P-Type ZnO Films Made by Atomic Layer Deposition and Ion Implantation.

Zinc oxide (ZnO) is a wide bandgap semiconductor that holds significant potential for various applications. However, most of the native point defects in ZnO like Zn interstitials typically cause an n-type conductivity. Consequently, achieving p-type doping in ZnO is challenging but crucial for comprehensive applications in the field of optoelectronics. In this work, we investigated the electrical and optical properties of ex situ doped p-type ZnO films. The p-type conductivity has been realized by ion implantation of group V elements followed by rapid thermal annealing (RTA) for 60 s or flash lamp annealing (FLA) on the millisecond time scale in nitrogen or oxygen ambience. The phosphorus (P)-doped ZnO films exhibit stable p-type doping with a hole concentration in the range of 1014 to 1018 cm-3, while antimony (Sb) implantation produces only n-type layers independently of the annealing procedure. Microstructural studies of Sb-doped ZnO show the formation of metallic clusters after ms range annealing and SbZn-oxides after RTA.

Optical Design of a Hyperspectral Remote-Sensing System Based on an Image-Slicer Integral Field Unit in the Short-Wave Infrared Band.

Grating-type spectral imaging systems are frequently employed in scenes for high-resolution remote-sensing observations of the Earth. However, the entrance of the grating-type spectral imaging system is a slit or a pinhole. This structure relies on the push broom method, which presents a challenge in capturing spectral information of transiently changing targets. To address this issue, the IFU is used to slice the focal plane of the telescope system, thereby expanding the instantaneous field of view (IFOV) of the grating-type spectral imaging system. The aberrations introduced by the expansion of the single-slice field of view (FOV) of the IFU are corrected, and the conversion of the IFU's FOV from arcseconds to degrees is achieved. The design of a spectral imaging system based on an image-slicer IFU for remote sensing is finally completed. The system has a wavelength range of 1400 nm to 2000 nm, and a spectral resolution of better than 3 nm. Compared with the traditional grating-type spectral imaging system, its IFOV is expanded by a factor of four. And it allows for the capture of complete spectral information of transiently changing targets through a single exposure. The simulation results demonstrate that the system has good performance at each sub-slit, thereby validating the effectiveness and advantages of the proposed system for dynamic target capture in remote sensing.

Balanced Solution versus Normal Saline in Predicted Severe Acute Pancreatitis: A Stepped Wedge Cluster Randomized Trial.

OBJECTIVE: To compare the effect of balanced multielectrolyte solutions(BMES) versus normal saline(NS) for intravenous fluid on chloride levels and clinical outcomes.in patients with predicted severe acute pancreatitis (pSAP). SUMMARY BACKGROUND DATA: Isotonic crystalloids are recommended for initial fluid therapy in acute pancreatitis, but whether the use of BMES in preference to NS confers clinical benefits is unknown. METHODS: In this multicenter, stepped-wedge, cluster-randomized trial, we enrolled patients with pSAP (APACHE II score ≥8 and C-reactive protein >150 mg/L) admitted within 72 hours of the advent of symptoms. The study sites were randomly assigned to staggered start dates for one-way crossover from the NS phase (NS for intravenous fluid) to the BMES phase(Sterofudin for intravenous fluid). The primary endpoint was the serum chloride concentration on trial day3. Secondary endpoints included a composite of clinical and laboratory measures. RESULTS: Overall, 259 patients were enrolled from eleven sites to receive NS(n=147) or BMES(n=112). On trial day3, the mean chloride level was significantly lower in patients who received BMES(101.8 mmol/L(SD4.8) versus 105.8 mmol/L(SD5.9), difference -4.3 mmol/L [95%CI -5.6 to -3.0 mmol/L];P<0.001). For secondary endpoints, patients who received BMES had less systemic inflammatory response syndrome(19/112,17.0% versus 43/147,29.3%, P=0.024) and increased organ failure-free days (3.9 d(SD2.7) versus 3.5days(SD2.7), P<0.001) by trial day7. They also spent more time alive and out of ICU(26.4 d(SD5.2) versus 25.0days(SD6.4), P=0.009) and hospital(19.8 d(SD6.1) versus16.3days(SD7.2), P<0.001) by trial day30. CONCLUSIONS: Among patients with pSAP, using BMES in preference to NS resulted in a significantly more physiological serum chloride level, which was associated with multiple clinical benefits(Trial registration number: ChiCTR2100044432).

GPX7 reduces chondrocyte inflammation and extracellular matrix degradation triggered by IL­1ß, via a mechanism mediated by ferroptosis.

