) organized experts in the area to form the consensus based the previous studiesand the long term practice of critical care ultrasound and TEE, aiming at clarifying the nature and characteristics of TEECC, promoting the rational and standardized clinical application and the coming researches.The consensus of Chinese experts on clinical application of TEECC (2019) were 33 in total, of whichthe main items were as follows: (1) TEECC is a significant means, which is expanded and improved from the traditional transesophageal echocardiography according to characteristics of critically ill patients and is applied in ICU based on critically clinical scenarios and requirements by the critical care physician, to promote visualized, refined and precisely management of critically ill patients.(2) TEE possesses distinctive superiority in implementation in ICU. It has characteristics of images with good quality, operations with good stability and low-dependent of operators, monitoring with continuity, and visualization with all-dimensional and detail of heart and blood vessels.(3)As a means of refined monitoring that could resulted in precise diagnosis and treatment, TEECC expands the dimension of intensive monitoring and improves the performance of critical care. (4) Indications of TEECC application include clinical etiological searching and invasive procedures guiding when it acted as a traditional role; and also refined hemodynamic monitoring based on critical care rationale and over-all management under specific critical clinical scenarios. (5) TEE and TTE assessments are complementary; they are not alternative. Integrated assessment of TTE and TEE is required under many critical clinical scenarios.(6) TEE should be a necessary configuration in ICU. (7) All-round and significant information regarding to the mechanism of acute circulatory disorders can be provided by TEECC; it is a non-substitutable means of identifying the causes of shock under some special clinical scenarios. (8) Focal extracardiac hematoma can be accurately and rapidly detected by TEE in patients with open-thoracic cardiac surgery or severe chest trauma when highly suspected pericardial tamponade.(9) The priority of pathophysiologic mechanism of septic shock can be rapidly and accurately identified by TEE; even if its pathophysiological changes are complex, including hypovolemia and/or vasospasm and/or left and right heart dysfunction. (10) Causes of hemodynamic disorders can be rapidly and qualitatively evaluated so that the orientation of treatment can be clarified by TEECC. (11) A full range of quantitative indicators for refined hemodynamic management in critically ill patients can be provided by TEECC. (12) TEECC helps to accurately assess volume status and predict fluid responsiveness.(13) TEECC is specially suitable for accurate quantitative assessment of cardiac function.(14) Mini TEE provides long-term continuous hemodynamic monitoring. (15) Standard views are easy to be acquired by TEECC, which is a premise for accurate and repeatable measurements, and a guarantee for assessment of effect and risk of therapy. (16) Compared with invasive hemodynamic monitoring, TEECC is minimally invasive, with low infection risk and high safety.(17) In patients with acute cor pulmonale (ACP) under condition of right ventricular dysfunction and low cardiac output, TEECC is a key tool for assessment. (18) TEECC should be implemented actively when suspicious of left to right shunt in critically ill patients who occurred hypotension that hard to explain the cause. (19) TEECC should be implemented actively when suspicious of right to left shunt in critically ill patients who occurred hypoxemia that hard to explain the cause. (20) TEECC is preferred in hemodynamics monitoring under prone position of ventilated patients.(21) TEECC is an imperative means to achieve over-all management of extracorporeal membrane oxygenation (ECMO) therapy, especially for all-round hemodynamic monitoring. (22) Three basic views is recommended to be used to simplify TEE assessment during cardiac arrest so that reversible causes could be identified, and resuscitation could be guided. (23) The flow related echodynamic evaluation (TEECC-FREE) workflow is preferred in refined hemodynamics monitoring and therapy. (24) Simple workflow of TEECC could be implemented in special critical clinical scenarios. (25) Application of TEECC is highly secure; however, impairments of procedure should also be alert by operators. (26) Pitfalls in application of TEE should be paid attention to by the critical care physician. (27) Timely and rationally application of TEECC is in favor of diagnosis and treatment of critically ill patients and may improve the prognosis.

Critical ultrasonography(CUS) is different from the traditional diagnostic ultrasound,the examiner and interpreter of the image are critical care medicine physicians.The core content of CUS is to evaluate the pathophysiological changes of organs and systems and etiology changes.With the idea of critical care medicine as the soul,it can integrate the above information and clinical information,bedside real-time diagnosis and titration treatment,and evaluate the therapeutic effect so as to improve the outcome.CUS is a traditional technique which is applied as a new application method.The consensus of experts on critical ultrasonography in China released in 2016 put forward consensus suggestions on the concept,implementation and application of CUS.It should be further emphasized that the accurate and objective assessment and implementation of CUS requires the standardization of ultrasound image acquisition and the need to establish a CUS procedure.At the same time,the standardized training for CUS accepted by critical care medicine physicians requires the application of technical specifications,and the establishment of technical specifications is the basis for the quality control and continuous improvement of CUS.Chinese Critical Ultrasound Study Group and Critical Hemodynamic Therapy Collabration Group,based on the rich experience of clinical practice in critical care and research,combined with the essence of CUS,to learn the traditional ultrasonic essence,established the clinical application technical specifications of CUS,including in five parts:basic view and relevant indicators to obtain in CUS;basic norms for viscera organ assessment and special assessment;standardized processes and systematic inspection programs;examples of CUS applications;CUS training and the application of qualification certification.The establishment of applied technology standard is helpful for standardized training and clinical correct implementation.It is helpful for clinical evaluation and correct guidance treatment,and is also helpful for quality control and continuous improvement of CUS application.