Cell Cross-Talk in Alveolar Microenvironment: From Lung Injury to Fibrosis.

Alveoli are complex microenvironments composed of various cell types, including epithelial, fibroblast, endothelial, and immune cells, which work together to maintain a delicate balance in the lung environment, ensuring proper growth, development, and an effective response to lung injuries. However, prolonged inflammation or aging can disrupt normal interactions among these cells, leading to impaired repair processes and a substantial decline in lung function. Therefore, it is essential to understand the key mechanisms underlying the interactions among the major cell types within the alveolar microenvironment. We explored the key mechanisms underlying the interactions among the major cell types within the alveolar microenvironment. These interactions occur through the secretion of signaling factors and play crucial roles in the response to injury, repair mechanisms, and the development of fibrosis in the lungs. Specifically, we focused on the regulation of alveolar type 2 cells by fibroblasts, endothelial cells, and macrophages. In addition, we explored the diverse phenotypes of fibroblasts at different stages of life and in response to lung injury, highlighting their impact on matrix production and immune functions. Furthermore, we summarize the various phenotypes of macrophages in lung injury and fibrosis as well as their intricate interplay with other cell types. This interplay can either contribute to the restoration of immune homeostasis in the alveoli or impede the repair process. Through a comprehensive exploration of these cell interactions, we aim to reveal new insights into the molecular mechanisms that drive lung injury toward fibrosis and identify potential targets for therapeutic intervention.

Therapeutic drug monitoring of linezolid and exploring optimal regimens and a toxicity-related nomogram in elderly patients: a multicentre, prospective, non-interventional study.

BACKGROUND: The concentrations of linezolid, its optimal regimen and the associated side effects in elderly patients remain unclear. METHODS: In this multicentre, prospective study, elderly patients receiving linezolid at four tertiary hospitals in Beijing between May 2021 and December 2022 were included. Linezolid concentrations and haematological toxicity were monitored dynamically. Risk factors for linezolid overexposure and moderate-to-severe linezolid-induced thrombocytopenia (M/S LIT) were analysed, and a predictive model of M/S LIT was developed. RESULTS: A total of 860 linezolid concentrations were measured in 313 patients. The median trough concentrations of linezolid were 24.4 (15.3, 35.8) mg/L at 36-72 h and 26.1 (17.0, 38.1) mg/L at 5-10 days (P = 0.132). Severe linezolid exposure was independently associated with age, estimated glomerular filtration rate (eGFR) and the worst SOFA score (SOFA1), and we further recommended dose regimens for elderly patients based on these findings. The incidences of linezolid-induced thrombocytopenia(LIT) and M/S LIT were 73.5% and 47.6%, respectively. M/S LIT was independently correlated with treatment duration, average trough concentration (TDMa), baseline platelet count, eGFR and baseline SOFA score (SOFA0). The developed nomogram predicted M/S LIT with an area under the curve of 0.767 (95% CI 0.715-0.820), a sensitivity of 71.1% and a specificity of 73.2%. CONCLUSIONS: Linezolid trough concentrations increased dramatically in the elderly, by about 10 mg/L in patients aged 65-80 years, followed by a further increase of 10 mg/L for every 10 years of age. Therapeutic drug monitoring is recommended in elderly patients receiving linezolid. The developed nomogram may predict M/S LIT and guide dosage adjustments of linezolid. Clinical trial registration number: ChiCTR2100045707.

Hyperglycemia Induces Tear Reduction and Dry Eye in Diabetic Mice through the Norepinephrine-α1 Adrenergic Receptor-Mitochondrial Impairment Axis of Lacrimal Gland.

