A validated model to predict spread through air space in lung adenocarcinoma.

Background: Spread through air space (STAS) is currently considered to be a significant predictor of a poor outcome of pulmonary adenocarcinoma. Preoperative prediction of STAS is of great importance for treatment planning. The aim of the present study was to establish a nomogram based on computed tomography (CT) features for predicting STAS in lung adenocarcinoma and to assess the prognosis of the patients with STAS. Methods: A retrospective cohort study was performed in Wuhan Union Hospital from December 2015 to March 2021. The sample was divided into training and testing cohorts. Clinicopathologic and radiologic variables were recorded. The independent risk factors for STAS were determined by stepwise regression and then incorporated into the nomogram. Receiver operating characteristic (ROC) curves and calibration curves analysed by the Hosmer-Lemeshow test were used to evaluate the performance of the model. Decision curve analysis (DCA) was conducted to determine the clinical value of the nomogram. The Kaplan-Meier method was used for survival analysis and the multivariable Cox proportional hazards regression model was used to identify independent predictors for recurrence-free survival (RFS) and overall survival (OS). Results: The sample included 244 patients who underwent surgical resection for primary lung adenocarcinoma. The training cohort included 199 patients (68 STAS-positive and 131 STAS-negative patients), and the testing cohort included 45 patients (15 STAS-positive and 30 STAS-negative patients). The preoperative CT features associated with STAS were shape, ground-glass opacity (GGO) ratio and spicules. The nomogram including these three factors had good discriminative power, and the areas under the ROC curve were 0.875 and 0.922 for the training and testing data sets, respectively, with well-fitted calibration curves. DCA showed that the nomogram was clinically useful. STAS-positive patients had significantly worse OS and RFS than STAS-negative patients (both P<0.01). OS and RFS at 5-year for STAS-positive patients were 63.1% and 59.5%, respectively. Multivariate analysis showed that age [hazard ratio (HR), 1.1; 95% confidence interval (CI): 1.035-1.169; P=0.002], diameter (HR, 1.06; 95% CI: 1.04-1.11; P=0.03) and surgical margin (HR, 32.8; 95% CI: 6.8-158.3; P<0.001) were independent risk factors for OS. Adjuvant therapy (HR, 7.345; 95% CI: 2.52-21.41; P<0.001), N stage (N2) (HR, 0.239; 95% CI: 0.069-0.828; P=0.02) and surgical margin (HR, 15.6; 95% CI: 5.9-41.1; P<0.001) were found to be independent risk factors for RFS. Conclusions: The outcome of STAS-positive patients was worse. The nomogram incorporating the identified CT features could be applied to facilitate individualized preoperative prediction of STAS and selection of rational therapy.

Integrated metabolomics revealed the photothermal therapy of melanoma by Mo2C nanosheets: toward rehabilitated homeostasis in metabolome combined lipidome.

Melanoma, the most aggressive and life-threatening form of skin cancer, lacks innovative therapeutic approaches and deeper bioinformation. In this study, we developed a photothermal therapy (PTT) based on Mo2C nanosheets to eliminate melanoma while utilizing integrated metabolomics to investigate the metabolic shift of metabolome combined lipidome during PTT at the molecular level. Our results demonstrated that 1 mg ml-1 Mo2C nanosheets could efficiently convert laser energy into heat with a strong and stable photothermal effect (74 ± 0.9 °C within 7 cycles). Furthermore, Mo2C-based PTT led to a rapid decrease in melanoma volume (from 3.299 to 0 cm2) on the sixth day, indicating the effective elimination of melanoma. Subsequent integrated metabolomics analysis revealed significant changes in aqueous metabolites (including organic acids, amino acids, fatty acids, and amines) and lipid classes (including phospholipids, lysophospholipids, and sphingolipids), suggesting that melanoma caused substantial fluctuations in both metabolome and lipidome, while Mo2C-based PTT helped improve amino acid metabolism-related biological events (such as tryptophan metabolism) impaired by melanoma. These findings suggest that Mo2C nanosheets hold significant potential as an effective therapeutic agent for skin tumors, such as melanoma. Moreover, through exploring multidimensional bioinformation, integrated metabolomics technology provides novel insights for studying the metabolic effects of tumors, monitoring the correction of metabolic abnormalities by Mo2C nanosheet therapy, and evaluating the therapeutic effect on tumors.

