Acute Coronary Artery Air Embolism Complicating a CT-guided percutaneous lung biopsy: A case report.

Systemic air embolism is a fatal complication of computed tomography-guided percutaneous lung biopsy. Here, we report a case of acute coronary artery air embolism following computed tomography (CT) guided percutaneous lung biopsy. The patient exhibited cardiac symptoms, and CT showed air density in left ventricle and aorta, indicating air embolism. Trendelenburg positioning and coronary angiography were performed during the treatment, and the patient was discharged without obvious complications.

In Situ-Sprayed Bioinspired Adhesive Conductive Hydrogels for Cavernous Nerve Repair.

Cavernous nerve injury (CNI), resulting in erectile dysfunction (ED), poses a significant threat to the quality of life for men. Strategies utilizing conductive hydrogels have demonstrated promising results for the treatment of peripheral nerves with a large diameter (>2 mm). However, integrating convenient minimally invasive operation, antiswelling and immunomodulatory conductive hydrogels for treating small-diameter injured cavernous nerves remains a great challenge. Here, a sprayable adhesive conductive hydrogel (GACM) composed of gelatin, adenine, carbon nanotubes, and mesaconate designed for cavernous nerve repair is developed. Multiple hydrogen bonds provide GACM with excellent adhesive and antiswelling properties, enabling it to establish a conformal electrical bridge with the damaged nerve and aiding in the regeneration process. Additionally, mesaconate-loaded GACM suppresses the release of inflammatory factors by macrophages and promotes the migration and proliferation of Schwann cells. In vivo tests demonstrate that the GACM hydrogel repairs the cavernous nerve and restores erectile function and fertility. Furthermore, the feasibility of sprayable GACM in minimally invasive robotic surgery in beagles is validated. Given the benefits of therapeutic effectiveness and clinical convenience, the research suggests a promising future for sprayable GACM materials as advanced solutions for minimally invasive nerve repair.

Mechanical Stimulation of Anti-Inflammatory and Antioxidant Hydrogels for Rapid Re-Epithelialization.

The epithelium, an essential barrier to protect organisms against infection, exists in many organs. However, rapid re-epithelialization to restore tissue integrity and function in an adverse environment is challenging. In this work, a long-term anti-inflammatory and antioxidant hydrogel with mechanical stimulation for rapid re-epithelialization, mainly composed of the small molecule thioctic acid, biocompatible glycine, and γ-Fe2O3 nanoparticles is reported. Glycine-modified supramolecular thioctic acid is stable and possesses outstanding mechanical properties. The incorporating γ-Fe2O3 providing the potential contrast function for magnetic resonance imaging observation, can propel hydrogel reconfiguration to enhance the mechanical properties of the hydrogel underwater due to water-initiated release of Fe3+. In vitro experiments show that the hydrogels effectively reduced intracellular reactive oxygen species, guided macrophages toward M2 polarization, and alleviated inflammation. The effect of rapid re-epithelialization is ultimately demonstrated in a long urethral injury model in vivo, and the mechanical stimulation of hydrogels achieves effective functional replacement and ultimately accurate remodeling of the epithelium. Notably, the proposed strategy provides an advanced alternative treatment for patients in need of large-area epithelial reconstruction.

3D-Printed Flat-Bone-Mimetic Bioceramic Scaffolds for Cranial Restoration.

The limitations of autologous bone grafts necessitate the development of advanced biomimetic biomaterials for efficient cranial defect restoration. The cranial bones are typical flat bones with sandwich structures, consisting of a diploe in the middle region and 2 outer compact tables. In this study, we originally developed 2 types of flat-bone-mimetic ß-tricalcium phosphate bioceramic scaffolds (Gyr-Comp and Gyr-Tub) by high-precision vat-photopolymerization-based 3-dimensional printing. Both scaffolds had 2 outer layers and an inner layer with gyroid pores mimicking the diploe structure. The outer layers of Gyr-Comp scaffolds simulated the low porosity of outer tables, while those of Gyr-Tub scaffolds mimicked the tubular pore structure in the tables of flat bones. The Gyr-Comp and Gyr-Tub scaffolds possessed higher compressive strength and noticeably promoted in vitro cell proliferation, osteogenic differentiation, and angiogenic activities compared with conventional scaffolds with cross-hatch structures. After implantation into rabbit cranial defects for 12 weeks, Gyr-Tub achieved the best repairing effects by accelerating the generation of bone tissues and blood vessels. This work provides an advanced strategy to prepare biomimetic biomaterials that fit the structural and functional needs of efficacious bone regeneration.

