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1.
Zhonghua Bing Li Xue Za Zhi ; 53(4): 377-383, 2024 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-38556822

RESUMO

Objective: To study the clinicopathological features of Sjogren's syndrome (SS) with liver injury and to improve the understanding of this disease. Methods: Forty-nine patients with SS complicated with liver injury were collected from Beijing Ditan Hospital, Capital Medical University from October 2008 to January 2022. All patients underwent ultrasound-guided liver biopsy, and all specimens were stained with HE. The histopathologic characteristics were observed and the pathologic indexes were graded. Immunohistochemical stains for CK7, CK19, CD38, MUM1 and CD10 were performed by EnVision method; and special histochemical stains for reticulin, Masson's trichrome, Rhodanine, Prussian blue, periodic acid Schiff (PAS) and D-PAS stains were conducted. Results: The age of patients ranged from 31 to 66 years, including 3 males and 46 females. SS combined with drug-induced liver injury was the most common (22 cases, 44.9%), followed by autoimmune liver disease (13 cases, 26.5%, including primary biliary cholangitis in eight cases, autoimmune hepatitis in 3 cases, and PBC-AIH overlap syndrome in 2 cases), non-alcoholic fatty liver disease (NAFLD, 9 cases, 18.4%) and other lesions (5 cases, 10.2%; including 3 cases of nonspecific liver inflammation, 1 case of liver amyloidosis, and 1 case of porto-sinusoidal vascular disease). Among them, 28 cases (57.1%) were associated with obvious interlobular bile duct injury, mainly in SS combined with PBC group and drug-induced liver injury group. Twenty-three cases (46.9%) were associated with hepatocyte steatosis of varying degrees. In SS with autoimmune liver disease group, ISHAK score, degree of fibrosis bile duct injury, bile duct remodeling, lymphocyte infiltration of portal area, and plasma cell infiltration, MUM1 and CD38 expression; serum ALP and GGT, IgM; elevated globulin; positive AMA, proportion of AMA-M2 positive and IgM positive were all significantly higher than those in other groups(all P<0.05). Serum ALT, direct bilirubin and SSA positive ratio in SS combined with drug liver group were significantly higher than those in other groups(all P<0.05). The serum total cholesterol level in SS combined with PBC group (P=0.006) and NALFD group (P=0.011) were significantly higher than those in other groups (P<0.05). Conclusions: The pathologic manifestations of SS patients with liver injury are varied. The inflammatory lesions of SS patients with autoimmune liver disease are the most serious, and the inflammatory lesions of SS patients with non-alcoholic fatty liver disease and non-specific inflammation are mild. Comprehensive analysis of liver histopathologic changes and laboratory findings is helpful for the diagnosis of SS complicated with different types of liver injury.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Hepatite Autoimune , Cirrose Hepática Biliar , Hepatopatia Gordurosa não Alcoólica , Síndrome de Sjogren , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Síndrome de Sjogren/complicações , Cirrose Hepática Biliar/complicações , Cirrose Hepática Biliar/diagnóstico , Hepatopatia Gordurosa não Alcoólica/complicações , Fígado , Hepatite Autoimune/complicações , Hepatite Autoimune/diagnóstico , Inflamação/complicações , Doença Hepática Induzida por Substâncias e Drogas/complicações , Imunoglobulina M
2.
Eur Rev Med Pharmacol Sci ; 28(5): 1837-1846, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38497866

RESUMO

OBJECTIVE: The aim of this study was to evaluate the efficacy and adverse effects of venetoclax in combination with hypomethylating agents in elderly with acute myeloid leukemia. MATERIALS AND METHODS: A comprehensive literature search identified related studies from PubMed, Medline, Embase, Scopus, and Cochrane Library. Overall complete remission (CR) and overall response rate (ORR) were applied to evaluate the efficacy of venetoclax in combination with hypomethylating agents in elderly with acute myeloid leukemia, and incidence of grade 3-4 adverse events were used to evaluate the safety. RESULTS: 10 studies, including a total of 930 patients, were identified in our study and analyzed using the random-effects model. Meta-analysis showed the pooled overall CR rate of 70% (95% CI: 63-77%), the pooled ORR rate of 53% (95% CI: 39-67%), and the median overall survival ranged from 7.7 to 16.9 months. A total of 6 studies reported related adverse events, mainly including thrombocytopenia, febrile neutropenia, neutropenia, leukopenia, anemia, and pneumonia. The pooled incidence of overall adverse events was 30% (95% CI: 22-38%), and all adverse events were tolerable and resolved with treatment. CONCLUSIONS: The combination of venetoclax and demethylating drugs has a good therapeutic effect on elderly patients with acute myeloid leukemia, but it also induces some adverse events. Although this therapy has a small impact on the quality of life, further attention is still needed to reduce the occurrence of such adverse events.


