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2.
Clin Radiol ; 78(10): e689-e697, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37460338

RESUMO

AIM: To develop a deep-learning model using contrast-enhanced chest computed tomography (CT) images to predict programmed death-ligand 1 (PD-L1) expression in patients with non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Preoperative enhanced chest CT images and immunohistochemistry results for PD-L1 expression (<1% and ≥1% were defined as negative and positive, respectively) were collected retrospectively from 125 NSCLC patients to train and validate a deep-learning radiomics model (DLRM) for the prediction of PD-L1 expression in tumours. The DLRM was developed by combining the deep-learning signature (DLS) obtained from a convolutional neural network and clinicopathological factors. The indexes of the area under the curve (AUC), integrated discrimination improvement (IDI), and decision curve analysis (DCA) were used to evaluate the efficiency of the DLRM. RESULTS: DLS and tumour stage were identified as independent predictors of PD-L1 expression by the DLRM. The AUCs of the DLRM were 0.804 (95% confidence interval: 0.697-0.911) and 0.804 (95% confidence interval: 0.679-0.929) in the training and validation cohorts, respectively. IDI analysis showed the DLRM had better diagnostic accuracy than DLS (0.0028 [p<0.05]) in the validation cohort. Additionally, DCA revealed that the DLRM had more net benefit than the DLS for clinical utility. CONCLUSION: The proposed DLRM using enhanced chest CT images could function as a non-invasive diagnostic tool to differentiate PD-L1 expression in NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Aprendizado Profundo , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Antígeno B7-H1 , Estudos Retrospectivos , Neoplasias Pulmonares/diagnóstico por imagem
3.
Zhonghua Gan Zang Bing Za Zhi ; 31(5): 556-560, 2023 May 20.
Artigo em Chinês | MEDLINE | ID: mdl-37365036

RESUMO

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) transport and transmit intercellular information and play an essential role in physiological and pathological processes. MSC-EVs, MSC-EVs-microRNA, and genetically modified MSC-EVs are involved in the onset and progression of different liver diseases and play a role in reducing liver cell damage, promoting liver cell regeneration, inhibiting liver fibrosis, regulating liver immunity, alleviating liver oxidative stress, inhibiting liver cancer occurrence, and others. Hence, it will replace MSCs as a research hotspot for cell-free therapy. This article reviews the research progress of MSC-EVs in liver diseases and provides a new basis for cell-free therapy of clinical liver diseases.


Assuntos
Vesículas Extracelulares , Neoplasias Hepáticas , Células-Tronco Mesenquimais , MicroRNAs , Humanos , MicroRNAs/genética
4.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 34(3): 269-276, 2022 Jul 05.
Artigo em Chinês | MEDLINE | ID: mdl-35896490

RESUMO

OBJECTIVE: To evaluate the storage stability of metabolites from actinomycetes Streptomyces nigrogriseolus XD 2-7 and the mollcuscicidal activity against Oncomelania hupensis in the laboratory, and to preliminarily explore the mechanisms of the molluscicidal activity. METHODS: The fermentation supernatant of S. nigrogriseolus XD 2-7 was prepared and stored at -20, 4 °C and 28 °C without light for 10 d; then, the molluscicidal effect was tested against O. hupensis following immersion for 72 h. The fermentation supernatant was boiled in a 100 °C water bath for 30 min and recovered to room temperature, and then the molluscicidal effect was tested against O. hupensis following immersion for 72 h. The pH values of the fermentation supernatant were adjusted to 4.0, 6.0 and 9.0 with concentrated hydrochloric acid and sodium hydroxide, and the fermentation supernatant was stilled at room temperature for 12 h, with its pH adjusted to 7.0; then, the molluscicidal effect was tested against O. hupensis following immersion for 72 h. The fermentation product of S. nigrogriseolus XD 2-7was isolated and purified four times with macroporous resin, silica gel and octadecylsilane bonded silica gel. The final products were prepared into solutions at concentrations of 10.00, 5.00, 2.50, 1.25 mg/L and 0.63 mg/L, and the molluscicidal effect of the final productswas tested against O. hupensis following immersion for 72 h, while dechlorination water served as blank controls, and 0.10 mg/L niclosamide served as positive control. The adenosine triphosphate (ATP) and adenosine diphosphate (ADP) levels were measured in in O. hupensis soft tissues using high performance liquid chromatography (HPLC) following exposure to the final purified fermentation products of S. nigrogriseolus XD 2-7. RESULTS: After the fermentation supernatant of S. nigrogriseolus XD 2-7 was placed at -20, 4 °C and 28 °C without light for 10 d, immersion in the stock solution and solutions at 10- and 50-fold dilutions for 72 h resulted in a 100% (30/30) O. hupensis mortality. Following boiling at 100 °C for 30 min, immersion in the stock solution and solutions at 10- and 50-fold dilutions for 72 h resulted in a 100.00% (30/30) O. hupensis mortality. Following storage at pH values of 4.0 and 6.0 for 12 h, immersion in the fermentation supernatant of S. nigrogriseolus XD 2-7 for 72 h resulted in a 100.00% (30/30) O. hupensis mortality, and following storage at a pH value of 9.0 for 12 h, immersion in the fermentation supernatant of S. nigrogriseolus XD 2-7 for 72 h resulted in a 33.33% (10/30) O. hupensis mortality (χ2 = 30.000, P < 0.05). The minimum concentration of the final purified fermentation products of S. nigrogriseolus XD 2-7 was 1.25 mg/L for achieving a 100% (30/30) O. hupensis mortality. The ATP level was significantly lower in O. hupensis soft tissues exposed to 0.10 mg/L and 1.00 mg/L of the final purified fermentation products of S. nigrogriseolus XD 2-7 than in controls (F = 7.274, P < 0.05), while no significant difference was detected in the ADP level between the treatment group and controls (F = 2.485, P > 0.05). CONCLUSIONS: The active mollcuscicidal ingredients of the S. nigrogriseolus XD 2-7 metabolites are maintained stably at -20, 4 °C and 28 °C for 10 d, and are heat and acid resistant but not alkali resistant. The metabolites from S. nigrogriseolus XD 2-7 may cause energy metabolism disorders in O. hupensis, leading to O. hupensis death.