Incidence, process of care, and outcomes of out-of-hospital cardiac arrest in China: a prospective study of the BASIC-OHCA registry.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is an important global public health issue, but its epidemiology and outcomes in low-income and middle-income countries remain largely unknown. We aim to comprehensively describe the incidence, process of care, and outcomes of OHCA in China. METHODS: In the prospective, multicentre, population-based Baseline Investigation of Out-of-hospital Cardiac Arrest (BASIC-OHCA) registry study, participating sites were selected from both urban and rural areas in all seven geographical regions across China. All patients with OHCA assessed by emergency medical service (EMS) staff were consecutively enrolled from Aug 1, 2019, to Dec 31, 2020. Patients with suspected cardiac arrest assessed by bystanders whose return of spontaneous circulation was achieved without the need for defibrillation or EMS personnel cardiopulmonary resuscitation were excluded. Patients with all key variables missing were excluded, including resuscitation attempt, age, sex, witnessed status, cause, all process of care indicators, and all outcome measures. In this analysis, we included data for EMS agencies serving 25 monitoring sites (20 urban and five rural) that included the entire serving population, data for the whole of 2020, and at least 50 OHCA patients in 2020. Data were collected and reported using the Utstein template. We calculated the crude incidence of EMS-assessed OHCA in 2020. We also report data on baseline characteristics (including sex, cause, location of OHCA, and presence of shockable rhythm), process of care (including EMS response time, cardiopulmonary resuscitation, defibrillation, and advanced life support), and outcomes of non-traumatic OHCA between Aug 1, 2019, and Dec 31, 2020, including survival and survival with favourable neurological outcomes at discharge or 30 days, and at 6 and 12 months. FINDINGS: Of 115·1 million people served by the 25 participating sites, 132 262 EMS-assessed patients with OHCA were enrolled, and resuscitation was attempted for 42 054 (31·8%) patients between Aug 1, 2019, and Dec 31, 2020. The crude incidence of EMS-assessed OHCA was 95·7 per 100 000 population (95% CI 95·6-95·8) in 2020. Among 38 227 individuals with non-traumatic OHCA, 25 958 (67·9%) were male, 30 282 (79·2%) had a cardiac arrest at home, 32 523 (85·1%) had a presumed cardiac cause, and 2297 (6·0%) presented with an initial shockable rhythm. 4049 (11·5%) of 35 090 patients with an unwitnessed or bystander-witnessed OHCA received dispatcher-assisted cardiopulmonary resuscitation and 7121 (20·3%) received bystander cardiopulmonary resuscitation; only 14 (<0·1%) patients were assessed by bystanders with an automated external defibrillator. The median EMS response time was 12 min (IQR 9-16). At hospital discharge or 30 days, 441 (1·2%) of 38 227 survived, 304 (0·8%) survived up to 6 months, and 269 (0·7%) up to 12 months. At hospital discharge or 30 days, 309 (0·8%) survived with favourable neurological outcomes, 257 (0·7%) had favourable neurological outcomes at 6 months, and 236 (0·6%) at 12 months. INTERPRETATION: Our findings revealed a high burden of EMS-assessed OHCA with a low proportion of resuscitation attempts. The suboptimal implementation of chain of survival and unsatisfactory prognosis call for national efforts to improve the care and outcomes of patients with OHCA in China. FUNDING: The National Science & Technology Fundamental Resources Investigation Program of China, the State Key Program of the National Natural Science Foundation of China, Taishan Pandeng Scholar Program of Shandong Province, the Key Research & Development Program of Shandong Province, the Interdisciplinary Young Researcher Groups Program of Shandong University, the Clinical Research Center of Shandong University, the ECCM Program of Clinical Research Center of Shandong University, and the Natural Science Foundation of Shandong Province.

The impact of non-optimum temperatures, heatwaves and cold spells on out-of-hospital cardiac arrest onset in a changing climate in China: a multi-center, time-stratified, case-crossover study.

Background: Out-of-hospital cardiac arrest (OHCA) is a time-critical and fatal medical emergency that has been linked to non-optimal temperatures. However, the future burden of OHCA due to non-optimal temperatures, heatwaves, and cold spells under climate change has not been well evaluated. Methods: We conducted a time-stratified case-crossover study in 15 Northern Chinese cities throughout 2020 to estimate the exposure-response relationships of non-optimal temperatures, heatwaves, and cold spells with hourly OHCA onset in hot and cold seasons. We obtained future daily average temperatures by using 20 general circulation models under two greenhouse gas emission scenarios: one with certain emission control and the other with relaxed control. Lastly, we projected the change of OHCA burden under these two climate scenarios. Findings: We analyzed a total of 29,671 OHCA patients and found that high temperatures and heatwaves as well as low temperatures and cold spells were all significantly associated with an increased risk of OHCA onset. Under the scenario of uncontrolled emissions, the attributable fraction (AF) of OHCA due to high temperatures and heatwaves would increase by 4.94% and 6.99% from the 2010s to 2090s, respectively. The AF due to low temperatures would decrease by 1.27% by the 2090s and the effects of cold spells were projected to be marginal after the 2050s. Under a medium emission control scenario, the upward trend of heat-related OHCA burden would become flat, and the decline in cold-related OHCA burden would also slow down. Interpretation: Our study provides evidence of significant morbidity risk and burden of OHCA associated with global warming across Northern China. Our findings indicate that the increase in OHCA burden attributable to heat could not be offset by the decrements attributable to cold, emphasizing the importance of mitigation policies for limiting global warming and reducing the associated risks of OHCA onset. Funding: National Science & Technology Fundamental Resources Investigation Project (2018FY100600, 2018FY100602), National Key R&D Program of China (2020YFC1512700, 2020YFC1512705, 2020YFC1512703), Key R&D Program of Shandong Province (2021ZLGX02, 2021SFGC0503), Natural Science Foundation of Shandong Province (ZR2021MH231), Taishan Pandeng Scholar Program of Shandong Province (tspd20181220), the Interdisciplinary Young Researcher Groups Program of Shandong University (2020QNQT004), ECCM Program of Clinical Research Center of Shandong University (2021SDUCRCA001, 2021SDUCRCA002), foundation from Clinical Research Center of Shandong University (2020SDUCRCB003), National Natural Science Foundation of China (82272240).

