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1.
Int J Med Sci ; 18(11): 2276-2284, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33967603

RESUMO

Objectives: To develop and validate radiomics nomograms for the pretreatment predictions of overall survival (OS) and time to progression (TTP) in the patients with advanced hepatocellular carcinoma (HCC) treated with apatinib plus transarterial chemoembolization (TACE), and to assess the incremental value of the clinical-radiomics nomograms for estimating individual OS and TTP. Methods: A total of 60 patients with advanced HCC (BCLC stage C) treated with apatinib plus TACE were divided into a training set (n=48) and a validation set (n=12). The predictors identified from the clinical variables and the radiomics signature constructed from the computed tomography images, such as ɑ-fetoprotein level (AFP), formfactor, the grey level co-occurrence matrix, the gray level size zone matrix, and the gray level run-length matrix, were used to build the clinical-radiomics nomograms and the radiomics nomograms for the prediction of OS and TTP. Results: Apatinib plus TACE benefited the patients with advanced HCC, with a 579-day median OS and a 270-day median TTP. The nomograms were built with the radiomics signature and AFP, and achieved favorable prediction efficacy with acceptable calibration curves. Decision curve analyses demonstrated that the clinical-radiomics nomograms outperformed the radiomics nomograms for the predictions of OS and TTP. Conclusions: Apatinib plus TACE may improve OS and prolonged TTP in the patients with advanced HCC. The clinical-radiomics nomograms, a noninvasive pretreatment prediction tool that incorporate radiomics signature and AFP, demonstrated good prediction accuracy for OS and TTP in these patients. These results indicate that the clinical-radiomics nomograms may provide novel insight for precise personalized medicine approaches in the patients with advanced HCC.

2.
Cancer Sci ; 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33932069

RESUMO

Reactive oxygen species (ROS) derived from aberrant tumor metabolism could contribute to tumor invasion and metastasis. NAD(P)HX Epimerase (NAXE), an epimerase that allows the repair of damaged forms of antioxidant NADPH, is a potential cellular ROS scavenger and its role in tumor development is still elusive. Here, we found that NAXE is significantly downregulated in hepatocellular carcinoma (HCC) tissues and cell lines. NAXE downregulation is associated with poor clinicopathological characteristics and is an independent risk factor for overall and disease-free survival of HCC patients after liver resection. In addition, low NAXE expression could identify worse prognosis of HCC patients before vascular invasion or in early stages of disease. In particularly, low NAXE expression in HCC is markedly associated with microvascular invasion (MVI) and its combination with MVI predicts poorer prognosis of HCC patients after liver resection. Furthermore, in vitro and in vivo experiments both showed that knockdown of NAXE expression in HCC cells promoted migration, invasion, and metastasis by inducing epithelial-mesenchymal transition (EMT), whereas NAXE overexpression causes the opposite effects. Mechanistically, low NAXE expression reduced NADPH levels and further caused ROS level increase and hypoxia-inducible factor-1α (HIF-1α) activation, thereby promoting invasion and metastasis of HCC by facilitating EMT. What is more, the tumor-promoting effect of NAXE knockdown in HCC xenograft can be abolished by giving mice N-acetyl-l-cysteine (NAC) in drinking water. Taken together, our findings uncovered a tumor suppressor role for NAXE in HCC by scavenging excessive ROS and inhibiting tumor-promoting signaling pathways, suggesting a new strategy for HCC therapy by targeting redox signaling.

3.
Int J Lab Hematol ; 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33847065

RESUMO

INTRODUCTION: Infantile leukemia encompasses a heterogeneous group which needs stratifying for treatment selection. METHODS: We collected 78 cases of infantile leukemia and retrospectively analyzed their clinicopathological data. RESULTS: Infantile leukemia featured a ratio of acute myeloid leukemia (AML) to B-lymphoblastic leukemia (B-ALL) of 1:2, with a better survival for AML than B-ALL (median survival 36 vs 24 months). When stratified by age, "early" infantile B-ALL (2-6 months) showed a high rate of KMT2A rearrangement (100%), similar to the rate seen in congenital B-ALL (1 month) (100%) and higher than seen in "late" infantile B-ALL (≥7 months) (68%). The three categories of infantile B-ALL exhibited an age-dependent increase in survival (median survival 8.5, 24, and >24 months, respectively). The age-dependent survival benefit remained after excluding the cases negative for KMT2A rearrangement. Conversely, infantile AML lacked an age-dependent pattern of survival. CONCLUSION: The clinical outcome of infantile leukemia depends on the type of leukemia. Given the age-dependent survival, infantile B-ALL can be divided into three subcategories.

