Background and Aims
The study objective was to compare the effectiveness of microwave ablation (MWA) and laparoscopic liver resection (LLR) on solitary 3–5‐cm HCC over time.
Approach and Results
From ...2008 to 2019, 1289 patients from 12 hospitals were enrolled in this retrospective study. Diagnosis of all lesions were based on histopathology. Propensity score matching was used to balance all baseline variables between the two groups in 2008–2019 (n = 335 in each group) and 2014–2019 (n = 257 in each group) cohorts, respectively. For cohort 2008–2019, during a median follow‐up of 35.8 months, there were no differences in overall survival (OS) between MWA and LLR (HR: 0.88, 95% CI 0.65–1.19, p = 0.420), and MWA was inferior to LLR regarding disease‐free survival (DFS) (HR 1.36, 95% CI 1.05–1.75, p = 0.017). For cohort 2014–2019, there was comparable OS (HR 0.85, 95% CI 0.56–1.30, p = 0.460) and approached statistical significance for DFS (HR 1.33, 95% CI 0.98–1.82, p = 0.071) between MWA and LLR. Subgroup analyses showed comparable OS in 3.1–4.0‐cm HCCs (HR 0.88, 95% CI 0.53–1.47, p = 0.630) and 4.1–5.0‐cm HCCs (HR 0.77, 95% CI 0.37–1.60, p = 0.483) between two modalities. For both cohorts, MWA shared comparable major complications (both p > 0.05), shorter hospitalization, and lower cost to LLR (all p < 0.001).
Conclusions
MWA might be a first‐line alternative to LLR for solitary 3–5‐cm HCC in selected patients with technical advances, especially for patients unsuitable for LLR.
A patient's infectivity is determined by the presence of the virus in different body fluids, secretions, and excreta. The persistence and clearance of viral RNA from different specimens of patients ...with 2019 novel coronavirus disease (COVID-19) remain unclear. This study analyzed the clearance time and factors influencing 2019 novel coronavirus (2019-nCoV) RNA in different samples from patients with COVID-19, providing further evidence to improve the management of patients during convalescence.
The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20, 2020 to February 10, 2020 were collected retrospectively. The reverse transcription polymerase chain reaction (RT-PCR) results for patients' oropharyngeal swab, stool, urine, and serum samples were collected and analyzed. Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive (minimum 24 h sampling interval) negative RT-PCR results for viral RNA from oropharyngeal swabs. The effects of cluster of differentiation 4 (CD4)+ T lymphocytes, inflammatory indicators, and glucocorticoid treatment on viral nucleic acid clearance were analyzed.
In the 292 confirmed cases, 66 patients recovered after treatment and were included in our study. In total, 28 (42.4%) women and 38 men (57.6%) with a median age of 44.0 (34.0-62.0) years were analyzed. After in-hospital treatment, patients' inflammatory indicators decreased with improved clinical condition. The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9.5 (6.0-11.0) days. By February 10, 2020, 11 convalescent patients (16.7%) still tested positive for viral RNA from stool specimens and the other 55 patients' stool specimens were negative for 2019-nCoV following a median duration of 11.0 (9.0-16.0) days after symptom onset. Among these 55 patients, 43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs, with a median delay of 2.0 (1.0-4.0) days. Results for only four (6.9%) urine samples were positive for viral nucleic acid out of 58 cases; viral RNA was still present in three patients' urine specimens after throat swabs were negative. Using a multiple linear regression model (F = 2.669, P = 0.044, and adjusted R = 0.122), the analysis showed that the CD4+ T lymphocyte count may help predict the duration of viral RNA detection in patients' stools (t = -2.699, P = 0.010). The duration of viral RNA detection from oropharyngeal swabs and fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (15 days vs. 8.0 days, respectively; t = 2.550, P = 0.013) and the duration of viral RNA detection in fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (20 days vs. 11 days, respectively; t = 4.631, P < 0.001). There was no statistically significant difference in inflammatory indicators between patients with positive fecal viral RNA test results and those with negative results (P > 0.05).
