A novel compound alleviates oxidative stress via PKA/CREB1-mediated DJ-1 upregulation.

Oxidative stress is one of the major culprits causing dopaminergic neuron loss in Parkinson's disease (PD). DJ-1 is a protein with multiple actions against oxidative stress, apoptosis, neuroinflammation, etc. DJ-1 expression is decreased in sporadic PD, therefore increasing DJ-1 expression might be beneficial in PD treatment. However, drugs known to upregulate DJ-1 are still lacking. In this study, we identified a novel DJ-1-elevating compound called ChemJ through luciferase assay-based high-throughput compound screening in SH-SY5Y cells and confirmed that ChemJ upregulated DJ-1 in SH-SY5Y cell line and primary cortical neurons. DJ-1 upregulation by ChemJ alleviated MPP+-induced oxidative stress. In exploring the underlying mechanisms, we found that the transcription factor CREB1 bound to DJ-1 promoter and positively regulated its expression under both unstressed and 1-methyl-4-phenylpyridinium-induced oxidative stress conditions and that ChemJ promoted DJ-1 expression via activating PKA/CREB1 pathway in SH-SY5Y cells. Our results demonstrated that ChemJ alleviated the MPP+-induced oxidative stress through a PKA/CREB1-mediated regulation of DJ-1 expression, thus offering a novel and promising avenue for PD treatment.

Summary of best evidence for prevention and management of frailty.

BACKGROUND: Frailty in older people can seriously affect their quality of life and increase the demand for long-term care and health care expenses. Aims of this study are to provide an evidence-based basis for clinical practice of frailty in older people by systematically searching for the best current evidence on interventions for the prevention and management of frailty. METHODS: According to the '6S' evidence resource model, evidence retrieval is searched from the top-down and collected relevant guidelines, best practices, evidence summaries, systematic reviews and expert consensus. The retrieval time limit was from the database establishment to 20 March 2023. Two reviewers independently screened and evaluated the literature, and then extracted and summarised the evidence according to the JBI grading of evidence and recommendation system. RESULTS: A total of 44 publications were finally included, including 12 guidelines, 5 best practices, 4 expert consensus, 5 evidence summaries and 18 systematic reviews. Through the induction and integration of the evidence, the evidence was finally summarised from eight aspects: frailty screening, frailty assessment, exercise intervention, nutrition intervention, multi-domain intervention, drug administration, social support and health education, and 43 best evidences were formed. CONCLUSIONS: This study summarised the best evidence for the prevention and management of frailty from eight aspects, which can provide guidance for clinical or community medical staff to develop and apply frailty intervention and practice programmes for older people and improved the clinical outcome and quality of life of older people.

SHOOT MERISTEMLESS participates in the heterophylly of Hygrophila difformis (Acanthaceae).

In heterophyllous plants, leaf shape shows remarkable plasticity in response to environmental conditions. However, transgenic studies of heterophylly are lacking and the molecular mechanism remains unclear. Here, we cloned the KNOTTED1-LIKE HOMEOBOX family gene SHOOT MERISTEMLESS (STM) from the heterophyllous plant Hygrophila difformis (Acanthaceae). We used molecular, morphogenetic, and biochemical tools to explore its functions in heterophylly. HdSTM was detected in different organs of H. difformis, and its expression changed with environmental conditions. Heterologous, ectopic expression of HdSTM in Arabidopsis (Arabidopsis thaliana) increased leaf complexity and CUP-SHAPED COTYLEDON (CUC) transcript levels. However, overexpression of HdSTM in H. difformis did not induce the drastic leaf change in the terrestrial condition. Overexpression of HdSTM in H. difformis induced quick leaf variations in submergence, while knockdown of HdSTM led to disturbed leaf development and weakened heterophylly in H. difformis. HdCUC3 had the same spatiotemporal expression pattern as HdSTM. Biochemical analysis revealed a physical interaction between HdSTM and HdCUC3. Our results provide genetic evidence that HdSTM is involved in regulating heterophylly in H. difformis.

Inhibition of ACSS2 attenuates alcoholic liver steatosis via epigenetically regulating de novo lipogenesis.