Dry eye syndrome is a common complication in diabetic patients with a prevalence of up to 54.3%. However, the pathogenic mechanisms underlying hyperglycemia-induced tear reduction and dry eye remain less understood. The present study indicated that both norepinephrine (NE) and tyrosine hydroxylase levels were elevated in the lacrimal gland of diabetic mice, accompanied by increased Fos proto-oncogene (c-FOS)+ cells in the superior cervical ganglion. However, the elimination of NE accumulation by surgical and chemical sympathectomy significantly ameliorated the reduction in tear production, suppressed abnormal inflammation of the lacrimal gland, and improved the severity of dry eye symptoms in diabetic mice. Among various adrenergic receptors (ARs), the α1 subtype played a predominant role in the regulation of tear production, as treatments of α1AR antagonists improved tear secretion in diabetic mice compared with ßAR antagonist propranolol. Moreover, the α1AR antagonist alfuzosin treatment also alleviated functional impairments of the meibomian gland and goblet cells in diabetic mice. Mechanically, the α1AR antagonist rescued the mitochondrial bioenergetic deficit, increased the mitochondrial DNA copy numbers, and elevated the glutathione levels of the diabetic lacrimal gland. Overall, these results deciphered a previously unrecognized involvement of the NE-α1AR-mitochondrial bioenergetics axis in the regulation of tear production in the lacrimal gland, which may provide a potential strategy to counteract diabetic dry eye by interfering with the α1AR activity.

Association between the triglyceride-glucose index and all-cause and CVD mortality in the young population with diabetes.

BACKGROUND: Although studies have demonstrated the value of the triglyceride-glucose (TyG) index for cardiovascular disease (CVD) and cardiovascular mortality, however, few studies have shown that the TyG index is associated with all-cause or CVD mortality in young patients with diabetes. This study aimed to investigate the association between the TyG index and all-cause and CVD mortality in young patients with diabetes in the United States. METHODS: Our study recruited 2440 young patients with diabetes from the National Health and Nutrition Examination Survey (NHANES) 2001-2018. Mortality outcomes were determined by linking to National Death Index (NDI) records up to December 31, 2019. Cox regression modeling was used to investigate the association between TyG index and mortality in young patients with diabetes. The nonlinear association between TyG index and mortality was analyzed using restricted cubic splines (RCS), and a two-segment Cox proportional risk model was constructed for both sides of the inflection point. RESULTS: During a median follow-up period of 8.2 years, 332 deaths from all causes and 82 deaths from cardiovascular disease were observed. Based on the RCS, the TyG index was found to have a U-shaped association with all-cause and CVD mortality in young patients with diabetes, with threshold values of 9.18 and 9.16, respectively. When the TyG index was below the threshold value (TyG index < 9.18 in all-cause mortality and < 9.16 in CVD mortality), its association with all-cause and CVD mortality was not significant. When the TyG index was above the threshold (TyG index ≥ 9.18 in all-cause mortality and ≥ 9.16 in CVD mortality), it showed a significant positive association with all-cause mortality and CVD mortality (HR 1.77, 95% CI 1.05-2.96 for all-cause mortality and HR 2.38, 95% CI 1.05-5.38 for CVD mortality). CONCLUSION: Our results suggest a U-shaped association between TyG index and all-cause and CVD mortality among young patients with diabetes in the United States, with threshold values of 9.18 and 9.16 for CVD and all-cause mortality, respectively.

Enhancing Nix-dependent mitophagy relieves AKI by restricting TREM-1-mediated hyperactivation of inflammasome in platelets.

Platelets are highly involved in inflammation and organ injury under pathological conditions. The mitophagy in platelets may restrict hyperactivation of the inflammasome and relieve acute kidney injury (AKI). Cecal ligation puncture (CLP)/LPS-induced AKI Triggering receptor expressed on myeloid cells (TREM-1)-knockout mice models were established. Additionally, septic patients with AKI were also included. TREM-1 expression in platelets and inflammasome activation were examined. Platelet transfer assays were performed to investigate the contribution of platelet TREM-1 to renal injury. Mitophagy was evaluated in the context of inflammation. BNIP3L/Nix knockout mice were used to examine the relationship between platelet mitophagy and inflammatory activation. The results showed that the level of TREM-1 was increased and the platelet inflammasome was hyperactivated in CLP mice and septic patients, and TREM-1 activated platelet inflammasomes. TREM-1 deletion significantly abrogated hyperactivation of the platelet inflammasome and dramatically reduced AKI, whereas ablation of the mitophagy receptor BNIP3L/Nix induced the accumulation of damaged mitochondria and hyperactivation of platelet inflammasomes in CLP mice. BNIP3L/Nix controlled platelet inflammasome activation, and an amplification loop of platelet inflammasome activation and dysfunctional mitochondria controlled sepsis-related AKI. Therefore, targeting TREM-1 and NLRP3/BNIP3L in platelets may represent a novel therapeutic strategy for treating septic AKI.

