Development of a haematological indices-based nomogram for prognostic prediction and immunotherapy response assessment in primary pulmonary lymphoepithelioma-like carcinoma patients.

Background: Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare yet aggressive malignancy. This study aims to investigate a deep learning model based on hematological indices, referred to as haematological indices-based signature (HIBS), and propose multivariable predictive models for accurate prognosis prediction and assessment of therapeutic response to immunotherapy in PPLELC. Methods: This retrospective study included 117 patients with PPLELC who received immunotherapy and were randomly divided into a training (n=82) and a validation (n=35) cohort. A total of 41 hematological features were extracted from routine laboratory tests and the least absolute shrinkage and selection operator (LASSO) algorithm were utilized to establish the HIBS. Additionally, we developed a nomogram using the HIBS and clinical characteristics through multivariate Cox regression analysis. To evaluate the nomogram's predictive performance, we used calibration curves and calculated the time-dependent area under the curve (AUC). Kaplan-Meier survival analysis was performed to estimate progression-free survival (PFS) in both cohorts. Results: The proposed HIBS comprised 14 hematological features and showed that patients who experienced disease progression had significantly higher HIBS scores compared to those who did not progress (P<0.001). Five prognostic factors, including HIBS, tumor-node-metastasis (TNM) stage, presence of bone metastasis and the specific immunotherapy regimen, were found to be independent factors and were used to construct a nomogram, which effectively categorized PPLELC patients into a high-risk and a low-risk group, with patients in the high-risk patients demonstrating worse PFS (7.0 vs. 18.0 months, P<0.001) and lower overall response rates (22.2% vs. 52.7%, P<0.001). The nomogram showed satisfactory discrimination for PFS, with AUC values of 0.837 and 0.855 in the training and validation cohorts, respectively. Conclusions: The HIBS-based nomogram could effectively predict the PFS and response of patients with PPLELC regarding immunotherapy and serve as a valuable tool for clinical decision making.

Patterns of Drug Resistance and Bacterial Pathogen Distribution in Patients with Urinary Tract Infections in the Jiaxing Region from 2020 to 2022.

Background: Urinary tract infections (UTIs) and the antibiotic resistance of pathogenic bacteria pose severe threats to public health in the current healthcare environment. Objective: The purpose of this study was to assess the frequency distribution of bacterial pathogens causing UTIs as well as the characteristics of antibiotic susceptibility and resistance. Methods: The retrospective study was conducted on 32,391 samples of midstream urine culture from January 1, 2020, to December 31, 2022, in Jiaxing. Bacteria were cultivated on blood agar and identified using MALDI-TOF, and their susceptibility to different antibiotics was assessed using the Kirby-Bauer disk diffusion method and drug sensitivity reaction cards. The SPSS 22 software was used for data analysis. Bivariate logistic regression was used to analyze the risk factors for multidrug resistance. Results: The total number of positive growth samples was 5378 (16.6%), including 3206 females (59.6%) and 2172 males (40.4%). The four most common urinary pathogens were Escherichia coli (39.2%), Enterococcus faecalis (12.4%), Klebsiella pneumoniae (7.6%), and Enterococcus faecium (7.6%). As far as antibiotic resistance was concerned, Escherichia coli had a greater than 50% resistance rate to ampicillin (76.1%), ciprofloxacin (58.6%), and levofloxacin (51.2%). The multidrug resistance rate was high (41.8%). Low levels of resistance were seen to ertapenem (0.1%), imipenem (0.7%), meropenem (0.7%), piperacillin/tazobactam (0.7%), and nitrofurantoin (1.8%). Klebsiella pneumoniae was highly sensitive to ertapenem (100%). The resistance rates to nitrofurantoin, ceftriaxone, and ciprofloxacin were 37.4%, 37.1%, and 35.1%, respectively. Up to 41% of Escherichia coli strains and 26% of Klebsiella pneumoniae strains produced extended-spectrum lactamases (ESBL). Two species of enterococci were highly sensitive to tigecycline and linezolid (100%), and a small number of norvancomycin-resistant strains (0.2%/two strains) were found. Conclusion: Escherichia coli and Enterococcus faecium were the most common urinary pathogens in this study. The isolated pathogens showed different sensitivity patterns. Antibiotics should be selected reasonably according to the sensitivity mode of pathogenic bacteria to effectively treat and prevent urinary tract infections.

Molecular characterization and comparison of bla NDM-1-carrying and bla NDM-5-harboring IncX3-type plasmids in carbapenem-resistant Klebsiella pneumoniae.