During osteoarthritis (OA), chondrocytes become highly active, with increased matrix synthesis and inflammatory cytokine­induced catabolic pathways. Early intervention strategies targeting pathological changes may attenuate or halt disease progression. The present study aimed to reveal the role of glutathione peroxidase (GPX)7 in OA. For this purpose, a research model was established by inducing C28/I2 human chondrocytes with interleukin (IL)­1ß, and the expression level of GPX7 was determined. To explore its roles, C28/I2 cells were transfected to gain GPX7 overexpression. The effects of GPX7 overexpression on intracellular inflammation, extracellular matrix (ECM) degradation, apoptosis and ferroptosis were then evaluated. In addition, the cells were treated with the ferroptosis inducer, erastin, and its effects on the aforementioned phenotypes were assessed. The level of GPX7 was decreased in response to IL­1ß treatment, and GPX7 overexpression suppressed cellular inflammation, ECM degradation and apoptosis. Moreover, the reduction of lipid peroxidation, ferrous ions and transferrin indicated that GPX7 overexpression inhibited ferroptosis. Subsequently, inflammation, ECM degradation and apoptosis were found to be promoted in the cells upon treatment with erastin. These findings suggested that the regulatory role of GPX7 may be mediated by a pathway involving ferroptosis. On the whole, the present study revealed that GPX7 reduces IL­1ß­induced chondrocyte inflammation, apoptosis and ECM degradation partially through a mechanism involving ferroptosis. The results of the present study lay a theoretical foundation for subsequent OA­related research and may enable the development of translational strategies for the treatment of OA.

Study of the image motion compensation method for a vertical orbit dynamic scanning TDICCD space camera.

In this study, a collaborative compensation method for low-dimensional attitude maneuvering and time delay integration charge-coupled device (TDICCD) line-frequency matching is proposed. The method is combined with the validation and analysis of the coordinate system transformation model to address the mismatch between the TDI charge transfer speed and the speed of the target. This mismatch is caused by the inconsistency between the rotational scanning direction of the double-sided mirror used for dynamic vertical orbit scanning imaging in low Earth-orbit satellites and the direction of the satellite along its orbit. The image motion per unit exposure time is decreased from 0.619µm to 0.023µm compared with the uncompensated maneuver mode, and the image quality is noticeably higher.

Effect of an Herbal-Based Injection on 28-Day Mortality in Patients With Sepsis: The EXIT-SEP Randomized Clinical Trial.

Importance: Previous research has suggested that Xuebijing injection (XBJ), an herbal-based intravenous preparation, may reduce mortality among patients with sepsis. Objective: To determine the effect of XBJ vs placebo on 28-day mortality among patients with sepsis. Design, Setting, and Participants: The Efficacy of Xuebijing Injection in Patients With Sepsis (EXIT-SEP) trial was a multicenter, randomized double-blind, placebo-controlled trial conducted in intensive care units at 45 sites and included 1817 randomized patients with sepsis (sepsis 3.0) present for less than 48 hours. Patients aged 18 to 75 years with a Sequential Organ Failure Assessment score of 2 to 13 were enrolled. The study was conducted from October 2017 to June 2019. The final date of follow-up was July 26, 2019. Data analysis was performed from January 2020 to August 2022. Interventions: The patients were randomized to receive either intravenous infusion of XBJ (100 mL, n = 911) or volume-matched saline placebo (n = 906) every 12 hours for 5 days. Main Outcomes and Measures: The primary outcome was 28-day mortality. Results: Among the 1817 patients who were randomized (mean [SD] age, 56.5 [13.5] years; 1199 [66.0%] men), 1760 (96.9%) completed the trial. In these patients, the 28-day mortality rate was significantly different between the placebo group and the XBJ group (230 of 882 patients [26.1%] vs 165 of 878 patients [18.8%], respectively; P < .001). The absolute risk difference was 7.3 (95% CI, 3.4-11.2) percentage points. The incidence of adverse events was 222 of 878 patients (25.3%) in the placebo group and 200 of 872 patients (22.9%) in the XBJ group. Conclusions and Relevance: In this randomized clinical trial among patients with sepsis, the administration of XBJ reduced 28-day mortality compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT03238742.

Low dose Taxol ameliorated renal fibrosis in mice with diabetic kidney disease by downregulation of HIPK2.