Real-world effectiveness of nirmatrelvir-ritonavir versus azvudine in hospitalized patients with COVID-19 during the omicron wave in Beijing: a multicenter retrospective cohort study.

BACKGROUND AND AIM: Two oral antivirals (Nirmatrelvir- ritonavir and Azvudine) are widely used in China practice during the Omicron wave of the pandemic. However, little evidence regarding the real-world effectiveness of these two oral antivirals in in-hospital patients. We aimed to evaluate the clinical effectiveness of nirmatrelvir-ritonavir versus azvudine among adult hospitalized patients with COVID-19. METHODS: This retrospective cohort study used data from three Chinese PLA General Hospital medical centres. Hospitalized patients with COVID-19 treated with azvudine or nirmatrelvir-ritonavir from Dec 10, 2022, to February 20, 2023, and did not require invasive ventilation support on admission were eligible for inclusion. RESULTS: After exclusions and propensity-score matching, the final analysis included 486 azvudine recipients and 486 nirmatrelvir-ritonavir recipients. By 28 days of initiation of the antivirus treatment, the crude incidence rate of all-cause death was similar in both types of antivirus treatment (nirmatrelvir-ritonavir group 2.8 events 1000 person-days [95% CI, 2.1-3.6] vs azvudine group 3.4 events/1000 person-days [95% CI, 2.6-4.3], P = 0.38). Landmark analysis showed that all-cause death was lower in the nirmatrelvir-ritonavir (3.5%) group than the azvudine (6.8%, P = 0.029) within the initial 10-day admission period, while no significant difference was observed for results between 10 and 28 days follow-up. There was no significant difference between the nirmatrelvir-ritonavir group and the azvudine group in cumulative incidence of the composite disease progression event (8.6% with nirmatrelvir-ritonavir vs. 10.1% with azvudine, HR, 1.22; 95% CI 0.80-1.86, P = 0.43). CONCLUSION: Among patients hospitalized with COVID-19 during the omicron wave in Beijing, similar in-hospital clinical outcomes on 28 days were observed between patients receiving nirmatrelvir-ritonavir and azvudine. However, it is worth noticing that nirmatrelvir-ritonavir appears to hold an advantage over azvudine in reducing early mortality. Further randomized controlled trials are needed to verify the efficacy of those two antivirus medications especially in early treatment.

Loss of LEAP-2 alleviates obesity-induced myocardial injury by regulating macrophage polarization.

BACKGROUND: Obesity is a serious public health issue worldwide, which is a risk factor of cardiovascular disorders. Obesity has been shown to be associated with subclinical myocardial injury, increasing the risk of heart failure. Our study aims to explore novel mechanisms underlying obesity-induced myocardial injury. METHODS: Mice were fed a high-fat diet (HFD) to establish a mouse model of obesity, and serum levels of TG, TCH, LDL, CK-MB, LDH, cTnI and BNP were examined. Inflammatory response was evaluated by determining the expression and secretion of proinflammatory cytokines IL-1ß and TNF-α. Macrophage infiltration in the heart was examined by IHC staining, and H&E staining was applied to evaluate myocardial injury. Primary peritoneal macrophages were isolated from mice and treated with palmitic acid (PA). Macrophage polarization was evaluated by determine the expression of CCL2, iNOS, CD206 and arginase I via Western blot, RT-qPCR, and flow cytometry. Co-IP assays were performed to examine the interaction between LEAP-2, GHSR and ghrelin. RESULTS: Hyperlipidemia, increased proinflammatory cytokines and myocardial injury were observed in mice with obesity, and silencing of LEAP-2 ameliorated HFD-induced hyperlipidemia, inflammation, and myocardial injury. Moreover, HFD-induced macrophage infiltration and M1 polarization were reversed by LEAP-2 knockdown in mice. Furthermore, silencing of LEAP-2 suppressed PA-induced M1 polarization but enhanced M2 polarization in vitro. LEAP-2 interacted with GHSR in macrophages, and knockdown of LEAP-2 promoted the interaction of GHSR and ghrelin. Overexpression of ghrelin enhanced LEAP-1 silencing-mediated suppression of inflammatory response and upregulation of M2 polarization in PA-induced macrophages. CONCLUSION: Knockdown of LEAP-2 ameliorates obesity-induced myocardial injury via promoting M2 polarization.