Carbapenem-resistant Klebsiella pneumoniae (CRKP), which harbors the bla NDM plasmid, has been reported extensively and is considered a global threat clinically. However, characterization and comparisons of bla NDM-1-carrying and bla NDM-5-harboring IncX3-type plasmids in CRKP are lacking. Here, we systematically compared the differences in the characteristics, genetic backgrounds, transferability, and fitness costs between bla NDM-1-carrying and bla NDM-5-carrying plasmids in K. pneumoniae isolates. Fifteen NDM-producing CRKP isolates were recovered from 1376 CRKP isolates between 2019 and 2021, of which 4 were positive for bla NDM-1 and 11 were positive for bla NDM-5. All strains were highly resistant to carbapenem but remained susceptible to tigecycline and colistin. Core-genome-based phylogenetic analyses revealed that these strains were not clonally related. Whole-genome sequencing showed that bla NDM-1 and bla NDM-5 were located on ~54 kb and ~46 kb IncX3-type plasmids, respectively. The backbone, genetic context, and fitness cost of the bla NDM-1-bearing plasmid were highly similar to those of the bla NDM-5-carrying plasmid, but the transferability of the bla NDM-1-positive plasmid was greater than that of the bla NDM-5-positive plasmid. In conclusion, the transmission of bla NDM-1 or bla NDM-5 is mainly disseminated by plasmids rather than clonal spread. The high transfer frequency of the IncX3 plasmid facilitates the prevalence and dissemination of NDM-KP among Enterobacteriaceae. IMPORTANCE The emergence of NDM-producing Klebsiella pneumoniae is a severe challenge to public health. The widespread presence of bla NDM-1 and bla NDM-5 in Enterobacteriaceae has aroused broad concern. In this study, we performed molecular characterization of bla NDM-1-carrying and bla NDM-5-harboring IncX3-type plasmids in carbapenem-resistant Klebsiella pneumoniae (CRKP) and compared their phenotypes between strains with different bla NDM subtype. Our findings highlight the importance of IncX3-type plasmids in the transfer of the bla NDM-1 and bla NDM-5 genes and demonstrate that the bla NDM-1 plasmid possesses higher transfer ability. These data will provide important insights into carbapenem resistance gene transfer via plasmids and their further spread in clinical settings.

miR-4739 promotes epithelial-mesenchymal transition and angiogenesis in "driver gene-negative" non-small cell lung cancer via activating the Wnt/ß-catenin signaling.

PURPOSE: "Driver gene-negative" non-small cell lung cancer (NSCLC) currently has no approved targeted drug, due to the lack of common actionable driver molecules. Even though miRNAs play crucial roles in various malignancies, their roles in "driver gene-negative" NSCLC keep unclear. METHODS: miRNA expression microarrays were utilized to screen miRNAs associated with "driver gene-negative" NSCLC malignant progression. Quantitative real-time PCR (RT-qPCR) and in situ hybridization (ISH) were employed to validate the expression of miR-4739, and its correlation with clinicopathological characteristics was analyzed in tumor specimens using univariate and multivariate analyses. The biological functions and underlying mechanisms of miR-4739 were investigated both in vitro and in vivo. RESULTS: our research demonstrated, for the first time, that miR-4739 was substantially increased in "driver gene-negative" NSCLC tumor tissues and cell lines, and overexpression of miR-4739 was related to clinical staging, metastasis, and unfavorable outcomes. Functional experiments discovered that miR-4739 dramatically enhanced tumor cell proliferation, migration, and metastasis by promoting the epithelial-to-mesenchymal transition (EMT). Meanwhile, miR-4739 can be transported from cancer cells to the site of vascular epithelial cells through exosomes, consequently facilitating the proliferation and migration of vascular epithelial cells and inducing angiogenesis. Mechanistically, miR-4739 can activate Wnt/ß-catenin signaling both in tumor cells and vascular epithelial cells by targeting Wnt/ß-catenin signaling antagonists APC2 and DKK3, respectively. CONCLUSION: Our work identifies a valuable oncogene, miR-4739, that accelerates malignant progression in "driver gene-negative" NSCLC and serves as a potential therapeutic target for this group of tumors.

A Clinical Tool to Predict the Microvascular Invasion Risk in Patients with Hepatocellular Carcinoma.