In brief, as the clearance of viral RNA in patients' stools was delayed compared to that in oropharyngeal swabs, it is important to identify viral RNA in feces during convalescence. Because of the delayed clearance of viral RNA in the glucocorticoid treatment group, glucocorticoids are not recommended in the treatment of COVID-19, especially for mild disease. The duration of RNA detection may relate to host cell immunity.
COVID‐19 is characterized by dysregulated immune responses, metabolic dysfunction and adverse effects on the function of multiple organs. To understand host responses to COVID‐19 pathophysiology, we ...combined transcriptomics, proteomics, and metabolomics to identify molecular markers in peripheral blood and plasma samples of 66 COVID‐19‐infected patients experiencing a range of disease severities and 17 healthy controls. A large number of expressed genes, proteins, metabolites, and extracellular RNAs (exRNAs) exhibit strong associations with various clinical parameters. Multiple sets of tissue‐specific proteins and exRNAs varied significantly in both mild and severe patients suggesting a potential impact on tissue function. Chronic activation of neutrophils, IFN‐I signaling, and a high level of inflammatory cytokines were observed in patients with severe disease progression. In contrast, COVID‐19‐infected patients experiencing milder disease symptoms showed robust T‐cell responses. Finally, we identified genes, proteins, and exRNAs as potential biomarkers that might assist in predicting the prognosis of SARS‐CoV‐2 infection. These data refine our understanding of the pathophysiology and clinical progress of COVID‐19.
SYNOPSIS
Proteomics, metabolomics and RNAseq data map immune responses in COVID‐19 patients with different disease severity, revealing molecular makers associated with disease progression and alterations of tissue‐specific proteins.
A multi‐omics profiling of the host response to SARS‐CoV2 infection in 66 clinically diagnosed and laboratory confirmed COVID‐19 patients and 17 uninfected controls.
Significant correlations between multi‐omics data and key clinical parameters.
Alteration of tissue‐specific proteins and exRNAs.
Enhanced activation of immune responses is associated with COVID‐19 pathogenesis.
Biomarkers to predict COVID‐19 clinical outcomes pending clinical validation as prospective marker.
Proteomics, metabolomics and RNAseq data map immune responses in COVID‐19 patients with different disease severity, revealing molecular makers associated with disease progression and alterations of tissue‐specific proteins.
Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health
. Despite intense research efforts, how, when and where ...new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing
of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here 'WH-Human 1' coronavirus (and has also been referred to as '2019-nCoV'). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China
. This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans.
The realization of high strength, large ductility, and great toughness for polymeric materials is a vital factor for practical applications in industry. Unfortunately, until now this remains a huge ...challenge due to the common opposing trends that exist when promoting improvements in these properties using materials design strategies. In the natural world, the cuticle of mussel byssus exhibits a breaking strain as high as 100%, which is revealed to arise from an architectural granular microphase‐separated structure within the protein matrix. Herein, a facile biomimetic designed granular nanostructured polymer film is reported. Such biomimetic nanostructured polymer films show a world‐record toughness of 122 (± 6.1) J g−1 as compared with other polyvinyl alcohol films, with a breaking strain as high as 205% and a high tensile strength of 91.2 MPa, which is much superior to those of most engineering plastics. This portfolio of outstanding properties can be attributed to the unique nanoscale granular phase‐separated structure of this material. These biomimetic designed polymer films are expected to find promising applications in tissue engineering and biomaterials fields, such as artificial skin and tendon, which opens up an innovative methodology for the design of robust polymer materials for a range of innovative future applications.
Creating advanced polymers with the desired combination of high strength, great toughness, and large ductility is very challenging due to mutual exclusion between these performances. High‐performance polymer films combining exceptional toughness, large ductility, and high strength are successfully created through the design of a granular phase‐separated nanostructure by mimicking the attractive microstructure of the cuticle of mussel byssus.