Our previous studies reported that low-dose paclitaxel (Taxol) ameliorated renal fibrosis in the unilateral ureteral obstruction and remnant kidney models. However, the regulatory role of Taxol in diabetic kidney disease (DKD) is still unclear. Herein, we observed that low-dose Taxol attenuated high glucose-increased expression of fibronectin, collagen I and collagen IV in Boston University mouse proximal tubule cells. Mechanistically, Taxol suppressed the expression of homeodomain-interacting protein kinase 2 (HIPK2) via disrupting the binding of Smad3 to HIPK2 promoter region, and consequently inhibited the activation of p53. Besides, Taxol ameliorated RF in Streptozotocin mice and db/db-induced DKD via suppression of Smad3/HIPK2 axis as well as inactivation of p53. Altogether, these results suggest that Taxol can block Smad3-HIPK2/p53 axis, thereby attenuating the progression of DKD. Hence, Taxol is a promising therapeutic drug for DKD.

MiR-6918-5p prevents renal tubular cell apoptosis by targeting MBD2 in ischemia/reperfusion-induced AKI.

AIMS: Although previous studies reported that miRNAs are involved in the progression of acute kidney injury (AKI), their exact function and mechanism in ischemic AKI remains largely unknown. This study aims to define the role of miR-6918-5p in ischemia-reperfusion AKI. Materials and methods The renal arteries of C57BL/6J mice were clamped to establish a model of ischemia-reperfusion renal injury. BUMPT cells were added with Antimycin A and calcium ionophore to establish a model of ATP depletion in vitro. Cell apoptosis was detected by CCK8, flow cytometry and western blot, while HE staining and TUNEL staining were used to assess the degree of kidney damage. KEY FINDINGS: We suppressed mmu_miR-6918-5p by ischemic injury in vitro and in vivo. We found that ischemia-reperfusion (I/R)-induced renal tubular cell apoptosis and the expression of cleaved caspase3 were enhanced by the inhibitor of mmu_miR-6918-5p; this effect was attenuated by an mmu_miR-6918-5p mimic. Mechanistically, mmu_miR-6918-5p binds to the 3' UTR region of MBD2 and represses its expression. The mmu_miR-6918-5p mimic alleviated the ischemic AKI by targeting MBD2. Conversely, the inhibitor of mmu_miR-6918-5p enhanced the ischemic AKI; this was diminished by MBD2-KO. SIGNIFICANCE: Mmu_miR-6918-5p protected against the development of ischemic AKI by targeting MBD2.

Immune enhancement in patients with predicted severe acute necrotising pancreatitis: a multicentre double-blind randomised controlled trial.

PURPOSE: Infected pancreatic necrosis (IPN) is a highly morbid complication of acute necrotising pancreatitis (ANP). Since there is evidence of early-onset immunosuppression in acute pancreatitis, immune enhancement may be a therapeutic option. This trial aimed to evaluate whether early immune-enhancing Thymosin alpha 1 (Tα1) treatment reduces the incidence of IPN in patients with predicted severe ANP. METHODS: We conducted a multicentre, double-blind, randomised, placebo-controlled trial involving ANP patients with an Acute Physiology and Chronic Health Evaluation II (APACHE II) score ≥ 8 and a computed tomography (CT) severity score ≥ 5 admitted within 7 days of the advent of symptoms. Enrolled patients were assigned to receive a subcutaneous injection of Tα1 1.6 mg every 12 h for the first 7 days and 1.6 mg once a day for the subsequent 7 days or matching placebos (normal saline). The primary outcome was the development of IPN during the index admission. RESULTS: A total of 508 patients were randomised, of whom 254 were assigned to receive Tα1 and 254 placebo. The vast majority of the participants required admission to the intensive care unit (ICU) (479/508, 94.3%). During the index admission, 40/254(15.7%) patients in the Tα1 group developed IPN compared with 46/254 patients (18.1%) in the placebo group (difference -2.4% [95% CI - 7.4 to 5.1%]; p = 0.48). The results were similar across four predefined subgroups. There was no difference in other major complications, including new-onset organ failure (10.6% vs. 15%), bleeding (6.3% vs. 3.5%), and gastrointestinal fistula (2% vs. 2.4%). CONCLUSION: The immune-enhancing Tα1 treatment of patients with predicted severe ANP did not reduce the incidence of IPN during the index admission.

Silencing of specificity protein 1 protects H9c2 cells against lipopolysaccharide-induced injury via binding to the promoter of chemokine CXC receptor 4 and suppressing NF-κB signaling.