BACKGROUND: Microvascular invasion (MVI) plays an important role in tumor progression. The aim of this study is to establish and validate an effective hematological nomogram for MVI prediction in hepatocellular carcinoma (HCC). METHODS: A retrospective study was performed in a primary cohort that includes 1306 patients clinicopathologically diagnosed with HCC, and a validation cohort contained 563 continuous patients. Univariate logistic regression was used to assess the association between variables included both clinicopathologic factors and coagulation parameters (prothrombin time, activated partial thromboplastin time, fibrinogen, and thrombin time [TT]) and MVI. Multiple logistic regression was used to construct a prediction nomogram. We tested the accuracy of the nomogram by discrimination and calibration, and then plotted decision curves to assess the benefits of the nomogram-assisted decisions in a clinical context. RESULTS: In the two cohorts, patients without MVI had the longest overall survival (OS), compared the OS with MVI. The multivariate analysis indicated that age, sex, tumor node metastasis (TNM) stage, aspartate aminotransferase, alpha fetoprotein, C-reactive protein, and TT were identified as significant independent predictors of MVI of HCC patients. The Hosmer-Lemeshow test showed good point estimate associated P value between predicted risk and observed risk across the deciles. Moreover, the calibration performance of the nomogram risk scores in each decile of the primary cohort was within 5 percentage points of the mean predicted risk score, and in the validation cohort, the observed risk in 90% decile was within 5 percentage points of the mean predicted risk score. CONCLUSIONS: A noninvasive and easy-to-use nomogram was established and may be used to predict preoperative MVI in HCC.

Significance of Dynamic Changes of VCA-IgA Levels in Pre- and Post-treatment Plasma of Patients with Nasopharyngeal Carcinoma: Development of a Clinically-Oriented Model.

INTRODUCTION: Nasopharyngeal carcinoma (NPC) responds well to radiotherapy but recurrence and metastasis are common. Currently, there is no widely used biomarker for accurately predicting the recurrence and metastasis of NPC. In this study, we aimed to evaluate the prognostic ability of Epstein-Barr virus (EBV) capsid antigen (VCA-IgA) kinetics by assessing the dynamic changes of VCA-IgA levels in the pre- and post-treatment plasma of patients with NPC and have proposed a prognostic model for clinical use. METHODS: The clinical records of patients with NPC diagnosed at Sun Yat-sen University Cancer Center were retrieved and classified into a respondent (n = 83) or non-respondent (n = 25) cohort based on their response to antitumor therapy. Factors associated with the outcomes of the patients were assessed and incorporated in a nomogram. For internal validation, bootstrapping with 1000 resamples was used. The prediction accuracy and discriminative ability of the nomogram were investigated by calibration and concordance index (C-index) and plotted decision curves to assess the benefits of nomogram-assisted decisions in a clinical context. RESULTS: Plasma VCA-IgA level of the non-respondent cohort at the 6th month after treatment was found significantly higher than the respondent cohort. Post-treatment VCA-IgA level, smoking, and distant metastases were identified as independent risk factors for disease-free survival (DFS), and were used to stratify patients with NPC into three risk groups. The median DFS of the low-, middle- and high-risk groups were 48.5, 35.0, and 15.5 months, respectively. The C-index of the nomogram was 0.848 (95% CI 0.769-0.926), demonstrating good clinical accuracy for predicting the DFS of patients with NPC. The decision curve showed that the nomogram in predicting DFS was better than VCA-IgA level, smoking, and distant metastases. CONCLUSION: The proposed VCA-IgA-based nomogram demonstrated a promising ability to predict the DFS of patients with NPC after antitumor therapy. It could be used as a clinical guidance to improve the therapeutic/surveillance strategies of these patients.

Endonasopharyngeal ultrasound and magnetic resonance imaging features of recurrent retropharyngeal nodes in nasopharyngeal carcinoma patients: A radiologic-histopathologic study.

BACKGROUND: The imaging criteria of malignant retropharyngeal lymph node (RLN) in nasopharyngeal cancer (NPC) have yet to be fully elucidated. This study aimed to establish predictive models based on ultrasound (US) and magnetic resonance (MR) characteristics for identifying malignant RLN in NPC patients after radiotherapy. METHODS: 81 post-radiotherapy NPC patients with abnormal enlargement of RLN underwent endonasopharyngeal ultrasound-guided fine-needle aspirations (EPUS-FNA) to access the nature of RLN. The following features were assessed on US and MR: size, margin, vascular signal, echogenicity, enhancement signal and accompany with suspicious cervical nodes or not. A multivariate analysis was performed to screen out high-risk imaging features for recurrent RLN (RRLN), and models for the diagnosis of RRLN was constructed and tested with internal verification. We evaluated the clinical usefulness of the models through comparison of C-index and decision curve analysis. RESULTS: High-risk features of RRLN were heterogeneous echo (p < 0.01), vascular signal (p < 0.01) on EPUS, heterogeneous enhancement (p < 0.01) and minimum axis diameter > 10 mm (p < 0.01) on MR. The models based on the US and MR features showed good discrimination (AUC of 0.76 in the US model, 0.74 in the MR model and 0.77 in the US + MR model) and good net benefit in the validation group. CONCLUSION: Prediction models based on the US and MR features show good diagnostic performance for RRLN after radiotherapy in NPC patients. The combination of EPUS and MR may be constructed to provide prompt and reliable guidance to manage RLN.