Assuntos
Leucemia Mieloide Aguda , Trombocitopenia , Idoso , Humanos , Qualidade de Vida , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Sulfonamidas/efeitos adversos , Leucemia Mieloide Aguda/tratamento farmacológico , Resposta Patológica Completa
3.
Zhonghua Nei Ke Za Zhi ; 62(11): 1288-1294, 2023 Nov 01.
Artigo em Chinês | MEDLINE | ID: mdl-37935494

RESUMO

Objective: To investigate the intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) in the differential diagnosis of diabetic nephropathy (DN) and non-diabetic renal disease (NDRD) among patients with type 2 diabetes mellitus (T2DM). Methods: A diagnostic test. In this prospective study, patients with T2DM who underwent both IVIM-DWI and renal biopsy at the First Medical Center of Chinese PLA General Hospital between October 2017 and September 2021 were consecutively enrolled. IVIM-DWI parameters including perfusion fraction (f), pure diffusion coefficient (D), and pseudo-diffusion coefficient (D*) were measured in the renal cortex, medulla, and parenchyma. Patients were divided into the DN group and NDRD group based on the renal biopsy results. IVIM-DWI parameters, clinical information, and diabetes-related biochemical indicators between the two groups were compared using Student's t-test or Mann-Whitney U test. The correlation of IVIM-DWI parameters with diabetic nephropathy histological scores were analyzed using Spearman's correlation analyzes. The diagnostic efficiency of IVIM-DWI parameters for distinguishing between DN and NDRD were assessed using the receiver operating characteristic (ROC) curves. Results: A total of 27 DN patients and 23 NDRD patients were included in this study. The DN group comprised 19 male and 8 female patients, with an average age of 52±9 years. The NDRD group comprised 16 male and 7 female patients, with an average age of 49±10 years. The DN group had a higher D* value in the renal cortex and a lower f value in the renal medulla than the NDRD group (9.84×10-3 mm2/s vs. 7.35×10-3 mm2/s, Z=-3.65; 41.01% vs. 46.74%, Z=-2.29; all P<0.05). The renal medulla D* value was negatively correlated with DN grades, interstitial lesion score, and interstitial fibrosis and tubular atrophy (IFTA) score (r=-0.571, -0.409, -0.409; all P<0.05) while the renal cortex f value was positively correlated with vascular sclerosis score (r=0.413, P=0.032). The renal cortex D* value had the highest area under the curve (AUC) for discriminating between the DN and NDRD groups (AUC=0.802, sensitivity 91.3%, specificity 55.6%). Conclusion: IVIM-derived renal cortex D* value can be used non-invasively to differentiate DN from NDRD in patients with T2DM that can potentially facilitate individualized treatment planning for diabetic patients.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Nefropatias Diabéticas/diagnóstico por imagem , Rim/diagnóstico por imagem , Diabetes Mellitus Tipo 2/complicações , Estudos Prospectivos , Imagem de Difusão por Ressonância Magnética/métodos
6.
Zhonghua Yi Xue Za Zhi ; 103(28): 2163-2167, 2023 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-37482728

