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1.
Haemophilia ; 30(4): 959-969, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38853005

RESUMO

INTRODUCTION: Reduced doses of emicizumab improve the affordability among patients in developing countries. However, the relationship between variant dose selection and efficacy in the real world of China is still unclear. AIM: This study aimed to investigate the efficacy and safety of emicizumab especially in those on reduced dose regimens in a real-world setting. METHODS: We carried out a multicentre study from 28 hospitals between June 2019 and June 2023 in China and retrospectively analysed the characteristics including demographics, diagnosis, treatment, bleeding episodes, and surgical procedures. RESULTS: In total, 127 patients with haemophilia A, including 42 with inhibitors, were followed for a median duration of 16.0 (IQR: 9.0-30.0) months. Median age at emicizumab initiation was 2.0 (IQR: 1.0-4.0) years. Median (IQR) consumption for loading and maintenance was 12.0 (8.0-12.0) and 4.2 (3.0-6.0) mg/kg/4 weeks, respectively. While on emicizumab, 67 (52.8%) patients had no bleeds, whereas 60 (47.2%) patients had any bleeds, including 26 with treated bleeds. Compared to previous treatments, patients on emicizumab had significantly decreased annualized bleeding rate, annualized joint bleeding rate, target joints and intracerebral haemorrhage. Different dosages had similar efficacy except the proportion of patients with treated spontaneous bleeds and target joints. Adverse events were reported in 12 (9.4%) patients. Postoperative excessive bleeding occurred following two of nine procedures. CONCLUSION: This is the largest study describing patients with HA receiving emicizumab prophylaxis on variant dose regimens in China. We confirmed that nonstandard dose is efficacious and can be considered where full-dose emicizumab is ill affordable.


Assuntos
Anticorpos Biespecíficos , Anticorpos Monoclonais Humanizados , Hemofilia A , Humanos , Anticorpos Biespecíficos/uso terapêutico , Anticorpos Biespecíficos/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , China , Hemofilia A/tratamento farmacológico , Masculino , Estudos Retrospectivos , Pré-Escolar , Feminino , Resultado do Tratamento , Lactente , Hemorragia , Criança , Relação Dose-Resposta a Droga
2.
Chem Biodivers ; 19(3): e202100610, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35083851

RESUMO

A series of chalcone derivatives (3a-3m) containing 4-phenylquinoline and benzohydrazide were designed and synthesized, and their anti-inflammatory, analgesic, and antidepressant activities were evaluated. Using the classic antidepressant model, except for compounds 3a and 3d, 11 compounds all showed certain antidepressant activity at a dose of 100 mg/kg, among which compounds 3f, 3h, and 3m showed good antidepressant activity (inhibition rate, respectively 63.0 %, 73.2 %, and 76.4 %), which was equivalent to the positive control fluoxetine (inhibition rate of 70.0 %). Secondly, the inhibitory activity of these compounds on mouse MAOA was evaluated. At 10 mM, compounds 3f and 3j showed a certain selective inhibitory effect on mouse MAOA , while compounds 3b, 3d, 3g, 3i, and 3m had a good inhibitory effect on mouse MAOA (inhibition rate is 42.3-71.4 %). The mouse ear edema model was used to evaluate the anti-inflammatory activity of compounds 3a-3m. At 30 mg/kg, compounds 3b, 3c, 3e, 3f, 3g, and 3m showed certain anti-inflammatory effects (inhibition rate of 51.5-99.9 %), which was equivalent to the positive control indomethacin (inhibition rate of 69.7 %). Results of the acetic acid-induced abdominal writhing test showed that, at 30 mg/kg, excepted for compounds 3a, 3b and 3d, all the other 10 compounds can show certain analgesic activity (inhibition rate 67-99.9 %). The use of Auto dock Vina (simina) to simulate molecular target docking shows that the development of quinoline and benzohydrazide groups is of great significance to MAOA inhibitors.