Characterization of site-specific N-glycosylation signatures of isolated uromodulin from human urine.

Uromodulin (Umod, Tamm-Horsfall protein) is the most abundant urinary N-glycoprotein produced exclusively by the kidney. It can form filaments to antagonize the adhesion of uropathogens. However, the site-specific N-glycosylation signatures of Umod in healthy individuals and patients with IgA nephropathy (IgAN) remain poorly understood due to the lack of suitable isolation and analytical methods. In this study, we first presented a simple and fast method based on diatomaceous earth adsorption to isolate Umod. These isolated glycoproteins were digested by trypsin and/or Glu-C. Intact N-glycopeptides with or without HILIC enrichment were analyzed using our developed EThcD-sceHCD-MS/MS. Based on the optimized workflow, we identified a total of 780 unique intact N-glycopeptides (7 N-glycosites and 152 N-glycan compositions) from healthy individuals. As anticipated, these glycosites exhibited glycoform heterogeneity. Almost all N-glycosites were modified completely by the complex type, except for one N-glycosite (N275), which was nearly entirely occupied by the high-mannose type for mediating Umod's antiadhesive activity. Then, we compared the N-glycosylation of Umod between healthy controls (n = 9) and IgAN patients (n = 9). The N-glycosylation of Umod in IgAN patients will drastically decrease and be lost. Finally, we profiled the most comprehensive site-specific N-glycosylation map of Umod and revealed its alterations in IgAN patients. Our method provides a high-throughput workflow for characterizing the N-glycosylation of Umod, which can aid in understanding its roles in physiology and pathology, as well as serving as a potential diagnostic tool for evolution of renal tubular function.

The inflammatory cytokine profiles and ocular biometric characteristics of primary angle-closure glaucoma.

OBJECTIVE: To investigate the pathogenesis of primary angle-closure disease (PACG) by measuring the anatomical structures of the anterior and posterior segments of the eye and inflammatory markers in the peripheral blood. METHODS: This case-control study enrolled patients diagnosed with acute PACG (APACG) and chronic PACG (CPACG). It also enrolled control subjects without PACG. The anterior and posterior anatomical features were measured in all study participants. The levels of interleukin (IL)-6, tumour necrosis factor-α and the neutrophil-to-lymphocyte ratio (NLR) in the peripheral blood were measured. RESULTS: This study analysed a total of 99 eyes: 34 eyes from 34 patients with APACG, 28 eyes from 28 patients with CPACG and 37 eyes from 37 control patients with senile cataract. The axis length, corneal diameter, anterior chamber depth and anterior chamber volume were significantly smaller in the APACG and CPACG groups compared with the controls. The level of IL-6 in the peripheral blood of patients with PACG was significantly lower than that of the controls. The NLR in the peripheral blood of patients with PACG was significantly greater than that of the controls. CONCLUSIONS: Changes in the ocular anatomy and some inflammatory markers might be involved in the pathogenesis of PACG.

Site-specific N-glycosylation characterization of micro monoclonal immunoglobulins based on EThcD-sceHCD-MS/MS.