4.
Virol Sin ; 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33835391

RESUMO

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused more than 96 million infections and over 2 million deaths worldwide so far. However, there is no approved vaccine available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the disease causative agent. Vaccine is the most effective approach to eradicate a pathogen. The tests of safety and efficacy in animals are pivotal for developing a vaccine and before the vaccine is applied to human populations. Here we evaluated the safety, immunogenicity, and efficacy of an inactivated vaccine based on the whole viral particles in human ACE2 transgenic mouse and in non-human primates. Our data showed that the inactivated vaccine successfully induced SARS-CoV-2-specific neutralizing antibodies in mice and non-human primates, and subsequently provided partial (in low dose) or full (in high dose) protection of challenge in the tested animals. In addition, passive serum transferred from vaccine-immunized mice could also provide full protection from SARS-CoV-2 infection in mice. These results warranted positive outcomes in future clinical trials in humans.

5.
Drug Metab Dispos ; 49(5): 369-378, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33674269

RESUMO

Deoxycholic acid (DCA, 3α, 12α-dihydroxy-5ß-cholan-24-oic acid) is the major circulating secondary bile acid, which is synthesized by gut flora in the lower gut and selectively oxidized by CYP3A into tertiary metabolites, including 1ß,3α,12α-trihydroxy-5ß-cholan-24-oic acid (DCA-1ß-ol) and 3α,5ß,12α-trihydroxy-5ß-cholan-24-oic acid (DCA-5ß-ol) in humans. Since DCA has the similar exogenous nature and disposition mechanisms as xenobiotics, this work aimed to investigate whether the tertiary oxidations of DCA are predictive of in vivo CYP3A activities in beagle dogs. In vitro metabolism of midazolam (MDZ) and DCA in recombinant canine CYP1A1, 1A2, 2B11, 2C21, 2C41, 2D15, 3A12, and 3A26 enzymes clarified that CYP3A12 was primarily responsible for either the oxidation elimination of MDZ or the regioselective oxidation metabolism of DCA into DCA-1ß-ol and DCA-5ß-ol in dog liver microsomes. Six male dogs completed the CYP3A intervention studies including phases of baseline, inhibition (ketoconazole treatments), recovery, and induction (rifampicin treatments). The oral MDZ clearance after a single dose was determined on the last day of the baseline, inhibition, and induction phases, and subjected to correlation analysis with the tertiary oxidation ratios of DCA detected in serum and urine samples. The results confirmed that the predosing serum ratios of DCA oxidation, DCA-5ß-ol/DCA, and DCA-1ß-ol/DCA were significantly and positively correlated both intraindividually and interindividually with oral MDZ clearance. It was therefore concluded that the tertiary oxidation of DCA is predictive of CYP3A activity in beagle dogs. Clinical transitional studies following the preclinical evidence are promising to provide novel biomarkers of the enterohepatic CYP3A activities. SIGNIFICANCE STATEMENT: Drug development, clinical pharmacology, and therapeutics are under insistent demands of endogenous CYP3A biomarkers that avoid unnecessary drug exposure and invasive sampling. This work has provided the first proof-of-concept preclinical evidence that the CYP3A catalyzed tertiary oxidation of deoxycholate, the major circulating secondary bile acid synthesized in the lower gut by bacteria, may be developed as novel in vivo biomarkers of the enterohepatic CYP3A activities.