Assuntos
Chalcona , Chalconas , Animais , Anti-Inflamatórios/farmacologia , Chalcona/farmacologia , Camundongos , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade
3.
BMC Infect Dis ; 21(1): 365, 2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33865314

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) share similar symptoms with influenza A (IA), but it is more worthwhile to understand the disparities of the two infections regarding their clinical characteristics on admission. METHODS: A total of 71 age-matched pediatric IA and COVID-19 patient pairs were formed and their clinical data on admission were compared. RESULTS: Fever, cough, nasal congestion and nausea/vomiting were the most common symptoms on admission for both infections but occurred less often in COVID-19. The IA patients were more likely to have lower-than-normal levels of lymphocyte count and percentage and to have higher-than-normal levels of activated partial thromboplastin time, prothrombin time, serum C-reactive protein, and serum procalcitonin, while the COVID-19 patients had higher odds of having lower-than-normal levels of neutrophil count and percentage. CONCLUSIONS: This study suggests that influenza A is more symptomatic than COVID-19 for children and might be an overall more severe infection at the time of admission.


Assuntos
COVID-19/diagnóstico , Diagnóstico Diferencial , Influenza Humana/diagnóstico , Avaliação de Sintomas , Adolescente , Proteína C-Reativa , COVID-19/patologia , Criança , Pré-Escolar , China , Tosse , Feminino , Febre , Hospitalização , Humanos , Lactente , Recém-Nascido , Influenza Humana/patologia , Contagem de Leucócitos , Masculino , Náusea , Neutrófilos , Tempo de Tromboplastina Parcial , Pró-Calcitonina , Estudos Retrospectivos , Vômito
4.
Mycoses ; 64(10): 1170-1176, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34110649

RESUMO

BACKGROUND: Talaromyces marneffei, formerly known as Penicillium marneffei, is a significant emerging pathogenic fungus in Southeast Asia which can generate life-threatening systemic infections. Human immunodeficiency virus (HIV) infection is considered as the most underlying disease among systemic infections. However, infections due to T. marneffei without HIV are increasing in recent years. OBJECTIVES: Research the characteristics of T. marneffei infection in non-HIV individuals in mainland China. METHODS: In this study, we searched Pubmed, China National Knowledge Infrastructure (CNKI) and WanFang from inception to 31 December 2019 for studies reporting T. marneffei infection. Our research concentrates on non-HIV-infected cases and their epidemiology, clinical manifestations, laboratory findings, treatment methods and prognosis. RESULTS: T. marneffei infections in non-HIV individuals are increasing. Due to frequent present with atypical symptoms, these non-HIV-infected cases were usually misdiagnosed as other diseases, containing tuberculosis (80.7%), bacterial pneumonia (20.5%), lung cancer (5.1%) or other diseases (5.1%). CONCLUSIONS: T. marneffei infection in non-HIV individuals should be taken seriously. Their symptoms and signs are not typical. Accurate diagnosis and timely antifungal agent treatment is the key to the treatment for the disease.


Assuntos
Micoses , Infecções Oportunistas , Talaromyces , Antifúngicos/uso terapêutico , China/epidemiologia , Infecções por HIV , Humanos , Micoses/diagnóstico , Micoses/tratamento farmacológico , Micoses/epidemiologia , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/tratamento farmacológico , Infecções Oportunistas/epidemiologia
5.
Virol J ; 17(1): 193, 2020 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-33302983

RESUMO

BACKGROUND: The new emerging coronavirus disease 2019 (COVID-19) overall shares similar symptoms with other common respiratory viral infections. We aimed in this study to compare COVID-19 and human adenovirus (HAdV) infections in pediatric patients regarding the frequencies of major clinical symptoms and the potential disparities in laboratory and imaging parameters. METHODS: Following a case-control-like design, we built 72 age-matched pediatric COVID-19 and HAdV patient pairs. Their early symptoms and laboratory and imaging characteristics were then retrieved and compared. RESULTS: Fever and cough were the most common symptoms for both infections but were seen more often in HAdV than in COVID-19 patients (92% vs. 66% and 60% vs. 18%, respectively). Compared with COVID-19 patients, children with HAdV infection had statistically significantly higher values of neutrophil count, neutrophil percentage, activated partial thromboplastin time, prothrombin time, lactate dehydrogenase, C-reactive protein, procalcitonin but lower values of lymphocyte percentage, total bilirubin, potassium and sodium. Thoracic computed tomography also revealed more anomalies in HAdV patients than in COVID-19 patients (95% vs. 67%). CONCLUSIONS: COVID-19 is an overall less symptomatic and less severe infection at admission compared to HAdV respiratory infection in pediatric population.


