Transcutaneous cervical vagus nerve stimulation improved motor cortex excitability in healthy adults: a randomized, single-blind, self-crossover design study.

Purpose: To investigate the effect of transcutaneous cervical vagus nerve stimulation (tcVNS) on motor cortex excitability in healthy adults. Method: Twenty eight healthy subjects were assigned to receive real and sham tcVNS for 30 min. The interval between the real and sham conditions was more than 24 h, and the sequence was random. The central and peripheral motor-evoked potential (MEP) of the right first dorsal interosseous (FDI) muscle was measured by transcranial magnetic stimulation (TMS) before and after stimulation. MEP latency, MEP amplitude and rest motor threshold (rMT) were analyzed before and after stimulation. Results: MEP amplitude, MEP latency and rMT had significant interaction effect between time points and conditions (p < 0.05). After real stimulation, the MEP amplitude was significantly increased (p < 0.001). MEP latency (p < 0.001) and rMT (p = 0.006) was decreased than that of baseline. The MEP amplitude on real condition was higher than that of sham stimulation after stimulation (p = 0.027). The latency after the real stimulation was significantly shorter than that after sham stimulation (p = 0.005). No significantly difference was found in rMT after stimulation between real and sham conditions (p > 0.05). Conclusion: tcVNS could improve motor cortex excitability in healthy adults.

Construction of an Artificial Light-Harvesting System with Efficient Photocatalytic Activity in an Aqueous Solution Based on a FRET-Featuring Metallacage.

Over the past few decades, the design and construction of high-efficiency artificial light-harvesting systems (LHSs) involving multistep fluorescence-resonance energy transfer (FRET) processes have gradually received considerable attention within wide fields ranging from supramolecular chemistry to chemical biology and even materials science. Herein, through coordination-driven self-assembly, a novel tetragonal prismatic metallacage featuring a FRET process using tetraphenylethene (TPE) units as donors and BODIPY units as acceptors has been conveniently synthesized. Subsequently, taking advantage of supramolecular hydrophobic interactions, a promising artificial LHS involving two-step FRET processes from TPE to BODIPY and then to Nile Red (NiR) has been successfully fabricated in an aqueous solution using the FRET-featuring metallacage, NiR, and an amphiphilic polymer (mPEG-DSPE). Notably, this obtained aqueous LHS exhibits highly efficient photocatalytic activity in the dehalogenation of a bromoacetophenone derivate. This study provides a unique strategy for fabricating artificial LHSs in aqueous solutions with multistep FRET processes and further promotes the future development of mimicking the photosynthesis process.

Low-intensity transcranial ultrasound stimulation facilitates hand motor function and cortical excitability: A crossover, randomized, double blind study.

Objective: Transcranial ultrasound stimulation (TUS) is a new form of non-invasive brain stimulation. Low-intensity TUS is considered highly safe. We aimed to investigate the effect of low-intensity TUS on hand reaction responses and cortical excitability in healthy adults. Methods: This study used a crossover, randomized, and double-blind design. A total of 20 healthy participants were recruited for the study. All the participants received TUS and sham stimulation on separate days in random order. The finger tapping test (tapping score by using a tablet) and motor evoked potential (MEP) were assessed before and after stimulation, and discomfort levels were assessed using a visual analog scale (VAS) score. Results: No significant differences in tapping score or MEP amplitude between the two experimental conditions were registered before stimulation. After stimulation, tapping scores were increased regardless of the specific treatment, and the real stimulation condition receiving TUS (90.4 ± 11.0 points) outperformed the sham stimulation condition (86.1 ± 8.4 points) (p = 0.002). The MEP latency of real TUS (21.85 ± 1.33 ms) was shorter than that of sham TUS (22.42 ± 1.43 ms) (p < 0.001). MEP amplitude of real TUS (132.18 ± 23.28 µV) was higher than that of sham TUS (114.74 ± 25.5 µV, p = 0.005). There was no significant difference in the discomfort score between the two conditions (p = 0.163). Conclusion: Transcranial ultrasound stimulation (TUS) can decrease the hand reaction response time and latency of the MEP, enhance the excitability of the motor cortex, and improve hand motor function in healthy individuals without obvious discomfort.

Transcutaneous Electrical Acustimulation Ameliorates Motion Sickness Induced by Rotary Chair in Healthy Subjects: A Prospective Randomized Crossover Study.

