DSN-DDI: an accurate and generalized framework for drug-drug interaction prediction by dual-view representation learning.

Drug-drug interaction (DDI) prediction identifies interactions of drug combinations in which the adverse side effects caused by the physicochemical incompatibility have attracted much attention. Previous studies usually model drug information from single or dual views of the whole drug molecules but ignore the detailed interactions among atoms, which leads to incomplete and noisy information and limits the accuracy of DDI prediction. In this work, we propose a novel dual-view drug representation learning network for DDI prediction ('DSN-DDI'), which employs local and global representation learning modules iteratively and learns drug substructures from the single drug ('intra-view') and the drug pair ('inter-view') simultaneously. Comprehensive evaluations demonstrate that DSN-DDI significantly improved performance on DDI prediction for the existing drugs by achieving a relatively improved accuracy of 13.01% and an over 99% accuracy under the transductive setting. More importantly, DSN-DDI achieves a relatively improved accuracy of 7.07% to unseen drugs and shows the usefulness for real-world DDI applications. Finally, DSN-DDI exhibits good transferability on synergistic drug combination prediction and thus can serve as a generalized framework in the drug discovery field.

Exploring ways to improve China's ecological well-being amidst air pollution challenges using mixed methods.

Ecological well-being performance (EWP), a novel concept in sustainable development research, diverges from traditional ecological efficiency in terms of perspectives, core content, and driving factors. However, research on EWP remains insufficiently comprehensive, particularly the corresponding theoretical and methodological investigations into driving pathways. To address this gap, this study develops an "economy-environment-health" framework, incorporating air pollution and associated health losses into the evaluation system, and employs a two-stage Super-NSBM and Window DEA model for reevaluating EWP. The study further investigates the primary pathways of EWP, focusing on environmental regulations, technological innovation, and structural adjustments through both quantitative and qualitative methods. Quantitative spatial econometric analysis reveals that factors such as market-driven environmental regulations, green invention patents, and industrial and energy consumption structures significantly enhance EWP. While examining the "net effects" contributions of individual variables using spatial econometric models, the fsQCA method is employed to identify four effective driving paths for EWP from a configurational perspective. These paths are 1) technological innovation and structural adjustment under environmental regulations with public participation; 2) a combination of environmental regulation, technological innovation, and structural adjustment; 3) structural adjustment with minimal influence from environmental regulations and technological innovation; and 4) structural adjustment directed by market-incentive environmental regulations.

An online delirium detection tool: Cross-cultural adaptation of a Chinese version of the Family Confusion Assessment Method.

BACKGROUND: Intensive care unit (ICU) delirium is a common complication in older critically ill patients that has a significant impact. The Family Confusion Assessment Method (FAM-CAM) is a vital tool for assisting family members in identifying delirium; however, no study has yet been reported on the Chinese version of the scale. OBJECTIVES: The objective of this study was to translate the FAM-CAM into a Chinese version and to verify its effectiveness for delirium detection in an online patient visit setting. METHODS: This was a cross-sectional study. The FAM-CAM was translated to Chinese according to the International Society for Pharmacoeconomics and Outcomes Research guidelines. Patients and family members were recruited to participate in delirium assessments in three ICUs of one hospital. Family members then used the Chinese version of the FAM-CAM to assess for delirium via online visitation, and ICU nurses assessed patients for delirium using the Intensive Care Delirium Screening Checklist (ICDSC). Results were then compared between family members' and nurses' assessments. RESULTS: Overall, 190 critically ill patients and 190 family members were included, of whom 117 (61.6%) were assessed for delirium using the Intensive Care Delirium Screening Checklist. The Cohen's kappa coefficient between the Intensive Care Delirium Screening Checklist and FAM-CAM was 0.759 (P < 0.01). The sensitivity of the Chinese version of the FAM-CAM was 0.880, specificity was 0.890, positive predictive value was 0.928, negative predictive value was 0.823, and area under the receiver operating characteristic curve was 0.881 (95% confidence interval: 0.872-0.935, P < 0.01). CONCLUSION: The Chinese version of the FAM-CAM was shown to effectively help families detect delirium and was suggested as a crucial tool for assisting ICU nurses in the early identification of delirium. This tool may effectively be used to assess delirium during online visits.