Assuntos
Infecções por Adenovirus Humanos/patologia , COVID-19/patologia , SARS-CoV-2 , Infecções por Adenovirus Humanos/sangue , Infecções por Adenovirus Humanos/diagnóstico por imagem , Adenovírus Humanos , COVID-19/sangue , COVID-19/diagnóstico por imagem , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Tomografia Computadorizada por Raios X
6.
Med Mycol ; 58(3): 351-361, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31290549

RESUMO

Talaromyces marneffei (T. marneffei), which used to be known as Penicillium marneffei, is the causative agent of the fatal systemic mycosis known as talaromycosis. For the purpose of understanding the role of methylcitrate cycle in the virulence of T. marneffei, we generated MCD deletion (ΔMCD) and complementation (ΔMCD+) mutants of T. marneffei. Growth in different carbon sources showed that ΔMCD cannot grow on propionate media and grew slowly on the valerate, valine, methionine, isoleucine, cholesterol, and YNB (carbon free) media. The macrophage killing assay showed that ΔMCD was attenuated in macrophages of mice in vitro, especially at the presence of propionate. Finally, virulence studies in a murine infection experiment revealed attenuated virulence of the ΔMCD, which indicates MCD is essential for T. marneffei virulence in the host. This experiment laid the foundation for the further study of the specific mechanisms underlying the methylcitrate cycle of T. marneffei and may provide suitable targets for new antifungals.


Assuntos
Genes Fúngicos , Talaromyces/genética , Talaromyces/patogenicidade , Fatores de Virulência/genética , Animais , Meios de Cultura/química , Feminino , Deleção de Genes , Macrófagos/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células RAW 264.7 , Organismos Livres de Patógenos Específicos , Talaromyces/crescimento & desenvolvimento , Virulência
7.
Bioorg Med Chem Lett ; 30(17): 127376, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32738961

RESUMO

A series of benzo[d]thiazole analogs were synthesized and evaluated for their anti-inflammatory and analgesic effects. Using an ear edema model, except for compounds 2k, 2m-2q and 3a, other compounds showed the anti-inflammatory effects. Among them, compounds 2c, 2d, and 2g showed the best anti-inflammatory activity (inhibition rate: 86.8%, 90.7% and 82.9%, respectively). By the acetic acid-induced abdominal writhing test, except for compounds 2e, 2l, 2m, 2o, 2p and 3a, other compounds showed the analgesic effects with inhibition rate values of 51.9-100% (2a-2r) and 68.6-100% (3a-3g). Next, compounds 2c, 2d, 2g, 3d, 3f, 3g that displayed the excellent anti-inflammatory and analgesic activities were evaluated for their inhibitory effect against ovine COX-1 and COX-2. Compounds 2c, 2d, 2g, 3d, 3f, 3g were weak inhibitors of the COX-1 isozyme but exhibited the moderate COX-2 isozyme inhibitory effects IC50 from 0.28 to 0.77 µM and COX-2 selectivity indexes (SI: 18.6 to 7.2). This benzo[d]thiazole moiety will be proved to be of great significance for developing more potent COX-2 inhibitors.


Assuntos
Inibidores de Ciclo-Oxigenase 2/síntese química , Ciclo-Oxigenase 2/metabolismo , Tiazóis/química , Analgésicos/síntese química , Analgésicos/química , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Ciclo-Oxigenase 1/química , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/química , Inibidores de Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Desenho de Fármacos , Edema/induzido quimicamente , Edema/tratamento farmacológico , Camundongos , Relação Estrutura-Atividade , Tiazóis/metabolismo , Tiazóis/uso terapêutico
8.
Mycoses ; 61(4): 231-236, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29178398

RESUMO

We report a case of chromoblastomycosis due to the presence of large plaque and verrucous hyperplasia lesions on the left upper limb, with elbow abnormal activities, in a 56-year-old male. The diagnosis of chromoblastomycosis was based on gross and microscopic morphologies, histopathological examination and clinical manifestation. Molecular tools were applied to identifying the causative agent Fonsecaea nubica, which is rarely reported to be associated with chromoblastomycosis. The patient was initially treated orally with terbinafine (250 mg/day) and itraconazole (200 mg/day), subsequently patient received thermotherapy (45-50°C, 3 h/day) for 1 month. The patient was successfully cured. A literature review was performed to assess general features, treatment and outcome of chromoblastomycosis due to F.  nubica. All the 5 reviewed patients were male, over 30 years old and their lesions occurred after traumatic inoculation.