BACKGROUND AND AIMS: Steatosis is the early pathological change in alcohol-associated liver disease. However, its precise mechanism is still unclear. The present study is aimed to explore the role and mechanism of acetyl-CoA synthetase 2 (ACSS2) in acute alcohol-induced lipogenesis. METHODS: The increase in ACSS2 nuclear import and histone H3 acetylation were observed in mice after intraperitoneally injected with 2 g/kg ethanol or oral administration of 5 g/kg ethanol and also validated in hepatocytes stimulated with ethanol or acetate. The role of ACSS2 was further explored in liver-specific ACSS2 knockdown mice fed with ethanol-containing diet. RESULTS: Alcohol challenge induced hepatic lipid deposition and upregulated lipogenic genes in mice. It also promoted ACSS2 nuclear import and increased histone H3 acetylation. In hepatocytes, ethanol induced similar phenomena whereas ACSS2 knockdown blocked histone acetylation and lipogenic gene induction. P300/CBP associated factor (PCAF), but not general control nonderepressible 5, CREB-binding protein (CBP) and p300, facilitated H3K9 acetylation responding to ethanol challenge. CUT&RUN assay showed the enrichment of acetylated histone H3K9 surrounding Fasn and Acaca promoters. These results indicated that ethanol metabolism promoted ACSS2 nuclear import to support lipogenesis via H3K9 acetylation. In alcohol-feeding mice, liver-specific ACSS2 knockdown blocked the interaction between PCAF and H3K9 and suppressed lipogenic gene induction in the liver, demonstrating the critical role of ACSS2 in lipogenesis. CONCLUSIONS: Our study demonstrated that alcohol metabolism generated acetyl-CoA in the nucleus dependently on nuclear ACSS2, contributing to epigenetic regulation of lipogenesis in hepatic steatosis. Targeting ACSS2 may be a potential therapeutical strategy for acute alcoholic liver steatosis.

Phaco-goniosynechialysis versus phaco-trabeculectomy in patients with refractory primary angle-closure glaucoma: a comparative study.

PURPOSE: To compare the effects of phacoemulsification with intraocular lens implantation (phaco) combined with goniosynechialysis (phaco + GSL) versus phaco with trabeculectomy (phaco + trab) for the management of primary angle-closure glaucoma (PACG) refractory to peripheral anterior synechiae (PAS) of over 180°. METHODS: This retrospective study followed 77 eyes of 77 patients for at least 6 months. Intraocular pressure (IOP), best-corrected visual acuity (BCVA), number of glaucoma drugs, and PAS were recorded at the preoperative baseline and evaluated at each postoperative follow-up visit. The National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) was administered to patients enrolled in this study. Pearson's correlation analysis and multivariate linear analysis were performed to identify factors influencing changes in NEI VFQ-25 scores and to identify factors associated with increases in NEI VFQ-25 scores after the operation. RESULTS: In total, seventy-seven eyes were included (43 with phaco + GSL and 34 with phaco + trab). Comparing preoperative baseline and month 6 after surgery measurements revealed that both groups found significant improvements in IOP, PAS, BCVA and the number of glaucoma drugs (P < 0.05). Baseline NEI VFQ-25 scores were similar in the two groups, but there was a significant difference in postoperative NEI VFQ-25 scores (74.47 ± 10.39 in phaco + GSL vs. 69.57 ± 8.54 in phaco + trab, P = 0.048 < 0.05), and the phaco + GSL group had better scores at the time of the last follow-up. The change in preoperative scores and the number of glaucoma drugs was significantly correlated with postoperative scores in the phaco + GSL group. CONCLUSION: Phaco + GSL treatment is as safe and effective as phaco + trab for refractory PACG patients, and patients' subjective experience improved significantly after phaco + GSL surgery.

Pembrolizumab and Trastuzumab in High Tumor Mutational Burden and POLE-Mutated HER2-Positive Refractory Breast Cancer.

Metastatic breast cancer (mBC) is an incurable disease, and it is not sensitive to immunotherapy due to its low immunogenicity. Recently, inactivated DNA polymerase epsilon (POLE) mutations have been found to be associated with high tumor mutational burden (TMB), which is an effective immuno-oncology biomarker. Patients with POLE mutations with different types of cancer have properly responded to immunotherapy. We aimed to report the first case of programmed death-ligand 1 (PD-L1)-negative mBC presenting with high TMB and POLE mutations, in which a complete response to 5 cycles of chemotherapy and 1 year of pembrolizumab and trastuzumab was noted after failing several lines of HER2-targeted therapies. Our findings also suggest that biomarker-driven patient selection is highly significant for further clinical development of combination therapies via anti-HER2 plus immune-checkpoint inhibitors for HER2+ BC patients.