Recurrence risk stratification based on Epstein-Barr virus DNA to identify enlarged retropharyngeal lymph nodes of nasopharyngeal carcinoma: A model-histopathologic correlation study.

Background: Accurate assessment of the nature of enlarged retropharyngeal lymph nodes (RLN) of nasopharyngeal carcinoma (NPC) patients after radiotherapy is related to selecting appropriate treatments and avoiding unnecessary therapy. This study aimed to develop a non-invasive and effective model for predicting the recurrence of RLN (RRLN) in NPC. Materials and methods: The data of post-radiotherapy NPC patients (N = 76) with abnormal enlargement of RLN who underwent endonasopharyngeal ultrasound-guided fine-needle aspirations (EPUS-FNA) were examined. They were randomly divided into a discovery (n = 53) and validation (n = 23) cohort. Univariate logistic regression was used to assess the association between variables (magnetic resonance imaging characteristics, EBV DNA) and RRLN. Multiple logistic regression was used to construct a prediction model. The accuracy of the model was assessed by discrimination and calibration, and decision curves were used to assess the clinical reliability of the model for the identification of high risk RLNs for possible recurrence. Results: Abnormal enhancement, minimum axis diameter (MAD) and EBV-DNA were identified as independent risk factors for RRLN and could stratify NPC patients into three risk groups. The probability of RRLN in the low-, medium-, and high-risk groups were 37.5, 82.4, and 100%, respectively. The AUC of the final predictive model was 0.882 (95% CI: 0.782-0.982) in the discovery cohort and 0.926 (95% CI, 0.827-1.000) in the validation cohort, demonstrating good clinical accuracy for predicting the RRLN of NPC patients. The favorable performance of the model was confirmed by the calibration plot and decision curve analysis. Conclusion: The nomogram model constructed in the study could be reliable in predicting the risk of RRLN after radiotherapy for NPC patients.

Hyperammonemia in a septic patient with Ureaplasma parvum arthritis: a case report.

BACKGROUND: Septic arthritis requires prompt diagnosis and treatments. Rare pathogens should be considered when patients respond poorly to the initial antibiotic treatments. Ureaplasma parvum is an opportunistic pathogen that commonly resides in the human urogenital tract. Its infection commonly causes hyperammonemia. Hyperammonemia from Ureaplasma parvum septic arthritis has never been reported previously. CASE PRESENTATION: A 65-year-old male presented with fever and left lower leg pain and swelling for more than ten days. Septic arthritis and sepsis were considered after laboratory tests and arthrocentesis. However, he responded poorly to the antibiotic treatments, including cefoperazone-sulbactam, imipenem-cilastatin, and linezolid. His mental status deteriorated rapidly with elevated blood ammonia levels with unremarkable liver function test and sonogram examination results. Despite the treatments with lactulose, L-ornithine L-aspartate, mannitol, and hemodialysis therapy to lower his ammonia level, his blood ammonia level remained persistently high. Finally, metagenomic sequencing of the left knee synovial fluid reported Ureaplasma parvum, which was considered to contribute to his hyperammonemia. CONCLUSION: Ureaplasma parvum could cause septic arthritis with hyperammonemia. Genetic tests, such as polymerase chain reaction and next-generation sequencing techniques, could provide a sensitive and fast diagnosis of Ureaplasma parvum.

Concurrent severe pulmonary tuberculosis with Evans syndrome: a case report with literature review.

BACKGROUND: Tuberculosis is a bacterial infection involving multiple organs and systems. Its hematological presentation mainly includes anemia and leukocytosis. Evans syndrome is a rare autoimmune disease characterized by autoimmune hemolytic anemia, immune thrombocytopenia, and neutropenia, with positive results for the direct Coombs test and platelet antibodies. The cooccurrence of tuberculosis and Evans syndrome is rarely reported. CASE PRESENTATION: A 69-year-old female presented with a fever and shortness of breath. Her chest computerized tomography scan showed extensive miliary nodules in the bilateral lung fields. She rapidly developed respiratory failure that required endotracheal intubation and mechanical ventilation. The acid-fast bacilli sputum smear results indicated a grade of 3+. Later on, blood testing revealed hemolytic anemia, a positive direct Coombs test result, and the presence of the platelet antibody IgG. This patient was diagnosed as having disseminated pulmonary tuberculosis and Evans syndrome. She successfully recovered after treatment with antituberculosis drugs and glucocorticoids. CONCLUSIONS: Tuberculosis can occur together with Evans syndrome. Affected patients should receive both antituberculosis and immunosuppressive drugs.