Assuntos
Moluscocidas , Caramujos , Difosfato de Adenosina/farmacologia , Trifosfato de Adenosina , Animais , Moluscocidas/farmacologia , Sílica Gel/farmacologia , Streptomyces , Água
5.
Zhonghua Wei Chang Wai Ke Za Zhi ; 25(4): 305-308, 2022 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-35461197

RESUMO

The extent of D3 lymphadenectomy for right colon cancer, especially the medial border of central lymph node dissection remains controversial. D3 lymphadenectomy and complete mesocolon excision (CME) are two standard procedures for locally advanced right colon carcinoma. D3 lymphadenectomy determines the medial border according to the distribution of the lymph nodes. The mainstream medial border should be the left side of superior mesenteric vein (SMV) according to the definition of D3, but there are also some reports that regards the left side of superior mesenteric artery (SMA) as the medial border. In contrast, the CME procedure emphasizes the beginning of the colonic mesentery and the left side of SMA should be considered as the medial border. Combined with the anatomical basis, oncological efficacy and technical feasibility of D3 lymph node dissection, we think that it is safe and feasible to take the left side of SMA as the medial boundary of D3 lymph node dissection. This procedure not only takes into account the integrity of mesangial and regional lymph node dissection, but also dissects more distant lymph nodes at risk of metastasis. It has its anatomical basis and potential oncological advantages. However, at present, this technical concept is still in the exploratory stage in practice, and the related clinical evidence is not sufficient.


Assuntos
Neoplasias do Colo , Laparoscopia , Mesocolo , Colectomia/métodos , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Humanos , Laparoscopia/métodos , Excisão de Linfonodo/métodos , Mesocolo/cirurgia
6.
Peptides ; 146: 170675, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34655691

RESUMO

The urotensin 2 (uts2) gene family consists of four paralogs called uts2, uts2-related peptide (urp), urp1 and urp2. uts2 is known to exert a large array of biological effects, including osmoregulation, control of cardiovascular functions and regulation of endocrine activities. Lately, urp1 and urp2 have been shown to regulate axial straightening during embryogenesis. In contrast, much less is known about the roles of urp. The aim of the present study was to investigate the expression and the functions of urp by using the zebrafish as a model. For this purpose, we determined the expression pattern of the urp gene. We found that urp is expressed in motoneurons of the brainstem and the spinal cord, as in tetrapods. This was confirmed with a new Tg(urp:gfp) fluorescent reporter line. We also generated a urp knockout mutant by using CRISPR/Cas9-mediated genome editing and analysed its locomotor activity in larvae. urp mutant did not exhibit any apparent defect of spontaneous swimming when compared to wild-type. We also tested the idea that urp may represent an intermediary of urp1 and urp2 in their role on axial straightening. We found that the upward bending of the tail induced by the overexpression of urp2 in 24-hpf embryos was not altered in urp mutants. Our results indicate that urp does probably not act as a relay downstream of urp2. In conclusion, the present study showed that zebrafish urp gene is primarily expressed in motoneurons but is apparently dispensable for locomotor activity in the early larval stages.


Assuntos
Larva/metabolismo , Locomoção , Neurônios Motores/metabolismo , Peptídeos/metabolismo , Urotensinas/metabolismo , Peixe-Zebra/metabolismo , Animais , Animais Geneticamente Modificados , Sistemas CRISPR-Cas , Edição de Genes/métodos , Hibridização In Situ , Peixe-Zebra/crescimento & desenvolvimento
7.
Hum Mol Genet ; 30(19): 1833-1850, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34089062