Analysis of risk factors associated with healthcare-associated carbapenem-resistant Klebsiella pneumoniae infection in a large general hospital: a case-case-control study.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection is a major public health threat in the world. To inform the prevention and control of CRKP infection in hospitals, this study analyzed the factors associated with CRKP infection and resistance to carbapenems in K. pneumoniae. This case-case-control study was carried out in a large general hospital in China from January 2016 to December 2018, comprising 494 hospitalized patients infected with CRKP (case group 1) and 2429 hospitalized patients infected with carbapenem-susceptible K. pneumoniae (CSKP, case group 2). We selected control groups from hospitalized patients without K. pneumoniae infections for the two case groups separately, with a 1:3 case-control ratio, to analyze the risk factors of the two case groups using the conditional logistic regression. Multivariate analysis showed that the risk factors of CRKP infection were intensive care unit (ICU) admission (odds ratio [OR], 6.85; 95% confidence interval [CI], 4.90-9.58; P < 0.001), respiratory failure (OR, 1.93; 95% CI, 1.34-2.77; P < 0.001), age-adjusted Charlson comorbidity index (aCCI; OR, 1.08; 95% CI, 1.02-1.15; P = 0.007), admission from the Emergency (OR, 1.37; 95% CI, 1.02-1.85; P = 0.036), and imipenem use (OR, 1.80; 95% CI, 1.30-2.49; P < 0.001). Among the aforementioned five risk factors, aCCI (OR, 1.09; 95% CI, 1.06-1.13; P < 0.001) was also identified as a risk factor of CSKP infections in multivariate analysis. The risk factors for resistance to carbapenems in K. pneumoniae were ICU admission, respiratory failure, admission from the Emergency, and imipenem use.

Fluid Balance and Ventilator-Associated Events Among Patients Admitted to ICUs in China: A Nested Case-Control Study.

OBJECTIVES: Fluid therapy is an important component of intensive care management, however, optimal fluid management is unknown. The relationship between fluid balance and ventilator-associated events has not been well established. This study investigated the dose-response relationship between fluid balance and ventilator-associated events. DESIGN: Nested case-control study. SETTING: The study was based on a well-established, research-oriented registry of healthcare-associated infections at ICUs of West China Hospital system (Chengdu, China). PATIENTS: A total of 1,528 ventilator-associated event cases with 3,038 matched controls, who consistently underwent mechanical ventilation for at least 4 days from April 1, 2015, to December 31, 2018, were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We calculated cumulative fluid balance within 4 days prior to ventilator-associated event occurrence. A weighted Cox proportional hazards model with restricted cubic splines was used to evaluate the dose-response relationship. A nonlinear relationship between fluid balance and all three tiers of ventilator-associated events, patients with fluid balance between -1 and 0 L had the lowest risk (p < 0.05 for nonlinear test). The risk of ventilator-associated event was significantly higher in patients with positive fluid balance (4 d cumulative fluid balance: 1 L: 1.19; 3 L: 1.92; 5 L: 2.58; 7 L: 3.24), but not in those with negative fluid balance (-5 L: 1.34; -3 L: 1.14; -1 L: 0.98). CONCLUSIONS: There was nonlinear relationship between fluid balance and all three tiers of ventilator-associated event, with an fluid balance between -1 and 0 L corresponding to the lowest risk. Positive but not negative fluid balance increased the risk of ventilator-associated events, with higher positive fluid balance more likely to lead to ventilator-associated events.

Current Pharmacological Management of Aortic Aneurysm.