6.
Cancer Lett ; 506: 128-141, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-33705863

RESUMO

Metastasis remains the major obstacle of improving the survival of patients with hepatocellular carcinoma (HCC). Epithelial-mesenchymal transition (EMT) is critical to cancer metastasis. Successful induction of EMT requires dramatic cytoskeleton rearrangement. However, the significance of microtubule (MT), one of the core components of cell cytoskeleton, in this process remains largely unknown. Here we revealed that STMN2, an important MT dynamics regulator, is barely expressed in normal live tissues but markedly up-regulated in HCCs, especially in those with early recurrence. High STMN2 expression correlates with aggressive clinicopathological features and predicts poor prognosis of HCC patients. STMN2 overexpression in HCC cells promotes EMT, invasion and metastasis in vitro and in vivo, whereas STMN2 knockdown has opposite results. Mechanistically, STMN2 modulates MTs disassembly, disrupts MT-Smad complex, and facilitates release from MT network, phosphorylation and nuclear translocation of Smad2/3 even independent of TGFß stimulation, thereby enhancing TGFß signaling. Collectively, STMN2 orchestrates MT disassembly to facilitate EMT via TGF-ß signaling, providing a novel insight into the mechanisms underlying cancer metastasis. STMN2 is a promising prognostic biomarker and potential therapeutic target for HCC.

7.
Clin Sci (Lond) ; 135(7): 847-864, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33755094

RESUMO

Metastasis is the main cause of poor postoperative survival of hepatocellular carcinoma (HCC) patients. Cytoskeleton rearrangement is a key event in cancer metastasis. However, the significance of microtubule (MT), one of the core components of cytoskeleton, in this process is only beginning to be revealed. Here, we find that the MT dynamics regulator end-binding protein 2 (EB2) is highly expressed in HCC and predicts poor prognosis of HCC patients. Functional studies show that EB2 overexpression promotes HCC proliferation, invasion and metastasis in vitro and in vivo, while EB2 knockdown has opposite results. Mechanistically, EB2 mediates MTs destabilization, increases Src (Src proto-oncogene non-receptor tyrosine kinase) activity, and thus facilitates extracellular signal-regulated kinase (ERK) signaling activation, which could in turn promote EB2 expression in HCC, eventually resulting in enhanced HCC proliferation, invasion and metastasis. Furthermore, U0126, a specific ERK inhibitor, could effectively inhibit EB2-mediated HCC proliferation and metastasis in vitro and in vivo. In conclusion, EB2 coordinates MT cytoskeleton and intracellular signal transduction, forming an EB2-MT-ERK positive feedback loop, to facilitate HCC proliferation, invasion and metastasis. EB2 could serve as a promising prognostic biomarker and potential therapeutic target for HCC; HCC patients with high EB2 expression may benefit from treatment with ERK inhibitors.

8.
Pharmacol Res ; 166: 105527, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33667689

RESUMO

The invasion and metastasis of tumor cells are the hallmarks of malignant diseases and the greatest obstacle to overcome. Heparanase-mediated degradation of heparan sulfate (HS) is the critical process for tumor angiogenesis and metastasis, therefore, heparanase become an attractive target for cancer research. Herein, we reported a native fucosylated glycosaminoglycan (nHG) extracted from sea cucumber Holothuria fuscopunctata and a depolymerized nHG (dHG) and its contained oligosaccharides (hs17, hs14, hs11, hs8 and hs5), acting as heparanase inhibitors. nHG and its derivatives have the ability to bind with heparanase directly, leading to significant inhibition of heparanase activity. Moreover, their apparent binding affinity to heparanase was comparable to their inhibitory effect, which was elevated along with the increase of chain length, similar to the effect of heparins. In addition, oligosaccharides inhibited the migration and invasion of 4T1 mammary carcinoma cells and human umbilical vein endothelial cells (HUVECs) and also suppressed tube formation in Matrigel matrix and angiogenesis in the chick chorioallantoic membrane (CAM) assay. In the metastatic mouse model, oligosaccharides exhibited practical antimetastatic effects on 4T1 mammary carcinoma cells. According to the reported anticoagulant activity and the low bleeding tendency of dHG and its oligosaccharides, the use of the oligosaccharides may lead to better effects on tumor patients with thrombosis tendency.

