Intelligent diagnosis of the severity of disease conditions in COVID-19 patients based on the LASSO method.

Purpose: The purpose of this study is to develop an intelligent diagnosis model based on the LASSO method to predict the severity of COVID-19 patients. Methods: The study uses the clinical data of 500 COVID-19 patients from a designated hospital in Guangzhou, China, and selects eight features, including age, sex, dyspnea, comorbidity, complication, lymphocytes (LYM), CRP, and lung injury score, as the most important predictors of COVID-19 severity. The study applies the LASSO method to perform feature selection and regularization, and compares the LASSO method with other machine learning methods, such as ridge regression, support vector machine, and random forest. Results: The study finds that the ridge regression model has the best performance among the four models, with an AUROC of 0.92 in the internal validation and 0.91 in the external validation. Conclusion: The study provides a simple, robust, and interpretable model for the intelligent diagnosis of COVID-19 severity, and a convenient and practical tool for the public and the health care workers to assess COVID-19 severity. However, the study also has some limitations and directions for future research, such as the need for more data from different sources and settings, and from prospective, longitudinal, multi-class classification models. The study hopes to contribute to the prevention and control of COVID-19, and to the improvement of the diagnosis and treatment of COVID-19 patients.

Two-dimensional photonic crystals as selective filters for thermophotovoltaic applications.

The optical properties and performance of the two-dimensional photonic crystal (2D PhC) filters at normal incidence were simulated, and the best geometric parameters were obtained with the help of a global optimization program. The honeycomb structure has better performance, including high in-band transmittance, high out-band reflectance, and low parasitic absorption. The power density performance and conversion efficiency can reach 80.6% and 62.5%. Furthermore, the deeper cavity structure and multi-layer structure were designed to improve the performance of the filter. The deeper one can reduce the influence of transmission diffraction, increases the power density performance and conversion efficiency. The multi-layer structure reduces the parasitic absorption significantly and increases the conversion efficiency to 65.5%. These filters have both high efficiency and high power density, avoid the challenge of high-temperature stability faced by emitters, also easier and cheaper to fabricate compared to the 2D PhC emitters. These results suggest that the 2D PhC filters can be used in thermophotovoltaic systems for long-duration missions to improve the conversion efficiency.

Effects of dexmedetomidine administration on outcomes in critically ill patients with acute kidney injury: A propensity score-matching analysis.

PURPOSE: To evaluate the effects of dexmedetomidine (DEX) on outcomes of critically ill patients with acute kidney injury (AKI). MATERIALS AND METHODS: Data were extracted from the Medical Information Mart for Intensive Care III database (MIMIC III). Propensity score matching (PSM) analysis (1 : 3), Cox proportional hazards model, linear regression and logistic regression model were used to assess the effect of DEX on clinical outcomes. RESULTS: After PSM, 324 pairs of patients were matched between the patients with DEX administration and those without. DEX administration was associated with decreased in-hospital mortality (hazard ratio (HR) 0.287; 95% CI 0.151 - 0.542; p < 0.001) and 90-day mortality (HR 0.344; 95% CI 0.221 - 0.534; p < 0.001), and it was also associated with reduced length of stay (LOS) in ICU (4.54 (3.13,7.72) vs. 5.24 (3.15,10.91), p < 0.001) and LOS in hospital (11.63 (8.02,16.79) vs 12.09 (7.83,20.44), p = 0.002). Subgroup analysis showed that the above associations existed only in the mild and moderate AKI subgroups, but not in the severe AKI subgroup. Nevertheless, DEX administration was not associated with recovery of renal function (HR 1.199; 95% CI 0.851 - 1.688; p = 0.300). CONCLUSION: DEX administration improved outcomes in critically ill patients with mild and moderate AKI and could be a good choice of sedation.

CLINICAL AND PROGNOSTIC FEATURES OF CHRONIC CRITICAL ILLNESS/PERSISTENT INFLAMMATION IMMUNOSUPPRESSION AND CATABOLISM PATIENTS: A PROSPECTIVE OBSERVATIONAL CLINICAL STUDY.