OBJECTIVES: Motion sickness (MS) is a common physiological response to real or virtual motion. The purpose of this study was to investigate the effects of transcutaneous electrical acustimulation (TEA) on MS and the underlying mechanisms in healthy subjects. MATERIALS AND METHODS: A total of 50 healthy participants were recruited and randomly assigned into two groups to complete two separate sessions in a crossover study. A Coriolis rotary chair was used as a model to provoke severe MS. The total tolerable rotation time and Graybiel scoring scale were recorded. Gastric slow waves were detected by electrogastrogram. The autonomic nervous function, including the vagal activity, was evaluated by the analysis of heart rate variability derived from the electrocardiogram recording. The serum levels of arginine vasopressin (AVP) and norepinephrine (NE) were examined. RESULTS: Of note, 22 participants in TEA and only 11 participants in the sham-TEA session completed the entire five-rotation MS stimuli (p = 0.019). TEA significantly prolonged the total tolerable rotation time of MS stimuli (220.4 ± 11.59 vs 173.6 ± 12.3 seconds, p < 0.001) and lowered MS symptom scores (12.56 ± 2.03 vs 22.06 ± 3.0, p < 0.001). TEA improved the percentage of normal gastric slow waves, compared with sham-TEA (56.0 ± 2.1% vs 51.6 ± 2.0%, p = 0.033). TEA also significantly enhanced vagal activity compared with sham-TEA (0.41 ± 0.02 vs 0.31 ± 0.02, p < 0.001). In addition, the increased serum levels of AVP and NE on MS stimulation were markedly suppressed by TEA treatment, compared with sham-TEA (AVP, 56.791 ± 4.057 vs 79.312 ± 10.036 ng/mL, p = 0.033; NE, 0.388 ± 0.037 vs 0.501 ± 0.055 ng/mL, p = 0.021). CONCLUSIONS: Needleless TEA is a potent therapeutic approach for severe MS, as it increases participants' tolerance and ameliorates MS symptoms, which may be attributed to the integrative effects of TEA on autonomic functions and neuroendocrine balance.

Retrospective Study of Critically Ill COVID-19 Patients With and Without Extracorporeal Membrane Oxygenation Support in Wuhan, China.

Background: Extracorporeal membrane oxygenation (ECMO) might benefit critically ill COVID-19 patients. But the considerations besides indications guiding ECMO initiation under extreme pressure during the COVID-19 epidemic was not clear. We aimed to analyze the clinical characteristics and in-hospital mortality of severe critically ill COVID-19 patients supported with ECMO and without ECMO, exploring potential parameters for guiding the initiation during the COVID-19 epidemic. Methods: Observational cohort study of all the critically ill patients indicated for ECMO support from January 1 to May 1, 2020, in all 62 authorized hospitals in Wuhan, China. Results: Among the 168 patients enrolled, 74 patients actually received ECMO support and 94 not were analyzed. The in-hospital mortality of the ECMO supported patients was significantly lower than non-ECMO ones (71.6 vs. 85.1%, P = 0.033), but the role of ECMO was affected by patients' age (Logistic regression OR 0.62, P = 0.24). As for the ECMO patients, the median age was 58 (47-66) years old and 62.2% (46/74) were male. The 28-day, 60-day, and 90-day mortality of these ECMO supported patients were 32.4, 68.9, and 74.3% respectively. Patients survived to discharge were younger (49 vs. 62 years, P = 0.042), demonstrated higher lymphocyte count (886 vs. 638 cells/uL, P = 0.022), and better CO2 removal (PaCO2 immediately after ECMO initiation 39.7 vs. 46.9 mmHg, P = 0.041). Age was an independent risk factor for in-hospital mortality of the ECMO supported patients, and a cutoff age of 51 years enabled prediction of in-hospital mortality with a sensitivity of 84.3% and specificity of 55%. The surviving ECMO supported patients had longer ICU and hospital stays (26 vs. 18 days, P = 0.018; 49 vs. 29 days, P = 0.001 respectively), and ECMO procedure was widely carried out after the supplement of medical resources after February 15 (67.6%, 50/74). Conclusions: ECMO might be a benefit for severe critically ill COVID-19 patients at the early stage of epidemic, although the in-hospital mortality was still high. To initiate ECMO therapy under tremendous pressure, patients' age, lymphocyte count, and adequacy of medical resources should be fully considered.

Critical roles of cytokine storm and secondary bacterial infection in acute kidney injury development in COVID-19: A multi-center retrospective cohort study.