ABSTRACT: Aortic aneurysm (AA) remains one of the primary causes of death worldwide. Of the major treatments, prophylactic operative repair is used for AA to avoid potential aortic dissection or rupture. To halt the development of AA and alleviate its progression into aortic dissection, pharmacological treatment has been investigated for years. Currently, ß-adrenergic blocking agents, losartan, irbesartan, angiotensin-converting-enzyme inhibitors, statins, antiplatelet agents, doxycycline, and metformin have been investigated as potential candidates for preventing AA progression. However, the paradox between preclinical successes and clinical failures still exists, with no medical therapy currently available for ideally negating the disease progression. This review describes the current drugs used for pharmacological management of AA and their individual potential mechanisms. Preclinical models for drug screening and evaluation are also discussed to gain a better understanding of the underlying pathophysiology and ultimately find new therapeutic targets for AA.

The epidemiology and clinical outcomes of ventilator-associated events among 20,769 mechanically ventilated patients at intensive care units: an observational study.

BACKGROUND: Ventilator-associated pneumonia (VAP) is the most common hospital-acquired infection (HAI) in intensive care units (ICUs). Ventilator-associated event (VAE), a more objective definition, has replaced traditional VAP surveillance and is now widely used in the USA. However, the adoption outside the USA is limited. This study aims to describe the epidemiology and clinical outcomes of VAEs in China, based on a prospectively maintained registry. METHODS: An observational study was conducted using an ICU-HAI registry in west China. Patients that were admitted to ICUs and underwent mechanical ventilation (MV) between April 1, 2015, and December 31, 2018, were included. The characteristics and outcomes were compared between patients with and without VAEs. The rates of all VAEs dependent on different ICUs were calculated, and the pathogen distribution of patients with possible VAP (PVAP) was described. RESULTS: A total of 20,769 ICU patients received MV, accounting for 21,723 episodes of mechanical ventilators and 112,697 ventilator-days. In all, we identified 1882 episodes of ventilator-associated condition (VAC) events (16.7 per 1000 ventilator-days), 721 episodes of infection-related ventilator-associated complications (IVAC) events (6.4 per 1000 ventilator-days), and 185 episodes of PVAP events (1.64 per 1000 ventilator-days). The rates of VAC varied across ICUs with the highest incidence in surgical ICUs (23.72 per 1000 ventilator-days). The median time from the start of ventilation to the onset of the first VAC, IVAC, and PVAP was 5 (3-8), 5 (3-9), and 6 (4-13) days, respectively. The median length of hospital stays was 28.00 (17.00-43.00), 30.00 (19.00-44.00), and 30.00 (21.00-46.00) days for the three VAE tiers, which were all longer than that of patients without VAEs (16.00 [12.00-23.00]). The hospital mortality among patients with VAEs was more than three times of those with non-VAEs. CONCLUSIONS: VAE was common in ICU patients with ≥ 4 ventilator days. All tiers of VAEs were highly correlated with poor clinical outcomes, including longer ICU and hospital stays and increased risk of mortality. These findings highlight the importance of VAE surveillance and the development of new strategies to prevent VAEs.

Handwashing Sink Contamination and Carbapenem-resistant Klebsiella Infection in the Intensive Care Unit: A Prospective Multicenter Study.

