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1.
Zhongguo Gu Shang ; 34(11): 1034-9, 2021 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-34812021

RESUMO

OBJECTIVE: To explore the clinical application of Orthopedic Tianji Robot in the treatment of thoracolumbar fractures with minimally invasive percutaneous pedicle screw internal fixation. METHODS: The clinical data of 46 patients with thoracolumbar fractures treated by minimally invasive percutaneous pedicle screw internal fixation from June 2018 to January 2020 in Gansu Provincial People's Hospital was retrospectively analyzed. According to the different aided equipments, the patients were divided into a C-arm X-ray plus robot assisted nail placement group (observation group) and simple C-arm X-ray assisted nail placement group (control group). Twenty-two patients in observation group, including 12males and 10 females, aged from 24 to 61 years old, with a mean of(40.23±12.19) years, 3 cases were T11 vertebrae fracture, 8 cases were T12, 9 cases were L1, and 2 cases were L2. And there were 24 cases in control group, including 15 males and 9 females, aged from 26 to 58 years old, with a mean of (42.88±10.31) years, 3 cases were T11 vertebrae fracture, 10 cases were T12, 7 cases were L1, and 4 cases were L2. The operation time, the number of intraoperative fluoroscopy, intraoperative blood loss, the days of hospitalization, and postoperative complications were recorded. Preoperative and postoperative VAS at 3 days, 1 week and 3 months were compared between two groups. The sagittal Cobb angle of the injured vertebral body and the percentage of the anterior edge height of the vertebral body were observed before and after operation, and evaluate the accuracy of nail placement according to the Gertzbein-Robbins classification criteria with collected postoperative CT images. RESULTS: All patients were followed up for 5 to 12 months with an average of (7.07±0.83) months. There was no significant differences in intraoperative blood loss, operation time and hospitalization days between two groups (P>0.05). The number of intraoperative fluoroscopy was (5.62±0.51) times in observation group and (12.54±0.52) in control group, the difference between two groups was statistically significant (P<0.05). The VAS, the percentage of the height of the injured vertebra anterior edge and the Cobb angle of the injured vertebral plane at each time point after operation were improved(P<0.05), but the difference between two groups was not statistically significant (P>0.05). One case of postoperative incision infection occurred in the control group, which was cured after active dressing changes. There were no serious complications such as screw loosening and breakage in all patients, and there was no statistically significant difference in the incidence of complications between two groups(P>0.05). The postoperative nail placement accuracy ratesof the observation group and the control group were 98.4% (126/128) and 90.3% (121/134), respectively, and the difference was statistically significant (P<0.05). CONCLUSION: In the surgical treatment of thoracolumbar fractures, compared with simple C-arm fluoroscopy, the pedicle screw placement assisted by Orthopedic Tianji Robot overcomes the shortcomings of surgeon's physiological tremor, fatigue and multiple intraoperative fluoroscopy, improves the accuracy of screw placement, and is a more accurate and safer way of pedicle screw placement for thoracolumbar fractures.


Assuntos
Parafusos Pediculares , Robótica , Adulto , Feminino , Fixação Interna de Fraturas , Humanos , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
2.
Hepatobiliary Pancreat Dis Int ; 20(5): 452-459, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34256994

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the main liver diseases, and its pathologic profile includes nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). However, there is no reliable non-invasive parameter in distinguishing NASH from NAFL in clinical practice. The present study was to find a non-invasive way to differentiate these two categories of NAFLD via lipidomic analysis. METHODS: Lipidomic analysis was used to determine the changes of lipid moieties in blood from 20 NAFL and 10 NASH patients with liver biopsy. Liver histology was evaluated after hematoxylin and eosin staining and Masson's trichrome staining. The profile of lipid metabolites in correlation with steatosis, inflammation, hepatocellular necroptosis, fibrosis, and NAFLD activity score (NAS) was analyzed. RESULTS: Compared with NAFL patients, NASH patients had higher degree of steatosis, ballooning degeneration, lobular inflammation. A total of 434 different lipid molecules were identified, which were mainly composed of various phospholipids and triacylglycerols. Many lipids, such as phosphatidylcholine (PC) (P-22:0/18:1), sphingomyelin (SM) (d14:0/18:0), SM (d14:0/24:0), SM (d14:0/22:0), phosphatidylethanolamine (PE) (18:0/22:5), PC (O-22:2/12:0), and PC (26:1/11:0) were elevated in the NASH group compared to those in the NAFL group. Specific analysis revealed an overall lipidomic profile shift from NAFL to NASH, and identified valuable lipid moieties, such as PCs [PC (14:0/18:2), PE (18:0/22:5) and PC (26:1/11:0)] or plasmalogens [PC (O-22:0/0:0), PC (O-18:0/0:0), PC (O-16:0/0:0)], which were significantly altered in NASH patients. In addition, PC (14:0/18:2), phosphatidic acid (18:2/24:4) were positively correlated with NAS; whereas PC (18:0/0:0) was correlated positively with fibrosis score. CONCLUSIONS: The present study revealed overall lipidomic profile shift from NAFL to NASH, identified valuable lipid moieties which may be non-invasive biomarkers in the categorization of NAFLD. The correlations between lipid moieties and NAS and fibrosis scores indicate that these lipid biomarkers may be used to predict the severity of the disease.