Acute kidney injury (AKI) may develop in patients with coronavirus disease 2019 (COVID-19) and is associated with in-hospital death. We investigated the incidence of AKI in 223 hospitalized COVID-19 patients and analyzed the influence factors of AKI. The incidence of cytokine storm syndrome and its correlation with other clinicopathologic variables were also investigated. We retrospectively enrolled adult patients with virologically confirmed COVID-19 who were hospitalized at three hospitals in Wuhan and Guizhou, China between February 13, 2020, and April 8, 2020. We included 124 patients with moderate COVID-19 and 99 with severe COVID-19. AKI was present in 35 (15.7%) patients. The incidence of AKI was 30.3% for severe COVID-19 and 4.0% for moderate COVID-19 (p < 0.001). Furthermore, cytokine storm was found in 30 (13.5%) patients and only found in the severe group. Kidney injury at admission (odds ratio [OR]: 3.132, 95% confidence interval [CI]: 1.150-8.527; p = 0.025), cytokine storm (OR: 4.234, 95% CI: 1.361-13.171; p = 0.013), and acute respiratory distress syndrome (ARDS) (OR: 7.684, 95% CI: 2.622-22.523; p < 0.001) were influence factors of AKI. Seventeen (48.6%) patients who received invasive mechanical ventilation developed AKI, of whom 64.7% (11/17) died. Up to 86.7% of AKI patients with cytokine storms may develop a secondary bacterial infection. The leukocyte counts were significantly higher in AKI patients with cytokine storm than in those without (13.0 × 109/L, interquartile range [IQR] 11.3 vs. 8.3 × 109/L, IQR 7.5, p = 0.005). Approximately 1/6 patients with COVID-19 eventually develop AKI. Kidney injury at admission, cytokine storm and ARDS are influence factors of AKI. Cytokine storm and secondary bacterial infections may be responsible for AKI development in COVID-19 patients.

Correction: Exosomal miR-25-3p from mesenchymal stem cells alleviates myocardial infarction by targeting pro-apoptotic proteins and EZH2.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Correction: Exosomal miR-25-3p from mesenchymal stem cells alleviates myocardial infarction by targeting proapoptotic proteins and EZH2.

Since online publication of this article, the authors noticed that an incorrect image was used during the compilation of Fig. 2a, which was caused during manuscript preparation. The correct Fig. 2a is shown below.

Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: An evidence-based clinical practice guideline (updated version).

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.

Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: an evidence-based clinical practice guideline (updated version)

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID19 patients

Exosomal miR-25-3p from mesenchymal stem cells alleviates myocardial infarction by targeting pro-apoptotic proteins and EZH2.

Mesenchymal stem cell (MSC) therapy is a promising approach against myocardial infarction (MI). Studies have demonstrated that MSCs can communicate with other cells by secreting exosomes. In the present study, we aimed to identify exosomal microRNAs that might contribute to MSC-mediated cardioprotective effects. Primary cardiomyocytes were deprived of oxygen and glucose to mimic MI in vitro. For the animal model of MI, the left anterior descending artery was ligated for 1 h, followed by reperfusion for 12 h. MSC-derived exosomes were used to treat primary cardiomyocytes or mice. Cardioprotection-related microRNAs were determined, followed by target gene identification and functional studies with quantitative PCR, western blotting, MTT assay, flow cytometry assay, chromatin immunoprecipitation and dual-luciferase assay. We found that MSC co-culture reduced OGD-induced cardiomyocyte apoptosis and inflammatory responses. Cardioprotection was also observed upon treatment with MSC-derived exosomes in vitro and in vivo. In line with this, exosome uptake led to a significant increase in miR-25-3p in cardiomyocytes. Depletion of miR-25-3p in MSCs abolished the protective effects of exosomes. Mechanistically, miR-25-3p directly targeted the pro-apoptotic genes FASL and PTEN and reduced their protein levels. Moreover, miR-25-3p decreased the levels of EZH2 and H3K27me3, leading to derepression of the cardioprotective gene eNOS as well as the anti-inflammatory gene SOCS3. Inhibition of EZH2 or overexpression of miR-25-3p in cardiomyocytes was sufficient to confer cardioprotective effects in vitro and in vivo. We concluded that exosomal miR-25-3p from MSCs alleviated MI by targeting pro-apoptotic proteins and EZH2.

CircMTO1 Attenuated Acute Kidney Injury Through Regulating miR-337.