RESUMO

Mutations of SPINT2, the gene encoding the integral membrane, Kunitz-type serine inhibitor HAI-2, primarily affect the intestine, while sparing many other HAI-2-expressing tissues, causing sodium loss in patients with syndromic congenital sodium diarrhea. The membrane-bound serine protease prostasin was previously identified as a HAI-2 target protease in intestinal tissues but not in the skin. In both tissues, the highly related inhibitor HAI-1 is, however, the default inhibitor for prostasin and the type 2 transmembrane serine protease matriptase. This cell-type selective functional linkage may contribute to the organ-selective damage associated with SPINT 2 mutations. To this end, the impact of HAI-2 deletion on matriptase and prostasin proteolysis was, here, compared using Caco-2 human colorectal adenocarcinoma cells and HaCaT human keratinocytes. Greatly enhanced prostasin proteolytic activity with a prolonged half-life and significant depletion of HAI-1 monomer were observed with HAI-2 loss in Caco-2 cells but not HaCaT cells. The constitutive, high level prostasin zymogen activation observed in Caco-2 cells, but not in HaCaT cells, also contributes to the excessive prostasin proteolytic activity caused by HAI-2 loss. HAI-2 deletion also caused increased matriptase zymogen activation, likely as an indirect result of increased prostasin proteolysis. This increase in activated matriptase, however, only had a negligible role in depletion of HAI-1 monomer. Our study suggests that the constitutive, high level of prostasin zymogen activation and the cell-type selective functional relationship between HAI-2 and prostasin renders Caco-2 cells more susceptible than HaCaT cells to the loss of HAI-2, causing a severe imbalance favoring prostasin proteolysis.


Assuntos
Células Epiteliais , Glicoproteínas de Membrana , Células CACO-2 , Células Epiteliais/metabolismo , Humanos , Intestinos , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Proteínas Secretadas Inibidoras de Proteinases/genética , Proteínas Secretadas Inibidoras de Proteinases/metabolismo , Proteólise , Serina Endopeptidases
8.
Zhonghua Zhong Liu Za Zhi ; 43(5): 546-552, 2021 May 23.
Artigo em Chinês | MEDLINE | ID: mdl-34034474

RESUMO

Objective: To assess the optimal cut-off value between early recurrence and late recurrence of patients with hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA), and to construct a nomogram to predict early recurrence. Methods: A total of 119 patients with HCC who recurred after RFA in Cancer Hospital, Chinese Academy of Medical Sciences from January 2012 to December 2017 were identified. The optimal cut-off value to distinguish early and late recurrence was determined based on differences in post recurrence survival (PRS) by minimum P-value approach. The clinical and radiographic risk factors for early recurrence were identified by univariate and multivariate Logistic regression analysis. The predictive nomogram was constructed by these factors and internally validated. Results: The optimal cut-off value to distinguish early recurrence and late recurrence was 12 months after RFA (P=0.005). The patients were divided into early recurrence group (47 cases) and late recurrence group (72 cases). The lower quartile PRS (Q1-PRS) and lower quartile overall survival (Q1-OS) were 11.1 and 19.1 months in the early recurrence group, which were shorter than 31.6 and 81.0 months in the late recurrence group (P=0.005 and P<0.001, respectively). The independent risk factors of early recurrence were alpha fetoprotein (AFP) (OR=8.459, 95%CI: 2.231-32.073), albumin(ALB) (OR=0.251, 95%CI: 0.047-1.339), number of lesions (OR=3.842, 95%CI: 1.424-10.365) and peritumoral enhancement (OR=8.05, 95%CI: 1.23-52.80), which were further incorporated into constructing the predictive nomogram of early recurrence of HCC after RFA. Internal validation results showed the area under the curve, sensitivity, specificity of the receiver operating characteristic (ROC) curve were 0.839, 68.1% and 93.1%, respectively. The calibration curve showed the predicted curve of nomogram was close to the ideal curve. Hosmer-Lemeshow test showed there was no significant difference between the predicted results of nomogram and the actual results (P=0.424). Conclusions: An interval of 12 months after RFA is the optimal cut-off value for defining early recurrence and late recurrence. The nomogram is integrated by clinical and radiographic features, which can potentially predict early recurrence of HCC after RFA and may offer useful guidance for individual treatment or follow up.


Assuntos
Carcinoma Hepatocelular , Ablação por Cateter , Neoplasias Hepáticas , Ablação por Radiofrequência , Carcinoma Hepatocelular/cirurgia , Humanos , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/cirurgia , Nomogramas , Estudos Retrospectivos , Fatores de Risco
9.
Zhonghua Zhong Liu Za Zhi ; 43(3): 312-317, 2021 Mar 23.
Artigo em Chinês | MEDLINE | ID: mdl-33752311