Monoclonal immunoglobulin produced by clonal plasma cells is the main cause in multiple myeloma and monoclonal gammopathy of renal significance. Because of the complicated purification method and the low stoichiometry of purified protein and glycans, site-specific N-glycosylation characterization for monoclonal immunoglobulin is still challenging. To profile the site-specific N-glycosylation of monoclonal immunoglobulins is of great interest. Therefore, in this study, we presented an integrated workflow for micro monoclonal IgA and IgG purification from patients with multiple myeloma in the HYDRASYS system, in-agarose-gel digestion, LC-MS/MS analysis without intact N-glycopeptide enrichment, and compared the identification performance of different mass spectrometry dissociation methods (EThcD-sceHCD, sceHCD, EThcD and sceHCD-pd-ETD). The results showed that EThcD-sceHCD was a better choice for site-specific N-glycosylation characterization of micro in-agarose-gel immunoglobulins (~2 µg) because it can cover more unique intact N-glycopeptides (37 and 50 intact N-glycopeptides from IgA1 and IgG2, respectively) and provide more high-quality spectra than sceHCD, EThcD and sceHCD-pd-ETD. We demonstrated the benefits of the alternative strategy in site-specific N-glycosylation characterizing micro monoclonal immunoglobulins obtained from bands separated by electrophoresis. This work could promote the development of clinical N-glycoproteomics and related immunology.

Apigenin suppresses tumor angiogenesis and growth via inhibiting HIF-1α expression in non-small cell lung carcinoma.

Tumor angiogenesis inhibitors such as Bevacizumab, Ramucirumab and Endostar have been applied to the therapy of non-small cell lung carcinoma (NSCLC) patients, especially for lung adenocarcinoma (LUAD). However, several safe concerns such as neutropenia, febrile neutropenia and hypertension pulmonary hemorrhage limit their further development. And they often showed poor efficacy and serious side effect for lung squamous cell carcinoma (LUSC) patient. Thus, identification of effective and safe tumor angiogenesis inhibitor for NSCLC therapy is warranted. Apigenin is a bioflavonoid with potential anti-tumor effect and perfect safety, but its effect on tumor angiogenesis and underlying mechanism are still unclear. Herein, we found that apigenin not merely suppressed endothelial cells related motilities but also reduced pericyte coverage. Further research showed that apigenin had strong suppressive activity against HIF-1α expression and its downstream VEGF-A/VEGFR2 and PDGF-BB/PDGFßR signaling pathway. Apigenin also reduced microvessel density and pericyte coverage on the xengraft model of NCI-H1299 cells, leading to suppression of tumor growth. Moreover, apigenein showed perfect anti-angiogenic effect in xengraft model of LUSC cell NCI-H1703 cells, indicating it may be developed into a potential angiogenesis inhibitor for LUSC patient. Collectively, our study provides new insights into the anti-tumor mechanism of apigenin and suggests that apigenin is a safe and effective angiogenesis inhibitor for NSCLC therapy.

PIWI-Interacting RNA Pathway Genes: Potential Biomarkers for Clear Cell Renal Cell Carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) is one of the most lethal malignancies in the urinary system, yet effective diagnostic and prognostic markers are lacking. Recently, several of piRNA pathway genes have been reported to be associated with cancer diagnosis and prognosis, but their role in ccRCC is still unclear. Methods: We analysed the expression of 27 piRNA pathway genes in 539 kidney renal clear cell carcinoma (KIRC) and 72 nontumor tissue samples (data from TCGA), and 12 mRNAs were significantly different. The aim was to sift the piRNA pathway genes that are correlated with ccRCC patient survival and to construct a piRNA pathway gene risk prognostic model using Kaplan-Meier survival curve and ROC curve, respectively. Results: 5 piRNA pathway genes (TDRD7, GPAT2, PLD6, SUV39H1, and DOM3Z) were picked out and used to construct the piRNA pathway gene risk model. Kaplan-Meier survival curve analysis showed that compared with that of the low-risk group of ccRCC patients, the OS of the high-risk group of ccRCC patients was significantly reduced. The predictive performance of the prognostic risk model was measured using a ROC curve, which individually showed AUC values for 1 year of 0.707, for 3 years of 0.713, and for 5 years of 0.701. Moreover, the mRNA and protein expression levels of TDRD7 were overexpressed in the ccRCC datasets (data from our cohort, TCGA, GEO, and CPTAC) and ccRCC cell lines, and the expression levels correlated with the clinicopathological characteristics in ccRCC. The Tumor Immune Estimation Resource (TIMER) showed that the mRNA expression level of TDRD7 was positively related to tumor immune infiltrating cells (TICs) in ccRCC. Mechanistically, gene set enrichment analysis (GSEA) was performed to uncover the mechanism of TDRD7 in ccRCC. In summary, the piRNA pathway genes,especially TDRD7, may be potential cancer diagnostic and prognostic biomarkers of ccRCC.