BACKGROUND: Handwashing sinks can become contaminated by carbapenem-resistant Klebsiella (CRK), including carbapenem-resistant Klebsiella pneumoniae (CRKP) and carbapenem-resistant Klebsiella oxytoca (CRKO), but whether they are major sources of CRK infections remains unknown. METHODS: We performed a prospective multicenter study in 16 intensive care units (ICUs) (9 general and 7 neonatal) at 11 hospitals. All sinks at these locations were sampled to screen CRK. All CRK clinical isolates recovered between 2 weeks before and 3 months after sampling in ICUs with CRK-positive sinks or other participating ICUs at the same hospital were collected. Whole-genome sequencing of all isolates was performed. Isolates of the same sequence type (ST) were assigned to clones by calling single-nucleotide polymorphisms. RESULTS: Among 158 sinks sampled, 6 CRKP and 6 CRKO were recovered from 12 sinks in 7 ICUs, corresponding to a 7.6% CRK contamination rate. Twenty-eight clinical isolates were collected, and all were CRKP. The 34 CRKP isolates belonged to 7 STs, including ST789 (n = 14, all had blaNDM-5); ST11 (n = 12, 5 belonged to KL64 and 7 to KL47, all had blaKPC-2); ST709 (n = 4, all had blaNDM-5); and ST16, ST20, ST1027, and ST2407 (n = 1 each). One particular ST789 clone caused an outbreak and contaminated a sink. ST11_KL47 sink isolates were likely the source of a cluster of clinical isolates. Two ST11_KL64 isolates belonged to a common clone but were from 2 hospitals. CONCLUSIONS: Contaminated sinks were not the major source of CRK in our local settings. ST789 blaNDM-5-carrying CRKP might represent an emerging lineage causing neonatal infections.

The clinical impacts and risk factors for non-central line-associated bloodstream infection in 5046 intensive care unit patients: an observational study based on electronic medical records.

BACKGROUND: Most of the previous studies focused on central line-associated bloodstream infection (CLABSI), while non-central line-associated bloodstream infection (N-CLABSI) was poorly studied. This study was performed to investigate the clinical impacts and risk factors for N-CLABSI in intensive care unit (ICU) patients. METHODS: An observational study was conducted in an adult general ICU. The electronic medical records from 2013 to 2017 of all patients aged ≥ 18 years admitted to the ICU > 2 days were analyzed retrospectively. Patients with N-CLABSI and without N-CLABSI or with CLABSI were compared for clinical features and outcomes. Predicted death in ICU included death in ICU and discharging from ICU against medical advice because of critical conditions and the desire to pass away at home. Propensity score (PS) matching was used to ensure that both two groups had similar baseline characteristics. Multivariate regression models were used to confirm whether N-CLABSI was an independent risk factor for each of the outcomes and to analyze the risk factors for N-CLABSI in ICU patients. RESULTS: Of 5046 patients included, 155 developed 168 ICU-acquired N-CLABSI episodes (2.1 episodes per 1000 patient-days) in the ICU, accounted for the majority of nosocomial bloodstream infections (NBSIs; 71.8%). After PS matching, patients with N-CLABSI had prolonged length of stay (LOS) in ICU (median 15 days, p <  0.001) and LOS in hospital (median 13 days, p <  0.001), excess hospitalization costs (median, $27,668 [in US dollar 2017, 1:6.75], p <  0.001), and increased mortality in ICU (8.8%, p = 0.013) and predicted mortality in ICU (22.7%, p <  0.001), compared with those without N-CLABSI. There were no significant differences in all the outcomes between N-CLABSI and CLABSI. N-CLABSI was an independent risk factor for each of the outcomes. Gastrointestinal bleeding (adjusted odds ratio [aOR] 2.30), trauma (aOR 2.52), pancreatitis (aOR 3.45), surgical operation (aOR 1.82), intravascular catheters (aOR 2.93), sepsis (aOR 1.69), pneumonia (aOR 1.53), intraabdominal infection (IAI, aOR 8.37), or healthcare-associated infections other than NBSI, pneumonia, and IAI (aOR 3.89) were risk factors for N-CLABSI in ICU patients. CONCLUSIONS: N-CLABSI was associated with similar poor outcomes with CLABSI, including prolonged LOS in ICU and in hospital and increased hospitalization costs and predicted mortality in ICU. The risk factors for N-CLABSI identified in this study provide further insight in preventing N-CLABSI.

Fusion of Near-Infrared and Raman Spectroscopy for In-Line Measurement of Component Content of Molten Polymer Blends.