G protein-coupled protein receptor CXC chemokine receptor 4 (CXCR4) has been shown to be involved in the development of sepsis; however, it remains unclear whether CXCR4 participates in the septic myocardial injury. In our study, treatment with lipopolysaccharide (LPS) increased the expression of specificity protein 1 (SP1) and CXCR4 in H9c2 cells. Notably, a positive association between SP1 and CXCR4 expression was observed in LPS-treated H9c2 cells, and SP1 positively regulated CXCR4 expression in H9c2 cells. Moreover, silencing of SP1 or CXCR4 suppressed LPS-induced inflammation and cell apoptosis in H9c2 cells, as evidenced by the increase in cell viability and decrease in lactate dehydrogenase release, interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α levels, and caspase-3 activity. Additionally, overexpression of CXCR4 abolished the protective effects of SP1 silencing on LPS-induced injury in H9c2 cells. SP1 was also shown to enhance the promoter activity of CXCR4 by directly binding with the binding motif site - 109/-100 in CXCR4 promoter. Besides, downregulation of SP1 or CXCR4 blocked LPS-induced activation of the NF-кB signaling in H9c2 cells. Furthermore, inhibition of NF-кB signaling by DHMEQ abolished LPS-induced myocardial inflammation and apoptosis. In conclusion, silencing of SP1 protected H9c2 cells against LPS-induced injury by binding to the promoter of CXCR4 and suppressing the NF-κB signaling pathway. Hence, our findings provide evidence that manipulation of SP1 or CXCR4 may be an effective approach to promote prevention or recovery of septic myocardial injury, and thereby, may serve as a potential therapeutic strategy for sepsis.

The Impact of Normal Saline or Balanced Crystalloid on Plasma Chloride Concentration and Acute Kidney Injury in Patients With Predicted Severe Acute Pancreatitis: Protocol of a Phase II, Multicenter, Stepped-Wedge, Cluster-Randomized, Controlled Trial.

Introduction/aim: The supraphysiologic chloride concentration of normal saline may contribute to acute kidney injury (AKI). Balanced crystalloids can decrease chloride concentration and AKI in critically ill patients. We aim to test the hypothesis that, in patients with predicted severe acute pancreatitis (pSAP), compared with saline, fluid therapy with balanced crystalloids will decrease plasma chloride concentration. Methods/Design: This is a multicenter, stepped-wedge, cluster-randomized, controlled trial. All eligible patients presenting to the 11 participating sites across China during the study period will be recruited. All sites will use saline for the first month and sequentially change to balanced crystalloids at the pre-determined and randomly allocated time point. The primary endpoint is the plasma chloride concentration on day 3 of enrollment. Secondary endpoints will include major adverse kidney events on hospital discharge or day 30 (MAKE 30) and free and alive days to day 30 for intensive care admission, invasive ventilation, vasopressors, and renal replacement therapy. Additional endpoints include daily serum chloride and sequential organ failure assessment (SOFA) score over the first seven days of enrollment. Discussion: This study will provide data to define the impact of normal saline vs. balanced crystalloids on plasma chloride concentration and clinical outcomes in pSAP patients. It will also provide the necessary data to power future large-scale randomized trials relating to fluid therapy. Ethics and Dissemination: This study was approved by the ethics committee of Jinling Hospital, Nanjing University (2020NZKY-015-01) and all the participating sites. The results of this trial will be disseminated in peer-reviewed journals and at scientific conferences. Trial registration: The trial has been registered at the Chinese Clinical Trials Registry (ChiCTR2100044432).

Geranylgeranyl diphosphate synthase 1 knockdown suppresses NLRP3 inflammasome activity via promoting autophagy in sepsis-induced acute lung injury.