Identification and expression analysis of GARP superfamily genes in response to nitrogen and phosphorus stress in Spirodela polyrhiza.

BACKGROUND: GARP transcription factors perform critical roles in plant development and response to environmental stimulus, especially in the phosphorus (P) and nitrogen (N) sensing and uptake. Spirodela polyrhiza (giant duckweed) is widely used for phytoremediation and biomass production due to its rapid growth and efficient N and P removal capacities. However, there has not yet been a comprehensive analysis of the GRAP gene family in S. polyrhiza. RESULTS: We conducted a comprehensive study of GRAP superfamily genes in S. polyrhiza. First, we investigated 35 SpGARP genes which have been classified into three groups based on their gene structures, conserved motifs, and phylogenetic relationship. Then, we identified the duplication events, performed the synteny analysis, and calculated the Ka/Ks ratio in these SpGARP genes. The regulatory and co-expression networks of SpGARPs were further constructed using cis-acting element analysis and weighted correlation network analysis (WGCNA). Finally, the expression pattern of SpGARP genes were analyzed using RNA-seq data and qRT-PCR, and several NIGT1 transcription factors were found to be involved in both N and P starvation responses. CONCLUSIONS: The study provides insight into the evolution and function of GARP superfamily in S. polyrhiza, and lays the foundation for the further functional verification of SpGARP genes.

Giant dielectric response and relaxation behavior in (Tm + Ta) co-doped TiO2 ceramics.

Dielectric materials with huge dielectric constants are attracting attention due to the growing demand for microelectronics and high energy-storage devices. In this work, Tm + Ta co-doped TiO2 ceramics were prepared by a solid-state reaction (SSR) method, and the microstructure and dielectric behavior were investigated. A ultrahigh permittivity (εr ∼ 2.26 × 104) and very low loss (tan δ ∼ 0.011) are achieved at 1 kHz for (Tm0.5Ta0.5)0.01Ti0.99O2 ceramics. XPS analysis confirms that the high dielectric constant and low dielectric loss are attributed to the electron pinned defect dipole (EPDD) response formed by the coupling of Ti3+ and oxygen vacancies. In addition, impedance analysis and frequency dependent dielectric constant under a DC bias indicate that the presence of the internal barrier layer capacitance (IBLC) response and electrode response at low to medium frequencies (<106 Hz) also contribute significantly to the dielectric constant. The findings reported in this work provide valuable insights into the simultaneous realization of a low dielectric loss and high permittivity in Tm + Ta co-doped TiO2 ceramics and other related dielectric ceramics.

The value of cystatin C in predicting perioperative and long-term prognosis of renal transplantation.

This study aimed to evaluate the value of cystatin C (Cys C) in predicting the perioperative and long-term prognosis of renal transplantation (RT). The clinical data of 198 RT recipients were collected. Blood samples were obtained daily until 7 d after transplantation and then discharge day to determine the serum levels of Cys C. The receiver-operating characteristic (ROC) analysis and the area under the curve (AUC) were used to determine the diagnostic accuracy of Cys C for delayed graft function (DGF). The presence of shrunken pore syndrome (SPS) with a cystatin C-based estimate of glomerular filtration rate less than 70% of a creatinine-based estimate, was also evaluated as a prognostic factor for the development of DGF. The serum Cys C levels of patients with DGF were higher than those of the non-DGF group. Cys C showed a higher AUC (0.928) in the ROC analysis than did sCr (0.862). Compared to the non-SPS group, there were more patients diagnosed with SPS in the DGF group (p < .05). The follow-up data showed that patients diagnosed with SPS had higher levels of sCr and Cys C compared to other patients, suggesting a poor long-term prognosis. Our findings suggest that Cys C is a sensitive indicator of renal function during the perioperative period. Cys C at a concentration of 4.9 mg/L had the highest sum of sensitivity and specificity for prediction of DGF, with a sensitivity of 0.889 and a specificity of 0.8. SPS is associated with the development of DGF and the poor long-term prognosis of RT.