ABSTRACT: Objective: The aims of this study were to investigate and compare the clinical features and prognosis of chronic critical illness (CCI)/persistent inflammation immunosuppression and catabolism (PICS). Methods: This is a prospective observational clinical study. During this study period, we collect intensive care unit patients' data from Suzhou Municipal Hospital and Suzhou Ninth People's Hospital. All patients older than 18 years were included, and according to the corresponding exclusion and diagnostic criteria, they were divided into four groups: PICS group, CCI group, CCI and PICS group (CCI + PICS), and neither CCI nor PICS group (NCCI + NPICS) and collected and recorded age, sex, hospital time, hospital diagnosis, Acute Physiology and Chronic Health Evaluation II score, Sequential Organ Failure Assessment score, C-reactive protein, absolute value lymphocyte count, serum albumin, white blood cell count, absolute value neutrophil count, secondary infection, and 28-day case fatality rate separately. Results: A total of 687 patients were admitted to the intensive care unit during the study period. The hospitalization time less than 14 days were excluded, and 168 patients were eventually included. There are 17 in the PICS group, 71 in the CCI group, 50 in the CCI + PICS group, and 30 in the NCCI + NPICS group. Baseline characteristics showed statistically significant differences in Sequential Organ Failure Assessment, length of hospital stay, and 28-day mortality among four groups. Baseline main indicator and multiple comparisons showed that the CCI + PICS group had longer hospital stay, worse prognosis, and more adverse outcomes. Multivariate analysis showed that final age, C-reactive protein on days 14 and 21, and serum albumin on days 1 and 21 had an impact on the prognosis ( P < 0.05). Conclusion: The clinical prognosis of the four groups decreased in order of NCCI + NPICS, CCI, PICS, and CCI + PICS. Our finding of clinically isolated PICS may indicate that PICS acts as an inducement or independent factor to worsen the prognosis of CCI.

Dexmedetomidine Alleviates Ischemia/Reperfusion-Associated Acute Kidney Injury by Enhancing Autophagic Activity via the α2-AR/AMPK/mTOR Pathway.

BACKGROUND: Dexmedetomidine (DEX) reportedly protects against ischemia-reperfusion (I/R) injury and associated damage to the kidneys, but the underlying mechanisms have yet to be established. METHODS: Unilateral nephrectomy was performed in Wistar rats, and the remaining kidney was clamped for 1 h prior to reperfusion to establish an experimental model system. These animals were then randomized into Sham, DEX + Sham, DEX + I/R, ATI (Altepamizole, α2-adrenergic receptor inhibitor) + DEX + I/R, and 3-MA (3-methyladenine, autophagy inhibitor) + DEX + I/R groups. Serum renal function biomarkers, acute kidney injury (AKI) histopathological scores, serum inflammatory factors, redox biomarkers, markers of autophagic flux, and autophagosome numbers were assessed. Levels of proteins related to the autophagic pathway, including mTOR and AMPK, were also analyzed. RESULTS: Serum creatinine and urea nitrogen levels in the I/R group were significantly elevated over those in sham control rats, as were AKI scores, serum inflammatory cytokine concentrations (IL-6, IL-1ß, and TNF-α), and serum levels of the oxidative stress biomarker malondialdehyde (MDA). All of these parameters were significantly reduced in the DEX + I/R group relative to I/R model rats. I/R group rats also exhibited significant decreases in renal levels of autophagic flux-related biomarkers and autophagosome numbers relative to sham controls, while DEX administration partially restored normal autophagic flux in these rats. Acute I/R also suppress the expression of AMPK in the kidney while increasing mTOR expression, and DEX reversed these effects. The beneficial impact of DEX on I/R-associated AKI was ablated by ATI or 3-MA administration. CONCLUSIONS: These analyses provide strong evidence for the ability of DEX to protect against I/R-associated AKI via the α2-AR/AMPK/mTOR pathway-mediated enhancement of autophagic activity.