BACKGROUND: NOD-like receptor protein 3 (NLRP3) inflammasome activation has emerged as a crucial contributor to sepsis-induced lung injury. Geranylgeranyl diphosphate synthase 1 (GGPPS1) reportedly exerts the pro-inflammatory capability via activation of NLRP3 inflammasome. However, little is known about the role and mechanism of GGPPS1 in sepsis-induced lung injury. METHODS: Mice underwent cecal ligation and puncture (CLP) surgery to establish the in vivo model of sepsis. The lung injury of mice was assessed by analyzing the histological changes, the lung wet/dry ratio, PaO2/FiO2 ratio, myeloperoxidase (MPO) activity, total protein content, total cell, and polymorphonuclear leukocyte counts. Mouse alveolar macrophages MH-S were exposed to LPS for developing in vitro model of sepsis. The mRNA and protein expression levels of GGPPS1, beclin-1, and autophagy and inflammasome-related genes were detected using quantitative reverse transcription-polymerase chain reaction and western blot assays. Enzyme-linked immunosorbent assay was conducted to determine the levels of interleukin (IL)-1ß and IL-18. RESULTS: We successfully established sepsis-induced acute lung injury in vivo by CLP surgery. GGPPS1 was upregulated in the lung tissues of CLP-induced septic mice. The activation of autophagy and NLRP3 inflammasome were found in the lung tissues of CLP-induced septic mice. The addition of exogenous GGPP (synthesis products catalyzed by GGPPS1) and autophagic inhibitor 3-MA aggravated sepsis-induced hypoxemia, alveolar inflammatory response, intrapulmonary hemorrhage, and pulmonary edema, as evidenced by increased lung injury score, lung wet/dry weight ratio, MPO activity, total protein content, total cell, and PMNs counts, and decreased PaO2/FiO2 ratio. While NLRP3 inhibitor MCC950 exerted the opposite effects. Additionally, administration of exogenous GGPP could inhibit the activation of autophagy, enhance the activity of NLRP3 inflammasome, and the production of IL-1ß and IL-18. Inhibition of autophagy by 3-MA treatment also promoted the activity of NLRP3 inflammasome and the production of IL-1ß and IL-18. While MCC950 restrained the activity of NLRP3 inflammasome, but did not affect the activation of autophagy. Notably, the expression of GGPPS1 was unaltered in CLP-induced mice following GGPP, 3-MA, or MCC950 treatment. Moreover, GGPPS1 was upregulated in MH-S cells stimulated with LPS, and GGPPS1 knockdown enhanced the activation of autophagy and inhibited the activity of NLRP3 inflammasome in vitro. Importantly, depletion of GGPPS1 could alleviate LPS-induced inflammatory response by inducing autophagy-dependent NLRP3 inflammasome inhibition. CONCLUSION: GGPPS1 knockdown suppressed NLRP3 inflammasome activity via promoting autophagy and then attenuated sepsis-induced acute lung injury, revealing a novel target for treating sepsis-induced lung injury.

Depressive State in the Emergency Department During COVID-19: A National Cross-Sectional Survey in China.

Chinese emergency department (ED) staff encountered significant mental stress while fighting the coronavirus disease 2019 (COVID-19) pandemic. We sought to investigate the prevalence and associated factors for depressive symptoms among ED staff (including physicians, nurses, allied health, and auxiliary ED staff). A cross-sectional national survey of ED staff who were on duty and participated in combating the COVID-19 pandemic was conducted March 1-15, 2020. A total of 6,588 emergency medical personnel from 1,060 hospitals responded to this survey. A majority of respondents scored above 10 points on the PHQ-9 standardized test, which is associated with depressive symptoms. Those aged 31-45, those working in the COVID-19 isolation unit, and those with relatives ≤ 16 or ≥70 years old at home all had statistically significant associations with scoring >10 points. Depressive symptoms among Chinese emergency medical staff were likely quite common during the response to the COVID-19 pandemic and reinforce the importance of targeted ED staff support during future outbreaks.

Ultrasound-Induced Microbubble Cavitation Combined with miR-34a-Loaded Nanoparticles for the Treatment of Castration-Resistant Prostate Cancer.

Currently chemotherapy drugs are usually used as first-line treatments for castration-resistant prostate cancer (CRPC), but they are ineffective and accompanied by serious side effects. MicroRNA-34a (miR-34a) simultaneously targets multiple genes related to the cell apoptosis in CRPC cells without obvious side effects. It has shown great potential in the treatment of CRPC. Previous studies focused on miR-34a increasing the sensitivity of chemotherapy drugs to chemoresistant prostate cancer cells. There are few researches on miR-34a alone in the treatment of CRPC. But the macromolecular miR-34a is difficult to enter the cell and is easily degraded by nuclease. Therefore, we constructed methoxy polyethylene glycol-polylacticco-glycolic acid-polylysine (mPEG-PLGA-PLL) nanoparticles to encapsulate miR-34a (miR-34a/NP). The results showed that miR-34a/NP protects miR-34a from degradation by nucleases and can be phagocytized by PC-3 CRPC cells. Ultrasound induces microbubble cavitation (UIMC) improves cell membrane permeability and capillary gaps, and further promotes miR-34a/NP to enter cells PC-3 and prostate cancer xenografts. The miR-34a/NP that enters the cell and tumor tissue releases miR-34a, which suppressed CRPC cells PC-3 proliferation, promoted its apoptosis, and inhibited the growth of CRPC xenografts. Our research verified that miR-34a/NP, especially combined with UIMC, has a significant anti-tumor effect on CRPC.