RESUMO

Objective: To investigate the combined value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) in predicting pathological microvascular invasion (pMVI) preoperatively, and to determine the relationship between prediction results and prognosis in hepatocellular carcinoma (HCC) patients. Methods: A total of 181 newly diagnosed HCC patients were enrolled in this study. Imaging characteristics and the apparent diffusion coefficient (ADC) value of DWI were analyzed. The differences of imaging characteristics and ADC values between different pMVI groups were analyzed.Multivariate logistic regression and receiver operating characteristic (ROC) curve were used to analyze the value for pMVI prediction by using significant parameters. The patients were grouped based on MRI predicted MVI (mrMVI), and the relationship between mrMVI and recurrence free survival time (RFS) was analyzed. Results: Fifty-one patients were pMVI positive and 130 patients were pMVI negative. The ADC value in pMVI positive group were (1.10±0.17)×10(-3) mm(2)/s, significantly lower than (1.27±0.22)×10(-3) mm(2)/s of pEMVI negative group (P<0.001). The incidence rates of incomplete enhancing "capsule" , non-smooth tumor margin, arterial peritumoral enhancement, mosaic architecture and peritumoral hypointensity on hepatobiliary phase (HBP) in pMVI positive group were significantly higher than those of negative group (all P<0.05). Multivariate logistic regression analysis showed that tumor margin, arterial peritumoral enhancement, peritumoral hypointensity on HBP and ADC value were independently associated with pMVI. ROC analysis showed that the area under curve, sensitivity and specificity of pMVI predicted by combined parameters were 0.830, 76.5% and 81.5%, respectively. The median RFS of mrMVI positive group was 23.6 months, significantly lower than 38.2 months of mrEMVI negative group (P=0.004). Conclusion: Tumor margin, arterial peritumoral enhancement, peritumoral hypointensity on HBP and ADC value are independent predictors of pMVI in HCC, and mrMVI is related with RFS.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagem , Meios de Contraste , Imagem de Difusão por Ressonância Magnética , Gadolínio , Gadolínio DTPA , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética , Prognóstico , Estudos Retrospectivos
10.
J Mech Behav Biomed Mater ; 113: 104127, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33125950

RESUMO

Mechanotransduction, the encoding of local mechanical stresses and strains at sensory endings into neural action potentials at the viscera, plays a critical role in evoking visceral pain, e.g., in the distal colon and rectum (colorectum). The wall of the colorectum is structurally heterogeneous, including two major composites: the inner consists of muscular and submucosal layers, and the outer consists of circular muscular, intermuscular, longitudinal muscular, and serosal layers. In fact the colorectum presents biomechanical heterogenity across both the longitudinal and through-thickness directions thus highlighting the differential roles of sensory nerve endings within different regions of the colorectum in visceral mechanotransduction. We determined constitutive models and model parameters for individual layers of the colorectum from three longitudinal locations (colonic, intermediate, and distal) using nonlinear optimization to fit our experimental results from biaxial extension tests on layer-separated colorectal tissues (mouse model, 7×7 mm2, Siri et al., Am. J. Physiol. Gastrointest. Liver Physiol. 316, G473-G481 and 317, G349-G358), and quantified the thicknesses of the layers. In this study we also quantified the residual stretches stemming from separating colorectal specimens into inner and outer composites and we completed new pressure-diameter mechanical testing to provide an additional validation case. We implemented the constitutive equations and created two-layered, 3-D finite element models using FEBio (University of Utah), and incorporated the residual stretches. We validated the modeling framework by comparing FE-predicted results for both biaxial extension testing of bulk specimens of colorectum and pressure-diameter testing of bulk segments against corresponding experimental results independent of those used in our model fitting. We present the first theoretical framework to simulate the biomechanics of distal colorectum, including both longitudinal and through-thickness heterogeneity, based on constitutive modeling of biaxial extension tests of colon tissues from mice. Our constitutive models and modeling framework facilitate analyses of both fundamental questions (e.g., the impact of organ/tissue biomechanics on mechanotransduction of the sensory nerve endings, structure-function relationships, and growth and remodeling in health and disease) and specific applications (e.g., device design, minimally invasive surgery, and biomedical research).


Assuntos
Colo , Mecanotransdução Celular , Animais , Fenômenos Biomecânicos , Camundongos , Reto , Estresse Mecânico
11.
Zhonghua Xue Ye Xue Za Zhi ; 41(11): 903-907, 2020 Nov 14.
Artigo em Chinês | MEDLINE | ID: mdl-33333692

RESUMO

Objective: To study the orthopedic treatment strategy for hemophilia complicated with musculoskeletal disorders as well as the peri-operative consumption of clotting factor. Methods: Total 338 orthopedic surgeries were performed for 261 patients, average age of 30.6 y (6-65 y) , with hemophilia between January 1996 and December 2019 at our institute. Two hundred and twenty-six patients presented with bleeds within the joints. Sixty-one patients presented with intramuscular bleeds, 45 presented with hemophilic pseudotumors, and six presented with miscellaneous complaints. Strategy of clotting factor replacement therapy was designed as per differences in the level of the operation procedure. Information regarding clinical manifestation, operative strategy, clotting factor consumption, and re-operation for complications was retrospectively recorded. The costs for multiple joint procedure and single joint procedure were studied. Results: We found that 270 of the 338 surgical procedures were major surgical procedures (79.9%) . There were 203 procedures of joint arthroplasty (60%) . Fourteen patients underwent reoperations for local recurrence (4.2%) . The average factor Ⅷ consumption before the surgery was 44.4 ± 8.1 IU/kg. The average FⅧ consumption within postoperative 2 weeks was 40 962 IU (647±177 IU/kg) . Seven type A hemophilic patients developed F Ⅷ inhibitor following the surgical procedure, with an average level of 13.7±11.2 BU/mL. Sixty-eight patients underwent multiple joint procedures under one anesthesia session (26%) . There was no significant difference in the factor consumption between the multiple joint procedure and single joint procedure. Conclusions: Surgical treatment was found to be effective for hemophilic arthropathy and lesion of the musculoskeletal apparatus, with the clotting factor replacement therapy. Multiple joint procedures under one anesthesia were more cost effective for patients with hemophilia, with less factor consumption than staged single joint procedure.