3.
Int J Hyperthermia ; 38(1): 916-922, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34148494

RESUMO

PURPOSE: Ultrasound-guided thermal ablation (including microwave ablation [MWA] and radiofrequency ablation [RFA]) has emerged as a remarkable technology for the treatment of benign and malignant diseases. The objective of this multicenter study was to assess the efficacy and safety of thermal ablation in a large cohort of patients with papillary thyroid microcarcinoma (PTMC). MATERIALS AND METHODS: Retrospective study of 725 patients who underwent MWA/RFA at 11 centers between March 2015 and March 2020. The mean age of patients was 46 ± 11 years (range, 22-81); the mean follow-up time was 21 ± 13 months (range, 6-60). Changes in size of tumor, the rates of tumor disappearance, disease progression, and complications were assessed. RESULTS: From 6 months post-ablation, the size of tumors was significantly reduced compared with those recorded pre-ablation (p < 0.001 for all). Five hundred and fifteen (71.0%) PTMCs had completely disappeared as assessed by ultrasound examination. Six (0.8%) patients developed disease progression post-ablation; of these, 5 (0.7%) patients developed new PTMCs, while one (0.1%) patient developed cervical lymph node metastasis. Nineteen (2.6%) patients developed complications post-ablation; of these 14 (1.9%) patients developed voice hoarseness, 4 (0.6%) developed hematoma, and one (0.1%) patient developed cough. CONCLUSIONS: Ultrasound-guided thermal ablation represents an effective and safe treatment for patients with PTMC besides active surveillance and surgery.


Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/cirurgia , Criança , Pré-Escolar , Humanos , Lactente , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/cirurgia , Ultrassonografia de Intervenção
4.
Gland Surg ; 10(4): 1300-1314, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33968682

RESUMO

Background: Controversy remains regarding the predictive and prognostic value of serum human epidermal growth factor receptor 2 (HER2) in breast cancer. The purpose of this retrospective study was to determine the clinical utility and efficacy of serum HER2 (sHER2) in predicting treatment response and prognosis in patients with HER2-positive breast cancer undergoing neoadjuvant chemotherapy and trastuzumab treatment. Methods: A total of 309 HER2-positive breast cancer patients diagnosed at Fudan University Shanghai Cancer Center from July 2015 to January 2019 were analyzed. Baseline sHER2 levels were obtained for all patients and sHER2 levels were collected after 2 cycles of treatment in 208 patients. A sHER2 level ≥15 ng/mL was regarded as "high expression" and sHER2 <15 ng/mL was regarded as "low expression". Outcome measures of treatment efficacy and prognosis were pathological complete response (pCR) and invasive disease-free survival (iDFS), respectively. Results: In patients with high baseline sHER2, more were ER-negative (P=0.029), had larger tumor size (P=0.006), more advanced clinical stage (P=0.002), higher Miller-Payne grade (P=0.024) and higher likelihood of iDFS events (P=0.015). Patients with high sHER2 levels after 2 cycles of treatment had lower pCR rates (P=0.038), higher Miller-Payne grade (P=0.013) and higher likelihood of iDFS events (P=0.003). Kaplan-Meier analysis showed significant differences in iDFS between patients with high and low sHER2 levels at baseline (P=0.019) and after 2 cycles of treatment (P=0.000). Further analyses according to cancer subtypes found baseline sHER2 to be significantly correlated with the iDFS of Luminal B patients (p=0.002), while sHER2 levels after 2 cycles of treatment was significantly correlated with the iDFS of HER2-enriched patients (P=0.000). Univariate analysis showed significant association between iDFS and tumor size (P=0.026), lymph node status (P=0.008), clinical stage (P=0.031), baseline sHER2 (P=0.024), overall tumor response (P=0.011), pCR (P=0.043) and Miller-Payne grade (P=0.001). Multivariate analysis found Miller-Payne grade (P=0.037) to be significantly associated with iDFS. Conclusions: Our results demonstrate the clinical value of sHER2 in a population of Chinese breast cancer patients, suggesting that sHER2 levels after 2 cycles of neoadjuvant therapy may be more predictive of treatment outcomes and that the prognostic value of sHER2 may be time point and subtype dependent.