Fine and coarse particulate air pollution and out-of-hospital cardiac arrest onset: a nationwide case-crossover study in China.

Out-of-hospital cardiac arrest (OHCA) is a global public health concern. Nationwide studies on the effects of short-term exposure to particulate matter (PM) on OHCA risk are rare in regions with high PM levels, and evidence for coarse PM (PM2.5-10) is limited and inconsistent. To evaluate the associations between fine PM (PM2.5) and PM2.5-10 and OHCA onset, a time-stratified case-crossover study was conducted on 77,261 patients with cardiac OHCA in 26 cities across China in 2020. Daily PM2.5 and PM2.5-10 concentrations were assessed with high-resolution and full-coverage PM estimations. Conditional logistic regression models were applied in analyses. Each interquartile range of PM increase in 3-day moving average was associated with an increased risk of cardiac OHCA onset of 2.37% (95% CI, 1.20-3.56%) for PM2.5 and 2.12% (95% CI, 0.70-3.56%) for PM2.5-10. Stratified analyses showed higher susceptibility in patients over 75 years for PM2.5 exposure and with diabetes for PM2.5-10. This first nationwide study in region with high PM levels and great PM variability found not only PM2.5 but also PM2.5-10 were associated with a higher risk of OHCA onset, which could add powerful epidemiological evidence to this field and provide new evidence for the formulation of air quality guidelines.

Dl-3-n-butylphthalide improves intestinal microcirculation disorders in septic rats by regulating the PI3K/AKT signaling pathway and autophagy.

PURPOSE: Sepsis has complex pathophysiological mechanisms that bring new challenges in the treatment of sepsis at a time when the intestinal microcirculation in sepsis is receiving increasing attention. Dl-3-n-butylphthalide (NBP), which is a drug that can improve multiorgan ischemic diseases, is also worth examining to improve the intestinal microcirculation in sepsis. METHODS: In this study, male Sprague-Dawley rats were divided into the sham group (n = 6), CLP group (n = 6), NBP group (n = 6) and NBP + LY294002 group (n = 6). The rat model of severe sepsis was established by cecal ligation and puncture (CLP). Abdominal wall incisions and sutures were performed in the first group, and CLP was performed in the latter three groups. Normal saline/NBP/NBP + LY294002 solution was injected intraperitoneally 2 h or 1 h before modeling. Hemodynamic data (blood pressure and heart rate) were recorded at 0, 2, 4 and 6 h. Sidestream dark field (SDF) imaging and the Medsoft System were used to observe the intestinal microcirculation of rats and obtain data at 0, 2, 4, and 6 h. Six hours after the model was established, the serum levels of TNF-α and IL-6 were measured to evaluate the level of systemic inflammation. Pathological damage to the small intestine was evaluated by electron microscopy and histological analysis. The expression levels of P-PI3K, PI3K, P-AKT, AKT, LC3 and p62 in the small intestine were analyzed by Western blotting. The expressions of P-PI3K, P-AKT, LC3 and P62 in small intestine were detected by immunohistochemical staining. RESULTS: NBP improved intestinal microcirculation disturbances in septic rats, alleviated the systemic inflammatory response, reduced the destruction of the small intestinal mucosa and the disruption of microvascular endothelial cells, and alleviated autophagy in vascular endothelial cells. NBP increased the ratio of P-PI3K/total PI3K, P-AKT/total AKT, and P62/ß-actin and decreased the ratio of LC3 II/LC3 I. CONCLUSION: NBP ameliorated intestinal microcirculation disturbances and the destruction of small intestinal vascular endothelial cells in septic rats by activating the PI3K/Akt signaling pathway and regulating autophagy.

Identification of predictors for neurological outcome after cardiac arrest in peripheral blood mononuclear cells through integrated bioinformatics analysis and machine learning.