Assuntos
Hemofilia A , Doenças Musculoesqueléticas/complicações , Adulto , Artrite , Fatores de Coagulação Sanguínea , Hemofilia A/complicações , Humanos , Manipulação Ortopédica , Estudos Retrospectivos
12.
QJM ; 113(4): 245-252, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31605493

RESUMO

AIMS: The purpose of study is to evaluate the effect and complication of preoperative short-term daily recombinant human erythropoietin (rhEPO) treatment for blood-saving in patients undergoing unilateral primary total knee arthroplasty (TKA). METHODS: This three-arm randomized clinical trial compared three different rhEPO-based treatment protocols for unilateral primary TKA. Group A: application of daily doses of rhEPO combined with iron supplement starting 3 days before surgery; Group B: application of daily doses of rhEPO combined with iron supplement starting the day of surgery; Group C: iron supplement alone. Perioperative hemoglobin (Hb) level gaps, total perioperative blood loss, reticulocyte levels and treatment-related complications were studied. RESULTS: A total of 102 patients were included (35, 35 and 32 patients in Groups A, B and C, respectively). Total blood loss (TBL) in Groups A, B and C was 490.84, 806.76 and 924.21 ml, respectively. Patients in Group A had a significant lower TBL than Groups B and C (A vs. B: P = 0.010; A vs. C: P < 0.001). There was no difference as for TBL between Groups B and C (P = 0.377). Group A patients had significant smaller Hb decline than Group C on the third and fifth postoperative day (P = 0.049, P = 0.037), as well as than Group B on the fifth postoperative day (P = 0.048). There was no difference as for Hb decline between Groups B and C. No difference was shown in levels of inflammatory biomarkers or blood-saving protocol-related complications among three groups. CONCLUSIONS: Daily dose of rhEPO combined with iron supplement administered 3 days before TKA procedures could significantly decrease perioperative blood loss and improve postoperative Hb levels, without significantly elevating risks of complication, when compared with admission of rhEPO on the day of surgery and iron supplement alone. Preoperative daily rhEPO treatment could be a more effective blood-saving protocol in TKA procedures.


Assuntos
Artroplastia do Joelho , Eritropoetina/administração & dosagem , Ferro/administração & dosagem , Cuidados Pré-Operatórios , Proteínas Recombinantes/administração & dosagem , Idoso , Perda Sanguínea Cirúrgica/prevenção & controle , Suplementos Nutricionais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
13.
Zhonghua Yi Xue Za Zhi ; 99(40): 3158-3163, 2019 Oct 29.
Artigo em Chinês | MEDLINE | ID: mdl-31694107

RESUMO

Objective: To assess the oncologic outcomes of radical nephroureterectomy (RNU) combined with adjuvant chemotherapy (ACT) in patients with high risk upper tract urothelial carcinoma (UTUC). Methods: From January 2014, all high-risk UTUC patients after RNU surgery were enrolled in this prospective comparative trial. And these patients were randomized to ACT group (Gemcitabine+Cisplatin three weeks regimen) and observing group. Cox proportional hazard modeling and Kaplan-Meier analysis were used to determine overall survival (OS), cancer specific survival (CSS) and disease-free survival (PFS) in the cohort. Results: The median follow-up duration was36 months (range: 6-54) in the ACT group (n=94) and 30 months (range: 6-54) in the observing group (n=82). Oncologic outcomes of RNU treated high-risk UTUC patients were improved much significantly by ACT: OS [P=0.0397, HR: 1.39(0.91-1.75)], CSS [P=0.0255, HR: 1.26(1.07-1.45)] and PFS [P=0.0033, HR: 3.78(3.13-4.55)]. The further analysis in lymph node positive cohort displayed that median times of oncologic events were prolonged in the ACT group compared with the observing group: OS (26.8mon vs 36.3mon, P=0.0255), CSS (28.2mon vs39.3mon, P=0.0197) and PFS (11.4mon vs 31.9mon, P=0.0018). Additionally in T3/4 cohort, the significant growth in the median times of OS (20.6mon vs 32.2mon, P=0.0183), CSS (21.9mon vs 38.4mon, P=0.0226) and PFS (13.9mon vs 36.3mon, P=0.0217) were observed in ACT group. Conclusion: ACT could play the important synergistic role in improving the OS, CSS and PFS of high-risk UTUC patients after RNU.