RESUMO

Objective: To explore the rate of Helicobacter pylori (Hp) resistance to levofloxacin and clarithromycin and the common mutation patterns of resistance genes in Ningxia, and to assess the concordance between phenotypic resistance and genotypic resistance. Methods: Cross-sectional study. Patients diagnosed with Hp infection in 14 hospitals in Ningxia region from February 2020 to May 2022 were retrospectively selected. Hp strains were isolated from gastric biopsy specimens of Hp-infected patients and subjected to phenotypic drug sensitivity testing and detection of resistance genes to analyze the rate of Hp resistance to levofloxacin and clarithromycin and the common mutation patterns of resistance genes in Ningxia region; and the concordance rate and Kappa concordance test were used to assess the concordance between phenotypic resistance and genotypic resistance. Results: A total of 1 942 Hp strains were isolated and cultured, and among the infections, 1 069 cases (55.0%) were male and 873 cases (45.0%) were female, aged (50.0±12.5) years (15-86 years). The rates of Hp resistance to levofloxacin and clarithromycin in Ningxia were 42.1% (818/1 942) and 40.1% (779/1 942), respectively, and the rate of dual resistance to both was 22.8% (443/1 942). The rate of resistance to levofloxacin and clarithromycin of Hp strains from female patients was higher than in male patients (levofloxacin: 50.4%(440/873) vs 35.4%(378/1 069); clarithromycin: 44.4%(388/873) vs 36.6%(391/1 069), both P<0.001). Among the GyrA gene mutations associated with levofloxacin resistance, the differences in mutation rate of amino acid at positions 87 and 91 were statistically significant in both drug-resistant and sensitive strains(both P<0.001), except for Asn87Thr. Hp strains were statistically significant for levofloxacin (Kappa=0.834, P<0.001) and clarithromycin (Kappa=0.829, P<0.001) had good concordance in resistance at the phenotypic and genotypic levels. Conclusion: The resistance of Hp to levofloxacin and clarithromycin in Ningxia region is severe, and there is good consistency between genotypic and phenotypic resistance.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Feminino , Humanos , Masculino , Antibacterianos/farmacologia , Claritromicina/farmacologia , Estudos Transversais , Farmacorresistência Bacteriana/genética , Helicobacter pylori/genética , Levofloxacino/farmacologia , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais
7.
J Physiol Pharmacol ; 74(6)2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38345445

RESUMO

Paeonol (2-hydroxy-4-methoxyphenylacetophenone) is a natural phenolic component isolated from the root bark of peony with multiple pharmacological activities and has been proven to have anti-cancer effects. The objective of this study is to investigate the influence mechanism of paeonol on the proliferatory and apoptotic activities of ovarian cancer (OC) cells by modulating the transforming growth factor beta (TGF-ß)/Smad3 pathway. The SKOV3 cells were pretreated with various concentrations of paeonol (0, 25, 50, 100, 200, 400 µg/mL) for 48 hours to determine the optimal experimental concentration of paeonol. Following this, the TGF-ß overexpression vector was constructed and transfected into the SKOV3 cells. The assessment of cell proliferation, invasion, and migration was conducted through MTT, colony formation, flow cytometry, transwell, and wound-healing experiments. The detection of TGF-ß/Smad3 pathway-related proteins and apoptosis-related proteins (B-cell lymphoma (Bcl-2) Bcl-2-associated X protein (Bax)) was performed using Western blot analysis. Paeonol exhibited a significant inhibitory effect on SKOV3 cell viability when administered at concentrations ranging from 50-400 µg/mL, with an IC50 value of 200 µg/mL. Within the concentration range of 50 to 200 µg/mL, paeonol exhibited a dose-dependent effect on the progression of SKOV3 cells, including a reduction in the anti-apoptotic protein Bcl-2, an increase in the pro-apoptotic protein Bax (P<0.05), inhibition of cell migration and invasion (P<0.05), and promotion of cell apoptosis (P<0.05), particularly at a concentration of 200 µg/mL. These effects were found to be more pronounced. The aforementioned effects of paeonol can be ascribed to its inhibition of the TGFß/Smad3 pathway, according to a mechanistic viewpoint. It is noteworthy that the inhibitory impact of paeonol on SKOV3 cell progression is counteracted by the elevation of TGF-ß levels following overexpression. We conclude that paeonol exerts regulatory effects on the TGF-ß/Smad3 pathway, leading to the inhibition of proliferation, migration, and invasion of OC cells, thereby attenuating malignant behavior of cancer cells.