Neurological prognostication after cardiac arrest (CA) is important to avoid pursuing futile treatments for poor outcome and inappropriate withdrawal of life-sustaining treatment for good outcome. To predict neurological outcome after CA through biomarkers in peripheral blood mononuclear cells, four datasets were downloaded from the Gene Expression Omnibus database. GSE29546 and GSE74198 were used as training datasets, while GSE92696 and GSE34643 were used as verification datasets. The intersection of differentially expressed genes and hub genes from multiscale embedded gene co-expression network analysis (MEGENA) was utilized in the machine learning screening. Key genes were identified using support vector machine recursive feature elimination (SVM-RFE), least absolute shrinkage and selection operator (LASSO) logistic regression, and random forests (RF). The results were validated using receiver operating characteristic curve analysis. An mRNA-miRNA network was constructed. The distribution of immune cells was evaluated using cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT). Five biomarkers were identified as predictors for neurological outcome after CA, with an area under the curve (AUC) greater than 0.7: CASP8 and FADD-like apoptosis regulator (CFLAR), human protein kinase X (PRKX), miR-483-5p, let-7a-5p, and let-7c-5p. Interestingly, the combination of CFLAR minus PRKX showed an even higher AUC of 0.814. The mRNA-miRNA network consisted of 30 nodes and 76 edges. Statistical differences were found in immune cell distribution, including neutrophils, NK cells active, NK cells resting, T cells CD4 memory activated, T cells CD4 memory resting, T cells CD8, B cells memory, and mast cells resting between individuals with good and poor neurological outcome after CA. In conclusion, our study identified novel predictors for neurological outcome after CA. Further clinical and laboratory studies are needed to validate our findings.

Efforts to Improve Survival Outcomes of Out-of-Hospital Cardiac Arrest in China: BASIC-OHCA.

BACKGROUND: Establishing registries to collect demographic characteristics, processes of care, and outcomes of patients with out-of-hospital cardiac arrest (OHCA) can better understand epidemiological trends, measure care quality, and identify opportunities for improvement. This study aimed to describe the design, implementation, and scientific significance of a nationwide registry-the BASIC-OHCA (Baseline Investigation of Out-of-Hospital Cardiac Arrest)-in China. METHODS: BASIC-OHCA was designed as a prospective, multicenter, observational, population-based study. The BASIC-OHCA registry was developed based on Utstein templates. BASIC-OHCA includes all OHCA patients confirmed by emergency medical services (EMS) personnel regardless of age, sex, or cause. Patients declared dead at the scene by EMS personnel for any reasons are also included. To fully characterize an OHCA event, BASIC-OHCA collects data from 3 sources-EMS, the receiving hospital, and patient follow-up-and links them to form a single record. Once data entry is completed and quality is checked, individual identifiers are stripped from the record. RESULTS: Currently, 32 EMS agencies in 7 geographic regions contribute data to BASIC-OHCA. They are distributed in the urban and rural areas, covering ≈9% of the population of mainland China. Data collection started on August 1, 2019. By July 31, 2020, a total of 92 913 EMS-assessed OHCA patients were enrolled. Among 28969 (31.18%) EMS-treated OHCAs, the mean age was 65.79±17.36 years, and 68.35% were males. The majority of OHCAs (76.85%) occurred at home or residence. A shockable initial rhythm was reported in 5.43% of patients. Any return of spontaneous circulation, survival to hospital discharge, and favorable neurological outcome at hospital discharge were 5.98%, 1.15%, and 0.83%, respectively. CONCLUSIONS: BASIC-OHCA is the first nationwide registry on OHCA in China. It can be used as a public health surveillance system and as a platform to produce evidence-based practices to help identify opportunities for improvement. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03926325.

The first case series analysis on efficacy of esmolol injection for in-hospital cardiac arrest patients with refractory shockable rhythms in China.

Background: This study assessed the effects of esmolol injection in patients with in-hospital cardiac arrest (IHCA) with refractory ventricular fibrillation (VF)/pulseless ventricular tachycardia (pVT). Methods: From January 2018 to December 2021, 29 patients with IHCA with refractory shockable rhythm were retrospectively reviewed. Esmolol was administered after advanced cardiovascular life support (ACLS)-directed procedures, and outcomes were assessed. Results: Among the 29 cases, the rates of sustained return of spontaneous circulation (ROSC), 24-h ROSC, and 72-h ROSC were 79%, 62%, and 59%, respectively. Of those patients, 59% ultimately survived to discharge. Four patients with cardiac insufficiency died. The duration from CA to esmolol infusion was significantly shorter for patients in the survival group (SG) than for patients in the dead group (DG) (12 min, IQR: 8.5-19.5 vs. 23.5 min, IQR: 14.4-27 min; p = 0.013). Of those patients, 76% (22 of 29) started esmolol administration after the second dose of amiodarone. No significant difference was observed in the survival rate between this group and groups administered an esmolol bolus simultaneously or before the second dose of amiodarone (43% vs. 64%, p = 0.403). Of those patients, 31% (9 of 29) were administered an esmolol bolus for defibrillation attempts ≤ 5, while the remaining 69% of patients received an esmolol injection after the fifth defibrillation attempt. No significant differences were observed in the rates of ≥ 24-h ROSC (67% vs. 60%, p = 0.73), ≥ 72-h ROSC (67% vs. 55%, p = 0.56), and survival to hospital discharge (67% vs. 55%, p = 0.56) between the groups administered an esmolol bolus for defibrillation attempts ≤ 5 and defibrillation attempts > 5. Conclusion: IHCA patients with refractory shockable rhythms receiving esmolol bolus exhibited a high chance of sustained ROSC and survival to hospital discharge. Patients with end-stage heart failure tended to have attenuated benefits from beta-blockers. Further large-scale, prospective studies are necessary to determine the effects of esmolol in patients with IHCA with refractory shockable rhythms.