Spectral measurement techniques, such as the near-infrared (NIR) and Raman spectroscopy, have been intensively researched. Nevertheless, even today, these techniques are still sparsely applied in industry due to their unpredictable and unstable measurements. This paper put forward two data fusion strategies (low-level and mid-level fusion) for combining the NIR and Raman spectra to generate fusion spectra or fusion characteristics in order to improve the in-line measurement precision of component content of molten polymer blends. Subsequently, the fusion value was applied to modeling. For evaluating the response of different models to data fusion strategy, partial least squares (PLS) regression, artificial neural network (ANN), and extreme learning machine (ELM) were applied to the modeling of four kinds of spectral data (NIR, Raman, low-level fused data, and mid-level fused data). A system simultaneously acquiring in-line NIR and Raman spectra was built, and the polypropylene/polystyrene (PP/PS) blends, which had different grades and covered different compounding percentages of PP, were prepared for use as a case study. The results show that data fusion strategies improve the ANN and ELM model. In particular, mid-level fusion enables the in-line measurement of component content of molten polymer blends to become more accurate and robust.

Enhancing the spontaneous emission rate by modulating carrier distribution in GaN-based surface plasmon light-emitting diodes.

Based on the nanorod structure, we have fabricated GaN-based surface plasmon light-emitting diodes with Ag nanoparticles deposited laterally proximity to the multiple quantum wells (MQWs) region, which allows us to investigate the quantum well - surface plasmon (QW-SP) coupling effect. Our results show that the QW-SP coupling effect increases significantly when the SP resonant wavelength of Ag nanoparticles is close to the QW emission wavelength, especially by using a shorter wavelength light source, which will further enhance the spontaneous emission rate. Combined with the simulations, we find that the enhancement is due to the decreased excitation light penetration depth into the active region, which can modulate the carrier distribution and increase the proportion of SP-coupled carriers in the MQWs of LEDs. To increase the spontaneous emission rate for the electrical QW-SP coupled LEDs, we can use single QW or MQW structure to confine the carriers in the topmost QW, which will effectively increase the proportion of SP-coupled carriers. Our findings pave a way to design the ultrafast LED light source for the application of visible light communication (VLC).

[Personal characteristics of paradoxical insomnia: A case-control study].

OBJECTIVE: To compare the personal characteristics between the patients with paradoxical insomnia and the patients with primary insomnia or the normal sleepers.
 Methods: A case-control study with the proportion at 1:1:1 was carried out. The patients with paradoxical insomnia were diagnosed in Sleep Medicine Center of West China Hospital of Sichuan University between March 2013 and December 2013. A case of paradoxical insomnia was matched with two controls: a primary insomnia patient and a normal sleeper. A total of 63 matched cases were collected. A face-to-face survey was conducted by using the following scales: General Data Scale and Eysenck Personality Questionnaire (EPQ).
 Results: The average scores of psychoticism, extraversion, and neuroticism for paradoxical insomnia cases were (52.1±10.2), (49.6±9.8), and (56.0±12.0), respectively. In general, 31.7% of paradoxical insomnia patients had psychoticism or psychoticism tendency in their personality, which were more obvious than those in primary insomnia patients (7.9%) (χ2=11.228, P<0.0125) and normal sleepers (0) (χ2=23.774, P<0.0125). Moreover, 19.0% of paradoxical insomnia patients had extroversion or extroversion tendency in their personality, which were more significant than those in primary insomnia patients (3.2%) (Z=-4.047, P<0.0125) but less obvious than those in normal sleepers (60.3%) (Z=-4.754, P<0.0125). Also, 46.0% of paradoxical insomnia patients had neuroticism or neuroticism tendency in their personality, which were more significant than those in normal sleepers (0) (χ2=37.670, P<0.0125) but similar to those in primary insomnia patients (52.4%) (χ2=0.508, P>0.0125).
 Conclusion: The personal characteristics for paradoxical insomnia patients did not reached obviously abnormal level. However, their psychoticism tendency, extroversion tendency and neuroticism tendency needed to be paid attention.