Single-cell landscape of immunological responses in elderly patients with sepsis.

Sepsis is a dysregulated host response to severe infections, and immune dysfunction plays a crucial role in its pathogenesis. Elderly patients, a special population influenced by immunosenescence, are more susceptible to sepsis and have a worse prognosis. However, the immunopathogenic mechanisms underlying sepsis in elderly patients remain unclear. Here, we performed single-cell RNA sequencing of peripheral blood samples from young and old subjects and patients with sepsis. By exploring the transcriptional profiles of immune cells, we analyzed immune cell compositions, phenotype shifts, expression heterogeneities, and intercellular communication. In elderly patients with sepsis, innate immune cells (e.g., monocytes and DCs) exhibit decreased antigen presentation, presenting an overactive inflammatory and senescent phenotype. However, the immunophenotype of T cells shifted to characterize effector, memory, and exhaustion. Moreover, we identified strong interferon-γ responses of T cells in both aging and sepsis groups and a deranged inflammaging status in elderly sepsis patients. Tregs in elderly patients with sepsis showed increased abundance and enhanced immunosuppressive effects. In addition, metabolism-associated pathways were upregulated in T cells in elderly patients with sepsis, and the lysine metabolism pathway was enriched in Tregs. Cell-cell interaction analysis showed that the expression profile of ligand-receptor pairs was probably associated with aggravated immune dysfunction in elderly patients with sepsis. A novel HLA-KIR interaction was observed between Tregs and CD8 + T cells. These findings illustrate the immunological hallmarks of sepsis in elderly patients, and highlight that immunosuppressive and metabolic regulatory pathways may undergo important alterations in elderly patients with sepsis.

Sleep deprivation induces corneal endothelial dysfunction by downregulating Bmal1.

BACKGROUND: Sleep deprivation (SD) is a common public health problem that contributes to various physiological disorders and increases the risk of ocular diseases. However, whether sleep loss can damage corneal endothelial function remains unclear. This study aimed to determine the effect and possible mechanism of SD on the corneal endothelium. METHODS: Male C57BL/6J mice were subjected to establish SD models. After 10 days, quantitative RT-PCR (qRT-PCR) and western blot or immunostaining for the expression levels of zonula occludens-1 (ZO-1), ATPase Na+/K + transporting subunit alpha 1 (Atp1a1), and core clock genes in the corneal endothelium were evaluated. Reactive oxygen species staining and mitochondrial abundance characterized the mitochondrial function. The regulatory role of Bmal1 was confirmed by specifically knocking down or overexpressing basic helix-loop-helix ARNT like 1 protein (Bmal1) in vivo. In vitro, a mitochondrial stress test was conducted on cultured human corneal endothelial cells upon Bmal1 knockdown. RESULTS: SD damaged the barrier and pump functions of mouse corneal endothelium, accompanied by mitochondrial dysfunction. Interestingly, SD dramatically downregulated the core clock gene Bmal1 expression level. Bmal1 knockdown disrupted corneal endothelial function, while overexpression of Bmal1 ameliorated the dysfunction induced by SD. Mitochondrial bioenergetic deficiency mediated by Bmal1 was an underlying mechanism for SD induced corneal endothelial dysfunction. CONCLUSION: The downregulation of Bmal1 expression caused by SD led to corneal endothelial dysfunction via impairing mitochondrial bioenergetics. Our findings offered insight into how SD impairs the physiological function of the corneal endothelium and expanded the understanding of sleep loss leading to ocular diseases.

Necessity for higher teicoplanin doses in older adults: a multicenter prospective observational study in China.