We comprehensively analyzed clinical, genomic, and transcriptomic data of a cohort of 465 primary triple-negative breast cancer (TNBC). PIK3CA mutations and copy-number gains of chromosome 22q11 were ...more frequent in our Chinese cohort than in The Cancer Genome Atlas. We classified TNBCs into four transcriptome-based subtypes: (1) luminal androgen receptor (LAR), (2) immunomodulatory, (3) basal-like immune-suppressed, and (4) mesenchymal-like. Putative therapeutic targets or biomarkers were identified among each subtype. Importantly, the LAR subtype showed more ERBB2 somatic mutations, infrequent mutational signature 3 and frequent CDKN2A loss. The comprehensive profile of TNBCs provided here will serve as a reference to further advance the understanding and precision treatment of TNBC.
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•We build the genomic and transcriptomic landscape of 465 primary TNBCs•Chinese TNBC cases demonstrate more PIK3CA mutations and LAR subtype•Transcriptomic data classify TNBCs into four subtypes•Multi-omics profiling identifies potential targets within specific TNBC subtypes
Jiang et al. characterize primary Chinese triple-negative breast cancer (TNBC) and classify it into four subtypes. They find that these TNBCs have more frequent PIK3CA mutations and chromosome 22q11 copy-number gains than non-Asian TNBCs and that the LAR subtype has more ERBB2 somatic mutations and CDKN2A loss.
Type 2 diabetes (T2D) is a major comorbidity of COVID-19. However, the impact of blood glucose (BG) control on the degree of required medical interventions and on mortality in patients with COVID-19 ...and T2D remains uncertain. Thus, we performed a retrospective, multi-centered study of 7,337 cases of COVID-19 in Hubei Province, China, among which 952 had pre-existing T2D. We found that subjects with T2D required more medical interventions and had a significantly higher mortality (7.8% versus 2.7%; adjusted hazard ratio HR, 1.49) and multiple organ injury than the non-diabetic individuals. Further, we found that well-controlled BG (glycemic variability within 3.9 to 10.0 mmol/L) was associated with markedly lower mortality compared to individuals with poorly controlled BG (upper limit of glycemic variability exceeding 10.0 mmol/L) (adjusted HR, 0.14) during hospitalization. These findings provide clinical evidence correlating improved glycemic control with better outcomes in patients with COVID-19 and pre-existing T2D.
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•A cohort of 7,337 COVID-19 patients with or without diabetes was retrospectively studied•Diabetes status increased the need for medical interventions during COVID-19•Diabetes status increased the mortality risk of patients with COVID-19•Well-controlled blood glucose correlated with improved outcomes in infected patients
Type 2 diabetes (T2D) correlates with a worse outcome for COVID-19. Here, Zhu et al. show that among ∼7,300 cases of COVID-19, T2D is associated with a higher death rate, but diabetics with better controlled blood glucose die at a lower rate than diabetics with poorly controlled blood glucose.
Background and Aims
NAFLD is the most prevalent chronic liver disease without any Food and Drug Administration–approved pharmacological intervention in clinic. Fatty acid synthase (FASN) is one of ...the most attractive targets for NAFLD treatment because of its robust rate‐limiting capacity to control hepatic de novo lipogenesis. However, the regulatory mechanisms of FASN in NAFLD and potential therapeutic strategies targeting FASN remain largely unknown.