Development of a Clinically Oriented Model to Predict Antitumor Effects after PD-1/PD-L1 Inhibitor Therapy.

Immune checkpoint inhibitors (ICI) have created an advanced shift in the treatment of lung cancer (LC), but the existing biomarkers were not in clinical and widespread use. The purpose of this study was to develop a new nomogram with immune factors used for monitoring the response to ICI therapy. LC patients with PD-1/PD-L1 inhibitors treatment were included in this analysis. The immune biomarkers and clinicopathological characteristic values at baseline were used to estimate the tumor response. The nomogram was based on the factors that were determined by univariate and multivariate Cox hazard analysis. For internal validation, bootstrapping with 1000 resamples was used. The concordance index (C-index) and calibration curve were used to determine the predictive accuracy and discriminative ability of the nomogram. Overall survival (OS) was estimated using the Kaplan-Meier method. Patients with lung metastasis (P = 0.010), higher baseline neutrophil-lymphocyte ratio (NLR) level (P < 0.001), lower baseline lymphocyte-monocyte (LMR) (P = 0.019), and lower CD3+CD8+ T cell count (P = 0.009) were significantly related to the tumor response. The above biomarkers were contained into the nomogram. The calibration plot for the probability of OS showed an optimal agreement between the actual observation and prediction by nomogram at 3 or 5 years after therapy. The C-index of nomogram for OS prediction was 0.804 (95% CI: 0.739-0.869). Decision curve analysis demonstrated that the nomogram was clinically useful. Moreover, patients were divided into two distinct risk groups for OS by the nomogram: low-risk group (OS: 17.27 months, 95% CI: 14.75-19.78) and high-risk group (OS: 6.11 months, 95% CI: 3.57-8.65), respectively. A nomogram constructed with lung metastasis baseline NLR, LMR, and CD3+CD8+ T cell count could be used to monitor and predict clinical benefit and prognosis in lung cancer patients within ICI therapy.

The Correlation between 25-Hydroxyvitamin D3 and the Severity and Short-Term Prognosis of Pulmonary Tuberculosis.

BACKGROUND: Pulmonary tuberculosis is a chronic infectious disease caused by mycobacterium tuberculosis in the lungs. The present study aims to investigate the correlation between serum 25-hydroxyvitamin D3 (25-VD3) and the severity and short-term prognosis of tuberculosis. METHODS: The clinical data of 261 pulmonary tuberculosis patients, who were admitted to the Tuberculosis Diagnosis and Treatment Center of our hospital from January 1, 2017 to December 31, 2020, was retrospectively collected. Taking the median of 25-VD3 at admission (11.40 ng/mL) as the cutoff value, these patients were divided into two groups: high 25-VD3 group (> 11.40 ng/mL, n = 131) and low 25-VD3 group (≤ 11.40 ng/mL, n = 130). Then, Pearson's correlation analysis was performed using SPSS to determine the correlation between the 25-VD3 level and the length of hospitalization and Acute Physiology and Chronic Health Evaluation II (APACHE II) score of pulmonary tuberculosis patients. According to the clinical outcome after 28 days of treatment, these patients were divided again into two groups: improvement group (n = 170) and death group (n = 91). Then, Pearson's correlation analysis through SPSS was performed to determine the relationship between the 25-VD3 level and short-term prognosis of pulmonary tuberculosis patients. RESULTS: Compared to the low 25-VD3 group, pulmonary tuberculosis patients in the high 25-VD3 group were younger, had a higher percentage of improvement after 28 days of treatment, and had a lower APACHE II score (p < 0.05). However, the 25-VD3 level was not significantly correlated to the length of hospital stay of pulmonary tuberculosis patients (correlation coefficient r = 0.020, p = 0.746) and was significantly negatively correlated to the APACHE II score (correlation coefficient r = -0.211, p = 0.001). In addition, the age and APACHE II score of patients were lower in the improvement group, when compared to the death group, while the 25-VD3 level was higher and the length of hospital stay was longer, when compared to the death group (p < 0.01). The logistic regression analysis revealed that the length of hospital stay, APACHE II score, and 25-VD3 level are independent risk factors that affect the prognosis of pulmonary tuberculosis patients (p < 0.05). CONCLUSIONS: In summary, 25-VD3 is closely correlated to the severity of tuberculosis, and this can be used to evaluate and predict the prognosis of patients.