Assuntos
Antifúngicos/administração & dosagem , Ascomicetos/isolamento & purificação , Cromoblastomicose/tratamento farmacológico , Hipertermia Induzida , Itraconazol/administração & dosagem , Naftalenos/administração & dosagem , Ascomicetos/efeitos dos fármacos , Cromoblastomicose/microbiologia , Cromoblastomicose/patologia , Histocitoquímica , Humanos , Masculino , Microscopia , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular , Terbinafina , Resultado do Tratamento , Extremidade Superior/patologia
9.
Inflammopharmacology ; 25(6): 633-642, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28365854

RESUMO

Macrophage-derived foam cells are well known for their key role in development of atherosclerosis (AS). The present study aimed to examine whether dioscin exerts anti-atherosclerotic activity and inhibits foam cell formation. A high-fat induced AS model and ox-LDL treated macrophages were established and received treatment of dioscin. Anti-atherosclerotic activity in vivo was assessed by atherosclerotic lesions size and aortic lipid contents. Macrophage formed foam cells were positively identified by oil red o staining. Moreover, the expression of LOX-1 and NF-κB in aorta tissue and macrophages was examined by western blotting assay. Our results showed that dioscin not only reduced the levels of plasma lipid, TNF-a, IL-1ß and IL-6, but also inhibited atherosclerotic development in AS rats, as evidenced by decreased atherosclerotic lesions size and aortic lipid level. In vitro study revealed dioscin directly reduced foam cell formation, decreased intracellular cholesterol accumulation and lowered TNF-a, IL-1ß and IL-6 secretion in ox-LDL treated macrophages. Interestingly, further work found dioscin significantly reduced expression of LOX-1 and NF-κB in the aortic tissue and ox-LDL treated macrophages. In summary, our study was the first to confirm anti-atherosclerotic activity of dioscin in vivo and vitro. Moreover, the other important finding is dioscin mediated ox-LDL/LOX-1/NF-κB regulated contributions to the attenuate macrophage ox-LDL uptake and AS.


Assuntos
Aterosclerose/tratamento farmacológico , Diosgenina/análogos & derivados , Células Espumosas/efeitos dos fármacos , Hiperlipidemias/tratamento farmacológico , Animais , Aterosclerose/metabolismo , Células Cultivadas , Colesterol/metabolismo , Diosgenina/farmacologia , Células Espumosas/metabolismo , Hiperlipidemias/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Lipoproteínas LDL/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , NF-kappa B/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Depuradores Classe E/metabolismo
10.
Hepat Med ; 16: 31-36, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38660476

RESUMO

This study presents a case of dual primary liver cancer involving small cell neuroendocrine carcinoma and hepatocellular carcinoma. The 58-year-old Chinese male patient, who has a medical history of viral hepatitis B, presented with right upper abdominal pain persisting for one month. Imaging studies indicated the presence of multiple liver masses in segments V and VII-VIII, as well as a mass in the left lung. Subsequent hepatic biopsy performed on both segments confirmed the presence of hepatocellular carcinoma in segment V and small cell neuroendocrine carcinoma in segment VII-VIII. After undergoing one cycle of chemotherapy, the lung mass exhibited a reduction in size, while the liver masses showed an inadequate response. Subsequently, the patient underwent Transcatheter Arterial Chemoembolization (TACE) and Hepatic Artery Infusion Chemotherapy (HIAC), resulting in partial remission (PR). However, the patient was diagnosed with brain metastasis and subsequently treated with Sorafenib and Tirelizumab, a Programmed Death 1 (PD-1) immune checkpoint inhibitor. The efficacy evaluation indicated stability, and no severe adverse effects were observed at the time of writing. The patient's survival time was 16 months.