Comparative N-Glycoproteomics Analysis of Clinical Samples Via Different Mass Spectrometry Dissociation Methods.

Site-specific N-glycosylation characterization requires intact N-glycopeptide analysis based on suitable tandem mass spectrometry (MS/MS) method. Electron-transfer/higher-energy collisional dissociation (EThcD), stepped collision energy/higher-energy collisional dissociation (sceHCD), higher-energy collisional dissociation-product-dependent electron-transfer dissociation (HCD-pd-ETD), and a hybrid mass spectrometry fragmentation method EThcD-sceHCD have emerged as valuable approaches for glycoprotein analysis. However, each of them incurs some compromise, necessitating the systematic performance comparisons when applied to the analysis of complex clinical samples (e.g., plasma, urine, cells, and tissues). Herein, we compared the performance of EThcD-sceHCD with those previous approaches (EThcD, sceHCD, HCD-pd-ETD, and sceHCD-pd-ETD) in the intact N-glycopeptide analysis, and determined its applicability for clinical N-glycoproteomic study. The intact N-glycopeptides of distinct samples, namely, plasma from prostate cancer (PCa) patients, urine from immunoglobulin A nephropathy (IgAN) patients, human hepatocarcinoma cell line (HepG2), and thyroid tissues from thyroid cancer (TC) patients were analyzed by these methods. We found that EThcD-sceHCD outperformed other methods in the balance of depth and accuracy of intact N-glycopeptide identification, and sceHCD and EThcD-sceHCD have good complementarity. EThcD-sceHCD holds great potential for biomarker discovery from clinical samples.

Quantifying Myocardial Strain of the Left Ventricle in Normal People Using Feature-Tracking Based on Computed Tomography Imaging.

OBJECTIVE: The objective was to evaluate the normal value of left ventricular myocardial strain using the computed tomography feature-tracking technique and to explore the correlation between myocardial strains and cardiac function parameters. METHODS: Participants suspected of coronary heart disease were selected from 17 August 2020 to 5 November 2020 to undergo coronary computed tomography angiography using a third-generation dual-source CT scanner. Data were imported into a commercial software (Medis) after multiphase reconstruction. The cardiac function parameters, radial (Err), circumferential (Ecc), and longitudinal strain (Ell) of the left ventricle were recorded. RESULTS: A total of 87 normal subjects were enrolled, including 41 males and 46 females. For healthy subjects, the global radial strain (GRS), circumferential strain (GCS), and longitudinal strain (GLS) of the left ventricle were 74.5 ± 15.2%, -22.7 ± 3.0%, and -26.6 ± 3.2%, respectively. The Err and Ecc absolute values (|Ecc|) were the largest at the apex, and the |Ell| gradually increased from the base to the apex. The Err and |Ecc| were the largest in the lateral and inferior wall, respectively. |Ell| showed a clockwise decrease from the lateral wall in the short axis. Meanwhile, the GRS and |GLS| in females were higher than that in males. Multiple linear regression analysis showed that both SV and LVEF were the independent determinants of GRS, GCS, and GLS. BMI and CO were the independent determined factors of GCS. CONCLUSIONS: At a reasonable radiation dose, CT feature-tracking is a feasible and reproducible method to analyze left ventricular myocardial strain. Left ventricular myocardial strain in normal subjects varies in gender, segments, levels, and regions.

Deep diagnostic agent forest (DDAF): A deep learning pathogen recognition system for pneumonia based on CT.