Assuntos
Acetofenonas , Neoplasias Ovarianas , Humanos , Feminino , Proteína X Associada a bcl-2 , Neoplasias Ovarianas/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Fator de Crescimento Transformador beta/uso terapêutico , Apoptose , Transdução de Sinais , Proliferação de Células , Linhagem Celular Tumoral , Movimento Celular
8.
Eur Rev Med Pharmacol Sci ; 26(21): 8087-8097, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36394758

RESUMO

OBJECTIVE: Triplet regimens based on pomalidomide and dexamethasone have been applied to treat relapsed/refractory multiple myeloma, but the safety and efficacy are not yet very clear. This meta-analysis aimed at comparing the safety and efficacy of different triplet therapies and analyzing the best therapy regimen. MATERIALS AND METHODS: A comprehensive literature search identified a total of 615 studies, and 22 studies assessing 1,889 subjects met the inclusion criteria of this meta: phase II/III trial, over 2 median lines of prior therapy, and detailed efficacy outcomes like overall response rate (ORR), overall survival, and progression-free survival (PFS). All statistical analyses were performed by Revman version 5.3, and the heterogeneity was tested by I2 (25% indicating low heterogeneity, 50% moderate, and 75% high). For those with less heterogeneity, fixed-effect model was used. With a significant high heterogeneity, a random-effect model was used. RESULTS: Pooled analysis showed ORR 66.2% across all triplet regimens based on pomalidomide and dexamethasone. Among all triplet regimens, therapy containing bortezomib showed the highest ORR (90.3%), and the one containing elotuzumab showed the lowest ORR (41.2%). The pooled ORRs for the remaining treatment regimens are as follows: cyclophosphamide (70.1%), isatuximab (66.3%), daratumumab (61.2%), clarithromycin (60.0%), pembrolizumab (47.3%). A total of 21 adverse events appeared in the included studies, with neutropenia being the highest incidence of hematologic adverse events (32.1%) and cough being the highest incidence of non-hematologic adverse events (43.3.%). CONCLUSIONS: Three-drug regimens based on pomalidomide and dexamethasone could yield excellent overall response rate to relapsed/refractory multiple myeloma, but there are still various adverse events; therefore, consequent studies should address these adverse events.


Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dexametasona/efeitos adversos , Talidomida/efeitos adversos
9.
Beijing Da Xue Xue Bao Yi Xue Ban ; 54(5): 920-926, 2022 Oct 18.
Artigo em Chinês | MEDLINE | ID: mdl-36241234

RESUMO

OBJECTIVE: To better understand and revise the natural history and disease progression of chronic hepatitis B virus (HBV) infection through analysis of a single-center large-scale cohort of indivi-duals with chronic HBV infection. METHODS: Patients with chronic HBV infection who had undergone liver biopsy in the Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital from January 2014 to October 2020 were retrospectively recruited. Based on patient's hepatitis B e antigen (HBeAg) states and pathologic diagnosis, they were categorized into four disease progression statuses (or phases according to the old-terminology in the updated guidelines of chronic hepatitis B (CHB), such as European Association for the Study of the Liver (EASL) 2017, Clinical Practice Guidelines on the Management of Hepatitis B Virus Infection: HBeAg-positive chronic HBV infection (immune tolerance), HBeAg-positive CHB (immune active HBeAg positive), HBeAg-negative chronic HBV infection (inactive carrier), and HBeAg-negative CHB (immune reactive HBeAg negative). Then the demographic, laboratory tests and liver histological results of the patients in different disease progression stages were compared. Age differences between the two groups were evaluated using Mann-Whitney U test. RESULTS: A total of 760 eligible patients with a median age of 29 (interquartile range: 16-39) years were enrolled. Among them, 197 were underage individuals (age < 18 years) and 563 were adults; and 456 were males and 304 females. According to the pathological diagnosis, the patients were classified, and in each of the above four natural disease phases there were 173, 329, 95, and 163 individuals, respectively. Further comparison of the ages of the patients of the four disease progression statuses revealed that patients of HBeAg-negative CHB had a median age at 37 years, which was reasonably higher than those with HBeAg-positive CHB in immune active phase (37 vs. 24 years, P < 0.001), but was relatively younger than those with HBeAg-negative chronic HBV infection (37 vs. 39 years, P= 0.240). CONCLUSION: According to this study, it could be speculated that HBeAg-negative CHB patients probably not all reactivate from individuals of HBeAg-negative chronic HBV infection. Instead, certain HBeAg-negative CHB patients may also come from HBeAg-positive CHB patients who have undergone HBeAg clearance or seroconversion and still remain in the immune active state.