Development and evaluation of a predictive nomogram for survival in heat stroke patients: a retrospective cohort study.

BACKGROUND: This study aimed to establish an effective nomogram to predict the survival of heat stroke (HS) based on risk factors. METHODS: This was a retrospective, observational multicenter cohort study. We analyzed patients diagnosed with HS, who were treated between May 1 and September 30, 2018 at 15 tertiary hospitals from 11 cities in Northern China. RESULTS: Among the 175 patients, 32 patients (18.29%) died before hospital discharge. After the univariate analysis, mechanical ventilation, initial mean arterial pressure <70 mmHg, maximum heart rate, lab results on day 1 (white blood cell count, alanine aminotransferase, creatinine), and Glasgow admission prediction score were included in multivariate analysis. Multivariate Cox regression showed that invasive ventilation, initial mean arterial pressure <70 mmHg (1 mmHg=0.133 kPa), and Glasgow admission prediction score were independent risk factors for HS. The nomogram was established for predicting 7-d and 14-d survival in the training cohort. The nomogram exhibited a concordance index (C-index) of 0.880 (95% confidence interval [95% CI] 0.831-0.930) by bootstrapping validation (B=1,000). Furthermore, the nomogram performed better when predicting 14-d survival, compared to 7-d survival. The prognostic index cut-off value was set at 2.085, according to the operating characteristic curve for overall survival prediction. The model showed good calibration ability in the internal and external validation datasets. CONCLUSION: A novel nomogram, integrated with prognostic factors, was proposed; it was highly predictive of the survival in HS patients.

A national effort to improve outcomes for in-hospital cardiac arrest in China: The BASeline Investigation of Cardiac Arrest (BASIC-IHCA).

Background: In-hospital cardiac arrest (IHCA) is a common clinical event with poor outcomes. Former IHCA registries in China were local, inconsistent in data reporting, and lacked attention to the process of care. Therefore, we designed and implemented the BASeline Investigation of In-hospital Cardiac Arrest (BASIC-IHCA), the first national IHCA registry in China. Methods: BASIC-IHCA is a prospective, multicenter, observational study with a nationwide surveillance network covering urban and rural hospitals from seven geographic regions of China. IHCA patients were enrolled continuously, and data were collected from medical records by investigators at participating hospitals. Key variables referring to the updated Utstein Template included patient information, event variables, process of care, and outcomes. Follow-up was conducted by telephone interview to obtain details on long-term survival and neurological status. Results: Thirty-two urban hospitals and eight rural hospitals from twenty-nine provinces in seven geographic regions of China participated in BASIC-IHCA. The starting time of enrollment ranged from July 1, 2019, to January 1, 2020. By December 31, 2020, 35,451 IHCAs were enrolled in all participating hospitals, of which 19,493 (55%) received CPR, with a predominance of males (65%) and a median age of 65 years. Conclusion: BASIC-IHCA is the first national registry for IHCA in China. It will describe the epidemiology and outcomes of IHCA from a nationwide perspective, with a particular focus on details of the process of care for quality improvement. Meanwhile, it will help to facilitate the standardization of IHCA-related data reporting in China.

[Value of procalcitonin and critical illness score in etiological diagnosis and prognosis of sepsis caused by intra-abdominal infections].