[Predictive value of MB isoenzyme of creatine kinase and poisoning severity score in the prognosis of patients with wasp sting].

OBJECTIVE: To explore the predictive value of MB isoenzyme of creatine kinase (CK-MB) and poisoning severity score (PSS) in the clinical prognosis of patients with wasp sting. METHODS: A retrospective study was conducted. The clinical data of patients who were stung by wasps admitted to emergency department of the First Affiliated Hospital of Henan University of Science and Technology from July 2017 to November 2019 were collected. The 24-hour acute physiology and chronic health evaluation II (APACHE II), CK-MB and PSS scores of the patients were collected after admission, and 28-day outcome was recorded. Spearman correlation analysis method was used to analyze the correlation between CK-MB and PSS score. Logistic regression model was used to construct joint predictors, and the receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of various indicators for 28-day prognosis of patients with wasp stings. RESULTS: Finally 90 patients were included in the analysis. There were 67 patients survived at 28 days, and 23 dead with the 28-day mortality of 25.6%. APACHE II score, CK-MB and PSS score in the death group were significantly higher than those in the survival group [APACHE II score: 19.7±2.7 vs. 13.7±2.3, CK-MB (U/L): 183 (151, 243) vs. 36 (21, 75), PSS score: 17.7±2.6 vs. 9.3±4.5, all P < 0.01]. The correlation analysis showed that CK-MB and PSS score were positively correlated (r = 0.843, P < 0.01). Logistic regression model fitted CK-MB and PSS score, and Hosmer-Lemeshow test showed that the model fitted well. ROC curve analysis showed that the area under ROC curve (AUC) of CK-MB for predicting 28-day outcome was 0.957, the sensitivity was 91.3%, and the specificity was 88.1%; the AUC of PSS score was 0.908, the sensitivity was 91.3%, and the specificity was 90.8%. The AUC of CK-MB combined with PSS score was 0.964, the sensitivity was 100%, and the specificity was 79.4%, indicating that CK-MB combined with PSS score had higher predictive value and higher sensitivity for 28-day prognosis of patients with wasp sting. CONCLUSIONS: High CK-MB level and high PSS score in early stage of wasp sting injury indicate poor prognosis. Both CK-MB and PSS score can be used as predictors for predicting the prognosis of patients with wasp stings. In addition, CK-MB combined with PSS score have greater predictive value.

Thymosin alpha 1 in the prevention of infected pancreatic necrosis following acute necrotising pancreatitis (TRACE trial): protocol of a multicentre, randomised, double-blind, placebo-controlled, parallel-group trial.

INTRODUCTION: Infected pancreatic necrosis (IPN) and its related septic complications are the major causes of death in patients with acute necrotising pancreatitis (ANP). Therefore, the prevention of IPN is of great clinical value, and immunomodulatory therapy with thymosin alpha 1 may be beneficial. This study was designed to test the hypothesis that the administration of thymosin alpha 1 during the acute phase of ANP will result in a reduced incidence of IPN. METHODS AND ANALYSIS: This is a randomised, multicentre, double-blind, placebo-controlled study. 520 eligible patients with ANP will be randomised in a 1:1 ratio to receive either the thymosin alpha 1 or the placebo using the same mode of administration. The primary endpoint is the incidence of IPN during the index admission. Most of the secondary endpoints will be registered within the index admission including in-hospital mortality, the incidence of new-onset organ failure and new-onset persistent organ failure (respiration, cardiovascular and renal), receipt of new organ support therapy, requirement for drainage or necrosectomy, bleeding requiring intervention, human leucocyte antigens-DR(HLA-DR) on day 0, day 7, day 14, and so on and adverse events. Considering the possibility of readmission, an additional follow-up will be arranged 90 days after enrolment, and IPN and death at day 90 will also be served as secondary outcomes. ETHICS AND DISSEMINATION: This study was approved by the ethics committee of Jinling Hospital, Nanjing University (Number 2015NZKY-004-02). The thymosin alpha 1 in the prevention of infected pancreatic necrosis following acute necrotising pancreatitis(TRACE) trial was designed to test the effect of a new therapy focusing on the immune system in preventing secondary infection following ANP. The results of this trial will be disseminated in peer-reviewed journals and at scientific conferences. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT02473406).

[Early white blood cell count in predicting mortality after acute paraquat poisoning: a Meta-analysis].