Assuntos
Carcinoma de Células de Transição , Nefroureterectomia , Carcinoma de Células de Transição/tratamento farmacológico , Quimioterapia Adjuvante , Humanos , Nefrectomia , Prognóstico , Estudos Prospectivos , Resultado do Tratamento
14.
Eur Rev Med Pharmacol Sci ; 23(20): 9099-9107, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31696501

RESUMO

OBJECTIVE: Gliclazide is one of the most widely used therapeutic drugs for diabetes. As a second-generation sulfonylurea oral hypoglycemic drug, it can lower blood glucose level and delay the occurrence and development of diabetic nephropathy (DN). However, the underlying mechanism remains unclear. Therefore, the aim of this study was to explore whether gliclazide had protective effects on high glucose and advanced glycation end products (AGEs)-induced injury of human mesangial cells (HMCs) and renal tubular epithelial cells. MATERIALS AND METHODS: HMC and renal tubular epithelial cell lines [human kidney 2 (HK-2)] were cultured in vitro. All cells were then divided into the follow groups: 1) blank control group (5.6 mmol/L glucose), 2) AGEs group [400 µg/mL AGE-bovine serum albumin (AGE-BSA)], 3) high glucose group (25 mmol/L glucose), 4) gliclazide + AGEs group (400 µg/mL AGE-BSA + 20 µmol/L gliclazide) and 5) gliclazide + high glucose group (25 mmol/L glucose + 20 µmol/L gliclazide). Cell counting kit-8 (CCK-8) assay was adopted to determine cell viability. Flow cytometry was used to detect cell apoptosis. The levels of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured as well. Furthermore, the mRNA expressions of receptor for AGE (RAGE), p22phox and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were measured via fluorescence quantitative Real-time polymerase chain reaction (qRT-PCR). RESULTS: Compared with control group, significantly accelerated apoptosis of HMCs and HK-2, increased MDA level, decreased SOD and GSH-Px levels, and up-regulated mRNA expressions of RAGE, p22phox and NF-κB were observed in HMCs and HK-2 of high glucose group and AGEs group. Meanwhile, there were obviously alleviated apoptosis of HMCs and HK-2, decreased MDA level, increased SOD and GSH-Px levels, as well as down-regulated mRNA expressions of RAGE, p22phox and NF-κB in HMCs and HK-2 of gliclazide group compared with high glucose and AGEs group. Furthermore, significant correlations were found between the mRNA expression of RAGE and the apoptosis rate of HMCs and HK-2 (HMCs: r=0.701, p=0.004 and HK-2: r=0.633, p=0.011). CONCLUSIONS: Gliclazide has protective effects on high glucose and AGEs-induced damage of glomerular mesangial cells and renal tubular epithelial cells via inhibiting RAGE-NADPH oxidase-NF-kB pathway.


Assuntos
Gliclazida/farmacologia , Glucose/efeitos adversos , Produtos Finais de Glicação Avançada/efeitos adversos , Túbulos Renais/citologia , Células Mesangiais/citologia , Soroalbumina Bovina/efeitos adversos , Antígenos de Neoplasias/genética , Apoptose/efeitos dos fármacos , Células Cultivadas , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/metabolismo , Células Mesangiais/efeitos dos fármacos , Células Mesangiais/metabolismo , Proteínas Quinases Ativadas por Mitógeno/genética , NADPH Oxidases/genética , NF-kappa B/genética , Transdução de Sinais/efeitos dos fármacos
15.
Zhonghua Gan Zang Bing Za Zhi ; 27(8): 643-647, 2019 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-31594084

RESUMO

Objective: To understand the basic information of anti-mitochondrial antibody (anti-AMA)-positive patients after initial diagnosis, and to set groundwork for further exploring the clinical significance of AMA in various diseases. Methods: Demographic data and related clinical information recorded through the Information System of Peking University People's Hospital from January 2013 to December 2016 were collected. Patients whose AMA and/or AMA-M2 first- tested as positive were recorded. Complications were classified according to the International Classification of Diseases. Results: A total of 1323 AMA positive cases were discovered for the first time. Among them, 78.0% were women, and the age of initial diagnosis was 56.8 ± 16.0 years. The first three initially diagnosed departments were rheumatology and immunology (37.4%), liver Disease (15.9%) and hematology (15.9%) relevant to musculoskeletal and connective tissue diseases (45.2%), hematology and hematopoietic organs and immune diseases (30.6%) and circulatory system diseases (29.7%). There were 297 newly confirmed cases of primary biliary cholangitis (PBC); accounting for 89.2% of women, and the age of initial diagnosis was 60.1 ± 12.4 years. The top three departments of initially diagnosed as PBC were liver disease (37.7%), rheumatology (33.0%) and gastroenterology (15.2%), of which 39.7% had musculoskeletal and connective tissue diseases, 27.9% had circulatory diseases, and 24.9 % were combined with endocrine and metabolic diseases. Conclusion: Besides PBC and other autoimmune diseases, AMA and / or AMA-M2 positivity can be observed in a variety of diseases in several clinical departments, and its clinical significance remains to be further clarified.