OBJECTIVE: To compare the early and late predictive values of critical illness score (CIS) and procalcitonin (PCT) in septic patients with blood stream infection (BSI) induced by intra-abdominal infection (IAI), and to identify the value of PCT in etiological diagnosis. METHODS: The clinical data of patients with at least one positive blood culture within 24 hours admission to the emergency department of China-Japan Friendship Hospital from January 2014 to December 2019 and with final diagnosis of IAI induced sepsis were enrolled. Sequential organ failure assessment (SOFA), mortality in emergency department sepsis (MEDS), Logistic organ dysfunction system (LODS), and acute physiology and chronic health evaluation II (APACHE II) scores were calculated based on the parameters on the day of admission. Differences in various indicators among different Gram-stained bacterial infections and among patients with different prognosis at 28 days or 60 days were compared. Receiver operator characteristic curve (ROC curve) was used to analyze the value of PCT in differential etiological diagnosis of IAI induced sepsis caused by single bacterial infection, and the predictive value of CIS and PCT on 28-day and 60-day death of septic patients with BSI induced by IAI. RESULTS: A total of 221 septic patients with IAI caused by single bacterial infection were enrolled. The 28-day mortality was 19.9% (44/221), and the 60-day mortality was 25.8% (57/221). Mortality caused by Gram-positive (G+) bacterial infection of patients was significantly higher than that caused by Gram-negative (G-) bacterial infection (28 days: 34.6% vs. 11.4%, 60 days: 42.0% vs. 16.4%, both P < 0.01). Compared with patients with G+ bacterial infection, the PCT value of patients with G- bacterial infection was higher [µg/L: 4.31 (0.71, 25.71) vs. 1.29 (0.32, 10.83), P < 0.05]. Compared with survival group, the values of CIS and PCT in death group were higher, either in 28 days or in 60 days [death group vs. survival group in 28 days: SOFA score was 6.0 (4.0, 10.0) vs. 3.0 (2.0, 5.0), MEDS score: 11 (9, 14) vs. 6 (6, 9), LODS score: 4.0 (2.0, 6.0) vs. 1.0 (0, 2.0), APACHE II score: 17.0 (15.0, 24.0) vs. 12.0 (8.0, 15.0), PCT (µg/L): 3.48 (1.01, 26.70) vs. 2.45 (0.32, 15.65); death group vs. survival group in 60 days: SOFA score: 6.0 (4.0, 10.0) vs. 3.0 (2.0, 5.0), MEDS score: 9 (6, 14) vs. 6 (6, 9), LODS score: 4.0 (1.0, 5.0) vs. 1.0 (0, 2.0), APACHE II score: 16.5 (12.0, 20.0) vs. 12.0 (8.0, 15.0), PCT (µg/L): 2.67 (0.98, 17.73) vs. 2.22 (0.31, 16.75); all P < 0.05]. ROC curve showed that: (1) the area under ROC curve (AUC) of PCT in the diagnosis of IAI induced sepsis with single bacterial infection was 0.740 [95% confidence interval (95%CI) was 0.648-0.833]. When the optimal cut-off value of PCT was 1.82 µg/L, the sensitivity of diagnosis of G- bacterial infection was 74.0%, and the specificity was 68.2%. When PCT value was higher than 10.92 µg/L, the specificity of diagnosis of G- bacterial infection could reach 81.8%. (2) In the prediction of 28-day and 60-day mortality for septic patients with BSI induced by IAI, the APACHE II score achieved the highest AUC [28 days: 0.791 (95%CI was 0.680-0.902), 60 days: 0.748 (95%CI was 0.645-0.851)]. APACHE II score higher than 14.5 could help to predict 28-day and 60-day mortality for IAI patients with negative predictive values of 94.9% and 88.5%. However, the predictive value of PCT for septic patients with BSI induced by IAI was relatively lower [28-day AUC: 0.610 (95%CI was 0.495-0.725), 60-day AUC: 0.558 (95%CI was 0.450-0.667)]. CONCLUSIONS: PCT is more reliable in the identification of pathogen type among IAI induced sepsis with BSI, while APACHE II score may perform better in predicting early and late mortality.

Predictive performance of critical illness scores and procalcitonin in sepsis caused by different gram-stain bacteria.

OBJECTIVES: To compare the early and late predictive values of several critical illness scores (CISs) and biomarkers in sepsis-3 patients with bloodstream infections (BSIs) and to identify the prognostic value of procalcitonin (PCT) for different gram-stain bacteria infections. METHODS: Patients with at least one positive blood culture within 24h of emergency department admission and with a final diagnosis of sepsis/septic shock were enrolled. CISs were calculated based on the first parameters on the day of admission. The receiver operating characteristics curve was used to analyze the predictive value of CISs and biomarkers for early and late mortality. RESULTS: Of 834 enrolled patients with sepsis-3, death occurred in 214 patients within 28 days and in 273 patients within 60 days. Compared with biomarkers, CISs showed a significantly higher area under the curve (AUC) in the prediction of early and late mortality (p<0.01), especially for patients with GNB infection. The Sequential Organ Failure Assessment score showed a higher AUC for predicting early mortality than the Mortality in Emergency Department Sepsis score (p=0.036). Compared with GNB infections, the AUC values of the PCT for gram-positive bacteria (GPB) infections were higher for predicting early or late mortality; PCT showed higher AUC than high-sensitivity C-reactive protein and white blood cells for predicting early mortality (p<0.05). CONCLUSIONS: CISs were more advantageous in the assessment of early and late prognosis, especially for patients with GNB infections; however, for sepsis with GPB infection, PCT can be used for the prediction of early mortality.

Identification of Molecular Regulatory Features and Markers for Acute Type A Aortic Dissection.