5.
Ann Transl Med ; 9(5): 413, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33842634

RESUMO

Background: Melatonin (MT) has been shown to protect against various cardiovascular diseases. However, the effect of MT on lipopolysaccharide (LPS)-induced myocardial injury is poorly understood. This study aims to evaluate the effects of MT on LPS-induced myocardial injury in vitro. Methods: H9C2 cells were divided into a control group, MT group, LPS group, and MT + LPS group. The control group was treated with sterile saline solution, the LPS group received 8 µg/mL LPS for 24 h, MT + LPS cells were pretreated with 200 µmol/L MT for 2 h then with 8 µg/mL LPS for 24 h, and the MT group received only 200 µmol/L MT for 2 h. The CCK-8 assay and lactate dehydrogenase (LDH) activity assay were used to analyze cell viability and LDH release, respectively. Intracellular reactive oxygen species (ROS) and the rate of pyroptosis were measured using the fluorescent probe dichloro-dihydro-fluorescein diacetate (DCFH-DA) and propidium iodide (PI) staining, respectively. The cell supernatants were used to measure the levels of inflammatory cytokines, including IL-6, TNF-α, and IL-1ß by enzyme-linked immunosorbent assay (ELISA). The protein levels of iNOS, COX-2, NF-κB, p-NF-κB, NLRP3, caspase-1, and GSDMD were detected by western blot. Results: MT pretreatment significantly improved LPS-induced myocardial injury by inhibiting inflammation and pyroptosis in H9C2 cells. Moreover, MT inhibited the activation of the NF-κB pathway, and reduced the expression of inflammation-related proteins (iNOS and COX-2), and pyroptosis-related proteins (NLRP3, caspase-1, and GSDMD). Conclusions: Our data suggests that MT can alleviate LPS-induced myocardial injury, providing novel insights into the treatment of sepsis-induced myocardial dysfunction.

6.
Front Oncol ; 11: 585613, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33898305

RESUMO

Background and Purpose: Although tumor size and nodal status are the most important prognostic factors, it is believed that nodal status outperforms tumor size as a prognostic factor. In particular, when patients have a nodal stage greater than N2 (more than nine positive lymph nodes), it is well accepted that tumor size does not retain its prognostic value. Even in the newest American Joint Committee on Cancer (AJCC) prognostic staging system, which includes molecular subtype as an important prognostic factor, T1-3N2 patients are categorized as the same population. The same is true for T1-4N3 patients. Moreover, some physicians have speculated that for tumors staged N2 or greater, the smaller the tumor is, the more aggressive the tumor. Thus, this study aims to investigate the prognostic value of tumor stage (T stage) in patients with extensive nodal involvement and to compare the survival of T4N × M0 and T × N3M0. Patients and Methods: Female breast cancer patients with nine or more positive lymph nodes or with T4 tumors were identified in the SEER registry between 2010 and 2015. The effect of T stage on breast cancer-specific survival (BCSS) was assessed using the Kaplan-Meier survival curve method and risk-adjusted Cox proportional hazard regression modeling. Survival comparison of T4NxM0 and TxN3M0 patients was also achieved using the Kaplan-Meier survival curve method and risk-adjusted Cox proportional hazard regression model. Results: Overall, 21,696 women with N2-3 tumors were included from 284,073 patients.T stage, nodal stage (N stage), ER, PR, HER2 and grade were all independent prognostic factors (p <0.001). HRs for ER, PR, HER2, grade, and N stage were 0.662 (0.595-0.738), 0.488 (0.438-0.543), 0.541 (0.489-0.598), 1.534 (1.293-1.418) and 1.551 (1.435-1.676), respectively. Notably, HER2 positivity was correlated with better BCSS possibly due to the wide adoption of anti-HER2 therapy. Using T1 as a reference, HRs of T2, T3, and T4 were 1.363 (1.200-1.548), 2.092 (1.824-2.399) and 3.497 (3.045-4.017), respectively. The same results held true when subgroup analysis based on N stage were conducted. In the two subgroups, namely, women staged as T1-3N2 and women staged as T1-4N3, T stage was also a significant negative prognostic factor independent of ER, PR, HER2 and grade. Moreover, 8,328 women staged as T4 with different nodal statuses were also identified from the whole database. When we compared T4Nx with TxN3, it was found that T4 tumors exhibited worse outcomes than N3 tumors independent of other prognostic factors. When molecular subtype was included in the subgroup analysis, survival could not be distinguished between T4 and N3 only in TNBC. Conclusions: In patients with extensive nodal status, tumor stage remains a prognostic factor independent of other factors, such as ER, PR, HER2, and grade. In patients with T4Nx or TxN3 tumors, T4 tumors exhibit worse outcomes than N3 tumors independent of other prognostic factors. The AJCC staging system should be modified based on these findings.