BACKGROUND: Many older adult patients receive low-dose teicoplanin with varied regimens, leading to a lack of clarity on its optimal regimens and toxicity profiles in China. This study aimed to clarify these aspects by analyzing teicoplanin treatment concentrations and toxicities. METHODS: We included older adult patients administered teicoplanin at four tertiary hospitals in Beijing from June 2021 to July 2023, targeting a trough concentration (Cmin) ≥ 10 mg/L. Teicoplanin concentrations and toxicities were monitored dynamically. RESULTS: From 204 patients, we obtained 632 teicoplanin concentrations. Most patients (83.3%) received low-dose regimens. Suboptimal concentrations were found in 66.4% of patients within 7 days of treatment and 17.0% after 15 days. Cmin gradually increased with treatment duration and was influenced initially by creatinine and by both body weight and creatinine from days 8 to 14. The target concentration was achieved in 53.1%, 33.9%, 15.6%, and 5.5% of patients at 3, ≤ 7, 8-14, and ≥ 15 days after withdrawal, respectively. Slow elimination was associated with average Cmin and eGFR. Nephrotoxicity, hepatotoxicity, and thrombocytopenia occurred in 12.5%, 4.1%, and 31.5% of patients, respectively, without significant differences between concentrations. CONCLUSIONS: Most older adult patients were underdosed, indicating a need for dose adjustment. Given the varied risk factors for suboptimal concentrations in different treatment stages, a one-size-fits-all regimen was ineffective. We recommend an initial dose of 400 mg at 12-h intervals for the first three days, with subsequent doses from days 4 to 14 adjusted based on creatinine and body weight; after day 14, a maintenance dose of 200 mg daily is advised. TRIAL REGISTRATION: ChiCTR2100046811; 28/05/2021.

Polystyrene microplastic-induced endoplasmic reticulum stress contributes to growth plate endochondral ossification disorder in young rat.

BACKGROUND: Previous studies on the effects of microplastics (MPs) on bone in early development are limited. This study aimed to investigate the adverse effects of MPs on bone in young rats and the potential mechanism. METHODS: Three-week-old female rats were orally administered MPs for 28 days, and endoplasmic reticulum (ER) stress inhibitor salubrinal (SAL) and ER stress agonist tunicamycin (TM) were added to evaluate the effect of ER stress on toxicity of MPs. The indicators of growth and plasma markers of bone turnover were evaluated. Tibias were analyzed using micro-computed tomography (micro-CT). Histomorphological staining of growth plates was performed, and related gene expression of growth plate chondrocytes was tested. RESULTS: After exposure of MPs, the rats had decreased growth, shortened tibial length, and altered blood calcium and phosphorus metabolism. Trabecular bone was sparse according to micro-CT inspection. In the growth plate, the thickness of proliferative zone substantial reduced while the thickness of hypertrophic zone increased significantly, and the chondrocytes were scarce and irregularly arranged according to tibial histological staining. The transcription of the ER stress-related genes BIP, PERK, ATF4, and CHOP dramatically increased, and the transcription factors involved in chondrocyte proliferation, differentiation, apoptosis, and matrix secretion were aberrant according to RT-qPCR and western blotting. Moreover, the addition of TM showed higher percentage of chondrocyte death. Administration of SAL alleviated all of the MPs-induced symptoms. CONCLUSION: These results indicated that MPs could induce growth retardation and longitudinal bone damage in early development. The toxicity of MPs may attribute to induced ER stress and impaired essential processes of the endochondral ossification after MPs exposure.

Reverse Osmosis with Intermediate Chemical Demineralization: Scale Inhibitor Selection, Degradation, and Seeded Precipitation.

Two-stage reverse osmosis (RO) processes with intermediate concentrate demineralization (ICD) provide an efficient strategy to treat brines with high CaSO4 contents and reduce concentrate discharge. In this paper, an SRO concentrate is treated using ICD to remove CaSO4 and then mixed with a PRO concentrate for further desalination in SRO, thereby reducing the discharge of the concentrate. We investigate the selection and degradation of scale inhibitors, as well as seeded precipitation in the two-stage RO process with ICD, to achieve a high water recovery rate. A scale inhibitor is added to restrain CaSO4 crystallization on the membrane surface, and the optimized scale inhibitor, RO-400, is found to inhibit calcium sulfate scaling effectively across a wide range of the saturation index of gypsum (SIg) from 2.3 to 6. Under the optimized parameters of 40 W UV light and 70 mg/L H2O2, UV/H2O2 can degrade RO-400 completely in 15 min to destroy the scale inhibitor in the SRO concentrate. After scale inhibitor degradation, the SRO concentrate is desaturated by seeded precipitation, and the reaction degree of CaSO4 reaches 97.12%, leading to a concentrate with a low SIg (1.07) for cyclic desalination. Three UVD-GSP cycle tests show that the reused gypsum seeds can also ensure the effect of the CaSO4 precipitation process. This paper provides a combined UVD-GSP strategy in two-stage RO processes to improve the water recovery rate for CaSO4-contained concentrate.