BACKGROUND: Acute type A aortic dissection (ATAAD) is one of the most lethal cardiovascular diseases, and its molecular mechanism remains unclear. METHODS: Differentially expressed genes (DEGs) between ATAAD and control were detected by limma R package in GSE52093, GSE153434, GSE98770, and GSE84827, respectively. The coexpression network of DEGs was identified by the WGCNA package. Enrichment analysis was performed for module genes that were positively correlated with ATAAD using clusterProfiler R package. In addition, differentially methylated markers between aortic dissection and control were identified by ChAMP package. After comparing with ATAAD-related genes, a protein-protein interaction (PPI) network was established based on the STRING database. The genes with the highest connectivity were identified as hub genes. Finally, differential immune cell infiltration between ATAAD and control was identified by ssGSEA. RESULTS: From GSE52093 and GSE153434, 268 module genes were obtained with consistent direction of differential expression and high correlation with ATAAD. They were significantly enriched in T cell activation, HIF-1 signaling pathway, and cell cycle. In addition, 2060 differentially methylated markers were obtained from GSE84827. Among them, 77 methylation markers were ATAAD-related DEGs. Using the PPI network, we identified MYC, ITGA2, RND3, BCL2, and PHLPP2 as hub genes. Finally, we identified significantly differentially infiltrated immune cells in ATAAD. CONCLUSION: The hub genes we identified may be regulated by methylation and participate in the development of ATAAD through immune inflammation and oxidative stress response. The findings may provide new insights into the molecular mechanisms and therapeutic targets for ATAAD.

Predictive performance of critical illness scores and procalcitonin in sepsis caused by different gram-stain bacteria

OBJECTIVES: To compare the early and late predictive values of several critical illness scores (CISs) and biomarkers in sepsis-3 patients with bloodstream infections (BSIs) and to identify the prognostic value of procalcitonin (PCT) for different gram-stain bacteria infections. METHODS: Patients with at least one positive blood culture within 24h of emergency department admission and with a final diagnosis of sepsis/septic shock were enrolled. CISs were calculated based on the first parameters on the day of admission. The receiver operating characteristics curve was used to analyze the predictive value of CISs and biomarkers for early and late mortality. RESULTS: Of 834 enrolled patients with sepsis-3, death occurred in 214 patients within 28 days and in 273 patients within 60 days. Compared with biomarkers, CISs showed a significantly higher area under the curve (AUC) in the prediction of early and late mortality (p<0.01), especially for patients with GNB infection. The Sequential Organ Failure Assessment score showed a higher AUC for predicting early mortality than the Mortality in Emergency Department Sepsis score (p=0.036). Compared with GNB infections, the AUC values of the PCT for gram-positive bacteria (GPB) infections were higher for predicting early or late mortality; PCT showed higher AUC than high-sensitivity C-reactive protein and white blood cells for predicting early mortality (p<0.05). CONCLUSIONS: CISs were more advantageous in the assessment of early and late prognosis, especially for patients with GNB infections; however, for sepsis with GPB infection, PCT can be used for the prediction of early mortality.

[Diagnostic and predictive value of critical illness scores and biomarkers in bloodstream infection-associated pneumonia].

OBJECTIVE: To compare the early and late predictive value of several critical illness scores (CISs) and biomarkers in patients with bloodstream infection (BSI)-associated pneumonia, and to identify the value of procalcitonin (PCT) in etiological diagnosis. METHODS: Patients with at least one positive blood culture within 24 hours admission to department of emergency of China-Japan Friendship Hospital from January 2014 to December 2018 and with final diagnosis of pneumonia were enrolled. Sequential organ failure assessment (SOFA), mortality in emergency department sepsis (MEDS), Logistic organ dysfunction system (LODS), and acute physiology and chronic health evaluation II (APACHE II) scores were calculated based on the first parameters on the day of admission. Differences of various indicators among different Gram-stained bacterial infections and among patients with different prognosis at 28-day or 60-day were compared. Receiver operating characteristic (ROC) curve was used to analyze the value of biomarkers in differential diagnosis of pneumonia caused by single bacterial infection, and the predictive value of several CISs and biomarkers on 28-day and 60-day death of patients with pneumonia. RESULTS: Among 540 patients with pneumonia caused by single bacterial infection, 256 (47.4%) patients with Gram-positive bacteria (GPB) infection and 284 (52.6%) with Gram-negative bacteria (GNB) infection. The 28-day mortality was 29.4% (159/540) and the 60-day mortality was 36.3% (196/540). PCT level was significantly higher in patients with GNB infection than that in GPB infected patients [µg/L: 1.99 (0.32, 13.19) vs. 0.45 (0.13, 3.53), P < 0.01]. There were significant differences of CISs and biomarkers between death group and survival group in predicting 28-day and 60-day mortality in BSI-associated pneumonia. ROC curve analysis showed that: (1) the optimal cut-off value of PCT in the diagnosis of single bacterial infection was 0.48 µg/L, with the area under ROC curve (AUC) was 0.739 [95% confidence interval (95%CI) was 0.686-0.793]. When PCT value was greater than 4.49 µg/L, the specificity of diagnostic of GNB infection could reach 81.8%, and the positive predictive value (PPV) was 75.0%. When PCT value was greater than 10.16 µg/L, the diagnostic specificity could reach 91.2%. (2) In the prediction of 28-day and 60-day mortality, the SOFA score showed highest AUC [28-day: 0.818 (95%CI was 0.768-0.867), 60-day: 0.800 (95%CI was 0.751-0.849)]. SOFA score greater than 8.5 points could help to predict 28-day and 60-day mortality for pneumonia patients with specificity of 90.5% and 91.6%, respectively. AUC of PCT for predicting 28-day and 60-day mortality in patients with BSI associated with pneumonia was 0.637 (95%CI was 0.575-0.700) and 0.628 (95%CI was 0.569-0.688), respectively. When PCT value was greater than 8.15 µg/L, the specificity and negative predictive value (NPV) were 80.2% and 75.1% respectively, and they could reach 80.2% and 68.7% when PCT value was greater than 7.46 µg/L. CONCLUSIONS: PCT is more reliable in the identification of pathogen type in BSI-associated pneumonia, while CISs may be more advantageous in the assessment of early and late prognosis.