Assuntos
Hepatite B Crônica , Adolescente , Adulto , DNA Viral , Progressão da Doença , Feminino , Antígenos E da Hepatite B , Vírus da Hepatite B/genética , Hepatite B Crônica/diagnóstico , Humanos , Masculino , Estudos Retrospectivos , Adulto Jovem
10.
Zhonghua Yu Fang Yi Xue Za Zhi ; 56(10): 1499-1504, 2022 Oct 06.
Artigo em Chinês | MEDLINE | ID: mdl-36274621

RESUMO

Since April 2022, severe acute hepatitis of unknown origin in children has spread to 35 countries and regions around the world, and more than 1 010 cases have been reported. Since the severe acute hepatitis of unknown origin involves a wide range of areas and has a high rate, it is critical to identify the etiology and establish effective preventive, diagnostic and therapeutic measures as soon as possible. This study discusses the possible mechanisms and countermeasures of the severe acute hepatitis of unknown origin in children. It speculates that the occurrence of the recent severe acute hepatitis might be related to adenovirus, adeno-associated virus infection, and the COVID-19 epidemic, while the difference in HLA polymorphism among different races might be related to the fact that reported cases were more common in Europe and the United States. Based on the currently available evidence, it can be preliminarily judged that the risk of large-scale outbreak of severe acute hepatitis of unknown origin in children would be low in China, but the persistent awareness and vigilance of the etiology is still needed.


Assuntos
COVID-19 , Hepatite , Criança , Humanos , Estados Unidos , Surtos de Doenças , Hepatite/epidemiologia , China/epidemiologia
11.
Zhonghua Zhong Liu Za Zhi ; 44(6): 587-592, 2022 Jun 23.
Artigo em Chinês | MEDLINE | ID: mdl-35754235

RESUMO

Single-arm trial refers to a clinical trial design that does not set up parallel control group, adopts open design, and does not involve randomization and blind method. These features, on the one hand, speed up the process of clinical trials, significantly shorten the time to market and meet the needs of patients with advanced malignancies, but also lead to the uncertainty of single-arm clinical trials themselves. Recently, the US Food and Drug Administration held a meeting of the oncologic drug advisory committee to discuss six tumor indications that have been accelerated approved, which once again triggered the discussion of single-arm trials. The basis of accelerated approval by single-arm trial is actually a compromise on the level of evidence-based medical evidence requirements after assessing the benefit risk. Therefore, the sponsor should strictly grasp the applicable conditions of single-arm trial in anti-tumor drugs and conduct single-arm trial scientifically. Post-marketing clinical trial should be implement as early as possible to ensure the benefit of patients. Based on the characteristics of single-arm trial, combined with two guidance relevant to single-arm trial issued by National Medical Products Administration recently, this article is supposed to propose and summarize the strategy of single-arm trial supporting the marketing of anti-tumor drugs.


Assuntos
Antineoplásicos , Neoplasias , Antineoplásicos/uso terapêutico , Ensaios Clínicos como Assunto , Humanos , Marketing , Neoplasias/tratamento farmacológico , Projetos de Pesquisa , Estados Unidos , United States Food and Drug Administration
12.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 57(3): 280-286, 2022 Mar 09.
Artigo em Chinês | MEDLINE | ID: mdl-35280006