11.
Front Immunol ; 14: 1116944, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37006308

RESUMO

Epithelioid hemangioendotheliomas (EHEs), low-grade malignant tumors of vascular endothelial cell origin, are characterized by vascular endothelial proliferation. In 2002, the World Health Organization classified EHEs as locally aggressive tumors with the potential to metastasize. Currently, the diagnosis of EHE is based on pathology, histological and immunohistochemical examinations. There are no standard treatment guidelines. We here report a 69-year-old man who presented with left-sided chest and abdominal pain for more than 2 months. Enhanced computed tomography of the thorax and abdomen in another hospital suggested a mass in the left adrenal region that was considered malignant. Positron emission tomography- computed tomography in our hospital suggested a large multi-loculated, hypermetabolic, cystic mass in the left adrenal region that was considered malignant. Accordingly, a puncture biopsy of the mass was performed and the diagnosis of EHE confirmed by pathological examination, including immunohistochemical staining. This patient was treated with the programmed death 1 (PD-1) immune checkpoint inhibitor toripalimab with long-term success. The best response was stable disease (SD) with a progression-free survival (PFS) of more than 13 months. The patient is still alive now. Because the sample size of previous studies was small, further studies are needed to determine the safety and efficacy of toripalimab in the treatment of EHE.


Assuntos
Hemangioendotelioma Epitelioide , Masculino , Humanos , Idoso , Hemangioendotelioma Epitelioide/diagnóstico , Hemangioendotelioma Epitelioide/tratamento farmacológico , Hemangioendotelioma Epitelioide/patologia , Diagnóstico Diferencial , Biópsia por Agulha , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
12.
Front Med (Lausanne) ; 10: 1164394, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37250637

RESUMO

Incontinentia pigmenti (IP) is a rare neuroectodermal dysplasia caused by mutations in the IKBKG gene. We present a case of a 4-month-old female infant with erythematous vesicular skin lesions on the trunk and extremities. Histopathologic examination of the blisters revealed an eosinophilic infiltrate. Further investigation revealed that her mother had three unexplained miscarriages and two normal uncomplicated pregnancies, resulting in the birth of two male infants. We performed a comprehensive genetic evaluation to rule out the interference of pseudogene IKBKGP, and the infant was finally diagnosed with IP. During the subsequent 2-year follow-up, we observed a significant improvement in her dermatologic symptoms, with no evidence of recurrence, and there were no other associated symptoms in the hair, nails, oral mucosa, eyes, or central nervous system.

13.
Front Genet ; 14: 1254265, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38196513

RESUMO

Hemophilia, an X-linked recessive disorder, is characterized by spontaneous or trauma-induced prolonged bleeding. It is classified as hemophilia A when caused by variants in the F8 gene, and hemophilia B when caused by F9 variants. Few studies have described hemophilia variants in the Chinese population. This study aimed to investigate the clinical and genetic profiles of 193 hemophilia patients from southern China. Utilizing Sanger sequencing, multiplex ligation-dependent probe amplification, gap detection, long-range PCR, and multiplex PCR, we identified both F8 and F9 gene variants. Pregnant women with a history of hemophilia A offspring underwent amniocentesis or villus sampling for the variant detection. Variants in F8 and F9 were pinpointed in 183 patients, with 26 being novel discoveries. Notably, genetic testing was absent in the initial evaluation of 133 out of 161 patients, leading to a protracted average definitive diagnosis timeline of 2 years. Remarkably, two hemophilia A cases with anticipated severe phenotypes due to protein-truncating variants presented with only moderate or mild clinical manifestations. Among the 40 fetuses tested, 34 were males, with 17 exhibiting hemizygous variants in the F8 gene. Our results contribute to the broader understanding of F8 and F9 variant spectrum and highlight the underuse of genetic analyses in southern China.

14.
World J Clin Cases ; 11(35): 8411-8415, 2023 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-38130616

RESUMO

BACKGROUND: Cutaneous metastasis with gastric cancer (GC) origin is extremely rare and associated with poor prognosis. Nodular type is the most common type, while other forms are extremely rare. CASE SUMMARY: This study describes severe skin redness, swelling, pain, and fever in a 65-year-old man diagnosed with GC, whose left chest wall, left upper limb, and left back were mainly affected. Firstly, the patient was diagnosed with "lymphangitis" and treated to promote lymphatic return. However, the symptoms were constantly deteriorating, and skin thickening and scattered small nodules gradually appeared. Finally, the skin biopsy confirmed cutaneous metastases, and the patient died 7 d later. CONCLUSION: Our case highlights that cutaneous metastasis should be considered when skin lesions appear in patients with GC.