Gene identification and tissue expression analysis inform the floral organization and color in the basal angiosperm Magnolia polytepala (Magnoliaceae).

MAIN CONCLUSION: In Magnolia polytepala, the formation of floral organization and color was attributed to tissue-dependent differential expression levels of MADS-box genes and anthocyanin biosynthetic genes. In angiosperms, the diversity of floral morphology and organization suggests its value in exploring plant evolution. Magnolia polytepala, an endemic basal angiosperm species in China, possesses three green sepal-like tepals in the outermost whorl and pink petal-like tepals in the inner three whorls, forming unique floral morphology and organization. However, we know little about its underlying molecular regulatory mechanism. Here, we first reported the full-length transcriptome of M. polytepala using PacBio sequencing. A total of 16 MADS-box transcripts were obtained from the transcriptome data, including floral homeotic genes (e.g., MpAPETALA3) and other non-floral homeotic genes (MpAGL6, etc.). Phylogenetic analysis and spatial expression pattern reflected their putative biological function as their homologues in Arabidopsis. In addition, nine structural genes involved in anthocyanin biosynthesis pathway had been screened out, and tepal color difference was significantly associated with their tissue-dependent differential expression levels. This study provides a relatively comprehensive investigation of the MADS-box family and anthocyanin biosynthetic genes in M. polytepala, and will facilitate our understanding of the regulatory mechanism underlying floral organization and color in basal angiosperms.

Identifying potential prognosis markers in hepatocellular carcinoma via integrated bioinformatics analysis and biological experiments.

Background: Hepatocellular carcinoma is one kind of clinical common malignant tumor with a poor prognosis, and its pathogenesis remains to be clarified urgently. This study was performed to elucidate key genes involving HCC by bioinformatics analysis and experimental evaluation. Methods: We identified common differentially expressed genes (DEGs) based on gene expression profile data of GSE60502 and GSE84402 from the Gene Expression Omnibus (GEO) database. Gene Ontology enrichment analysis (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, REACTOME pathway enrichment analysis, and Gene Set Enrichment Analysis (GSEA) were used to analyze functions of these genes. The protein-protein interaction (PPI) network was constructed using Cytoscape software based on the STRING database, and Molecular Complex Detection (MCODE) was used to pick out two significant modules. Hub genes, screened by the CytoHubba plug-in, were validated by Gene Expression Profiling Interactive Analysis (GEPIA) and the Human Protein Atlas (HPA) database. Then, the correlation between hub genes expression and immune cell infiltration was evaluated by Tumor IMmune Estimation Resource (TIMER) database, and the prognostic values were analyzed by Kaplan-Meier plotter. Finally, biological experiments were performed to illustrate the functions of RRM2. Results: Through integrated bioinformatics analysis, we found that the upregulated DEGs were related to cell cycle and cell division, while the downregulated DEGs were associated with various metabolic processes and complement cascade. RRM2, MAD2L1, MELK, NCAPG, and ASPM, selected as hub genes, were all correlated with poor overall prognosis in HCC. The novel RRM2 inhibitor osalmid had anti-tumor activity, including inhibiting proliferation and migration, promoting cell apoptosis, blocking cell cycle, and inducing DNA damage of HCC cells. Conclusion: The critical pathways and hub genes in HCC progression were screened out, and targeting RRM2 contributed to developing new therapeutic strategies for HCC.

A novel computer vision-based assessment of neutrophil chemotaxis in patients with severe infection.