OBJECTIVE: To evaluate the prognostic value of early white blood cell count (WBC) in patient of acute paraquat poisoning. METHODS: The literatures about the studies on early WBC and prognosis after paraquat poisoning published in journals at home and abroad were searched. The Chinese literature database contained CNKI, VIP, Wanfang Database, and China Biomedicine Database (CBM), and the journals were limited to the core journals. The foreign language database included PubMed, Embase and Cochrane library clinical controlled trial database. The retrieval date was from the initial publication to April 22nd in 2019, without the limitation of languages. Two researchers independently extracted literature information, and the Newcastle-Ottawa Scale (NOS) was used to evaluate literature quality. The odds ratio (OR), sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and the area under the summary receiver operating characteristic (SROC) were combined and analyzed through the Stata 15.0 software to evaluate the predictive value of early WBC after acute paraquat poisoning. Publication bias was analyzed by Deeks funnel graph. RESULTS: There were 7 retrospective studies and 1 prospective study in a total of 980 paraquat poisoning patients, 5 of them were English literatures, the others were Chinese literatures. There was no heterogeneity among the studies (I2 = 43.5%, P > 0.05). The OR and its 95% confidence interval (95%CI) of the literature was combined through the fixed effect model. The Meta-analysis results were statistically significant (OR = 18.63, 95%CI = 13.63-25.48, P < 0.001), suggesting that the WBC was significantly correlated with the mortality of patients. The combined sensitivity, specificity, PLR, NLR and DOR were 0.75 (95%CI = 0.66-0.82), 0.85 (95%CI = 0.80-0.90), 5.14 (95%CI = 3.86-6.86), 0.29 (95%CI = 0.22-0.39), 17.53 (95%CI = 12.23-25.13) respectively, and the area under the SROC of the WBC was 0.88 (95%CI = 0.85-0.91). Deeks funnel plot was symmetrical (P = 0.21), and there was no obvious publication bias. CONCLUSIONS: The early WBC has a certain predictive value for the prognosis of acute paraquat poisoning patients.

The performance of a new shock advisory algorithm to reduce interruptions during CPR.

OBJECTIVE: To explore a new algorithm and strategy for rhythm analysis during chest compressions (CCs), and to improve the efficiency of cardiopulmonary resuscitation (CPR) by minimizing interruptions. METHODS: The clinical data and ECG of patients with sudden cardiac arrest (CA) from three hospitals in China were collected with Philips MRx monitor/defibrillators. The length of each analyzed ECG segment was 23 s, the first 11.5 s was selected to contain CPR compressions, the next 5 s had no compressions, and the last 6.5 s had no requirement. Three experienced emergency doctors annotated the ECG segments without compression artifacts. A two-step analysis through CPR (ATC) algorithm was applied to the selected data. The first step was analysis during chest compressions. If a shockable rhythm was not detected, compression-free analysis followed. The results of the ATC algorithm were compared with the annotations by the physicians, to determine the sensitivity and specificity of the algorithm. RESULTS: In total 166 CA patients were included with 100 out-of-hospital cardiac arrest (OHCA) patients and 66 in-hospital cardiac arrest (IHCA) patients. A total of 1578 ECG segments were analyzed, including 115 (7.3%) shockable rhythms, 1278 (81.0%) non-shockable rhythms, and 185 (11.7%) intermediate/unknown rhythms. The specificity of all non-shockable rhythms was 99.8% at the end of chest compressions, and 99.5% after analysis without compression artifact. 70.5% of ventricular fibrillation (VF) rhythms were detected by the end of chest compressions. After the CC-free analysis, 93.6% of VF was identified. CONCLUSION: The ATC algorithm achieved sensitivity of 93.6% and specificity of 99.5% after the two-step analysis, and 70.5% of the patients with shockable rhythms did not require CC-free analysis. Such an approach has the potential to substantially reduce CC interruptions when identifying shockable rhythms.

Enhanced cellulase production by decreasing intercellular pH through H+-ATPase gene deletion in Trichoderma reesei RUT-C30.

BACKGROUND: Cellulolytic enzymes produced by Trichoderma reesei are widely used for the industrial production of biofuels and chemicals from lignocellulose. We speculated that intracellular pH during the fermentation process can affect cellulase induction. RESULTS: In this study, two H+-ATPase genes, tre76238 and tre78757, were first identified in T. reesei. Deletion of tre76238 and tre78757 in T. reesei RUT-C30 confirmed that tre76238 has a major function in maintaining intracellular pH, whereas tre78757 has a minor function. The tre76238 deletion strain Δ76238 displayed a high level of cellulase production using cellulase-repressive glucose as a sole carbon source, along with intracellular acid accumulation and growth retardation. Our results indicated that intracellular acid accumulation in Δ76238 stimulated a significant increase in the cytosolic Ca2+ levels. Ca2+ channels were shown to be necessary for cellulase production using glucose as the carbon source in Δ76238. Delayed Δ76238 growth could be reversed by optimizing the medium's nitrogen sources to produce ammonia for intracellular acid neutralization in the early phase. This may be useful for scale-up of cellulase production using glucose as the carbon source. CONCLUSIONS: This study provides a new perspective for significant alterations in the cellulase expression pattern of T. reesei Δ76238, indicating a new mechanism for cellulase regulation under conditions of low intracellular pH.