Enhancement of the modulation bandwidth for GaN-based light-emitting diode by surface plasmons.

We have fabricated the surface plasmon (SP) coupled GaN-based nanorod LEDs with Ag nanoparticles (Nps), and demonstrate the enhancement of the optical modulation bandwidth by SPs. Compared with the LED without Ag Nps, the optical modulation bandwidth of the LED with Ag Nps increases by a factor of ~2 at 57 A/cm2. The photoluminescence (PL) and electroluminescence (EL) experimental results are consistent with each other, and both suggest the effective coupling between quantum wells (QWs) and SPs. Furthermore, the current dependent modulation frequency characteristics show that the QW-SP coupling can increase the modulation bandwidth, especially for LEDs with high intrinsic internal quantum efficiency (IQE). These findings will help to open a new solution to design the ultrafast LED light source for the application of the visible light communication.

Surface plasmon-enhanced nanoporous GaN-based green light-emitting diodes with Al2O3 passivation layer.

A surface plasmon (SP)-enhanced nanoporous GaN-based green LED based on top-down processing technology has been successfully fabricated. This SP-enhanced LED consists of nanopores passing through the multiple quantum wells (MQWs) region, with Ag nanorod array filled in the nanopores for SP-MQWs coupling and thin Al(2)O(3) passivation layer for electrical protection. Compared with nanoporous LED without Ag nanorods, the electroluminescence (EL) peak intensity for the SP-enhanced LED was greatly enhanced by 380% and 220% at an injection current density of 1 and 20A/cm(2), respectively. Our results show that the increased EL intensity is mainly attributed to the improved internal quantum efficiency of LED due to the SP coupling between Ag nanorods and MQWs.

Translation, cultural debugging, and validation of the Chinese version of the Sour Seven Questionnaire: a cross-sectional study.

Introduction: Intensive care unit delirium (ICUD) is an acute cerebral dysfunction accompanied by a change of level of consciousness, disorientation, and cognitive dysfunction, typically occurring over a short duration ranging from hours to days and resulting from underlying medical causes. Family members may sometimes detect changes in consciousness earlier than medical staff. The Sour Seven Questionnaire is a tool to assist family members in screening for delirium, but there is currently no Chinese version. This study aimed to translate and cross-culturally debug the Sour Seven Questionnaire and test the effectiveness of the Chinese version in screening for ICUD by family members. Methods: To create the Chinese version of the questionnaire, the questionnaire was first translated and then culturally debugged through expert consultation and cognitive interviews. Patients and their family members admitted to three ICUs in a Chinese hospital were selected to test the Chinese version of the Sour Seven Questionnaire and the results were compared with those of the validated and recommended Confusion Assessment Method for the intensive care unit (CAM-ICU) assessment. Results: A total of 190 ICU patients and their families were included in this study. Results of the CAM-ICU assessment showed that 73 (38.4%) patients developed ICUD compared to the 66 (34.7%) using the Chinese version of the Sour Seven Questionnaire, which had a Cohen's kappa coefficient of 0.853, a sensitivity of 0.863, and a specificity of 0.974. The positive predictive value was 0.954 and the negative predictive value was 0.919. Discussion: The Chinese version of the Sour Seven Questionnaire is a valid assessment tool for helping families screen for ICUD, and it is effective in identifying altered consciousness in patients even during online visits.

Sepsis one-hour bundle management combined with psychological intervention on negative emotion and sleep quality in patients with sepsis.