Al2O3 Grain Boundary Segregation in a Thermal Barrier Coating on a Ni-Based Superalloy.

The segregation of reactive elements (REs) along thermally grown oxide (TGO) grain boundaries has been associated to slower oxide growth kinetics and improved creep properties. However, the incorporation and diffusion of these elements into the TGO during oxidation of Ni alloys remains an open question. In this work, electron backscatter diffraction in transmission mode (t-EBSD) was used to investigate the microstructure of TGO within the thermal barrier coating on a Ni-based superalloy, and atom probe tomography (APT) was used to quantify the segregation behavior of REs to α-Al2O3 grain boundaries. Integrating the two techniques enables a higher level of site-specific analysis compared to the routine focused ion beam lift-out sample preparation method without t-EBSD. Needle-shaped APT specimens readily meet the thickness criterion for electron diffraction analysis. Transmission EBSD provides an immediate feedback on grain orientation and grain boundary location within the APT specimens to help target grain boundaries in the TGO. Segregation behavior of REs is discussed in terms of the grain boundary character and relative location in TGO.

Control of ice crystal nucleation and growth during the food freezing process.

Freezing can maintain a low-temperature environment inside food, reducing water activity and preventing microorganism growth. However, when ice crystals are large, present in high amounts, and/or irregularly distributed, irreversible damage to food can occur. Therefore, ice growth is a vital parameter that needs to be controlled during frozen food processing and storage. In this review, ice growth theory and control are described. Macroscopic heat and mass transfer processes, the relationship between the growth of ice crystals and macroscopic heat transfer factors, and nucleation theory are reviewed based on the reported theoretical and experimental approaches. The issues addressed include how heat transfer occurs inside samples, variations in thermal properties with temperature, boundary conditions, and the functional relationship between ice crystal growth and freezing parameters. Quick freezing (e.g., cryogenic freezing) and unavoidable temperature fluctuations (e.g., multiple freeze-thaw cycles) are both taken into consideration. The approaches for controlling ice crystal growth based on the ice morphology and content are discussed. The characteristics and initial mechanisms of ice growth inhibitors (e.g., antifreeze proteins (AFPs), polysaccharides, and phenols) and ice nucleation agents (INAs) are complex, especially when considering their molecular structures, the ice-binding interface, and the dose. Although the market share for nonthermal processing technology is low, there will be more work on freezing technologies and their theoretical basis. Superchilling technology (partial freezing) is also mentioned here.

LncRNA HOXA-AS2 regulates microglial polarization via recruitment of PRC2 and epigenetic modification of PGC-1α expression.

BACKGROUND: Microglia-mediated neuroinflammation plays an important role in Parkinson's disease (PD), and it exerts proinflammatory or anti-inflammatory effects depending on the M1/M2 polarization phenotype. Hence, promoting microglia toward the anti-inflammatory M2 phenotype is a potential therapeutic approach for PD. Long noncoding RNAs (lncRNAs) are crucial in the progression of neurodegenerative diseases, but little is known about their role in microglial polarization in PD. METHODS: In our study, we profiled the expression of lncRNAs in the peripheral blood mononuclear cells (PBMCs) of PD patients using a microarray. RT-qPCR was used to evaluate the lncRNA levels and mRNA levels of cytokines and microglial cell markers both in vitro and in vivo. RIP and ChIP assays were analyzed for the underlying mechanism of lncRNA regulating microglial polarization. RESULTS: We found that HOXA-AS2 was upregulated in the PBMCs of PD patients and negatively associated with peroxisome proliferator-activated receptor gamma coactivator-1a (PGC-1α) expression. Moreover, HOXA-AS2 knockdown significantly repressed microglial M1 polarization and promoted M2 polarization by regulating PGC-1α expression. Mechanistic investigations demonstrated that HOXA-AS2 could directly interact with polycomb repressive complex 2 (PRC2) and modulate the histone methylation of the promoter of PGC-1α. CONCLUSIONS: Our findings identify the upregulated lncRNA HOXA-AS2 promotes neuroinflammation by regulating microglial polarization through interacts with the PRC2 complex and epigenetically silencing PGC-1α. HOXA-AS2 may be a potential therapeutic target for microglia-mediated neuroinflammation in patients with PD.

Nab-paclitaxel-based regimens with docetaxel-based regimens as neoadjuvant treatment for early breast cancer.