The emergence of influenza B as a major respiratory pathogen in the absence of COVID-19 during the 2021-2022 flu season in China.

BACKGROUND: The emergence of COVID-19 and the implementation of preventive measures and behavioral changes have led to a significant decrease in the prevalence of other respiratory viruses. However, the manner in which seasonal viruses will reemerge in the absence of COVID-19-related restrictions remains unknown. METHODS: Patients presenting with influenza-like illness in two hospitals in Beijing were subjected to testing for COVID-19, influenza A, and influenza B to determine the causative agent for viral infections. The prevalence of influenza B across China was confirmed using data from the Centers for Disease Control, China (China CDC). Clinical characteristics, laboratory findings, imaging results, and mortality data were collected for a cohort of 70 hospitalized patients with confirmed influenza B from 9 hospitals across China. RESULTS: Starting from October 2021, a substantial increase in the number of patients visiting the designated fever clinics in Beijing was observed, with this trend continuing until January 2022. COVID-19 tests conducted on these patients yielded negative results, while the positivity rate for influenza rose from approximately 8% in October 2021 to over 40% by late January 2022. The cases started to decline after this peak. Data from China CDC confirmed that influenza B is a major pathogen during the season. Sequencing of the viral strain revealed the presence of the Victoria-like lineage of the influenza B strain, with minor variations from the Florida/39/2018 strain. Analysis of the hospitalized patients' characteristics indicated that severe cases were relatively more prevalent among younger individuals, with an average age of 40.9 ± 24.1 years. Among the seven patients who succumbed to influenza, the average age was 30 ± 30.1 years. These patients exhibited secondary infections involving either bacterial or fungal pathogens and displayed elevated levels of cell death markers (such as LDH) and coagulation pathway markers (D-dimer). CONCLUSION: Influenza B represents a significant infection threat and can lead to substantial morbidity and mortality, particularly among young patients. To mitigate morbidity and mortality rates, it is imperative to implement appropriate vaccination and other preventive strategies.

Analysis of multidrug-resistant determinants of clinically isolated Acinetobacter baumannii CYZ via whole genome sequencing.

Acinetobacter baumannii is a multidrug-resistant coccobacillus responsible for severe nosocomial infectious diseases. This study mainly focuses on investigating the antimicrobial resistance features of a clinically isolated strain (A. baumannii CYZ) using the PacBio Sequel II sequencing platform. The chromosomal size of A. baumannii CYZ is 3,960,760 bp, which contains a total of 3803 genes with a G + C content of 39.06%. Functional analysis performed using the Clusters of Orthologous Groups of Proteins (COGs), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, as well as the Comprehensive Antibiotic Resistance Database (CARD) revealed a complicated set of antimicrobial resistance determinants in the genome of A. baumannii CYZ, which were mainly classified into multidrug efflux pumps and transport systems, ß-lactamase relative and penicillin-binding proteins, aminoglycoside modification enzymes, alternation of antibiotic target sites, lipopolysaccharide relative, and other mechanisms. A total of 35 antibiotics were tested for the antimicrobial susceptibility of A. baumannii CYZ, and the organism exhibited a stronger antimicrobial resistance ability. The phylogenetic relationship indicated that A. baumannii CYZ has high homology with A. baumannii ATCC 17978; however, the former also exhibited its specific genome characteristics. Our research results give insight into the genetic antimicrobial-resistant features of A. baumannii CYZ as well as provide a genetic basis for the further study of the phenotype.

Therapeutic keratoplasty for severe Acanthamoeba keratitis: risk factors, clinical features, and outcomes of postoperative recurrence.