7.
Radiology ; 300(1): 209-216, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33904775

RESUMO

Background Microwave ablation (MWA) and radiofrequency ablation (RFA) have recently attracted interest as minimally invasive treatment modalities for papillary thyroid carcinoma (PTC). However, the ablation outcomes of T1N0M0 PTC are not well characterized. Purpose To evaluate the efficacy and safety of thermal ablation (MWA or RFA) of solitary T1N0M0 PTC in patients who were ineligible for (due to presence of comorbid cardiovascular disease, renal failure, other malignancy, etc) or who refused surgery. Materials and Methods This was a retrospective multicenter study of 847 patients (660 women) who underwent thermal ablation for PTC (673 T1a, 174 T1b) between March 2015 and March 2020; of these patients, 645 underwent MWA and 202 underwent RFA. The mean age of patients was 46 years ± 11 (standard deviation) (age range, 18-81 years); the mean follow-up time was 22 months ± 13 (range, 6-60 months). Changes in tumor size and volume and the rates of technical success, tumor disappearance, disease progression, and complications were assessed. Results The technical success rate was 100%. Relative to preablation measurements, the maximum diameter and volume of the ablation zone increased during the 1st month after ablation (P < .001), whereas there was no difference by the 3rd month; subsequently, the tumors showed reduction in size at 6, 9, and 12 months (all P < .001). Complete disappearance of tumors occurred in 68% of patients (577 of 847; 69% [466 of 673] in the T1a group vs 64% [111 of 174] in the T1b group; P < .001). The postablation disease progression rate was 1.1% (nine of 847 patients; 0.9% [six of 673 patients] in the T1a group vs 1.7% [three of 174 patients] in the T1b group; P = .54). The overall complication rate was 3.4% (29 of 847 patients; 2.7% [18 of 673 patients] in the T1a group vs 6.3% [11 of 174 patients] in the T1b group; P = .02). Conclusion This multicenter study provided evidence that thermal ablation is an effective and safe treatment option in selected -patients with solitary T1N0M0 papillary thyroid carcinoma. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Baek and Cho in this issue.


Assuntos
Micro-Ondas/uso terapêutico , Ablação por Radiofrequência , Câncer Papilífero da Tireoide/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Câncer Papilífero da Tireoide/patologia
8.
J Hazard Mater ; 416: 125783, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-33839503