Acute kidney injury (AKI) is an independent risk factor for the increased risk of death in patients with sepsis. In the current study, we first investigated the expression of circMTO1 in sepsis-induced AKI, and the underlying mechanism was further elucidated. The results showed that circMTO1 expression level was significantly decreased in serums and kidney tissues of US rats and RMCs treated with LPS. Besides, circMTO1 overexpression promoted cell viability, suppressed cell apoptosis and cytokines production of LPS-treated RMCs. Bioinformatics analysis showed that circMTO1 served as a sponge for miR-337. Furthermore, circMTO1 could inhibit the expression of KLF6. Altogether, our study first reported that circMTO1 expression was decreased in sepsis-induced AKI rat models and RMCs treated with LPS. CircMTO1 overexpression could attenuate AKI development by sponging miR-337 and regulating KLF6 expression, which may provide new ideas for evaluation the pathogenesis and the treatment of sepsis-induced AKI.

Analysis of Severe Fever With Thrombocytopenia Syndrome in Critical Ill Patients in Central China.

INTRODUCTION: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonosis infected by virus (SFTSV) in central and eastern China, which is associated with high mortality. However, limited clinical data have been reported about this critical illness. PATIENTS AND METHODS: Retrospective cohort study in intensive care unit (ICU) patients with SFTSV infection admitted in 2014 to 2019. Diagnosis was confirmed using reverse transcription polymerase chain reaction on serum samples. RESULTS: One hundred sixteen patients with SFTSV infection were included (mean age 63 ±â€Š9 years, 59 [51.3%] males). Non-survivors (43.1%) were older, and had lower Glasgow Coma Score, higher Acute Physiology and Chronic Health Evaluation II, and sequential organ failure assessment score at ICU admission. In addition, non-survivors had more severe respiratory failure (PaO2/FiO2: 208 ±â€Š14 mm Hg vs. 297 ±â€Š15 mm Hg), more frequent shock (25[50%] vs. 7[10.6%]), and required more frequently mechanical ventilation (78% vs. 19.7%; P < 0.001) and vasopressor support (56% vs. 9.1%; P < 0.001). Non-survivors experienced more obvious monocyte loss. After adjustment for potential confounding factors, older age, elevated lactate level, and elevated creatinine level were the independent risk factors for death. CONCLUSION: We provided knowledge about the clinical characteristics of SFTS admitted in ICU. Older age, elevated lactate level, and elevated creatinine level may be useful for identifying patients with poor outcome and intensive medical intervention can be provided for patients as soon as possible to reduce mortality.

A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version).

In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named "2019 novel coronavirus (2019-nCoV)" by the World Health Organization (WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world's attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.

Reactive Oxygen Species-Induced Lipid Peroxidation in Apoptosis, Autophagy, and Ferroptosis.

Reactive oxygen species- (ROS-) induced lipid peroxidation plays a critical role in cell death including apoptosis, autophagy, and ferroptosis. This fundamental and conserved mechanism is based on an excess of ROS which attacks biomembranes, propagates lipid peroxidation chain reactions, and subsequently induces different types of cell death. A highly evolved sophisticated antioxidant system exists that acts to protect the cells from oxidative damage. In this review, we discussed how ROS propagate lipid peroxidation chain reactions and how the products of lipid peroxidation initiate apoptosis and autophagy in current models. We also discussed the mechanism of lipid peroxidation during ferroptosis, and we summarized lipid peroxidation in pathological conditions of critical illness. We aim to bring a more global and integrative sight to know how different ROS-induced lipid peroxidation occurs among apoptosis, autophagy, and ferroptosis.

Downregulation of exosome-encapsulated miR-548c-5p is associated with poor prognosis in colorectal cancer.