Assuntos
Autoanticorpos/sangue , Colangite/diagnóstico , Cirrose Hepática Biliar/diagnóstico , Adulto , Idoso , Doenças Autoimunes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitocôndrias/imunologia
16.
Zhonghua Wai Ke Za Zhi ; 57(9): 666-672, 2019 Sep 01.
Artigo em Chinês | MEDLINE | ID: mdl-31474058

RESUMO

Objective: To analyze the status of domestic surgical treatment of synchronous peritoneal carcinomatosis from colorectal cancer in China. Methods: Clinicopathological data of patients who underwent surgery from October 2003 to October 2018 in 16 domestic medical centers was retrospectively analyzed. Excel database was created which covered 77 fields of 7 parts: baseline information of patients, laboratory tests, imaging tests, chemoradiotherapy information, intra-operative findings, postoperative pathology and follow-up data. The Wilcoxon rank-sum test was used for comparison of the measurement data between groups. The χ(2) test was used for comparison of the categorical data between groups. The survival curve was calculated by the Kaplan-Meier method. Results: Of the 1 003 patients, there were 575 male and 428 female patients with the age of (58.5±14.1) years (range: 18 to 92 years). In a total of 920 patients, the carcinoma of sigmoid colon was performed in 292 cases (31.8%) with the highest ratio. The proportion of patients with liver metastasis and lung metastasis were 27.9% (219/784) and 8.3% (64/769). Preoperative detection of carcino-embryonic antigen level was the most common method in China (87.74%, 880/1 003), and the positive rate was 64.5% (568/880). The correct rate of preoperative imaging tests was 40.7% (280/688). The ratio of peritoneal carcinomatosis index (PCI) scores between 0 and 10 was the highest (59.6%, 170/285). Two hundred and sixty-two (27.0%) patients were performed by totally laparoscopic operation in 971 patients. The resection of primary tumor was performed in 588 of the 817 patients (72.0%). In a total of 457 cases, 253 (55.4%) patients were performed cytoreduction which group scored completeness of cytoreduction (CCR) 0. The postoperative hyperthermic intraperitoneal chemotherapy was implemented in 70 of the 334 cases (21.0%). Among 1 003 cases, 562 cases (56.03%) had complete follow-up data and the median overall survival was 15 months. The primary tumor resection and the CCR scores were affected by the PCI scores. The patients underwent primary tumor resection (187/205 vs. 26/80, χ(2)=105.085, P=0.000) and the patients were performed cytoreduction which scored CCR 0 or CCR 1 (162/204 vs. 8/78, Z=-10.465, P=0.000) had significant difference between the groups of PCI<20 and ≥20. There was a close correlation between the surgical method and the CCR scores (Z=-3.246,P=0.001).When the maximum degree of tumor reduction was planned, most surgeons would choose laparotomy. The overall survival time was longer in patients with primary tumor resection (P=0.000). The median survival time was 18.6 months in the group of primary tumor resection. Conclusions: It is difficult to diagnose the synchronous peritoneal carcinomatosis from colorectal cancer before the operation. Primary tumor resection has an obvious effect to prolong the survival time. It is necessary to standardize the treatment of peritoneal metastasis.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/terapia , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , China , Neoplasias Colorretais/terapia , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Hipertermia Induzida , Laparoscopia , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/secundário , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
17.
Lupus ; 28(9): 1134-1140, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31296142

RESUMO

BACKGROUND: In recent years, hip arthroplasty rates in systemic lupus erythematosus (SLE) patients have been increasing rapidly. Although patients with SLE generally show beneficial or desirable functional outcomes following total hip arthroplasty (THA), it has been reported that SLE patients after THA have increased risk of postoperative complications, especially during the period of hospitalization. OBJECTIVES: In the present study, we aimed to identify possible factors associated with complications or transfusion of THA in SLE patients during hospitalization. METHODS: The present study was a retrospective study conducted in Peking Union Medical College Hospital. Data were collected from medical records of patients who underwent THA from January 2012 to June 2018. The primary outcome variable was perioperative complications, which was defined as having one or more of the following conditions: high fever, infection, impaired wound healing, venous thrombosis of the lower extremities, hematoma, arrhythmia, implant complications. The secondary outcome was perioperative transfusion. RESULTS: During January 2012 to June 2018, 100 patients had taken the surgery of THA. After multivariate analysis, independent risk factors for perioperative complications were: age ≥ 45 years (p = 0.001), SLE with other connective tissue diseases (p = 0.029), high temperature (p = 0.030), positive anti-dsDNA antibody (p = 0.043), and Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index ≥ 3 (p = 0.008). Independent risk factors for perioperative transfusion were bilateral THA (p = 0.029), low hemoglobin (p = 0.021) and abnormal renal function (p = 0.021). CONCLUSION: For SLE patients following THA, age > 45 years, SLE with other connective tissue disease, high temperature, positive anti-dsDNA antibody and SLICC/ACR Damage Index ≥ 3 were the risk factors of complications during hospitalization and bilateral THA, low hemoglobin and abnormal renal function were the risk factors of transfusion.