RESUMO

In order to investigate the explosion process of calcium carbide (CaC2) dust in the acetylene (C2H2) atmosphere, the explosion characteristics of C2H2 gas and C2H2/CaC2 dust gas-solid two-phase mixture were studied using a 20-L spherical vessel, and the chemical composition of solid residues after explosion were also analyzed. Experimental results showed that the Pex values of C2H2 gas explosion rose first and then remained stable with the increasing stoichiometric ratio values (φ) of C2H2/air, while the (dP/dt)ex values tended to increase at early stage and then decrease, the inflection point of (dP/dt)ex values was φ = 1.78. The explosion severity and risk of C2H2 gas were enhanced by adding CaC2 dust, and the optimum additive concentration of CaC2 dust was 100 g/m3. In the oxygen atmosphere, the C2H2/CaC2 hybrid explosion was divided into two stages when the concentration of CaC2 dust was over 300 g/m3. The explosion risk of the first stage (Stage Ⅰ) was much more serious, while the explosion severity of the second stage (Stage Ⅱ) was much more fierce. The solid residues of hybrid explosion only contained CaO in the oxygen atmosphere, however, Ca(OH)2 and CaO were detected in the solid residues in the air atmosphere, owing to the combustion heat of C2H2 gas in oxygen was higher than that in air. The hydrolysis reaction time of CaC2 particle with large particle size was prolonged, and the diffusion of solid product layer and surface chemical reaction both influenced the hydrolysis process according to the shrinking core model. Based on the explosion and chemical analysis experiments, the explosion mechanism of C2H2/CaC2 dust gas-solid two-phase mixture was analyzed systematically.

9.
Zhongguo Gu Shang ; 34(1): 15-9, 2021 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-33666014

RESUMO

OBJECTIVE: To investigate the clinical efficacy and advantage of minimally invasive transforaminal lumbar interbody fusion under microscope-assisted Zista channel in the treatment of degreeⅠandⅡdegenerative lumbar spondylolisthesis. METHODS: The clinical data of 18 patients with degenerative lumbar spondylolisthesis treated by microscope-assisted Zista channel MIS-TLIF operation from January 2017 to March 2018 were analyzed retrospectively. There were 10 males and 8 females with an average age of 59 years (48 to 70). The course of spondylolisthesis ranged from 6 months to 5 years with an average of 33 months. The segment of spondylolisthesis was L4 in 13 casesand L5 in 5 cases. According to Meyerding spondylolisthesis criteria, 11 cases were degreeⅠand 7 cases were degreeⅡ. The perioperative observation indexes were recorded. The VAS score and JOA score of lumbago and leg pain before and after operation were compared to evaluate the clinical efficacy. At 12 months after operation, the height of intervertebral space was measured by imaging data, the intervertebral fusion was evaluated by Brantigan-Steffee standard, and the curative effect was evaluated according to the modified Macnab standard. RESULTS: All the patients completed the operation successfully and were followed up more than 12 months after operation. Operation time was(160.45±34.98) min, intraoperative blood loss was (88.32±21.12) ml, postoperative drainage volume was (50.34 ±18.22)ml, and walking time after operation was (20.65±6.25) h. Preoperative and postoperative at 7 days, 3 months, 12 months, VAS score of low back pain was 7.81±2.16, 4.19±1.17, 2.25±0.62 and 1.53±0.58 respectively, VAS score of leg pain was 8.47± 2.21, 3.45±0.86, 2.31±0.73 and 1.43±0.47, JOA score was 12.01±2.33, 18.56±3.12, 23.54±3.31 and 26.34±2.65. There were significant differences in VAS and JOA scores between preoperative and postoperative (P<0.05). The height of intervertebral space increased from (4.46±0.72) mm preoperative to (10.24±1.48) mm at 12 months after operation (P<0.05). All operative segments got fusion (16 cases of grade E and 2 cases of grade D). According to Macnab standard, 15 cases obtained excellent results, 2 cases good, 1 case fair. CONCLUSION: MIS-TLIF under microscope-assisted Zista channel has obvious minimally invasive advantages in the treatment of degreeⅠandⅡdegenerative lumbar spondylolisthesis, and it is a safe and effective method.


Assuntos
Fusão Vertebral , Espondilolistese , Feminino , Humanos , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Estudos Retrospectivos , Espondilolistese/cirurgia , Resultado do Tratamento
10.
Biosens Bioelectron ; 174: 112738, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33257185