BACKGROUND: Even though antibiotics agents are widely used, pneumonia is still one of the most common causes of death around the world. Some severe, fast-spreading pneumonia can even cause huge influence on global economy and life security. In order to give optimal medication regimens and prevent infectious pneumonia's spreading, recognition of pathogens is important. METHOD: In this single-institution retrospective study, 2,353 patients with their CT volumes are included, each of whom was infected by one of 12 known kinds of pathogens. We propose Deep Diagnostic Agent Forest (DDAF) to recognize the pathogen of a patient based on ones' CT volume, which is a challenging multiclass classification problem, with large intraclass variations and small interclass variations and very imbalanced data. RESULTS: The model achieves 0.899 ± 0.004 multi-way area under curves of receiver (AUC) for level-I pathogen recognition, which are five rough groups of pathogens, and 0.851 ± 0.003 AUC for level-II recognition, which are 12 fine-level pathogens. The model also outperforms the average result of seven human readers in level-I recognition and outperforms all readers in level-II recognition, who can only reach an average result of 7.71 ± 4.10% accuracy. CONCLUSION: Deep learning model can help in recognition pathogens using CTs only, which might help accelerate the process of etiological diagnosis.

Sequential Analysis of the N/O-Glycosylation of Heavily Glycosylated HIV-1 gp120 Using EThcD-sceHCD-MS/MS.

Deciphering the glycosylation of the viral envelope (Env) glycoprotein is critical for evaluating viral escape from the host's immune response and developing vaccines and antiviral drugs. However, it is still challenging to precisely decode the site-specific glycosylation characteristics of the highly glycosylated Env proteins, although glycoproteomics have made significant advances in mass spectrometry techniques and data analysis tools. Here, we present a hybrid dissociation technique, EThcD-sceHCD, by combining electron transfer/higher-energy collisional dissociation (EThcD) and stepped collision energy/higher-energy collisional dissociation (sceHCD) into a sequential glycoproteomic workflow. Following this scheme, we characterized site-specific N/O-glycosylation of the human immunodeficiency virus type 1 (HIV-1) Env protein gp120. The EThcD-sceHCD method increased the number of identified glycopeptides when compared with EThcD, while producing more comprehensive fragment ions than sceHCD for site-specific glycosylation analysis, especially for accurate O-glycosite assignment. Finally, eighteen N-glycosites and five O-glycosites with attached glycans were assigned unambiguously from heavily glycosylated gp120. These results indicate that our workflow can achieve improved performance for analysis of the N/O-glycosylation of a highly glycosylated protein containing numerous potential glycosites in one process. Knowledge of the glycosylation landscape of the Env glycoprotein will be useful for understanding of HIV-1 infection and development of vaccines and drugs.

[Genotype and phenotype analysis of a family with Waardenburg syndrome type â caused by a novel mutation in PAX3 gene].

Objective:To identify gene mutation and analysis the association between clinical characterizes and the mutations in a family of Waardenburg syndrome （WS） type I in Yunnan, China. Methods:With informed consent, the proband with WS phenotype and his family members were given medical history collection, physical examination and audiological evaluation. Peripheral blood was obtained, genomic DNA was extracted, and deafness related genes were detected by high-throughput sequencing. Sanger sequencing was used to verify the mutation sites of proband and his family members. Results:C. 602C>G mutation in exon 5 of PAX3 gene was identified, which is nonsense mutation and may cause a truncated protein. The mutation cause 201 amino acid of the protein changed from serine to stop codon. According to the American College of Medical Genetics and Genomics （ACMG）, it is considered as Pathogenicity（PVS1+PM2+PP3）. This mutation has not been included in the database also not been reported in the literature. Conclusion:Combined with the results of clinical diagnosis and gene diagnosis, this mutation was considered as the cause of the disease. This study enriched mutation spectrum of PAX3 gene.

[Clinical characteristics of localized Langerhans cell histiocytosis in children].