Assuntos
Artroplastia de Quadril/métodos , Transfusão de Sangue/estatística & dados numéricos , Lúpus Eritematoso Sistêmico/complicações , Complicações Pós-Operatórias/epidemiologia , Adolescente , Adulto , Idoso , Anticorpos Antinucleares/imunologia , Artroplastia de Quadril/efeitos adversos , DNA/imunologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
18.
Clin Radiol ; 74(7): 570.e1-570.e11, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31056198

RESUMO

AIM: To evaluate the preoperative differentiation between the minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC) in patients with sub-solid pulmonary nodules using a radiomics nomogram. MATERIALS AND METHODS: A total of 100 patients with sub-solid pulmonary nodules who had pathologically confirmed MIA (43 patients, 13 male and 30 female) or IAC (57 patients, 26 male and 31 female) were recruited retrospectively. Radiomics features were extracted from computed tomography (CT) images. A radiomics signature was constructed by the least absolute shrinkage and selection operator (LASSO) algorithm. Solid presence, lesion size, shape regularity, and margins of pulmonary nodules were assessed to construct a subjective finding model. An integrated model of radiomics signatures and CT-based subjective findings, which was presented as a radiomics nomogram, was developed based on a multivariate logistic regression. The nomogram performance was assessed by its calibration, discrimination, and clinical usefulness. RESULTS: The radiomics signature, which consisted of 11 radiomics features, showed good discrimination accuracy. The radiomics nomogram showed good calibration and discrimination in the training set (AUC [area under the curve] 0.943; 95% confidence interval [CI]: 0.895-0.991) and validation set (AUC 0.912; 95% CI: 0.780-1.000). The radiomics nomogram was determined to be clinically useful in the decision curve analysis (DCA). CONCLUSION: The proposed radiomics nomogram has the potential to preoperatively differentiate MIA and IAC in patients with sub-solid pulmonary nodules.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/patologia , Tomografia Computadorizada por Raios X/métodos , Diagnóstico Diferencial , Feminino , Humanos , Imageamento Tridimensional/métodos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Nomogramas , Estudos Retrospectivos
19.
Zhonghua Yi Xue Za Zhi ; 99(16): 1237-1240, 2019 Apr 23.
Artigo em Chinês | MEDLINE | ID: mdl-31060163

RESUMO

Objective: To investigate the effect of the derepression of chemokine receptor-7 (CXCR7) in prostatic tissues from patients with Castration Resistant Prostate Cancer (CRPC) on the resistance to enzalutamide (Enza). Methods: During the period of January 2015 to December 2017 all CRPC cases who underwent radical radiotherapy or androgen deprivation therapy (ADT) were evaluated. After prostatic puncture biopsy, the tissues were treated for immunostaining with CXCR7. Cox proportional hazard modeling and Kaplan-Meier analysis were used to determine PSA Progression-Free Survival (PSAP-FS) and Clinical or Radiographic Progression-Free Survival (CRP-FS) in the cohort. At last, PSA response rates and progression outcomes in CXCR7 negative cases and CXCR7 positive cases were analyzed. Results: Total 39 CRPC patients were enrolled in this study. And 23 cases derepress CXCR7, 16 cases negatively express CXCR7. The median follow-up duration was 12 months (range: 6-18) in the cohort. Chi-square analysis confirmed that PSA response rates after Enza treatment were significantly associated with CXCR7 derepression (χ(2)=22.129, P=0.000 06). Compared with CXCR7 positive expression group, CXCR7 negative expression group displayed improved median PSAP-FS (4.4 mon vs 11.7 mon, P=0.040 8) and CRP-FS (5.2 mon vs 13.1 mon, P=0.036 2) after Enza treatment. Conclusion: Derepression of CXCR7 in CRPC patients may be associated with resistance to enzalutamide. This protein may be novel target for treatment of CRPC.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Receptores CXCR/metabolismo , Antagonistas de Androgênios , Benzamidas , Intervalo Livre de Doença , Humanos , Masculino , Nitrilas , Feniltioidantoína/análogos & derivados , Antígeno Prostático Específico
20.
Clin Microbiol Infect ; 25(9): 1120-1126, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30738995

RESUMO

OBJECTIVES: Elderly individuals in rural China have been known to be at increased risk of contracting tuberculosis (TB) and developing active disease. This study aims to estimate the burden of mycobacterium tuberculosis (MTB) infection and to identify potential targeted subgroups for infection control. METHODS: As part of the investigation of an interventional study, 50- to 70-year-old rural residents in Zhongmu County were targeted for MTB infection testing using QuantiFERON-TB Gold In-Tube (QFT). Questionnaires and physical examinations were conducted to acquire their demographic information and health status. RESULTS: A total of 20 486 individuals were included in the analysis. The prevalence of QFT positivity was 20.79% (4259/20 486) and 50 participants (0.24%) had indeterminate results. A positive dose-response relation was found for QFT positivity with smoking intensity. Compared with non-drinkers, the risk of MTB infection was lower among participants with moderate alcohol consumption (<10 g/day) with adjusted odds ratio (OR) of 0.82 (95% CI 0.71-0.94). In addition, gender of male, with a history of previous TB or silicosis, and hepatitis B/C virus infection were associated with increased risk of MTB infection. An indeterminate QFT result was related to being underweight (adjusted OR 3.18; 95% CI 1.09-9.26). CONCLUSIONS: Our results indicate a high burden of MTB infection among the elderly in this rural area. Smokers, individuals with a history of previous TB or silicosis, and those with hepatitis B/C virus infection should be prioritized for MTB infection control to reduce the risk of disease development from a new infection.


Assuntos
Tuberculose/epidemiologia , Idoso , China/epidemiologia , Feminino , Humanos , Testes de Liberação de Interferon-gama , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/imunologia , Prevalência , Fatores de Risco , População Rural , Tuberculose/diagnóstico
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