RESUMO

The high expression of sonic hedgehog ligand (SHh) is closely correlated to the metastasis, drug resistance and poor prognosis of hepatocellular carcinoma (HCC). Therefore, sensitive, specific and efficient detection methods for SHh are needed for the early diagnosis and assessment of prognosis. Herein, an aptamer, AP32 that specifically binds to SHh (KD = 25.7 ± 4.1 nM) was obtained by SELEX technology with further optimization. In vivo experiments confirmed that AP32 has the potential to be an imaging probe for Huh-7 cell-derived xenograft. The interaction mode in 3-dimensional configuration between the aptamer and SHh was established by molecular simulation and confirmed by mutations at key sites of the aptamer. An aptasensor-based assay was successfully developed by conjugating Texas-Red-labeled AP32 to microbeads, and was used to analyze SHh content in hepatoma cell lysates, serum and HCC specimens. The method exhibited a broad detection range from 0.07 to 62.5 nM with a low detection limit of 69 pM, and a recovery rate of 104.6 ± 3.9% in serum. When the assay was used to measure SHh content in tissue lysates, the results demonstrated that it possessed 57.1% positivity, 100% specificity in distinguishing 28 HCC specimens from normal tissues, and was compensatory for detection of HCC in AFP-negative cases. Moreover, elevated SHh levels are indicative of portal vein invasion at 77.8% positive rate. This novel aptasensor-based SHh assay may offer a reliable means in predicting early metastasis and poor prognosis in hepatocellular carcinoma.


Assuntos
Técnicas Biossensoriais , Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Proteínas Hedgehog/genética , Humanos , Ligantes , Neoplasias Hepáticas/genética , Veia Porta
11.
J Clin Endocrinol Metab ; 106(2): e573-e581, 2021 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-33107573

RESUMO

BACKGROUND: Ultrasound-guided thermal ablation plays an important role in the management of thyroid disease. The objective of this study was to evaluate the feasibility, efficacy, and safety of thermal ablation for patients with solitary T1bN0M0 papillary thyroid carcinoma (PTC) who are ineligible for or unwilling to undergo surgery. MATERIALS AND METHODS: Data pertaining to 172 patients (38 males and 134 females) who received thermal ablation therapy at 12 hospitals between April 2015 and March 2020 were retrospectively analyzed. The mean duration of follow-up was 24.9 ±â€…14.1 months (range, 12-60). The technical feasibility, technical success, efficacy, and safety of treatment were analyzed. Postablation tumor size at various time points was compared with preablation measurement. RESULTS: All patients selected for thermal ablation received enlarged ablation, according to contrast-enhanced ultrasound postablation. The maximum diameter and volume of ablation zone at 6, 12, 18, 24, 36, and 48 months postablation were significantly smaller than those recorded preablation (P < 0.05 for all). At the most recent follow-up, 106 (61.6%) tumors had completely disappeared. The rate of lymph node metastasis was 0.6% (1/172) and the incidence of new tumors was 1.2% (2/172). The overall complication rate was 5.2% (9/172) (major complications: 4.6% [8/172]; minor complications: 0.6% [1/172]). All major complications were relieved within 4 months postablation. CONCLUSION: Thermal ablation may be a feasible, effective, and safe treatment option for patients with solitary T1bN0M0 PTC who are ineligible for or unwilling to undergo surgery. It may provide a novel treatment option for selected patients.


Assuntos
Ablação por Radiofrequência , Câncer Papilífero da Tireoide/terapia , Neoplasias da Glândula Tireoide/terapia , Adolescente , Adulto , Idoso , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , China/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Micro-Ondas/efeitos adversos , Micro-Ondas/uso terapêutico , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Ablação por Radiofrequência/efeitos adversos , Estudos Retrospectivos , Câncer Papilífero da Tireoide/epidemiologia , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/patologia , Resultado do Tratamento , Ultrassonografia de Intervenção/efeitos adversos , Ultrassonografia de Intervenção/métodos , Adulto Jovem
12.
Breast Cancer Res Treat ; 185(2): 371-380, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32975708