9.
BMC Health Serv Res ; 21(1): 187, 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33639939

RESUMO

BACKGROUND: Smoking exerts substantial medical burdens on society. Precise estimation of the smoking-attributable medical expenditures (SAME) helps to inform tobacco control policy makers. Based on the epidemiological approach, prior studies in China only focused on a few smoking-related diseases to estimate SAME. In contrast, this study used the econometric approach, which is capable of capturing all of the potential costs. METHODS: Three waves of panel data from the 2011-2015 national China Health and Retirement Longitudinal Study (CHARLS) were used. A total of 34,503 observations aged 45 and above were identified. Estimates from econometric models were combined to predict the smoking-attributable fraction (SAF) and medical expenditures attributable to smoking by sex, registered residency and healthcare service categories. All monetary amounts were adjusted to 2015 dollars. RESULTS: In 2015, the overall smoking-attributable fraction (SAF) of China was 10.97%, ranging from 5.77% for self-medication to 16.87% for inpatient visits. The smoking-attributable medical expenditure (SAME) was about $45.28 billion, accounting for 7.24% of the total health expenditure. The SAME was $226.77 per smoker aged 45 and above. The regression results suggest that being a former smoker has the greatest impact, which decreases over time after quitting however, on the value of medical expenditures. CONCLUSIONS: Smoking-attributable medical expenditures was substantial and placed a heavy burden on Chinese society. Comprehensive tobacco control policies and regulations are still needed to promote progress toward curbing the tobacco related losses.


Assuntos
Custos de Cuidados de Saúde , Fumar , China/epidemiologia , Gastos em Saúde , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Modelos Econométricos , Fumar/epidemiologia
10.
Vet Parasitol ; 291: 109326, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33545560

RESUMO

Parabronemosis is a disease that severely threatens camel health, causing huge economic losses to industries involved in camel husbandry. Previous studies have reported that horn flies (Haematobia irritans) act as intermediate hosts of Parabronema skrjabini; however, the infection and developmental processes of P. skrjabini in horn flies remain unclear. In the present study, the infection rates of P. skrjabini were determined in morphologically and molecularly identified horn flies collected from Bactrian camels (Camelus bactrianus) producing regions in Inner Mongolia, China that have high P. skrjabini infection rates. The horn flies were dissected to obtain the nematode larvae at various instar stages. The P. skrjabini found in the different instar stages of horn fly instars were counted and identified to assess the infection and developmental status. Nematode larvae at different developmental stages were obtained from the horn fly instars for further molecular analysis. Sequencing results confirmed that the nematode larvae were P. skrjabini. Furthermore, we found that the mean growth rate of the nematode larva increased as the horn fly instars develops. The results suggested that P. skrjabini infected the horn flies at the larval instar stage, and that the nematode larvae developed simultaneously with the horn fly instars stages. Our findings provide useful information into the elucidation of P. skrjabini infection and life history by studying horn fly development.

11.
World Neurosurg ; 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33561552

RESUMO

BACKGROUND: This study explored diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) to assess the prognosis of thoracolumbar spinal cord injury (SCI). METHODS: Twenty patients with acute traumatic thoracolumbar complete SCI (T1-L1, American Spinal Injury Association Impairment Scale [AIS] grade A) underwent conventional magnetic resonance imaging and DTI examinations. DTI measured the fractional anisotropy (FA) and apparent diffusion coefficient adjacent to the lesion epicenter. DTT was used to detect the white matter fiber morphology and measure the imaginary white matter fiber volume and connection rates of fiber tractography (CRFT). The patients' neurological functions were evaluated by the AIS grades. RESULTS: At the final-follow-up, among the 20 patients with AIS grade A, 15 maintained the AIS grade (group A), and 5 patients showed improvement of AIS grade (group B). Group A's mean FA value was significantly lower than that of group B, whereas the mean apparent diffusion coefficient value among the 2 groups showed no significant difference. The white matter fibers of most patients in group A were completely ruptured (11/15), but the white matter fibers of all patients in group B were retained in different number (5/5). The mean CRFT of group B was significantly higher than that of group A (P < 0.05). The improvement of AIS grade was slightly positively correlated with FA values and highly positively correlated with CRFT. CONCLUSIONS: The prognosis of complete thoracolumbar SCI may be related to the FA value and the CRFT. The application of DTI and DTT may optimize the diagnosis of thoracolumbar SCI.