Objective:To explore the clinical features of cephalic and facial limited langerhans cell histiocytosis （LCH） in children for improving its diagnosis and treatment. Methods:Clinical data of 8 children with cephalic and facial limited LCH were retrospectively analyzed, including the onset time of disease, lesion location, imaging data, clinical manifestations and treatment strategies. Results:One case was preliminarily diagnosed as chronic inflammation with nasal back lesions, then conformed by repeated surgical pathology. Six cases were found to have simple cephalic and facial lumps without pain and swelling. One case was found to have temporal lump with suppurate in the lateral auditory canal. Five cases were treated with surgical excision of lesions. Three cases were treated with surgical excision of lesions, and continued with chemotherapy after confirmed pathological diagnosis. All cases were followed up for 2-3 years with good prognosis. Conclusion:Cephalic and facial limited LCH in children was easy to be misdiagnosed and should be regarded as animportant differential diagnosis of cephalic and facial lumps. Good outcome is achieved by treatment with surgical resection combined with adjuvant chemotherapy.

Elevated N-Glycosylation Contributes to the Cisplatin Resistance of Non-Small Cell Lung Cancer Cells Revealed by Membrane Proteomic and Glycoproteomic Analysis.

Chemoresistance is the major restriction on the clinical use of cisplatin. Aberrant changes in protein glycosylation are closely associated with drug resistance. Comprehensive study on the role of protein glycosylation in the development of cisplatin resistance would contribute to precise elucidation of the complicated mechanism of resistance. However, comprehensive characterization of glycosylated proteins remains a big challenge. In this work, we integrated proteomic and N-glycoproteomic workflow to comprehensively characterize the cisplatin resistance-related membrane proteins. Using this method, we found that proteins implicated in cell adhesion, migration, response to drug, and signal transduction were significantly altered in both protein abundance and glycosylation level during the development of cisplatin resistance in the non-small cell lung cancer cell line. Accordingly, the ability of cell migration and invasion was markedly increased in cisplatin-resistant cells, hence intensifying their malignancy. In contrast, the intracellular cisplatin accumulation was significantly reduced in the resistant cells concomitant with the down-regulation of drug uptake channel protein, LRRC8A, and over-expression of drug efflux pump proteins, MRP1 and MRP4. Moreover, the global glycosylation was elevated in the cisplatin-resistant cells. Consequently, inhibition of N-glycosylation reduced cell resistance to cisplatin, whereas promoting the high-mannose or sialylated type of glycosylation enhanced the resistance, suggesting that critical glycosylation type contributes to cisplatin resistance. These results demonstrate the high efficiency of the integrated proteomic and N-glycoproteomic workflow in discovering drug resistance-related targets, and provide new insights into the mechanism of cisplatin resistance.

[Clinic analysis of cervical lymph node lesions in children].

Objective:Explore the clinical features of cervical lymph node lesions in children with different pathological types, and provide help for the early diagnosis of the disease. Method:The data of 73 children with cervical lymph node disease diagnosed by lymph node biopsy were collected, and the gender composition, age distribution, lymph node characteristics and clinical manifestations of children with different pathological types were analyzed. Result:Among the 73 children with cervical lymph node disease, the incidence of male patients in the benign disease group was less than that of female ones, and the incidence of male patients in the malignant disease group was greater than that of female ones, the difference in gender composition between the two groups was statistically significant（P<0.05）. The benign disease group had the largest proportion in the school-age period（27.4%）, and the malignant disease group had a larger proportion in the preschool period（21.9%） and school-age period（20.5%）, both groups had a relatively smaller proportion in the infant and adolescent period, the difference in age distribution within the group was statistically significant（P<0.01）. Among the various pathological types, the proportion of 73 children with lymph node inflammatory reactive hyperplasia was the largest, 35.6%（26/73）, and was mainly at school age; the second was Hodgkin's lymphoma, accounting for 20.5%（15/73）, mainly in the preschool and school age. The average maximum transverse diameter of lymph nodes in the malignant disease group was greater than that in the benign disease group（P<0.05）. The lymph nodes in the benign disease group were mainly distributed in areas Ⅰ, Ⅱ, and Ⅲ, and the lymph nodes in the malignant disease group were mainly distributed in areas Ⅱ, Ⅲ, Ⅳ, and Ⅴ, there was a statistically significant difference in the distribution of enlarged lymph nodes between the two groups（P<0.01）. Conclusion:Different pathological types of cervical lymph node lesions in children are different in gender composition, age distribution, lymph node size and distribution, and cervical lymph node lesions in children have their own characteristics.