15.
Cancer Rep (Hoboken) ; 5(11): e1711, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36117246

RESUMO

BACKGROUND: Cardiac metastasis from small cell lung cancer (SCLC) origin is rare, whereas the incidence is anticipated to increase with the extended survival rates. CASE: We here describe a case report of a 48-year-old male patient diagnosis with SCLC in 2020. In June 2021, he resorted to hospital due to shortness of breath, no obvious changes were found in repeated echocardiography, electrocardiogram and chest computer tomography from June 2021 to September 2021. Due to the persistence of the complaints, cardiac magnetic resonance (CMR) imaging was performed in September 30th, 2021, which showed a mass in the right atrioventricular groove. The patient underwent pericardiocentesis and small cell carcinoma cells were found in the pericardial effusion, confirming the diagnosis of cardiac metastasis. CONCLUSION: Patients with a history of SCLC who develop new cardiac symptoms of unknown etiology should undergo imaging studies such as CMR. The importance of CMR for patients with SCLC is highlighted. The literature regarding metastatic cardiac tumors is reviewed.


Assuntos
Neoplasias Cardíacas , Neoplasias Pulmonares , Derrame Pericárdico , Carcinoma de Pequenas Células do Pulmão , Masculino , Humanos , Pessoa de Meia-Idade , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/complicações , Neoplasias Cardíacas/patologia , Pericardiocentese/efeitos adversos , Derrame Pericárdico/diagnóstico por imagem , Derrame Pericárdico/etiologia , Neoplasias Pulmonares/patologia , Melanoma Maligno Cutâneo
16.
Taiwan J Obstet Gynecol ; 61(4): 663-671, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35779918

RESUMO

OBJECTIVE: Cervical squamous cell carcinoma (CESC) is a cancer with high mortality caused by human papillomavirus. The aim of this study was to uncover potential CESC biomarkers to help early diagnosis and treatment. MATERIALS AND METHODS: The mRNA transcriptome data and DNA methylation data were downloaded from database for the identification of differentially expressed mRNAs (DEmRNAs) and DNA methylation analysis. Functional analysis was used to reveal the molecular functions. Then, the association between differential methylation and DEmRNA was analyzed. Protein-protein interaction (PPI) network analysis was performed on the selected differentially methylated genes (DEGs). Subsequently, we analyzed the prognosis and constructed a prognostic risk model. We also performed diagnostic analyses of risk model genes. In addition, we verified the protein expression level of identified DEGs. RESULTS: 1438 DEmRNAs, 1669 differentially methylated sites (DMSs), 46 differentially methylated CpG islands and 53 differential methylation genes (DMGs) were obtained. In PPI, the highest interaction scores were MX2 and IRF8, and their interaction score was 0.928. Interestingly, 5 DMGs were found to be associated with CESC prognosis. In addition, our results demonstrated that high risk score was associated with poor prognosis of CESC. Furthermore, it was found that ZIK1, ZNRF2, HHEX, VCAM1 could be diagnostic molecular markers for CESC. CONCLUSION: Analysis of methylated-differentially expressed genes may contribute to the identification of early diagnosis and therapeutic targets of CESC. In addition, a prognostic model based on 5 DMGs can be used to predict the prognosis of CESC.


Assuntos
Carcinoma de Células Escamosas , Metilação de DNA , Neoplasias do Colo do Útero , Feminino , Humanos , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Metilação de DNA/genética , Perfilação da Expressão Gênica/métodos , RNA Mensageiro/genética , Ubiquitina-Proteína Ligases/genética , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/genética
17.
Front Immunol ; 13: 928438, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35967411

RESUMO

Adenosine deaminases (ADAs) are enzymes of purine metabolism converting adenosine to inosine. There are two types of ADAs in humans ADA1 and ADA2. While both ADA1 and ADA2 share the same substrate, they differ in expression, cellular localization, and catalytic properties. The genetic deficiency of ADA1 results in severe combined immunodeficiency (SCID), while lack in ADA2 (DADA2) results in multiple phenotypes ranging from systemic inflammation to vascular pathology. Clinical studies have shown that the levels of ADAs in biological fluids are altered in pathophysiological conditions, suggesting that ADA activity could be a convenient marker for the diagnosis of immune diseases and cancer. Here, we describe sensitive and straightforward ELISA assays to measure ADA1 and ADA2 concentrations in biological fluids. Analysis of the serum and saliva samples from the healthy controls and DADA2 patients revealed that ADA2 enzyme concentration is significantly lower in patients than in healthy controls. In contrast, the concentration of ADA2 increases in the serum of patients with large granular leukocyte leukemia (LGLL) and patients' saliva with head and neck cancer. Thus, this simple, non-invasive method allows for distinguishing healthy controls from the affected patient. It can be implemented in screening and diagnosis of DADA2 and follow up the treatment of LGLL and several types of head and neck cancer.