Background Nanoparticle albumin-bound paclitaxel (nab-PTX) and docetaxel (DOC) both demonstrated favorable efficacy as neoadjuvant therapy in breast cancer. We retrospectively evaluated the efficacy and safety of nab-PTX-based chemotherapy (nPBC) and DOC-based chemotherapy (DBC) as neoadjuvant therapy in patients with breast cancer. Methods Breast cancer patients who received neoadjuvant nPBC or DBC and underwent surgery from January 2018 to June 2020 were consecutively analyzed. Pathologic complete response (pCR) was defined as no residual invasive cells in the breast and axillary nodes (ypT0/is ypN0) after surgery. The pCR, clinical complete response (cCR), and safety profiles were assessed in the two groups. Results A total of 104 breast cancer patients were included in this study. Fourty one patients received nPBC, and 63 patients received DBC The pCR was 34.1% in the nPBC group and 12.7% in the DBC group. Additionally, the cCR was 36.6% in the nPBC group and 15.9% in the DBC group. Peripheral sensory neuropathy was more common in the nPBC group, while hematologic toxicity was observed more frequently in the DBC group. Conclusions This study presented antitumor activity of nPBC and DBC in patients with early breast cancer receiving neoadjuvant treatment in a real-world setting. Further prospective research is warranted to confirm the results and to develop biomarkers for better patient selection.

Apolipoprotein C1 stimulates the malignant process of renal cell carcinoma via the Wnt3a signaling.

BACKGROUND: Renal cell carcinoma (RCC) is a clinically common tumor in the urinary system, showing an upward trend of both incidence and mortality. Apolipoprotein C1 (APOC1) has been identified as a vital regulator in tumor progression. This study aims to uncover the biological function of APOC1 in RCC process and the underlying mechanism. METHODS: Differential levels of APOC1 in RCC samples and normal tissues in a downloaded TCGA profile and clinical samples collected in our center were detected by quantitative reverse transcription PCR (qRT-PCR). The prognostic value of APOC1 in RCC was assessed by depicting Kaplan-Meier survival curves. After intervening APOC1 level by transfection of sh-APOC1 or oe-APOC1, changes in phenotypes of RCC cells were examined through CCK-8, colony formation, Transwell assay and flow cytometry. Subsequently, protein levels of EMT-related genes influenced by APOC1 were determined by Western blot. The involvement of the Wnt3a signaling in APOC1-regulated malignant process of RCC was then examined through a series of rescue experiments. Finally, a RCC xenograft model was generated in nude mice, aiming to further clarify the in vivo function of APOC1 in RCC process. RESULTS: APOC1 was upregulated in RCC samples. Notably, its level was correlated to overall survival of RCC patients, displaying a certain prognostic value. APOC1 was able to stimulate proliferative, migratory and invasive abilities in RCC cells. The Wnt3a signaling was identified to be involved in APOC1-mediated RCC process. Notably, Wnt3a was able to reverse the regulatory effects of APOC1 on RCC cell phenotypes. In vivo knockdown of APOC1 in xenografted nude mice slowed down the growth of RCC. CONCLUSIONS: APOC1 stimulates the malignant process of RCC via targeting the Wnt3a signaling.

Clinicopathological characteristics and survival outcomes in patients with synchronous lung metastases upon initial metastatic breast cancer diagnosis in Han population.

BACKGROUND: We investigated the clinicopathological characteristics and survival of breast cancer lung metastases (BCLM) patients at initial diagnosis of metastatic breast cancer (MBC) in the Han population. METHODS: We attained clinical data of 3155 MBC patients initially diagnosed between April 2000 and September 2019 from the China National Cancer Center and finally included 2263 MBC patients in this study, among which 809 patients presented with lung metastases at first MBC diagnosis. The risk factors for BCLM were determined using multivariate logistic regression analysis and the prognostic factors of BCLM patients were assessed by univariate and multivariate Cox regression analyses. RESULTS: Patients with triple-negative subtype (42.3%) harbored the highest incidence proportions of lung metastases. Age ≥ 50 years, Eastern Cooperative Oncology Group (ECOG) 2, M1, hormone receptor-negative (HR-)/human epidermal growth factor receptor 2-positive (HER2) + subtype, triple-negative subtype and disease-free survival (DFS) > 2 years were remarkably associated with higher incidence of lung metastases, while invasive lobular carcinoma (ILC) and bone metastases were significantly correlated with lower odds of lung metastases at diagnosis. The median survival of BCLM patients was 41.7 months, with triple-negative subtype experiencing the worst prognosis of 26.8 months. ECOG 2, triple-negative subtype, liver metastases, multi-metastatic sites and DFS ≤ 2 years were significantly correlated with poor survival of BCLM patients. CONCLUSIONS: Our study provides essential information on clinicopathological features and survival outcomes of BCLM patients at initial diagnosis of MBC in China.