Quantification of myocardial strain in patients with isolated left ventricular non-compaction and healthy subjects using deformable registration algorithm: comparison with feature tracking.

BACKGROUND: Systolic dysfunction of the left ventricle is frequently associated with isolated left ventricular non-compaction (iLVNC). Clinically, the ejection fraction (EF) is the primary index of cardiac function. However, changes of EF usually occur later in the disease course. Feature tracking (FT) and deformable registration algorithm (DRA) have become appealing techniques for myocardial strain assessment. METHODS: Thirty patients with iLVNC (36.7 ± 13.3 years old) and fifty healthy volunteers (42.3 ± 13.6 years old) underwent cardiovascular magnetic resonance (CMR) examination on a 1.5 T MR scanner. Strain values in the radial, circumferential, longitudinal directions were analyzed based on the short-axis and long-axis cine images using FT and DRA methods. The iLVNC patients were further divided based on the ejection fraction, into EF ≥ 50% group (n = 11) and EF < 50% group (n = 19). Receiver-operating-characteristic (ROC) analysis was performed to assess the diagnostic performance of the global strain values. Intraclass correlation coefficient (ICC) analysis was used to evaluate the intra- and inter-observer agreement. RESULTS: Global radial strain (GRS) was statistically lower in EF ≥ 50% group compared with control group [GRS (DRA)/% vs. controls: 34.6 ± 7.0 vs. 37.6 ± 7.2, P < 0.001; GRS (FT)/% vs. controls: 37.4 ± 13.2 vs. 56.9 ± 16.4, P < 0.01]. ROC analysis of global strain values derived from DRA and FT demonstrated high area under curve (range, 0.743-0.854). DRA showed excellent intra- and inter-observer agreement of global strain in both iLVNC patients (ICC: 0.995-0.999) and normal controls (ICC: 0.934-0.996). While for FT analysis, global radial strain of normal controls showed moderate intra-observer (ICC: 0.509) and poor inter-observer agreement (ICC: 0.394). CONCLUSIONS: In patients with iLVNC, DRA can be used to quantitatively analyze the strain of left ventricle, with global radial strain being an earlier marker of LV systolic dysfunction. DRA has better reproducibility in evaluating both the global and segmental strain.

Effect of a Previous History of Antiretroviral Treatment on Clinical Picture of Patients with Co-infection of SARS-CoV-2 and HIV: A Preliminary Study.

OBJECTIVES: We aimed to explore the effect of antiretroviral treatment (ART) history on clinical characteristics of patients with co-infection of SARS-CoV-2 and HIV. METHODS: We retrospectively reviewed 20 patients with laboratory-confirmed co-infection of SARS-CoV-2 and HIV in a designated hospital. Patients were divided into medicine group (n = 12) and non-medicine group (n = 8) according to previous ART history before SARS-CoV-2 infection. RESULTS: The median age was 46.5 years and 15 (75%) were female. Ten patients had initial negative RT-PCR on admission, 5 of which had normal CT appearance and 4 were asymptomatic. Lymphocytes were low in 9 patients (45%), CD4 cell count and CD4/CD8 were low in all patients. The predominant CT features in 19 patients were multiple (42%) ground-glass opacities (58%) and consolidations (32%). Erythrocyte sedimentation rate (ESR) in the medicine group was significantly lower than that in the non-medicine group [median (interquartile range, IQR):14.0 (10.0-34.0) vs. 51.0 (35.8-62.0), P = 0.005]. Nineteen patients (95%) were discharged with a median hospital stay of 30 days (IQR, 26-30). CONCLUSIONS: Most patients with SARS-CoV-2 and HIV co-infection exhibited mild to moderate symptoms. The milder extent of inflammatory response to SARS-CoV-2 infection might be associated with a previous history of ART in HIV-infected patients.