12.
Medicine (Baltimore) ; 100(6): e24699, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33578605

RESUMO

RATIONALE: Pulmonary artery intimal sarcoma is a rare tumor with exceptionally high mortality and easily misdiagnosed as pulmonary thromboembolism pulmonary thromboembolism (PTE) due to the nonspecific clinical presentation and symptom. Misdiagnosis or untimely diagnosis makes the disease progress to an advanced stage and eventually leads to a poor prognosis. PATIENT CONCERNS: A 37-year-old Chinese female presented with chest tightness and dyspnea for 3 months. Echocardiography and chest computed tomography revealed an intraluminal obstruction of the pulmonary arteries. Tests of serum tumor makers showed slight elevation for carbohydrate antigen-125, and α-fetoprotein. PTE was suspected according to the radiological and laboratory findings. DIAGNOSIS: Microscopic findings of the presumed thrombus showed prominent myxoid and edematous background with atypical spindled cells and curvilinear vascularity. Immunohistochemical staining demonstrated that the atypical spindled cells were positive for vimentin but negative for CK, S100, SMA, desmin, CD68, STAT6, CD34, ß-catenin, ALK-p80, p53, and MDM2. According to the radiological and pathological findings, the diagnosis of fibrosarcoma of pulmonary artery was made. INTERVENTIONS: The patient underwent surgical resection and the mass was excised as completely as possible. OUTCOME: Follow-up information showed no evidence of recurrence or metastasis after 3 months postresection. LESSONS: Because of the low incidence rate, nonspecific clinical symptoms, and radiological findings, primary fibrosarcoma of the pulmonary artery is commonly misdiagnosed as PTE. Pathological examination is necessary to confirm the diagnosis.


Assuntos
Fibrossarcoma/diagnóstico , Artéria Pulmonar/diagnóstico por imagem , Embolia Pulmonar/diagnóstico , Túnica Íntima/patologia , Adulto , Assistência ao Convalescente , Grupo com Ancestrais do Continente Asiático/etnologia , Antígeno Ca-125/metabolismo , Erros de Diagnóstico/prevenção & controle , Erros de Diagnóstico/estatística & dados numéricos , Ecocardiografia/métodos , Feminino , Fibrossarcoma/sangue , Fibrossarcoma/patologia , Fibrossarcoma/cirurgia , Humanos , Embolia Pulmonar/patologia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Vimentina/metabolismo , alfa-Fetoproteínas/metabolismo
13.
J Clin Pathol ; 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33542108

RESUMO

AIMS: Myeloid neoplasms occur in the setting of chronic lymphocytic leukaemia (CLL)/CLL-like disease. The underlying pathogenesis has not been elucidated. METHODS: Retrospectively analysed 66 cases of myeloid neoplasms in patients with CLL/CLL-like disease. RESULTS: Of these, 33 patients (group 1) had received treatment for CLL/CLL-like disease, while the other 33 patients (group 2) had either concurrent diagnoses or untreated CLL/CLL-like disease before identifying myeloid neoplasms. The two categories had distinct features in clinical presentation, spectrum of myeloid neoplasm, morphology, cytogenetic profile and clinical outcome. Compared with group 2, group 1 demonstrated a younger age at the diagnosis of myeloid neoplasm (median, 65 vs 71 years), a higher fraction of myelodysplastic syndrome (64% vs 36%; OR: 3.1; p<0.05), a higher rate of adverse unbalanced cytogenetic abnormalities, including complex changes, -5/5q- and/or -7/7q- (83% vs 28%; OR: 13.1; p<0.001) and a shorter overall survival (median, 12 vs 44 months; p<0.05). CONCLUSIONS: Myeloid neoplasm in the setting of CLL/CLL-like disease can be divided into two categories, one with prior treatment for CLL/CLL-like disease and the other without. CLL-type treatment may accelerate myeloid leukaemogenesis. The risk is estimated to be 13-fold higher in patients with treatment than those without. The causative agent could be attributed to fludarabine in combination with alkylators, based on the latency of myeloid leukaemogenesis and the cytogenetic profile.