A circulating exosomal microRNA panel as a novel biomarker for monitoring post-transplant renal graft function.

Accurate and effective biomarkers for continuous monitoring of graft function are needed after kidney transplantation. The aim of this study was to establish a circulating exosomal miRNA panel as non-invasive biomarker for kidney transplant recipients. Plasma exosomes of 58 kidney transplant recipients and 27 healthy controls were extracted by gel exclusion chromatography and characterized by transmission electron microscopy, nanoparticle tracking analysis and Western blotting. Post-transplant renal graft function was evaluated by estimated glomerular filtration rate (eGFR). Quantitative real-time polymerase chain reaction was used to determine the expression of exosomal microRNAs (miRNAs). Exosomal miR-21, miR-210 and miR-4639 showed negative correlations with eGFR in the training set and were selected for further analysis. In the validation set, miR-21, miR-210 and miR-4639 showed the capability to discriminate between subjects with chronic allograft dysfunction (eGFR < 60 mL/min/1.73 m2 ) and those with normal graft function (eGFR > 90 mL/min/1.73 m2 ). Three-miRNA panel exhibited higher accuracy compared with individual miRNAs or double indicators. One-year follow-up revealed a stable recovery of allograft function in subjects with low calculated score from three-miRNA panel (below the optimal cut-off value). In conclusion, a unique circulating exosomal miRNA panel was identified as an effective biomarker for monitoring post-transplant renal graft function in this study.

Platinum-based chemotherapy in advanced triple-negative breast cancer: A multicenter real-world study in China.

Platinum-based chemotherapy (PBC) has proven benefits in phase III studies for advanced triple-negative breast cancer (TNBC) patients; however, real-world data of large samples from multiple centers are lacking. Our study was to compare the effectiveness of PBC and non-PBC in advanced TNBC patients in multicenter real-world settings. Totally, 495 patients with advanced TNBC receiving PBC (n = 350) or non-PBC (n = 145) at four cancer centers in China between 2003 and 2019 were included. Treatment responses and outcomes were compared between the two groups from first-line to third-line treatment. Of patients with PBC, 249 (71.1%) received PBC from first-line chemotherapy, 86 (24.6%) from second-line and 15 (4.3%) from third-line treatment. In first-line treatment, PBC was superior to non-PBC in objective response rate (ORR, 53.0% vs 32.1%, P < .001) and median progression-free survival (PFS, 8.4 vs 6.0 months, P = .022), whereas overall survival (OS) was similar (19.2 vs 16.8 months, P = .439). When comparing patients receiving non-PBC doublets (n = 221) with those receiving PBC doublets (n = 249), the same trend was observed in ORR (32.6% vs 53.0%, P < .001), median first-line PFS (6.5 vs 8.4 months, P = .041) and median first-line OS(17.8 vs 19.2 months, P = .568). Paclitaxel/docetaxel + platinum was more likely to be used, followed by gemcitabine + platinum. In second/third-line treatment, PBC yielded a similar response and survival compared to non-PBC. Adding PBC in the first-line therapy was better than that in the latter-line of treatment in terms of ORR, PFS and OS (P < .001). Toxic effects of PBC were tolerable and the most common adverse event was neutropenia (38.6%). PBC doublets exhibited superior efficacy and manageable toxicity compared to non-PBC doublets in the first-line treatment for Chinese mTNBC patients.

Increased Serum Levels of Hepcidin and Ferritin Are Associated with Severity of COVID-19.