OBJECTIVES: To evaluate the value of chemotactic function of neutrophils in patients with severe infections. METHODS: A computer vision-based cellular chemotaxis analysis platform was established for the dynamic assessment of neutrophil chemotaxis. Fifty-three patients in the intensive care unit were eligible for the study. In parallel, 142 healthy volunteers were recruited to detect and establish the normal values for chemotactic function. Four chemotactic function indicators were determined-chemotaxis distance (CD), chemotaxis cell ratio (CCR), chemotaxis index (CI) and maximum speed of chemotaxis (Vmax). The chemotaxis function scores (CFS) were calculated for further correlation analysis with clinical data. RESULTS: The normal ranges of indicators were established as CD ≥ 1755.85 µm, CCR ≥ 3.34%, CI ≥ 39.63, Vmax ≥ 14.63 µm min-1 and CFS ≥ 15. We found that the chemotactic function of neutrophils in patients suffering from infections was significantly impaired. The mean values of CD, CCR, CI, Vmax and CFS were 1452.8 µm (P < 0.0001), 3.1% (P < 0.0001), 34.5 (P < 0.0001), 12.2 µm min-1 (P < 0.0001) and 9 (P < 0.0001), respectively. CD and CFS were significantly negatively correlated with the APACHE II score (rCD = -0.55, rCFS = -0.39), SOFA score (rCD = -0.68, rCFS = -0.56), procalcitonin concentration (rCD = -0.60, rCFS = -0.5) and the expression of P2RX1 (rCD = -0.76, rCFS = -0.56), respectively. CONCLUSIONS: CD, CCR, CI and Vmax can well reflect the neutrophil chemotactic function in patients with severe infections. CFS systematically indicated neutrophil function and has promising clinical application prospects.

Downregulation of IRF2 Alleviates Sepsis-Related Acute Kidney Injury in vitro and in vivo.

OBJECTIVE: We investigated the roles and mechanisms of IRF2 in sepsis-related acute kidney injury (S-AKI) in a lipopolysaccharide (LPS)-induced HK-2 cell line and caecal ligation and puncture (CLP)-induced IRF2-/- mouse model. METHODS: Quantitative real-time polymerase chain reaction assay was used to detect IRF2 in the serum of S-AKI patients and LPS-induced HK-2 cells. Cell proliferation, death, and apoptosis were analysed by CCK-8, lactate dehydrogenase release, and flow cytometry assays, respectively. The levels of interleukin (IL)-1ß, IL-18, IL-6, tumour necrosis factor (TNF)-α, non-canonical inflammasomes, including caspase-4 and gasdermin-D (GSDMD), and canonical inflammasomes, such as caspase-1, NLR family pyrin domain containing 3 (NLRP3), and apoptosis-associated speck-like protein (ASC) in S-AKI cells or animal models were analysed by enzyme-linked immunosorbent assay or Western blotting. RESULTS: IRF2 was upregulated in the serum of S-AKI patients and LPS-induced HK-2 cells. IRF2 downregulation promoted cell proliferation and inhibited cell death and apoptosis, respectively. IRF2 inhibition reduced the levels of IL-1ß, IL-18, IL-6, and TNF-α in S-AKI cells and animal models. IRF2 knockdown inhibited LPS-treated HK-2 cell pyroptosis by decreasing the expression of caspase-4 and GSDMD, instead of affecting caspase-1, NLRP3, and ASC. An elevated survival rate and alleviated pathological features and scores were observed in the CLP-induced IRF2-/- animal models. IRF2 deficiency also suppressed inflammation and pyroptosis by inhibiting non-canonical inflammasomes as indicated by the decreased expression of caspase-11 and GSDMD. CONCLUSION: Our findings suggest that IRF2 downregulation protects against S-AKI in vitro and in vivo.

miR-19a-3p targets cell adhersion molecule 2 to inhibit proliferation and metastasis of renal carcinoma 7867-O cells via blockingAKT pathway / 中国肿瘤生物治疗杂志