RESUMO

Objective: To summarize the clinical characteristics of patients with cleidocranial dysplasia (CCD) and analyze their treatment methods. Methods: From January 2000 to December 2020, patients with CCD who completed comprehensive treatment in the Department of Orthodontics and the First Dental Clinic, School and Hospital of Stomatology, China Medical University were retrospectively analyzed. A total of 14 CCD patients [7 males and 7 females, aged (16.1±4.5) years] were collected. There were 153 impacted permanent teeth in this study. In addition to the teeth that needed to be extracted due to special conditions, 147 impacted teeth were pulled into the dentition using closed traction. Patients were divided into adolescent group (≥12 years and<18 years, 10 patients) and adult group (≥18 years, 4 patients). Failure rate of traction was compared between the two groups. Factors affecting the success rate of closed traction such as vertical position of teeth (high, middle and low) and horizontal position of the teeth (palatal, median and buccal) were analyzed. Results: The incidence of maxillary impacted teeth [69.3% (97/140)] was higher than that of mandibular impacted teeth [40% (56/140)]. The difference was statistically significant (χ2=24.22, P<0.001). The supernumerary teeth were mainly located in the premolar area 61.4% (21/44), and most of them were in the palatal region of the permanent teeth 95.5% (42/44). They were generally located at the same height or the occlusal side of the corresponding permanent teeth. The success rate of closed traction was 93.9% (138/147). The success rate in the adolescent group [98.2% (108/110)] was higher than that in the adult group [81.1% (30/37)], and the difference was significant (χ2=14.09, P<0.05). Failure after closed traction of 9 teeth was found totally, including 7 second premolars. The success rate of traction in impacted second premolars at different vertical (χ2=11.44, P<0.05) and horizontal (χ2=9.71, P<0.05) positions in alveolar bone was different significantlly. The success rates of the second premolars were high (15/16), middle (12/13), low (2/7), and lingual palatine (10/17), median (19/19), lip-buccal (0/0), respectively. Conclusions: The closed traction of impacted teeth in patients with CCD was effective, and the age was the main variable affecting the outcome. The success rate of traction in impacted second premolars located in low position vertically or in palatal position was low, which required close observation during treatment.


Assuntos
Displasia Cleidocraniana , Dente Supranumerário , Adolescente , Adulto , Dente Pré-Molar , Criança , Displasia Cleidocraniana/terapia , Feminino , Humanos , Masculino , Mandíbula , Estudos Retrospectivos , Dente Supranumerário/cirurgia , Adulto Jovem
13.
Zhonghua Gan Zang Bing Za Zhi ; 30(1): 4-8, 2022 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-35152664

RESUMO

Golgi protein 73 (GP73) is a transmembrane protein on the Golgi apparatus and can be cut and released into the blood. In recent years, an increasing number of clinical studies have shown that the elevated serum GP73 level is closely related to liver diseases. And thus GP73 is expected to be used as a new serum marker for assessing progress of chronic liver diseases. Herein, the clinical application of serum GP73 in chronic hepatitis, liver fibrosis, liver cirrhosis and hepatocellular carcinoma with different etiologies was reviewed based on available literatures; and a research outlook in this field is made.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores , Complexo de Golgi , Humanos , Cirrose Hepática
14.
Artigo em Chinês | MEDLINE | ID: mdl-35090208

RESUMO

Objective: Using propensity score matching method(PSM) to investigate the clinical effect of surgical plus radio(chemo)therapy and non-surgery chemoradiotherapy treatment strategies for advanced tonsillar squamous cell carcinoma. Methods: A retrospective analysis was conducted on the clinical data of 324 patients diagnosed with advanced tonsillar squamous cell carcinoma and treated in Peking Union Medical College Hospital from 2000 to 2018, confirmed by pathology and without distant metastasis. Survival analysis was performed using Kaplan-Meier estimates, the Cox proportional hazards model, and propensity score matching(PSM). Results: Of the 324 patients, 102 were treated with non-surgery chemoradiotherapy treatment strategies and 222 with surgical plus radio(chemo)therapy treatment. Cox multivariate analysis showed that the non-surgery treatment group had a favorable prognosis than the surgical treatment group, however, these outcomes were not significantly different [overall survival(OS): adjusted Hazard Ratios(aHR): 0.92, 95% confidence interval(CI): 0.60-1.42; disease-specific survival(DSS): aHR: 0.71, 95%CI: 0.43-1.20; disease-free survival(DFS): aHR: 0.82, 95%CI: 0.53-1.28]. The new patient cohort consisted of 102 subpairs after PSM. There were no significant differences between two groups(OS: aHR: 0.85, 95%CI: 0.51-1.40; DSS: aHR: 0.62, 95%CI: 0.35-1.11; DFS: aHR: 0.80, 95%CI: 0.49-1.33). Conclusion: Our findings indicate that patients with non-surgical treatment do not have significantly better survival outcomes compared to surgical treatment group, while non-surgical treatment has advantages in improving the quality of life of patients, so comprehensive treatment based on radiotherapy and chemotherapy may be recommended for advanced tonsillar squamous cell carcinoma.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Tonsilares , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia , Humanos , Qualidade de Vida , Estudos Retrospectivos , Neoplasias Tonsilares/terapia
16.
ESMO Open ; 6(6): 100275, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34653800