14.
Sci Rep ; 11(1): 417, 2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33432072

RESUMO

This study aims to explore and compare a novel deep learning-based quantification with the conventional semi-quantitative computed tomography (CT) scoring for the serial chest CT scans of COVID-19. 95 patients with confirmed COVID-19 and a total of 465 serial chest CT scans were involved, including 61 moderate patients (moderate group, 319 chest CT scans) and 34 severe patients (severe group, 146 chest CT scans). Conventional CT scoring and deep learning-based quantification were performed for all chest CT scans for two study goals: (1) Correlation between these two estimations; (2) Exploring the dynamic patterns using these two estimations between moderate and severe groups. The Spearman's correlation coefficient between these two estimation methods was 0.920 (p < 0.001). predicted pulmonary involvement (CT score and percent of pulmonary lesions calculated using deep learning-based quantification) increased more rapidly and reached a higher peak on 23rd days from symptom onset in severe group, which reached a peak on 18th days in moderate group with faster absorption of the lesions. The deep learning-based quantification for COVID-19 showed a good correlation with the conventional CT scoring and demonstrated a potential benefit in the estimation of disease severities of COVID-19.


Assuntos
/diagnóstico por imagem , Aprendizado Profundo , Pulmão/diagnóstico por imagem , Tórax/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
15.
Spine (Phila Pa 1976) ; 46(10): 687-694, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33395024

RESUMO

STUDY DESIGN: Retrospective observational cohort study. OBJECTIVE: We explored the relationship between diffusion tensor imaging (DTI) parameters and prognosis in patients with acute traumatic cervical spinal cord injury (ATCSCI). SUMMARY OF BACKGROUND DATA: DTI has been used to diagnose spinal cord injury; nevertheless, its role remains controversial. METHODS: We analyzed retrospectively 24 patients with ATCSCI who were examined using conventional T2-weighted imaging and DTI. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were recorded at the injured site. Diffusion tensor tractography (DTT) was used to measure the spinal cord white matter fiber volume (MWFV). American Spinal Injury Association (ASIA) grades were recorded. Correlations between DTI parameters and ASIA scores were evaluated using Spearman correlation coefficients. RESULTS: FA values at injured sites were significantly lower than those of the control group, whereas ADC values in injured and control groups were not significantly different. DTT revealed that ATCSCI could be divided into four types: Type A1-complete rupture of spinal cord white matter fiber (MWF); Type A2-partial rupture of MWF; Type B-most MWF retained with severe compression or abnormal fiber conduction direction; and Type C-MWF basically complete with slight compression. Preoperative physical examinations revealed complete injury (ASIA A) in patients with A1 (n = 4) and A2 (n = 4). The ASIA grades or scores of A2 were improved to varying degrees, whereas there was no significant improvement in A1. FA values and MWFV of ASIA B, C, and D were significantly higher than those of ASIA A. FA and MWFV were correlated with ASIA motor score preoperatively and at final follow-up. CONCLUSION: We propose a classification for the severity of ATCSCI based on DTI and DTT that may explain why some patients with ASIA A recover, whereas others do not.Level of Evidence: 4.