BACKGROUND: Sepsis is a serious infectious disease caused by various systemic inflammatory responses and is ultimately life-threatening. Patients usually experience depression and anxiety, which affect their sleep quality and post-traumatic growth levels. AIM: To investigate the effects of sepsis, a one-hour bundle (H1B) management was combined with psychological intervention in patients with sepsis. METHODS: This retrospective analysis included 300 patients with sepsis who were admitted to Henan Provincial People's Hospital between June 2022 and June 2023. According to different intervention methods, the participants were divided into a simple group (SG, n = 150) and combined group (CG, n = 150). H1B management was used in the SG and H1B management combined with psychological intervention was used in the CG. The changes of negative emotion, sleep quality and post-traumatic growth and prognosis were compared between the two groups before (T0) and after (T1) intervention. RESULTS: After intervention (T1), the scores of the Hamilton Anxiety scale and Hamilton Depression scale in the CG were significantly lower than those in the SG (P < 0.001). Sleep time, sleep quality, sleep efficiency, daytime dysfunction, sleep disturbance dimension score, and the total score in the CG were significantly lower than those in the SG (P < 0.001). The appreciation of life, mental changes, relationship with others, personal strength dimension score, and total score of the CG were significantly higher than those of the SG (P < 0.001). The scores for mental health, general health status, physiological function, emotional function, physical pain, social function, energy, and physiological function in the CG were significantly higher than those in the SG (P < 0.001). The mechanical ventilation time, intensive care unit stay time, and 28-d mortality of the CG were significantly lower than those of the SG (P < 0.05). CONCLUSION: H1B management combined with psychological intervention can effectively alleviate the negative emotions of patients with sepsis and increase their quality of sleep and life.

A dynamic nomogram to predict invasive fungal super-infection during healthcare-associated bacterial infection in intensive care unit patients: an ambispective cohort study in China.

Objectives: Invasive fungal super-infection (IFSI) is an added diagnostic and therapeutic dilemma. We aimed to develop and assess a nomogram of IFSI in patients with healthcare-associated bacterial infection (HABI). Methods: An ambispective cohort study was conducted in ICU patients with HABI from a tertiary hospital of China. Predictors of IFSI were selected by both the least absolute shrinkage and selection operator (LASSO) method and the two-way stepwise method. The predictive performance of two models built by logistic regression was internal-validated and compared. Then external validity was assessed and a web-based nomogram was deployed. Results: Between Jan 1, 2019 and June 30, 2023, 12,305 patients with HABI were screened in 14 ICUs, of whom 372 (3.0%) developed IFSI. Among the fungal strains causing IFSI, the most common was C.albicans (34.7%) with a decreasing proportion, followed by C.tropicalis (30.9%), A.fumigatus (13.9%) and C.glabrata (10.1%) with increasing proportions year by year. Compared with LASSO-model that included five predictors (combination of priority antimicrobials, immunosuppressant, MDRO, aCCI and S.aureus), the discriminability of stepwise-model was improved by 6.8% after adding two more predictors of COVID-19 and microbiological test before antibiotics use (P<0.01).And the stepwise-model showed similar discriminability in the derivation (the area under curve, AUC=0.87) and external validation cohorts (AUC=0.84, P=0.46). No significant gaps existed between the proportion of actual diagnosed IFSI and the frequency of IFSI predicted by both two models in derivation cohort and by stepwise-model in external validation cohort (P=0.16, 0.30 and 0.35, respectively). Conclusion: The incidence of IFSI in ICU patients with HABI appeared to be a temporal rising, and our externally validated nomogram will facilitate the development of targeted and timely prevention and control measures based on specific risks of IFSI.

Autophagy activation ameliorates the fibrosis of trabecular meshwork cells induced by TGFß2 through the promotion of fibrotic proteins degradation.