RESUMO

PURPOSE: Resistance to paclitaxel remains a major challenge in treating breast cancer. Our preclinical study suggested that TEKT4 germline variations in breast cancer are associated with paclitaxel resistance and increase vinorelbine sensitivity. This clinical trial compared the efficacy of paclitaxel and vinorelbine in breast cancer neoadjuvant chemotherapy. METHODS: In this open-label, single-center, phase II trial, female patients with human epidermal growth factor receptor 2 (HER2)-negative, stage IIB-IIIC breast cancer harboring TEKT4 germline variations were randomly assigned to the paclitaxel plus epirubicin (PE) or vinorelbine plus epirubicin (NE). The primary endpoint was the pathologic complete response (pCR) rate, and the secondary endpoints were the objective response rate (ORR) and safety. Targeted sequencing of a panel comprising 484 breast-related genes was performed to identify pCR-associated somatic mutations in each group. RESULTS: 91 Patients were assigned to PE (46 patients) or NE (45 patients). NE numerically increased the pCR rate (22.2% versus 8.7%, P = 0.074). The ORRs for NE and PE were 82.2% and 76.1%, respectively. Interestingly, NE (15.4%) showed a significantly higher pCR rate than PE (0%) in the hormone receptor (HR)-positive subgroup (P = 0.044). Both regimens were well tolerated, with grade 3 and 4 toxicities reported at the expected levels. The biomarker analysis showed that UNC13D mutation predicted the pCR rate in NE (P = 0.011). CONCLUSIONS: Although the primary endpoint was not met, NE might bring clinical benefit to HR-positive patients or patients simultaneously carrying UNC13D mutations.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama , Epirubicina , Terapia Neoadjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Ciclofosfamida/uso terapêutico , Epirubicina/uso terapêutico , Feminino , Humanos , Proteínas de Membrana , Paclitaxel/efeitos adversos , Receptor ErbB-2/genética , Trastuzumab/uso terapêutico , Resultado do Tratamento , Vinorelbina/uso terapêutico
13.
Cell Res ; 31(2): 178-186, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32719455

RESUMO

Triple-negative breast cancer (TNBC) is a highly heterogeneous disease, and molecular subtyping may result in improved diagnostic precision and targeted therapies. Our previous study classified TNBCs into four subtypes with putative therapeutic targets. Here, we conducted the FUTURE trial (ClinicalTrials.gov identifier: NCT03805399), a phase Ib/II subtyping-based and genomic biomarker-guided umbrella trial, to evaluate the efficacy of these targets. Patients with refractory metastatic TNBC were enrolled and stratified by TNBC subtypes and genomic biomarkers, and assigned to one of these seven arms: (A) pyrotinib with capecitabine, (B) androgen receptor inhibitor with CDK4/6 inhibitor, (C) anti PD-1 with nab-paclitaxel, (D) PARP inhibitor included, (E) and (F) anti-VEGFR included, or (G) mTOR inhibitor with nab-paclitaxel. The primary end point was the objective response rate (ORR). We enrolled 69 refractory metastatic TNBC patients with a median of three previous lines of therapy (range, 1-8). Objective response was achieved in 20 (29.0%, 95% confidence interval (CI): 18.7%-41.2%) of the 69 intention-to-treat (ITT) patients. Our results showed that immunotherapy (arm C), in particular, achieved the highest ORR (52.6%, 95% CI: 28.9%-75.6%) in the ITT population. Arm E demonstrated favorable ORR (26.1%, 95% CI: 10.2%-48.4% in the ITT population) but with more high grade (≥ 3) adverse events. Somatic mutations of TOP2A and CD8 immunohistochemical score may have the potential to predict immunotherapy response in the immunomodulatory subtype of TNBC. In conclusion, the phase Ib/II FUTURE trial suggested a new concept for TNBC treatment, demonstrating the clinical benefit of subtyping-based targeted therapy for refractory metastatic TNBC.

14.
Diabetes Metab Syndr Obes ; 13: 4755-4761, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33299338

RESUMO

Purpose: The relationship between circulating selenium and diabetes mellitus (DM) remains inconsistent. Therefore, the relationship between circulating selenium and DM was investigated in the present study. Patients and Methods: All participants (aged ≥18 years) were included from the National Health and Nutrition Examination Survey (NHANES) 1999-2006. Selenium concentrations from the fasting serum samples were determined using inductively coupled mass spectrometry, then grouped into quartiles. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by using multivariate logistic regression analysis and the results were stratified by age and sex. Results: A total of 2,903 (61.9±13.7 years old) participants (49.3% males) were enrolled, and 580 (19.97%) of them had DM. The mean levels of selenium were 136.4±19.6 µg/L. Patients with DM (138.76±20.02 vs 135.88±19.44, P=0.002) had higher selenium levels compared to those without DM. The OR for DM was 1.12 (95% CI=1.01-1.24; P=0.0270) for each 10 µg/L increment in selenium, and subjects in the highest quartile of selenium levels (>147.00 uµg/L) had 2.82 (95% CI=1.55-5.11; P=0.0007) times higher risk of DM compared to the lowest quartile of selenium levels. Subgroup analysis showed that selenium was independently associated with DM only in female aged <65 years. Conclusion: Circulating selenium levels were positively associated with the odds of DM, but difference in sex and age.