[Diagnostic accuracy of recognition of stroke in the emergency room scale: a Meta-analysis].

OBJECTIVE: To systematically evaluate the diagnostic accuracy and clinical applicability of recognition of stroke in the emergency room (ROSIER) scale by systematic review and Meta-analysis. METHODS: The Chinese and English literatures concerning the diagnostic accuracy of ROSIER published from January 1st 2005 to December 31st 2018 by PubMed, Embase, Wanfang, VIP and CNKI databases were searched comprehensively and systematically. The sensitivity, specificity, and diagnostic odds ratio (DOR) of ROSIER in total population and subgroup analysis were pooled by using bivariate mixed effects model. Sensitivity analysis was used to evaluate the stability of the results. Deek funnel plot was utilized to evaluate publication bias. The clinical applicability of ROSIER was evaluated by Fagan Nomogram. RESULTS: A total of 28 studies incorporating 7 579 subjects were enrolled in this Meta-analysis. Meta-analysis in total population showed that the pooled sensitivity, specificity and DOR of ROSIER was 0.89 [95% confidence interval (95%CI) = 0.86-0.91, P = 0.00], 0.74 (95%CI = 0.67-0.80, P = 0.00) and 22.09 (95%CI = 14.86-32.82, P = 0.00), respectively. Subgroup analysis of pooled sensitivity of ROSIER showed that Asian patients was significantly higher than European patients [0.89 (95%CI = 0.86-0.92) vs. 0.74 (95%CI = 0.66-0.82), P < 0.01], prospective study was significantly higher than retrospective study [0.89 (95%CI = 0.87-0.92) vs. 0.74 (95%CI = 0.61-0.88), P < 0.05], pre-hospital emergency was significantly higher than emergency department [0.87 (95%CI = 0.80-0.94) vs. 0.85 (95%CI = 0.81-0.90), P < 0.01], study with sample size ≤ 200 was significantly higher than study with sample size > 200 [0.88 (95%CI = 0.83-0.93) vs. 0.82 (95%CI = 0.76-0.88), P < 0.05], but there was no significant difference between different evaluators or different male to female ratio subgroups. Subgroup analysis of pooled specificity of ROSIER showed that European patients was significantly higher than Asian patients [0.81 (95%CI = 0.73-0.89) vs. 0.79 (95%CI = 0.73-0.85), P < 0.05], retrospective study was significantly higher than prospective study [0.88 (95%CI = 0.78-0.97) vs. 0.79 (95%CI = 0.73-0.84), P < 0.05], pre-hospital emergency was significantly higher than emergency department [0.82 (95%CI = 0.73-0.91) vs. 0.79 (95%CI = 0.73-0.85), P < 0.01], emergency physicians was significantly higher than other medical workers [0.80 (95%CI = 0.74-0.86) vs. 0.79 (95%CI = 0.69-0.90), P < 0.05], study with sample size ≤ 200 was significantly higher than study with sample size > 200 [0.82 (95%CI = 0.76-0.89) vs. 0.78 (95%CI = 0.71-0.85), P < 0.05], but there was no significant difference between different male or female ratio subgroups. Sensitivity analysis showed that there was no significant change in pooled DOR before and after excluding each study, indicating that the results were stable. Funnel plot showed that there was a significant publication bias in the total population (P = 0.04), but there was no publication bias in the European population (P = 0.57) or the Asian population (P = 0.08). According to the results of the Fagan Nomogram, with the pretest probability of 50%, when ROSIER was positive, the probability of being diagnosed with stroke increased to 77%, and when ROSIER was negative, the probability of being diagnosed with non-stroke decreased to 13%. It was suggested that ROSIER had good applicability and high clinical diagnostic value. CONCLUSIONS: ROSIER has high diagnostic sensitivity and specificity, and has high clinical diagnostic value. It is a valid stroke identification tool which can be widely used in Asian population, pre-hospital emergency and be utilized by trained medical worker.