The role of circulating exosomal microRNAs (miRNAs) in colorectal cancer (CRC) has drawn more and more attention during the past few years. Previously, we have identified several specific miRNAs in serum exosomes as potential CRC biomarkers. However, little is known about the association between exosome-encapsulated miR-548c-5p and outcomes of patients with CRC. In the current study, the expression of serum exosomal miR-548c-5p was investigated by quantitative real-time polymerase chain reaction. Its correlation with CRC prognosis was estimated by Kaplan-Meier survival and log-rank tests. Cox regression analysis based on uni- and multivariate analyses was performed to estimate the relationship of exosome-encapsulated miR-548c-5p with the clinicopathological factors of patients with CRC. Reduced levels of serum exosomal miR-548c-5p were more significant in CRC patients with liver metastasis and at later TNM stage (III/IV tumor stages). Serum exosomal miR-548c-5p could inhibit the proliferation of CRC cells, while the precise molecular mechanisms warranted further elucidation. In addition, decreased levels of serum exosomal miR-548c-5p were independently associated with shorter overall survival in CRC adjusted by age, sex, tumor grade vascular infiltration, TNM stage (III/IV tumor stages) and metastasis (hazard ratio = 3.40, 95% confidence interval 1.02-11.27; P = 0.046). The downregulation of exosomal miR-548c-5p in serum predicts poor prognosis in patients with CRC. Exosomal miR-548c-5p may be a critical biomarker for CRC diagnosis and prognosis.

Downregulation of TIMP2 attenuates sepsis-induced AKI through the NF-κb pathway.

Acute kidney injury (AKI) is a frequent complication of sepsis and contributes to increased morbidity and mortality. Urinary tissue inhibitor of metalloproteinases-2 (TIMP2) has been recently recognized as an early biomarker to predict AKI in critically ill patients. However, the biological functions of TIMP2 remain largely unknown. In this study, we investigated the role of TIMP2 in mediating inflammation and tubular cell apoptosis in AKI. In kidney tissue taken from mice exposed to cecal ligation and puncture (CLP) and in human kidney 2 (HK-2) cells exposed to lipopolysaccharide (LPS) in culture, TIMP2 expression was significantly upregulated. The expression of TIMP2 in the kidney tissue correlated with the severity of AKI in vivo. In cultured HK-2 cells, LPS challenge markedly induced cytokine release, and recombinant cytokines promoted TIMP2 expression and apoptosis. However, TIMP2 silencing ameliorated LPS-induced cytokine release, apoptosis, and cell injury. We further found that the effects of downregulation of TIMP2 on a suppression of release of inflammatory cytokines were mediated by p-P65. Stable, kidney-specific TIMP2 knockdown mice were transduced by injecting the TIMP2 knockdown lentiviral vector into kidney parenchyma. TIMP2 silencing ameliorated CLP-induced proinflammatory cytokines, kidney dysfunction as measured by serum creatinine level, and histopathological changes. Downregulation of TIMP2 showed renoprotective effects on endotoxin-induced AKI, which was associated with the anti-inflammatory activity through inhibition of the nuclear factor (NF)-κB pathway. Collectively, our results indicate that TIMP2 plays an important role in mediating sepsis-induced AKI through regulation of NF-κB. These findings reveal the pathogenic role of TIMP2 in AKI and suggest a novel target for the treatment of AKI.

Incomplete intestinal obstruction as the possible main complaint in Behcet's disease after surgery for recurrent abdominal aortic pseudoaneurysms: a case report and literature review.

BACKGROUND: Behcet's disease (BD) is a systemic vasculitis characterized by oral and genital aphthosis, and ocular and skin lesions. The disease is involved in vascular, gastrointestinal, and central nervous systems. Vasculitis may exacerbate fatal problems, such as anastomotic pseudoaneurysms. If the mesenteric vessels are involved, severe abdominal symptoms such as intestinal obstruction may occur. CASE PRESENTATION: This case report describes a young female patient who suffered from BD with recurrent abdominal aortic pseudoaneurysms, as well as deep venous thrombosis and subsequent complications of incomplete intestinal obstruction. This patient first underwent stent grafting, which was followed by rupture of two newly formed anastomotic pseudoaneurysms within six months. Emergency open surgical repair (OSR) was then performed on the ruptured pseudoaneurysms. Thrombosis and incomplete ileus occurred five months after surgery. This case was unique due to the presence of incomplete intestinal obstruction being the possible main complaint for a patient with Behcet's disease, and it is the first ever case to be reported. CONCLUSION: Intestinal obstruction may present as the possible main complaint in BD. Careful and attentive strategy should be carried out to prevent fatal outcomes.

A National Multicenter Survey on Management of Pain, Agitation, and Delirium in Intensive Care Units in China.