PURPOSE: To investigate the effect of therapeutic keratoplasty (TKP) in patients with severe Acanthamoeba keratitis (AK) and to analyse the clinical features and risk factors for recurrence. METHODS: Clinical data of patients with severe AK treated with lamellar keratoplasty (LK) or penetrating keratoplasty (PK) due to ineffective drug therapy were analysed in this retrospective study. The effects of keratoplasty, clinical features, and risk factors for recurrence were analysed. RESULTS: The cohort comprised of 58 patients (59 eyes). Of these, 36 eyes were treated with PK and 23 were treated with LK. The probabilities of successful globe salvage were 91.7% and 91.3%, respectively. The final visual acuity (VA) was ≥ 20/60 in 14 eyes (38.9%) that underwent PK and 15 eyes (65.2%) that underwent LK. Postoperative recurrence of Acanthamoeba infection was detected in 10 eyes; 6 eyes (16.7%) showed recurrence after PK, and 4 eyes (17.4%) showed recurrence after LK. Recurrence occurred between 3 and 80 days (median, 14.5 days) after the operation. The risk factors for recurrence after LK were topical corticosteroid use before diagnosis (p = 0.040) and hypopyon (p = 0.009), while those after PK were topical corticosteroid use before diagnosis (p = 0.045). Clinical manifestations of postoperative recurrence include greyish-white infiltration of the recipient bed, anterior chamber inflammation, graft oedema, and keratic precipitate. CONCLUSION: TKP is a treatment option for severe AK that responds poorly to antiamoebic therapy (AAT), although Acanthamoeba infection may relapse, and the visual prognosis is guarded. Topical corticosteroid use before AAT and hypopyon is the two risk factors for recurrence.

Significance of platelets in the early warning of new-onset AKI in the ICU by using supervise learning: a retrospective analysis.

OBJECTIVE: To explore a machine learning model for the early prediction of acute kidney injury (AKI) and to screen the related factors affecting new-onset AKI in the ICU. METHODS: A retrospective analysis was performed used the MIMIC-III data source. New onset of AKI defined based on the serum creatinine changed. We included 19 variables for AKI assessment using four machine learning models: support vector machines, logistic regression, and random forest. and XGBoost, using accuracy, specificity, precision, recall, F1 score, and AUROC (area under the ROC curve) to evaluate model performance. The four models predicted new-onset AKI 3-6-9-12 h ahead. The SHapley Additive exPlanation (SHAP) value is used to evaluate the feature importance of the model. RESULTS: We finally respectively extracted 1130 AKI patients and non-AKI patients from the MIMIC-III database. With the extension of the early warning time, the prediction performance of each model showed a downward trend, but the relative performance was consistent. The prediction performance comparison of the four models showed that the XGBoost model performed the best in all evaluation indicators in all the time point at new-onset AKI 3-6-9-12 h ahead (accuracy 0.809 vs 0.78 vs 0.744 vs 0.741, specificity 0.856 vs 0.826 vs 0.797 vs 0.787, precision 0.842 vs 0.81 vs 0.775 vs 0.766, recall 0.759 vs 0.734 vs 0.692 vs 0.694, Fl score 0.799 vs 0.769 vs 0.731 vs 0.729, AUROC 0.892 vs 0.857 vs 0.827 vs 0.818). In the prediction of AKI 6, 9 and 12 h ahead, the importance of creatinine, platelets, and height was the most important based on SHapley. CONCLUSIONS: The machine learning model described in this study can predict AKI 3-6-9-12 h before the new-onset of AKI in ICU. In particular, platelet plays an important role.

The new-onset of AKI in ICU is a common and important problem, which early be identified the risk of AKI can improve patients' outcomes.We explored MIMIC-III and determined the exact time point of occurrence of AKI as the basis for the new-onset of AKI in ICU.XGBoost model performed the best prediction in all the time point at new-onset AKI 3­6­9­12 h ahead.For patients with the new-onset of AKI in ICU, platelets become an important factor associated with AKI.

[Modeling the noninvasive bi-level positive airway pressure ventilation therapy system and simulated application].

Without artificial airway though oral, nasal or airway incision, the bi-level positive airway pressure (Bi-PAP) has been widely employed for respiratory patients. In an effort to investigate the therapeutic effects and measures for the respiratory patients under the noninvasive Bi-PAP ventilation, a therapy system model was designed for virtual ventilation experiments. In this system model, it includes a sub-model of noninvasive Bi-PAP respirator, a sub-model of respiratory patient, and a sub-model of the breath circuit and mask. And based on the Matlab Simulink, a simulation platform for the noninvasive Bi-PAP therapy system was developed to conduct the virtual experiments in simulated respiratory patient with no spontaneous breathing (NSB), chronic obstructive pulmonary disease (COPD) and acute respiratory distress syndrome (ARDS). The simulated outputs such as the respiratory flows, pressures, volumes, etc, were collected and compared to the outputs which were obtained in the physical experiments with the active servo lung. By statistically analyzed with SPSS, the results demonstrated that there was no significant difference ( P > 0.1) and was in high similarity ( R > 0.7) between the data collected in simulations and physical experiments. The therapy system model of noninvasive Bi-PAP is probably applied for simulating the practical clinical experiment, and maybe conveniently applied to study the technology of noninvasive Bi-PAP for clinicians.