Highly Selective Tandem Electroreduction of CO2 to Ethylene over Atomically Isolated Nickel-Nitrogen Site/Copper Nanoparticle Catalysts.

Herein, an effective tandem catalysis strategy is developed to improve the selectivity of the CO2 RR towards C2 H4 by multiple distinct catalytic sites in local vicinity. An earth-abundant elements-based tandem electrocatalyst PTF(Ni)/Cu is constructed by uniformly dispersing Cu nanoparticles (NPs) on the porphyrinic triazine framework anchored with atomically isolated nickel-nitrogen sites (PTF(Ni)) for the enhanced CO2 RR to produce C2 H4 . The Faradaic efficiency of C2 H4 reaches 57.3 % at -1.1 V versus the reversible hydrogen electrode (RHE), which is about 6 times higher than the non-tandem catalyst PTF/Cu, which produces CH4 as the major carbon product. The operando infrared spectroscopy and theoretic density functional theory (DFT) calculations reveal that the local high concentration of CO generated by PTF(Ni) sites can facilitate the C-C coupling to form C2 H4 on the nearby Cu NP sites. The work offers an effective avenue to design electrocatalysts for the highly selective CO2 RR to produce multicarbon products via a tandem route.

Misdiagnosed tuberculosis being corrected as Nocardia farcinica infection by metagenomic sequencing: a case report.

BACKGROUND: Disseminated nocardiosis is liable to be misdiagnosed owing to the non-specific clinical manifestations and laboratory/imaging findings. Metagenomic next-generation sequencing (mNGS) is a culture-independent and rapid method for direct identification of all microorganisms in clinical specimens. CASE PRESENTATION: A 72-year-old man was admitted to our hospital on February 20, 2019 with a history of recurrent cough, expectoration, fever, and diarrhea since 1 month, and unconsciousness since 1 week. Contrast-enhanced magnetic resonance imaging of head showed multiple lesions in the bilateral cerebral hemispheres, brainstem, and cerebellar hemispheres. The presumptive diagnosis was disseminated tuberculosis, although all tests for mycobacterium were negative. However, the patient did not benefit from antituberculosis treatment. Repeat MRI showed multiple abnormal signals in the brain and progression of meningeal thickening. Cerebrospinal fluid and bronchoalveolar lavage fluid specimens were subsequently sent for PMSeq metagenomics sequencing; the results indicated Nocardia. farcinica as the predominant pathogen. The anti-TB treatment was stopped and the patient was prescribed sulphamethoxazole in combination with linezolid and meropenem for nocardiosis. He showed gradual neurological improvement and was transferred to Huashan Hospital. He was discharged from the hospital on April 19, 2019, but died of persistent diarrhea on May 26, 2019. CONCLUSIONS: Patients with suspected nocardiosis do not always respond to conventional treatment; therefore, mNGS can facilitate diagnosis and timely treatment decision-making.

The automated processing algorithm to correct the test result of serum neuron-specific enolase affected by specimen hemolysis.

INTRODUCTION: Serum neuron-specific enolase (NSE) is an important tumor marker for small cell lung cancer and neuroblastoma. However, the test of serum NSE compromised by specimen hemolysis is presented as a falsely higher result, which seriously disturbs clinical decision. This study aimed to establish a solution integrated with laboratory information system to clear the bias from hemolysis on serum NSE test. METHODS: The reference range of serum hemolysis index (HI) was first established, and specimen hemolysis rate was compared between HI test and visual observation. NSE concentration in serum pool with normal HI was spiked with serial diluted lysates from red blood cells to deduce individual corrective equation. The agreement between individual corrective equation and original NSE test was assayed by Bland and Altman plots. RESULTS: The high HI existed in 32.6% of specimens from patients. The NSE median of hemolyzed specimens was significant higher than the baseline (p = 0.038), while the corrected NSE median had no difference compared with the baseline (p = 0.757). The mean difference of corrected NSE and initial NSE was 1.92%, the SD of difference was 5.23%, and furthermore, the difference was independent of tendency of HI (Spearman r = -0.069, p = 0.640). The 95% confidence interval of mean difference (from -8.33% to 12.17%) was less than the acceptable bias range (±20%). CONCLUSION: The agreement between individual correction equation and NSE assay was satisfied. Our automated processing algorithm for serum NSE could provide efficient management of posttest data and correct positive bias from specimen hemolysis.

Construction of Donor-Acceptor Heterojunctions in Covalent Organic Framework for Enhanced CO2 Electroreduction.