BACKGROUND The aim of this study was to assess the diagnostic utility of iron homeostasis determinations for prediction of severity of COVID-19. MATERIAL AND METHODS This was a retrospective study enrolling a total of 50 patients diagnosed with the novel coronavirus disease-19 (COVID-19) from February 27, 2020 to March 30, 2020, including a severe group (12 patients) and a mild group (38 patients). For the control group, 50 healthy people were examined during the same period. We compared clinical laboratory data and iron homeostasis biomarkers among the 3 groups. ROC curve analysis was used to assess diagnoses. RESULTS Patients diagnosed with severe COVID-19 had higher hepcidin and serum ferritin levels than in other groups (p<0.001). A combination test of hepcidin and serum ferritin provided the best specificity and sensitivity in the prognosis of COVID-19 severity. Logistic regression analysis showed hepcidin and serum ferritin independently contributed to the severity of COVID-19. Hepcidin and serum ferritin tandem testing predicted COVID-19 severity with 94.6% specificity, while hepcidin and serum ferritin parallel testing had a sensitivity of 95.7%. CONCLUSIONS Iron homeostasis had a robust association with the occurrence of severe COVID-19. Iron homeostasis determinations were specific and sensitive for the early prediction of disease severity in COVID-19 patients and thus have clinical utility.

90 days impacts of remote ischemic preconditioning on patients undergoing open total aortic arch replacement: a post-hoc analysis of previous trial.

BACKGROUND: In the previous randomized controlled trial by our research group, we evaluated the effect of remote ischemic preconditioning (RIPC) in 130 patients (65 per arm) on acute kidney injury (AKI) within 7 days of open total aortic arch replacement. Significantly fewer RIPC-treated patients than sham-treated patients developed postoperative AKI, and, epically, RIPC significantly reduced serious AKI (stage II-III). However, the long-term effect of RIPC in patients undergoing open total aortic arch replacement is unclear. METHODS: This study was a post-hoc analysis. We aimed to assess the roles of RIPC in major adverse kidney events (MAKE), defined as consisting persistent renal dysfunction, renal replacement therapy and mortality, within 90 days after surgery in patients receiving open total aortic arch replacement. RESULTS: In this 90-day follow-up study, data were available for all study participants. We found that RIPC failed to improve the presence of MAKE within 90 days after surgery (RIPC: 7 of 65[10.8%]) vs sham: 15 of 65[23.1%]; P = 0.061). In those patients who developed AKI after surgery, we found that the rate of MAKE within 90 days after surgery differed between the RIPC group and the sham group (RIPC: 4 of 36[11.2%]; sham: 14 of 48[29.2%]; P = 0.046). CONCLUSIONS: At 90 days after open total aortic arch replacement, we failed to find a difference between the renoprotective effects of RIPC and sham treatment. The effectiveness or ineffectiveness of RIPC should be further investigated in a large randomized sham-controlled trial. TRIAL REGISTRATION: This study was approved by the Ethics Committee of Fuwai Hospital (No. 2016-835) and our previous study was registered at clinicaltrials.gov before patient enrollment ( NCT03141385 ; principal investigator: G.W.; date of registration: March 5, 2017).

Using Machine Learning to Predict Acute Kidney Injury After Aortic Arch Surgery.

OBJECTIVES: Machine learning models were compared with traditional logistic regression with regard to predicting kidney outcomes after aortic arch surgery. DESIGN: Retrospective review. SETTING: Single quaternary care center, Fuwai Hospital, Beijing, China. PARTICIPANTS: The study comprised 897 consecutive patients who underwent aortic arch surgery from January 2013 to May 2017. Three machine learning methods were compared with logistic regression with regard to the prediction of acute kidney injury (AKI) after aortic arch surgery. Perioperative characteristics, including patients' baseline medical condition and intraoperative data, were analyzed. The performance of the models was assessed using the area under the receiver operating characteristic curve. MEASUREMENTS AND MAIN RESULTS: The primary endpoint, postoperative AKI, was defined using the Kidney Disease: Improving Global Outcomes criteria. During the first 7 postoperative days, AKI was observed in 652 patients (72.6%), and stage 2 or 3 AKI developed in 283 patients (31.5%). Gradient boosting had the best discriminative ability for the prediction of all stages of AKI in both the binary classification and the multiclass classification (area under the receiver operating characteristic curve 0.8 and 0.71, respectively) compared with logistic regression, support vector machine, and random forest methods. CONCLUSION: Machine learning methods were found to predict AKI after aortic arch surgery significantly better than traditional logistic regression.