The level of transforming growth factor-beta2 (TGFß2) is elevated in aqueous humor of partial glaucoma patients, and induced trabecular meshwork (TM) fibrosis, which could cause TM cells dysfunction and lead to intraocular pressure (IOP) elevation. Autophagy is a dynamic process of bulk degradation of organelles and proteins under stress condition, while its functions in fibrotic development remain controversial. Meanwhile, it is still unclear if activation of autophagy could ameliorate TGFß2-induced fibrosis in TM cells. In this study, we demonstrated that autophagy activation with Rapamycin or Everolimus could ameliorate TM fibrosis induced by TGFß2. We also proved that activation of autophagy may decrease TM cells fibrosis and reduce elevated IOP induced by TGFß2 in vivo, while Rapamycin or Everolimus has no effect on TGFß/Smad3 pathway activity and fibrotic genes expression. However, when Chloroquine phosphate blocks autophagy-lysosome pathway, the protective effect of Rapamycin or Everolimus on fibrosis was weakened. We established that autophagy activation ameliorates TM fibrosis through promoting fibrotic proteins degradation.

Decrease of Prolylcarboxypeptidase Dose of Aqueous Humor is Involved in the Pathogenesis of Primary Open-Angle Glaucoma via Finetuning of the Local Ocular Renin-Angiotensin System.

Objective: In this study, we investigated the cause of the AngII dose elevation in aqueous humor of primary open-angle glaucoma (POAG) patients. Methods: Enzyme-linked immunosorbent assay (ELISA), western blotting were used to detect concentration of Angiotensin Converting Enzyme 2 (ACE2) and Prolylcarboxypeptidase (PRCP). AngII and AngII + Recombinant PRCP were injected into anterior chamber of mouse eye. Mouse Intraocular pressure (IOP) was measured every week, mouse eye sections were conducted Hematoxylin-and-Eosin (H&E) staining, Masson' staining and Immunofluorescence staining. Western blotting and Immunofluorescence staining assays to detected fibrosis of trabecular meshwork cells. Mass spectrometry was used to identify proteins of aqueous humor. Results: PRCP dose are decreased in aqueous humor of POAG patients. There is a negative correlation between PRCP and AngII levels in aqueous humor and between PRCP levels and the IOP. PRCP treatment reverses fibrosis of trabecular meshwork (TM) and prevents IOP elevation induced by AngII. Exogenous PRCP rescues fibrosis induced by AngII in HTMCs. Proteome profiling detected 502 differentially expressed proteins. Conclusion: Our study found PRCP dose was decreased in POAG patients' aqueous humor, and it might cause high level of AngII. Restoration of PRCP rescued fibrosis of TM cells and ameliorated IOP in AngII treatment mouse.

The relationship between professional quality of life and work environment among ICU nurses in Chinese: a cross-sectional study.

Objective: To explore the relationship between the professional quality of life and work environment among intensive care unit nurses, and identify the influencing factors of intensive care unit nurses' professional quality of life. Methods: This study design is cross-sectional and correlational descriptive. Four hundred fourteen intensive care unit nurses from Central China were recruited. Data were collected from three questionnaires of self-designed demographic questions, the professional quality of life scale and the nursing work environment scale. Descriptive statistics, Pearson's correlation, bivariate analysis and multiple linear regression were used to analyze the data. Results: A total of 414 questionnaires was collected, for an effective recovery rate of 98.57%. The original scores of the three sub-scales of professional quality of life were 33.58 ± 6.43, 31.83 ± 5.94, and 32.55 ± 5.74. Compassion satisfaction was positively correlated with the nursing working environment (p < 0.05), job burnout, and secondary trauma were negatively correlated with nursing work in environment (p < 0.05). Multiple linear regression analysis results show that, the nursing working environment entered into the influential factor model of professional quality of life scale (p < 0.001). The nursing working environment independently explained 26.9% of the changes in compassion satisfaction, 27.1% of the changes in job burnout, and 27.5% of the changes in secondary trauma. The nursing work environment is an important factor affecting the professional quality of life. Conclusion: The better the nursing working environment, the higher the professional quality of life of intensive care unit nurses. Decision makers and managers can focus on improving the working environment of nurses, which may be a new perspective for managers to improve the professional quality of life of nurses and stabilize the nursing team.