CT features associated with EGFR mutations and ALK positivity in patients with multiple primary lung adenocarcinomas.

BACKGROUND: In multiple primary lung adenocarcinomas (MPLAs), the relationship between imaging and gene mutations remains unclear. This retrospective study aimed to identify the correlation of epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) status with CT characteristics in MPLA patients. METHODS: Sixty-seven patients (135 lesions) with MPLAs confirmed by pathology were selected from our institution. All subjects were tested for EGFR mutations and ALK status and underwent chest CT prior to any treatment. The criteria for MPLA definitions closely adhered to the comprehensive histologic assessment (CHA). RESULTS: Among MPLA patients, EGFR mutations were more common in females (p = 0.002), in those who had never smoked (p = 0.010), and in those with less lymph node metastasis (p < 0.001), and the tumours typically presented with ground-glass opacity (GGO) (p = 0.003), especially mixed GGO (p < 0.001), and with air bronchograms (p = 0.012). Logistics regression analysis showed that GGO (OR = 6.550, p = 0.010) was correlated with EGFR mutation, while air bronchograms were not correlated with EGFR mutation (OR = 3.527, p = 0.060). A receiver operating characteristic (ROC) curve yielded area under the curve (AUC) values of 0.647 and 0.712 for clinical-only or combined CT features, respectively, for prediction of EGFR mutations, and a significant difference was found between them (p = 0.0344). ALK-positive status was found most frequently in MPLA patients who were younger (p = 0.002) and had never smoked (p = 0.010). ALK positivity was associated with solid nodules or masses in MPLAs (p < 0.004) on CT scans. Logistics regression analysis showed that solid nodules (OR = 6.550, p = 0.010) were an independent factor predicting ALK positivity in MPLAs. For prediction of ALK positivity, the ROC curve yielded AUC values of 0.767 and 0.804 for clinical-only or combined CT features, respectively, but no significant difference was found between them (p = 0.2267). CONCLUSION: Among MPLA patients, nonsmoking women with less lymph node metastasis and patients with lesions presenting GGO or mixed GGO and air bronchograms on CT were more likely to exhibit EGFR mutations. In nonsmoking patients, young patients with solid lesions on CT are recommended to undergo an ALK status test.

Hypolipidemia is associated with the severity of COVID-19.

BACKGROUND: Many patients with coronavirus disease 2019 (COVID-19) suffer multiple organ dysfunctions. However, whether patients develop dyslipidemia is unknown. OBJECTIVE: In this study, we aimed to investigate the pathological alterations of low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and total cholesterol (TC) in COVID-19 patients and their relationships with the disease severity. METHODS: A retrospective study was performed to examine serum levels of LDL-c, HDL-c, and TC on 597 COVID-19 patients (mild: 394; severe, 171; critical: 32) who were hospitalized in our center between February 1 and March 3, 2020. Age- and gender-matched normal subjects (n = 50) who had routine laboratory lipid tests between October 1 and November 1, 2019 in our center were included as the control group. RESULTS: LDL-c and TC levels were significantly lower in COVID-19 patients as compared with normal subjects (P < .001). There were significant and gradual decreases in levels of LDL-c (median (IQR) in mg/dL, mild: 91 (76, 104); severe: 86 (69, 102); critical: 69 (48, 81); P < .02) and TC (mild: 173 (148, 203); severe: 167 (138, 197); critical: 125 (95, 162); P < .05) across all three groups. HDL-c levels only decreased significantly in critical cases as compared with levels in mild and severe cases. LDL-c and TC levels inversely correlated with C-reactive protein and interleukin-6, and positively correlated with the number of lymphocytes in patients. CONCLUSIONS: Development of hypolipidemia begins in patients with mild symptoms. It progressively becomes worse in an association with the disease severity.