Covalent organic frameworks (COFs) are promising candidates for electrocatalytic reduction of carbon dioxide into valuable chemicals due to their porous crystalline structures and tunable single active sites, but the low conductivity leads to unmet current densities for commercial application. The challenge is to create conductive COFs for highly efficient electrocatalysis of carbon dioxide reduction reaction (CO2 RR). Herein, a porphyrin-based COF containing donor-acceptor (D-A) heterojunctions, termed TT-Por(Co)-COF, is constructed from thieno[3,2-b]thiophene-2,5-dicarbaldehyde (TT) and 5,10,15,20-tetrakis(4-aminophenyl)-porphinatocobalt (Co-TAPP) via imine condensation reaction. Compared with COF-366-Co without TT, TT-Por(Co)-COF displays enhanced CO2 RR performance to produce CO due to its favorable charge transfer capability from the electron donor TT moieties to the acceptor Co-porphyrin ring active center. The combination of strong charge transfer properties and enormous amount of accessible active sites in the 2D TT-Por(Co)-COF nanosheets results in good catalytic performance with a high Faradaic efficiency of CO (91.4%, -0.6 V vs reversible hydrogen electrode (RHE) and larger partial current density of 7.28 mA cm-2 at -0.7 V versus RHE in aqueous solution. The results demonstrate that integration of D-A heterojunctions in COF can facilitate the intramolecular electron transfer, and generate high current densities for CO2 RR.

Heat Shock Protein 90α Provides an Effective and Novel Diagnosis Strategy for Nasopharyngeal Carcinoma.

INTRODUCTION: Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated tumor occurring in southeastern Asia. Due to insidious onset, it is difficult to diagnose NPC from clinical symptoms. Thus, there is an urgent need for non-invasive, high-performance biomarkers to aid the clinical diagnosis of NPC. Heat shock protein 90α (HSP90α) is an important member of the heat shock protein family that significantly increases under stress conditions such as oxidation and tumors. This is the first investigation of the role of Hsp90α in the diagnosis and progress of NPC. METHODS: Plasma Hsp90α was detected by ELISA in 196 newly diagnosed NPC patients, 76 corresponding post-treatment NPC patients, 230 VCA-IgA-positive normal subjects and 106 healthy controls. RESULTS: (1) The level of Hsp90α in plasma of 196 NPC patients was (212.16 ± 144.32) ng/ml, which was significantly higher than that in VCA-IgA-positive normal subjects (68.12 ± 64.94 ng/ml, P < 0.001) and healthy controls (35.87 ± 17.47 ng/ml, P < 0.001); (2) the levels of Hsp90α in patients with NPC in the early stage (I + II), stage III and stage IV were significantly different (159.69 ± 117.12 pg/ml vs. 195.24 ± 126.38 pg/ml vs. 250.85 ± 164.66 pg/ml, P = 0.018 and P = 0.029, respectively). The level of Hsp90α in plasma in patients with metastasis of NPC and those without metastasis was significantly different (P < 0.001); (3) Hsp90α is closely related to EBV DNA levels, but not to the VCA-IgA titer and EA-IgA titer; (4) the levels of Hsp90α in plasma of patients with NPC before and after treatment were significantly different (212.16 ± 144.32 pg/ml vs. 62.36 ± 34.04 pg/ml, P < 0.001); (5) the ROC curves demonstrated that the sensitivity of plasma Hsp90α in distinguishing NPC patients from healthy controls was 74.50% and the specificity was 99.10% (AUC = 0.931, 95% CI 0.903-0.958). CONCLUSION: The study found that the plasma HSP90α level is closely related to the clinical stage, metastasis and therapeutic effect of NPC. HSP90α may serve as a new biomarker for diagnosis and treatment of NPC.

Prediction of Poor Outcomes in Patients with Colorectal Cancer: Elevated Preoperative Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT).