Methods and Results
Through a systematic interactomics analysis of FASN‐complex proteins, we screened and identified sorting nexin 8 (SNX8) as a binding partner of FASN. SNX8 directly bound to FASN and promoted FASN ubiquitination and subsequent proteasomal degradation. We further demonstrated that SNX8 mediated FASN protein degradation by recruiting the E3 ligase tripartite motif containing 28 (TRIM28) and enhancing the TRIM28–FASN interaction. Notably, Snx8 interference in hepatocytes significantly deteriorated lipid accumulation in vitro, whereas SNX8 overexpression markedly blocked hepatocyte lipid deposition. Furthermore, the aggravating effect of Snx8 deletion on NAFLD was validated in vivo as hepatic steatosis and lipogenic pathways in the liver were significantly exacerbated in Snx8‐knockout mice compared to wild‐type controls. Consistently, hepatocyte‐specific overexpression of Snx8 in vivo markedly suppressed high‐fat, high‐cholesterol diet (HFHC)–induced hepatic steatosis. Notably, the protective effect of SNX8 against NAFLD was largely dependent on FASN suppression.
Conclusions
These data indicate that SNX8 is a key suppressor of NAFLD that promotes FASN proteasomal degradation. Targeting the SNX8–FASN axis is a promising strategy for NAFLD prevention and treatment.
Statins are lipid-lowering therapeutics with favorable anti-inflammatory profiles and have been proposed as an adjunct therapy for COVID-19. However, statins may increase the risk of SARS-CoV-2 viral ...entry by inducing ACE2 expression. Here, we performed a retrospective study on 13,981 patients with COVID-19 in Hubei Province, China, among which 1,219 received statins. Based on a mixed-effect Cox model after propensity score-matching, we found that the risk for 28-day all-cause mortality was 5.2% and 9.4% in the matched statin and non-statin groups, respectively, with an adjusted hazard ratio of 0.58. The statin use-associated lower risk of mortality was also observed in the Cox time-varying model and marginal structural model analysis. These results give support for the completion of ongoing prospective studies and randomized controlled trials involving statin treatment for COVID-19, which are needed to further validate the utility of this class of drugs to combat the mortality of this pandemic.
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•Statin treatment among 13,981 patients with COVID-19 was retrospectively studied•Statin use in this cohort was associated with a lower risk of all-cause mortality•Adding an ACE inhibitor or an ARB did not affect statin-associated outcome in the cohort•The benefit of statins among this cohort may be due to immunomodulatory benefits
Statins have anti-inflammatory benefits and were suggested as an adjunct therapy for COVID-19. But statins may increase the expression of ACE2, the receptor for SARS-CoV-2. Here, Zhang et al. retrospectively analyzed 13,981 COVID-19 cases and found that in-hospital statin use is associated with a lower risk of all-cause mortality.
As an eco‐friendly oxide‐based thermoelectric material, Bi2O2Se exhibits considerable potential for practical device application, but its low electrical conductivity needs to be further improved to ...achieve higher thermoelectric performance. Here, a record‐high figure of merit, ZT of >0.7 at 773 K in the shear‐exfoliated nanostructured Bi2O2Se with graphite nanosheets as multifunctional secondary nanoinclusions, is achieved. The introduced graphite nanosheets regularize the arrangement of Bi2O2Se nanograins, strengthen the anisotropy, and act as the “expressway” to improve the electrical conductivity by simultaneously enhancing the electron carrier concentration and mobility of the hybrid materials, leading to a high power factor of ≈6.0 µW cm–1 K–2 at 773 K. Also, the liquid‐phase shear exfoliation refines both graphite and Bi2O2Se into nanosheets. Moreover, the as‐sintered hybrid bulk materials composed of these nanosheets possess dense grain and phase boundaries, as well as various lattice imperfections, such as lattice distortions and stacking faults formed by physical shearing, which can significantly scatter the phonons with different wavelengths and in turn contribute to a low thermal conductivity of only 0.63 W m–1 K–1 at 773 K, both contributing to a competitive ZT of ≈0.73 at this temperature, indicating the great potential for practical applications.
A high ZT of 0.73 at 773 K is achieved in graphite/Bi2O2Se hybrid bulk materials. Novel liquid‐phase shear exfoliation enables strong texturing effect on the structure, and graphite layers act as unique “expressways” to accelerate the carrier mobility. The single parabolic band model confirms the optimized carrier density and ZT.
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