16.
Acta Diabetol ; 58(5): 575-586, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33420614

RESUMO

AIMS: Increasing evidence suggests that poor glycemic control in diabetic individuals is associated with poor coronavirus disease 2019 (COVID-19) pneumonia outcomes and influences chest computed tomography (CT) manifestations. This study aimed to explore the impact of diabetes mellitus (DM) and glycemic control on chest CT manifestations, acquired using an artificial intelligence (AI)-based quantitative evaluation system, and COVID-19 disease severity and to investigate the association between CT lesions and clinical outcome. METHODS: A total of 126 patients with COVID-19 were enrolled in this retrospective study. According to their clinical history of DM and glycosylated hemoglobin (HbA1c) level, the patients were divided into 3 groups: the non-DM group (Group 1); the well-controlled blood glucose (BG) group, with HbA1c < 7% (Group 2); and the poorly controlled BG group, with HbA1c ≥ 7% (Group 3). The chest CT images were analyzed with an AI-based quantitative evaluation system. Three main quantitative CT features representing the percentage of total lung lesion volume (PLV), percentage of ground-glass opacity volume (PGV) and percentage of consolidation volume (PCV) in bilateral lung fields were used to evaluate the severity of pneumonia lesions. RESULTS: Patients in Group 3 had the highest percentage of severe or critical illness, with 12 (32%) cases, followed by 6 (11%) and 7 (23%) cases in Groups 1 and 2, respectively (p = 0.042). The composite endpoints, including death or using mechanical ventilation or admission to the intensive care unit (ICU), were 3 (5%), 5 (16%) and 10 (26%) in Groups 1, 2 and 3, respectively (p = 0.013). The PLV, PGV and PCV in bilateral lung fields were significantly different among the three groups (all p < 0.001): the median PLVs were 12.5% (Group 3), 3.8% (Group 2) and 2.4% (Group 1); the median PGVs were 10.2% (Group 3), 3.6% (Group 2) and 1.9% (Group 1); and the median PCVs were 1.8% (Group 3), 0.3% (Group 2) and 0.1% (Group 1). In the linear regression analyses, which were adjusted for age, sex, BMI, and comorbidities, HbA1c remained positively associated with PLV (ß = 0.401, p < 0.001), PGV (ß = 0.364, p = 0.001) and PCV (ß = 0.472, p < 0.001); this relationship was also observed between fasting blood glucose (FBG) and the three CT quantitative parameters. In the logistic regression analyses, PLV [OR 1.067 (1.032, 1.103)], PGV [OR 1.076 (1.034, 1.120)] and PCV [OR 1.280 (1.110, 1.476)] levels were independent predictors of the composite endpoints, as well as the areas under the ROC (AUCs) for PLV [AUC 0.796 (0.691, 0.900)], PGV [AUC 0.783 (0.678, 0.889)] and PCV [AUC 0.816 (0.722, 0.911)]; the ORs were still significant for CT lesions after adjusting for age, sex and poorly controlled diabetes. CONCLUSIONS: Increased blood glucose level was correlated with the severity of lung involvement, as evidenced by certain chest CT parameters, and clinical prognosis in diabetic COVID-19 patients. There was a positive correlation between blood glucose level (both HbA1c and FBG) on admission and lung lesions. Moreover, the CT lesion severity by AI quantitative analysis was correlated with clinical outcomes.


Assuntos
Glicemia/análise , Diabetes Mellitus/epidemiologia , Adulto , Idoso , Inteligência Artificial , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos
17.
Oncogene ; 40(8): 1440-1457, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33420372

RESUMO

Pancreatic cancer is lethal in over 90% of cases since it is resistant to current therapeutic strategies. The key role of STAT3 in promoting pancreatic cancer progression has been proven, but effective interventions that suppress STAT3 activities are limited. The development of novel anticancer agents that directly target STAT3 may have potential clinical benefits for pancreatic cancer treatment. Here, we report a new small-molecule inhibitor (N4) with potent antitumor bioactivity, which inhibits multiple oncogenic processes in pancreatic cancer. N4 blocked STAT3 and phospho-tyrosine (pTyr) peptide interactions in fluorescence polarization (FP) assay, specifically abolished phosphor-STAT3 (Tyr705), and suppressed expression of STAT3 downstream genes. The mechanism involved the direct binding of N4 to the STAT3 SH2 domain, thereby, the STAT3 dimerization, STAT3-EGFR, and STAT3-NF-κB cross-talk were efficiently inhibited. In animal models of pancreatic cancer, N4 was well tolerated, suppressed tumor growth and metastasis, and significantly prolonged survival of tumor-bearing mice. Our results offer a preclinical proof of concept for N4 as a candidate therapeutic compound for pancreatic cancer.