@# Objective: To explore the mechanism of miR-19a-3p regulating cell adhesion molecule 2 (CADM2) to inhibit the proliferation and metastasis of renal carcinoma cells via the AKT signaling pathway. Methods: A total of 42 patients with renal cancer admitted to Department of Nephrology, the First Affiliated Hospital of Suzhou University from April 2012 to November 2017 were enrolled to collect samples of surgically resected renal carcinoma tissues and paracancerous tissues. Expression of miR-19a-3p was detected in renal carcinoma tissues and 4 types of renal carcinoma cell lines such as 786-O by quantitative Real-time polymerase chain reaction (qPCR). The effects of miR-19a-3p knockdown on proliferation, invasion and epithelial mesenchymal transition (EMT) of renal carcinoma 786-O cells were evaluated by CCK-8 assay, Transwell assay and immunofluorescence, respectively. Subsequently, dual luciferase reporter assay was used to verify whether CADM2 was a target gene of miR-19a-3p. Furthermore, Wb was applied to detect the regulatory effect of miR-19a-3p onAKT signaling pathway through CADM2. Results: miR-19a-3p expression was significantly up-regulated in renal carcinoma tissues and cell lines (all P<0.01). Knockdown of miR-19a-3p could inhibit proliferation, invasion and EMT process of 786-O cells; furthermore, the results indicated that CADM2 was a direct target of miR-19a-3p and its expression was down-regulated (P <0.05 or P<0.01). Additionally, knockdown of miR-19a-3p obviously suppressed proliferation, migration and EMT process of 786-O cells via up-regulating CADM2 and blocking AKT pathway (all P<0.05 or P<0.01), thus alleviating the occurrence and development of renal carcinoma. Conclusion: The study demonstrates that miR-19a-3p has a high expression level in renal carcinoma tissues; knockdown of miR-19a-3p could significantly inhibit the proliferation, migration and EMT process of renal carcinoma tissues, and its mechanism may be associated with miR-19a-3p/CADM2/AKT axis.

Extracorporeal membrane oxygenation combined with continuous renal replacement therapy in cutaneous burn and inhalation injury caused by hydrofluoric acid and nitric acid.

RATIONALE: Hydrofluoric acid (HF) is a highly corrosive agent and can cause corrosive burns. HF can penetrate deeply into tissues through intact skin and the lipid barrier, leading to painful liquefactive necrosis, and inducing hypocalcemia and hypomagnesemia. In this study, we hypothesize that continuous renal replacement therapy (CRRT) may be beneficial in addressing hemodynamic instability in cases of HF poisoning. PATIENT CONCERNS: A 25-year-old man fell into an electroplating pool containing 10% HF and 50% nitric acid. DIAGNOSES: He had severe cutaneous injuries involving approximately 60% of his total body surface area including the head, face, neck, right upper arm, right hand, trunk, perineum, and both lower limbs and feet. Examination at admission showed the following electrolyte concentrations: ionic calcium 0.192 mmol/L, total calcium 0.72 mmol/L, magnesium 0.4 mmol/L, potassium 5.49 mmol/L, and sodium 136.8 mmol/L. INTERVENTIONS: An initial 20 mL intravenous bolus of 10% calcium gluconate was followed by a continuous infusion at 6 g/h plus continuous intravenous drip 25% magnesium sulfate at 1.5 g/h. Continuous cardiac monitoring was performed in the intensive care unit. Extracorporeal membrane oxygenation (ECMO) was used to improve oxygenation function at 38 hours post exposure. Antibiotic therapy using imipenem/cilastin plus vancomycin was required. OUTCOMES: After treatment for 12 hours, electrolyte concentrations returned to normal. On day 11, the hemodynamic parameters were stable and oxygenation function had improved. On day 26, the patient was weaned off CRRT. One month later, the patient twice received skin grafting, then was discharged from the hospital without pulmonary, cardiac, or neurological complications 3 months later. LESSONS: The present case study demonstrates that CRRT may be an effective and potentially lifesaving therapy after severe exposure to HF. Prolonged hemodialysis is recommended to remove delayed release fluoride ions to avoid delayed systemic injury. When conventional therapy can not improve oxygenation and/or carbon dioxide retention, ECMO should be performed as soon as possible.