BACKGROUND: The management of pain, agitation, and delirium (PAD) in Intensive Care Unit (ICU) is beneficial for patients and makes it widely applied in clinical practice. Previous studies showed that the clinical practice of PAD in ICU was improving; yet relatively little information is available in China. This study aimed to investigate the practice of PAD in ICUs in China. METHODS: A multicenter, nationwide survey was conducted using a clinician-directed questionnaire from September 19 to December 18, 2016. The questionnaire focused on the assessment and management of PAD by the clinicians in ICUs. The practice of PAD was compared among the four regions of China (North, Southeast, Northwest, and Southwest). The data were expressed as percentage and frequency. The Chi-square test, Fisher's exact test, and line-row Chi-square test were used. RESULTS: Of the 1011 valid questionnaire forms, the response rate was 80.37%. The clinicians came from 704 hospitals across 158 cities of China. The rate of PAD assessment was 75.77%, 90.21%, and 66.77%, respectively. The rates of PAD scores were 45.8%, 68.94%, and 34.03%, respectively. The visual analog scale, Richmond agitation-sedation scale, and confusion assessment method for the ICU were the first choices of scales for PAD assessment. Fentanyl, midazolam, and dexmedetomidine were the first choices of agents for analgesic, sedation, and delirium treatment. While choosing analgesics and sedatives, the clinicians put the pharmacological characteristics of drugs in the first place (66.07% and 76.36%). Daily interruption for sedation was carried out by 67.26% clinicians. Most of the clinicians (87.24%) used analgesics while using sedatives. Of the 738 (73%) clinicians titrating the sedatives on the basis of the proposed target sedation level, 268 (26.61%) clinicians just depended on their clinical experience. Totally, 519 (51.34%) clinicians never used other nondrug strategies for PAD. The working time of clinicians was an important factor in the management of analgesia and sedation rather than their titles and educational background. The ratios of pain score and sedation score in the Southwest China were the highest and the North China were the lowest. The ratios of delirium assessment and score were the same in the four regions of China. Moreover, the first choices of scales for PAD in the four regions were the same. However, the top three choices of agents in PAD treatment in the four regions were not the same. CONCLUSIONS: The practice of PAD in China follows the international guidelines; however, the pain assessment should be improved. The PAD practice is a little different across the four regions of China; however, the trend is consistent. TRIAL REGISTRATION: The study is registered at http://www.clinicaltrials.gov (No. ChiCTR-OOC-16009014, www.chictr. org.cn/index.aspx.).

Aerosolized Amikacin as Adjunctive Therapy of Ventilator-associated Pneumonia Caused by Multidrug-resistant Gram-negative Bacteria: A Single-center Randomized Controlled Trial.

BACKGROUND: Aerosolized amikacin (AA) is a current option for the management of ventilator-associated pneumonia (VAP) caused by multidrug-resistant Gram-negative bacteria (MDR-GNB), as it is reported that AA could increase the alveolar level of the drug without increasing systemic toxicity. This study aimed to evaluate the efficacy and safety of AA as an adjunctive therapy for VAP caused by MDR-GNB. METHODS: In this single-center, double-blind study conducted in a 36-bed general Intensive Care Unit (ICU) in a tertiary hospital from June 2014 to June 2016, 52 ICU patients with confirmed MDR-GNB VAP were randomized to two groups (AA group, n = 27 and placebo group, n = 25). Amikacin (400 mg, q8h) or saline placebo (4 ml, q8h) was aerosolized for 7 days. The attending physician determined the administration of systemic antibiotics for VAP. Patients were followed up for 28 days. Bacteriological eradication, clinical pulmonary infection score (CPIS), and serum creatinine were assessed on day 7 of therapy. New resistance to amikacin, cure rate of VAP, weaning rate, and mortality were assessed on day 28. RESULTS: The baseline characteristics of patients in both groups were similar. At the end of the treatment, 13 of the 32 initially detected bacterial isolates were eradicated in AA group, compared to 4 of 28 in placebo group (41% vs. 14%, P= 0.024). As for patients, 11 of 27 patients treated with AA and 4 of 25 patients treated with placebo have eradication (41% vs. 16%, P= 0.049). The adjunction of AA reduced CPIS (4.2 ± 1.6 vs. 5.8 ± 2.1, P= 0.007). New drug resistance to amikacin and the change in serum creatinine were not detected in AA group. No significant differences in the clinical cure rate in survivors (48% vs. 35%, P= 0.444), weaning rate (48% vs. 32%, P= 0.236), and mortality (22% vs. 32%, P= 0.427) were detected between the two groups on day 28. CONCLUSIONS: As an adjunctive therapy of MDR-GNB VAP, AA successfully eradicated existing MDR organisms without inducing new resistance to amikacin or change in serum creatinine. However, the improvement of mortality was not found.