18.
World Neurosurg ; 148: e227-e241, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33418121

RESUMO

OBJECTIVE: The cause of surfer myelopathy remains enigmatic and long-term follow-up outcomes are not well documented. In the present study, the mechanisms underlying surfer myelopathy in children are analyzed and the long-term follow-up outcomes are reported. METHODS: Clinical data from 3 institutions were retrospectively analyzed. Patients were assessed using the American Spinal Injury Association Impairment Scale (AIS) on admission and at follow-up. The mechanisms were studied by analyzing patients' medical history, magnetic resonance imaging, and magnetic resonance angiography. The prognosis of long-term follow-up was summarized. RESULTS: Thirty-one children were diagnosed with surfer myelopathy. Intramedullary high-intensity T2 signal from mid to lower thoracic level to conus was found during the acute stage. Follow-up magnetic resonance imaging in the subacute stage showed cranial progression of the T2 hyperintensity up to 1-10 vertebral segments, and no neurologic deterioration was found. Intramedullary lesion length between the complete and incomplete injury was significantly different (P < 0.01) in the subacute phase. Flow voids around nerve roots and in the epidural space were detected in 18 patients and 15 patients, respectively, on axial T2-weighted imaging. Enlarged tortuous veins were found in 3 of 6 patients who underwent spinal magnetic resonance angiography, which were discontinuous around nerve root. During long-term follow-up, no patients with AIS grade A recovered, and atrophic cord was observed in the later stage in 14 patients. Patients with incomplete injury had different recoveries. CONCLUSIONS: Surfer myelopathy in children is caused by spinal venous hypertension. The AIS grade on admission is a predictor of prognosis.

19.
Cell Res ; 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33262453

RESUMO

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic worldwide. Currently, however, no effective drug or vaccine is available to treat or prevent the resulting coronavirus disease 2019 (COVID-19). Here, we report our discovery of a promising anti-COVID-19 drug candidate, the lipoglycopeptide antibiotic dalbavancin, based on virtual screening of the FDA-approved peptide drug library combined with in vitro and in vivo functional antiviral assays. Our results showed that dalbavancin directly binds to human angiotensin-converting enzyme 2 (ACE2) with high affinity, thereby blocking its interaction with the SARS-CoV-2 spike protein. Furthermore, dalbavancin effectively prevents SARS-CoV-2 replication in Vero E6 cells with an EC50 of ~12 nM. In both mouse and rhesus macaque models, viral replication and histopathological injuries caused by SARS-CoV-2 infection are significantly inhibited by dalbavancin administration. Given its high safety and long plasma half-life (8-10 days) shown in previous clinical trials, our data indicate that dalbavancin is a promising anti-COVID-19 drug candidate.

20.
Int J Med Sci ; 17(17): 2653-2662, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33162793

RESUMO

Background and aim: To perform a longitudinal analysis of serial CT findings over time in patients with COVID-19 pneumonia. Methods: From February 5 to March 8, 2020, 73 patients (male to female, ratio of 43:30; mean age, 51 years) with COVID-19 pneumonia were retrospectively enrolled and followed up until discharge from three institutions in China. The patients were divided into the severe and non-severe groups according to treatment option. The patterns and distribution of lung abnormalities, total CT scores, single ground-glass opacity (GGO) CT scores, single consolidation CT scores, single reticular CT scores and the amounts of zones involved were reviewed by 2 radiologists. These features were analyzed for temporal changes. Results: In non-severe group, total CT scores (median, 9.5) and the amounts of zones involved were slowly increased and peaked in disease week 2. In the severe group, the increase was faster, with scores also peaking at 2 weeks (median, 20). In both groups, the later parameters began to decrease in week 4 (median values of 9 and 19 in the non-severe and severe groups, respectively). In the severe group, the dominant residual lung lesions were reticular (median single reticular CT score, 10) and consolidation (median single consolidation CT score, 7). In the non-severe group, the dominant residual lung lesions were GGO (median single GGO CT score, 7) and reticular (median single reticular CT score, 4). In both non-severe and severe groups, the GGO pattern was dominant in week 1, with a higher proportion in the severe group compared with the non-severe group (72% vs. 65%). The consolidation pattern peaked in week 2, with 9 (32%) and 19 (73%) in the non-severe and severe groups, respectively; the reticular pattern became dominant from week 4 (both group >40%). Conclusion: The extent of CT abnormalities in the severe and non-severe groups peaked in disease week 2. The temporal changes of CT manifestations followed a specific pattern, which might indicate disease progression and recovery.


Assuntos
Infecções por Coronavirus/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Pandemias , Pneumonia Viral/diagnóstico por imagem , Pneumonia/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/patogenicidade , China , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Pulmão/fisiopatologia , Pulmão/virologia , Masculino , Pessoa de Meia-Idade , Pneumonia/fisiopatologia , Pneumonia/virologia , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , Tomografia Computadorizada por Raios X
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