Hyperglycemia induces corneal endothelial dysfunction through attenuating mitophagy.

Hyperglycemia increases the risk of corneal endothelial dysfunction, resulting in damage to corneal endothelial structure and function. However, the effect and mechanism of hyperglycemia-induced corneal endothelial damage remain elusive. In this study, we demonstrated that hyperglycemia reduced the expression of pump-related protein Na+/K+ ATPase and barrier-related protein ZO-1. Moreover, we found hyperglycemia caused abnormal changes of morphological mitochondria and dynamics in vitro. In addition, the decreased levels of mitophagy were further confirmed Western blotting and LC3B-Mitotracker Immunofluorescence. Exogenous application of mitophagy agonist carbonyl cyanide m-chlorophenyl hydrazine (CCCP) increases the expression of Na+/K+ ATPase and ZO-1 in corneal endothelial cells through up-regulated mitophagy in vitro. In addition, CCCP effectively reverses the phenomenon of corneal opacity and increased corneal thickness in diabetic mice. Therefore, our demonstrated the novel function of mitophagy in the pathogenesis of diabetic cornea endothelial dysfunction, and provide potential approach for treating diabetic corneal endothelial dysfunction.

Effect of invasive mechanical ventilation on the diversity of the pulmonary microbiota.

Pulmonary microbial diversity may be influenced by biotic or abiotic conditions (e.g., disease, smoking, invasive mechanical ventilation (MV), etc.). Specially, invasive MV may trigger structural and physiological changes in both tissue and microbiota of lung, due to gastric and oral microaspiration, altered body posture, high O2 inhalation-induced O2 toxicity in hypoxemic patients, impaired airway clearance and ventilator-induced lung injury (VILI), which in turn reduce the diversity of the pulmonary microbiota and may ultimately lead to poor prognosis. Furthermore, changes in (local) O2 concentration can reduce the diversity of the pulmonary microbiota by affecting the local immune microenvironment of lung. In conclusion, systematic literature studies have found that invasive MV reduces pulmonary microbiota diversity, and future rational regulation of pulmonary microbiota diversity by existing or novel clinical tools (e.g., lung probiotics, drugs) may improve the prognosis of invasive MV treatment and lead to more effective treatment of lung diseases with precision.

Tannin coordinated nanozyme composite-based hybrid hydrogel eye drops for prophylactic treatment of multidrug-resistant Pseudomonas aeruginosa keratitis.

Pseudomonas aeruginosa infection is a severe acute suppurative ulcer that engulfs virtually the entire tissue in a short period and leads to devastating destruction. Antibiotic therapy is a common approach for the prophylaxis and treatment of P. aeruginosa infection. However, it is often associated with serious side effects, complications, and multidrug resistance. Therefore, it has been a long-standing challenge to explore safe and effective methods for controlling P. aeruginosa infection. Herein, tannin-coordinated nanozyme composite-based hybrid hydrogels (TCNH) are developed and characterized for the prophylactic treatment of P. aeruginosa and multidrug-resistant P. aeruginosa infections using mouse keratitis as the animal model. The TCNH eye drops are constructed by photoinitiated free radical polymerization of acetylated gelatin solution containing self-synthesized tannin-coordinated Co3O4/Ag nanozyme composite. The as-prepared TCNH displays good dispersibility, peroxidase-like activity and in vitro/in vivo biocompatibility. The nanozyme composite in TCNH seems to penetrate the interior of bacteria and exhibited significant broad-spectrum antibacterial activity owing to its intrinsic and nanozymic catalytic properties. Furthermore, TCNH eye drops can be successfully applied to treat P. aeruginosa and multidrug-resistant P. aeruginosa keratitis. The findings of this study reveal the potential of tannin-coordinated nanozyme composite-based hybrid hydrogel eye drops for treating infectious diseases.