Assuntos
Neoplasias , Poliarterite Nodosa , Imunodeficiência Combinada Severa , Adenosina , Adenosina Desaminase , Agamaglobulinemia , Ensaio de Imunoadsorção Enzimática , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Neoplasias/diagnóstico , Saliva/metabolismo , Imunodeficiência Combinada Severa/diagnóstico
18.
World J Clin Cases ; 10(11): 3478-3484, 2022 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-35611193

RESUMO

BACKGROUND: Both programmed cell death-1 (PD-1) inhibitors and lenvatinib, which have a synergistic effect, are promising drugs for tumor treatment. It is generally believed that combination therapy with a PD-1 inhibitor and lenvatinib is safe and effective. However, we report a case of toxic epidermal necrolysis (TEN), a grade 4 toxicity, after this combination therapy. CASE SUMMARY: A 39-year-old male presented with erythema, blisters and erosions on the face, neck, trunk and limbs 1 wk after receiving combination therapy with lenvatinib and toripalimab, a PD-1 inhibitor. The skin injury covered more than 70% of the body surface area. He was previously diagnosed with liver cancer with cervical vertebra metastasis. Histologically, prominent necrotic keratinocytes, hyperkeratosis, liquefaction of basal cells and acantholytic bullae were observed in the epidermis. Blood vessels in the dermis were infiltrated by lymphocytes and eosinophils. Direct immunofluorescence staining was negative. Thus, the diagnosis was confirmed to be TEN (associated with combination therapy with toripalimab and lenvatinib). Full-dose and long-term corticosteroids, high-dose intravenous immunoglobulin and targeted antibiotic drugs were administered. The rashes gradually faded; however, as expected, the tumor progressed. Therefore, sorafenib and regorafenib were given in succession, and the patient was still alive at the 10-mo follow-up. CONCLUSION: Cautious attention should be given to rashes that develop after combination therapy with PD-1 inhibitors and lenvatinib. Large-dose and long-course glucocorticoids may be crucial for the treatment of TEN associated with this combination treatment.

19.
World J Clin Cases ; 9(23): 6810-6815, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34447829

RESUMO

BACKGROUND: Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is relatively common in several cancers, such as small cell lung cancer. However, nedaplatin-induced SIADH is rare. We describe a case of SIADH mediated by nedaplatin. CASE SUMMARY: A 54-year-old female with nasopharyngeal carcinoma was treated with nedaplatin and developed severe hyponatremia due to SIADH. The side effects were successfully treated by fluid restriction and sodium supplementation. CONCLUSION: This case report highlights the importance of cautiously treating life-threatening hyponatremia in patients treated with nedaplatin.

20.
Signal Transduct Target Ther ; 5(1): 3, 2020 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-32296024

RESUMO

The ability to identify a specific type of leukemia using minimally invasive biopsies holds great promise to improve the diagnosis, treatment selection, and prognosis prediction of patients. Using genome-wide methylation profiling and machine learning methods, we investigated the utility of CpG methylation status to differentiate blood from patients with acute lymphocytic leukemia (ALL) or acute myelogenous leukemia (AML) from normal blood. We established a CpG methylation panel that can distinguish ALL and AML blood from normal blood as well as ALL blood from AML blood with high sensitivity and specificity. We then developed a methylation-based survival classifier with 23 CpGs for ALL and 20 CpGs for AML that could successfully divide patients into high-risk and low-risk groups, with significant differences in clinical outcome in each leukemia type. Together, these findings demonstrate that methylation profiles can be highly sensitive and specific in the accurate diagnosis of ALL and AML, with implications for the prediction of prognosis and treatment selection.


Assuntos
Biomarcadores Tumorais/genética , Metilação de DNA/genética , Leucemia/genética , Prognóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Ilhas de CpG/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Lactente , Leucemia/classificação , Leucemia/diagnóstico , Leucemia/patologia , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas/genética , Adulto Jovem
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