HDAC6 promotes sepsis development by impairing PHB1-mediated mitochondrial respiratory chain function.

OBJECTIVE: This study was aimed at investigating the regulation of mitochondrial function by histone deacetylase 6 (HDAC6) and the role of HDAC6 in the development and progression of sepsis. RESULTS: HDAC6 downregulated PHB1 and subsequently promoted the development of CLP-induced sepsis. Inhibition of HDAC6 significantly attenuated CLP-induced sepsis through inhibition of mitochondrial dysfunction and reduced oxidant production, thus protecting the rats from oxidative injury. CONCLUSIONS: In this sepsis model, HDAC6 inhibits the expression and function of PHB1 and alters the function of the mitochondrial respiratory chain mediated by PHB1, thus enhancing the production of oxidants and increasing oxidative stress and thereby leading to severe oxidative injury in multiple organs. METHODS: The expression of HDAC6 and prohibitin 1 (PHB1) in humans and in a rat model of sepsis was measured by quantitative reverse-transcription PCR and western blotting. Sepsis induction by cecal ligation and puncture (CLP) was confirmed by histological analysis. Concentrations of different sepsis markers were measured by an enzyme-linked immunosorbent assay, and mitochondrial function was assessed via the mitochondrial respiratory control rate.

Inhibitory Effects of Simvastatin on Oxidized Low-Density Lipoprotein-Induced Endoplasmic Reticulum Stress and Apoptosis in Vascular Endothelial Cells.

BACKGROUND: Oxidized low-density lipoprotein (ox-LDL)-induced oxidative stress and endothelial apoptosis are essential for atherosclerosis. Our previous study has shown that ox-LDL-induced apoptosis is mediated by the protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic translation initiation factor 2α-subunit (eIF2α)/CCAAT/enhancer-binding protein homologous protein (CHOP) endoplasmic reticulum (ER) stress pathway in endothelial cells. Statins are cholesterol-lowering drugs that exert pleiotropic effects including suppression of oxidative stress. This study aimed to explore the roles of simvastatin on ox-LDL-induced ER stress and apoptosis in endothelial cells. METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with simvastatin (0.1, 0.5, or 2.5 µmol/L) or DEVD-CHO (selective inhibitor of caspase-3, 100 µmol/L) for 1 h before the addition of ox-LDL (100 µg/ml) and then incubated for 24 h, and untreated cells were used as a control group. Apoptosis, expression of PERK, phosphorylation of eIF2α, CHOP mRNA level, and caspase-3 activity were measured. Comparisons among multiple groups were performed with one-way analysis of variance (ANOVA) followed by post hoc pairwise comparisons using Tukey's tests. A value of P < 0.05 was considered statistically significant. RESULTS: Exposure of HUVECs to ox-LDL resulted in a significant increase in apoptosis (31.9% vs. 4.9%, P < 0.05). Simvastatin (0.1, 0.5, and 2.5 µmol/L) led to a suppression of ox-LDL-induced apoptosis (28.0%, 24.7%, and 13.8%, F = 15.039, all P < 0.05, compared with control group). Ox-LDL significantly increased the expression of PERK (499.5%, P < 0.05) and phosphorylation of eIF2α (451.6%, P < 0.05), if both of which in the control groups were considered as 100%. Simvastatin treatment (0.1, 0.5, and 2.5 µmol/L) blunted ox-LDL-induced expression of PERK (407.8%, 339.1%, and 187.5%, F = 10.121, all P < 0.05, compared with control group) and phosphorylation of eIF2α (407.8%, 339.1%, 187.5%, F = 11.430, all P < 0.05, compared with control group). In contrast, DEVD-CHO treatment had no significant effect on ox-LDL-induced expression of PERK (486.4%) and phosphorylation of eIF2α (418.8%). Exposure of HUVECs to ox-LDL also markedly induced caspase-3 activity together with increased CHOP mRNA level; these effects were inhibited by simvastatin treatment. CONCLUSIONS: This study suggested that simvastatin could inhibit ox-LDL-induced ER stress and apoptosis in vascular endothelial cells.