BACKGROUND AND OBJECTIVE: Tools for the non-invasive assessment of colorectal cancer (CRC) prognosis have profound significance. Although plasma coagulation tests have been investigated in a variety of tumours, the prognostic value of the prothrombin time (PT) and activated partial thromboplastin time (APTT) in CRC has not been discussed. Our study objective was to explore the prognostic significance of preoperative PT and APTT in CRC patients. PATIENTS AND METHODS: A retrospective analysis of preoperative coagulation indexes including PT, PTA, INR, APTT, FIB, TT, PLT, NLR and PLR in 250 patients with CRC was performed. Kaplan-Meier and multivariate Cox regression analysis were used to demonstrate the prognostic value of these preoperative coagulation indexes. RESULTS: The overall survival (OS, p<0.05) and disease-free survival (DFS, p<0.05) of CRC patients with lower PT and APTT levels were significantly prolonged. Based on univariate analysis, PT levels (p<0.001, p<0.001), PTA levels (p=0.001, p=0.001), APTT levels (p=0.001, p<0.001), INR levels (p<0.001, p<0.001), fibrinogen levels (p=0.032, p=0.036), tumour status (p=0.005, p=0.003), nodal status (p<0.001, p<0.001), metastasis status (p<0.001, p<0.001) and TNM stages (p<0.001, p<0.001) were remarkably associated with DFS and OS. Multivariate Cox regression analysis suggested that the levels of PT (HR: 2.699, p=0.006) and APTT (HR: 1.942, p=0.015), metastasis status (HR: 2.091, p= 0.015) and TNM stage (HR: 7.086, p=0.006) were independent predictors of survival in CRC. In the whole cohort, the enrolled patients were then divided into three groups according to their PT and APTT levels. The OS and DFS differed notably among the low-risk (PT<11.85 sec and APTT<25.85 sec), medium-risk (PT≥11.85 sec or APTT≥25.85 sec), and high-risk (PT≥11.85 sec and APTT≥25.85 sec) groups. CONCLUSION: Elevated levels of preoperative PT and APTT were predictors of poor outcomes in CRC patients. Moreover, the combination of preoperative PT and APTT can be a new prognostic stratification approach for more precise clinical staging of CRC.

A Randomized Controlled Trial on Evaluation of Plasma Epstein-Barr Virus Biomarker for Early Diagnosis in Patients With Nasopharyngeal Carcinoma.

INTRODUCTION: Early diagnosis of nasopharyngeal carcinoma (NPC) remains a major problem in Southern China. Epstein-Barr virus (EBV) biomarkers have been widely used in NPC screening. This study aims to evaluate the early diagnostic performances of individual EBV biomarkers in NPC. METHODS: The levels of EBV biomarkers-IgA antibodies against EBV nuclear antigen 1 (EBNA1-IgA), EBV capsid antigen (VCA-IgA), EBV early antigen (EA-IgA), EBV BZLF1 transcription activator protein (Zta-IgA) and IgG antibodies against EBV BRLF1 transcription activator protein (Rta-IgG)-from 106 NPC patients (stage I and II) and 150 normal subjects were measured. VCA-IgA and EA-IgA were detected by immunofluorescence assay (IFA), EBNA1-IgA, Rta-IgG and Zta-IgA were measure by enzyme-linked immunosorbent assay (ELISA), and EBV DNA was detected by qPCR. Statistical analyses of a single index were conducted to evaluate the significance of NPC early diagnosis and TNM classification. RESULTS: The level of EBNA1-IgA, EBV DNA, VCA-IgA, EA-IgA, Rta-IgG and Zta-IgA in early-stage NPC was significantly higher than in healthy controls (all P < 0.001). EBNA1-IgA yielded the biggest area under the curve (AUC) of 0.962 in distinguishing early-stage NPC patients from the normal subjects, with a sensitivity of 91.5% and a specificity of 98.7%. However, EBV biomarker levels were not associated with tumor size (all P > 0.050), whereas four biomarker levels (EBNA1-IgA, EBV DNA, VCA-IgA, EA-IgA) were related to lymph node metastasis (N0 and N1-2), among which EBNA1-IgA and EBV DNA showed good performance. Finally, high correlation was found between VCA-IgA and EA-IgA (r > 0.800). CONCLUSION: A single EBNA1-IgA exhibits excellent discrimination performance in early diagnosis of NPC and could become a promising marker for NPC screening.

Sepsis secondary to multifocal Enterococcus faecium infection: A case report.

INTRODUCTION: Nosocomial Enterococcus faecium (E faecium) infections are common among immunocompromised patients; however, sepsis caused by E faecium is rarely encountered in the clinical setting. PATIENT CONCERNS: A 69-year-old woman with a previous history of tuberculosis (TB), developed symptoms of recurrent fever, paroxysmal cough, and exertional dyspnea for over 2 months before she presented to the hospital. DIAGNOSIS: The patient was initially misdiagnosed with recurrent TB, and did not respond to anti-TB therapy. Culture results of blood, endotracheal necrotic tissue, and urine confirmed a diagnosis of multifocal E faecium infection. INTERVENTIONS: On definitive diagnosis, the patient received intensive antimicrobial combination treatment with linezolid, teicoplanin, caspofungin, and voriconazole on the basis of antimicrobial susceptibility results. OUTCOMES: After transient improvement, the patient's condition deteriorated due to secondary infections, and the patient died after discharge against medical advice. CONCLUSION: E faecium bacteremia may cause sepsis in immunocompromised patients, and has a high mortality rate. Careful pathogen detection and early initiation of treatment is crucial to good patient outcome.