RESUMO

BACKGROUND: Biliary tract cancers (BTCs) are rare and highly heterogenous malignant neoplasms. Because obtaining BTC tissues is challenging, the purpose of this study was to explore the potential roles of bile as a liquid biopsy medium in patients with BTC. PATIENTS AND METHODS: Sixty-nine consecutive patients with suspected BTC were prospectively enrolled in this study. Capture-based targeted sequencing was performed on tumor tissues, whole blood cells, plasma, and bile samples using a large panel consisting of 520 cancer-related genes. RESULTS: Of the 28 patients enrolled in this cohort, tumor tissues were available in eight patients, and plasma and bile were available in 28 patients. Somatic mutations were detected in 100% (8/8), 71.4% (20/28), and 53.6% (15/28) of samples comprising tumor tissue DNA, bile cell-free DNA (cfDNA), and plasma cfDNA, respectively. Bile cfDNA showed a significantly higher maximum allele frequency than plasma cfDNA (P = 0.0032). There were 56.2% of somatic single-nucleotide variant (SNVs)/insertions and deletions (indels) shared between bile and plasma cfDNA. When considering the genetic profiles of tumor tissues as the gold standard, the by-variant sensitivity and positive predictive value for SNVs/indels in bile cfDNA positive for somatic mutations were both 95.5%. The overall concordance for SNVs/indels in bile was significantly higher than that in plasma (99.1% versus 78.3%, P < 0.0001). Moreover, the sensitivity of CA 19-9 combined with bile cfDNA achieved 96.4% in BTC diagnosis. CONCLUSION: We demonstrated that bile cfDNA was superior to plasma cfDNA in the detection of tumor-related genomic alterations. Bile cfDNA as a minimally invasive liquid biopsy medium might be a supplemental approach to confirm BTC diagnosis.


Assuntos
Neoplasias do Sistema Biliar , Ácidos Nucleicos Livres , Bile , Neoplasias do Sistema Biliar/genética , Biópsia , Ácidos Nucleicos Livres/genética , Humanos , Mutação
20.
Eur Rev Med Pharmacol Sci ; 24(12): 6665-6673, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32633356

RESUMO

OBJECTIVE: To explore the effects of micro ribonucleic acid-129-2 (miR-129-2) on proliferation and migration of liver cancer cells and its possible mechanism. PATIENTS AND METHODS: The expression level of miR-129-2 was measured in liver cancer tissues and adjacent tissues from patients with liver cancer. Its level in liver cancer HepG2 cells and normal liver cells L-02 was also detected via quantitative polymerase chain reaction (qPCR). MiR-192-2 overexpression model was established in the HepG2 cell line. The proliferation and apoptosis levels of cells were determined by methyl thiazolyl tetrazolium (MTT) assay and flow cytometry, respectively. Wound healing assay was performed to detect the migration ability of cells. The expressions level of genes in the Wnt signaling pathway were measured through Western blotting. Xenograft tumor model was conducted in nude mice for exploring the in vivo effects of miR-129-2 on liver cancer growth. RESULTS: The expression level of miR-129-2 was significantly lower in liver cancer tissues than that in adjacent tissues (p<0.01), and it was overtly lower in HepG2 cells than that in L-02 cells (p<0.01). Overexpression of miR-129-2 weakened proliferation and migration abilities of liver cancer cells (p<0.01), and evidently increased apoptosis level (p<0.01). Sex-determining region Y-related HMG-box 4 (Sox4) and matrix metalloproteinase-2 (MMP-2) were downregulated, while phosphorylated glycogen synthase kinase-3ß (p-GSK3ß) was upregulated in liver cancer cells overexpressing miR-129-2. Besides, the weight and volume of tumors in nude mice bearing liver cancer were significantly smaller after overexpression of miR-129-2. CONCLUSIONS: MiR-129-2 weakens proliferation and migration and stimulates apoptosis in liver cancer cells mainly by downregulating Sox4 and inactivating the Wnt signaling pathway.


Assuntos
Apoptose/fisiologia , Proliferação de Células/fisiologia , Neoplasias Hepáticas/metabolismo , MicroRNAs/biossíntese , Via de Sinalização Wnt/fisiologia , Animais , Células Hep G2 , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Nus , Carga Tumoral/fisiologia
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