15.
Ann Transl Med ; 8(21): 1458, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33313203

RESUMO

Background: Blood-brain barrier (BBB) impairment plays a significant role in the pathogenesis of sepsis-associated encephalopathy (SAE). However, the molecular mechanisms are poorly understood. In the present study, we aimed to investigate the regulatory relationship between the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway, microRNA (miR)-181b and its target genes in sepsis in vivo and in vitro. Methods: Four rat models (sham, sepsis, sepsis plus STAT3 inhibitor (Stattic), and sepsis plus miR-181b inhibitor [sepsis + anta-miR-181b]) were established. For the in vitro experiments, rat brain microvascular endothelial cells (rBMECs) and rat brain astrocytes (rAstrocytes) were cultured with 10% serum harvested from sham, sepsis, and sepsis + anta-miR-181b rats. Chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-QPCR) analysis was carried out to detect the binding and enrichment of the JAK/STAT3 signal core transcription complex in the miR-181b promoter region. Dual-luciferase reporter gene assay was conducted to test miR-181b and its target genes. The cell adhesion rate of rBMECs was also measured. Results: During our investigations, the expression levels of miR-181b, p-JAK2, p-STAT3, and C/EBPß were found to be significantly increased in the septic rats compared with the sham rats. STAT3 inhibitor halted BBB damage by downregulating the expression of miR-181b. In addition, miR-181b targeted sphingosine-1-phosphate receptor 1 (S1PR1) and neurocalcin delta (NCALD). The up-regulated miR-181b significantly decreased the cell adhesion rate of rBMECs. The administration of miR-181b inhibitor reduced damage to the BBB through increasing the expression of S1PR1 and NCALD, which again proved that miR-181b negatively regulates SIPR1 and NCALD to induce BBB damage. Conclusions: Our study demonstrated that JAK2/STAT3 signaling pathway induced expression of miR-181b, which promoted BBB impairment in rats with sepsis by downregulating S1PR1 and decreasing BBB cell adhesion. These findings strongly suggest JAK2/STAT3/miR-181b axis as therapeutic target in protecting against sepsis-induced BBB damage.

16.
Nat Commun ; 11(1): 5679, 2020 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-33173047

RESUMO

The remarkable advances in next-generation sequencing technology have enabled the wide usage of sequencing as a clinical tool. To promote the advance of precision oncology for breast cancer in China, here we report a large-scale prospective clinical sequencing program using the Fudan-BC panel, and comprehensively analyze the clinical and genomic characteristics of Chinese breast cancer. The mutational landscape of 1,134 breast cancers reveals that the most significant differences between Chinese and Western patients occurred in the hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer subtype. Mutations in p53 and Hippo signaling pathways are more prevalent, and 2 mutually exclusive and 9 co-occurring patterns exist among 9 oncogenic pathways in our cohort. Further preclinical investigation partially suggests that NF2 loss-of-function mutations can be sensitive to a Hippo-targeted strategy. We establish a public database (Fudan Portal) and a precision medicine knowledge base for data exchange and interpretation. Collectively, our study presents a leading approach to Chinese precision oncology treatment and reveals potentially actionable mutations in breast cancer.


Assuntos
/genética , Neoplasias da Mama , Terapia de Alvo Molecular , Mutação , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , China , Gerenciamento de Dados , Feminino , Marcadores Genéticos , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neurofibromina 2/genética , Oncogenes , Medicina de Precisão , Estudos Prospectivos , Transdução de Sinais/genética , Proteína Supressora de Tumor p53/genética
17.
Biochim Biophys Acta Rev Cancer ; 1874(2): 188441, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33007432

RESUMO

A couple of molecular-targeting medications, such as Lenvatinib, are available for the treatment of hepatocellular carcinoma (HCC) in addition to Sorafenib in an advanced stage. Approval for the use of immune check-point inhibitors, such as Nivolumab and Pembrolizumab has shifted the paradigm of current HCC treatment, and the monotherapy or in combination with Lenvatinib or Sorafenib has significantly extended overall survival or progression-free survival in a large portion of patients. A combination of programmed cell death ligand-1 (PD-L1) inhibitor Atezolizumab with a vascular endothelial growth factor (VEGF) inhibitor, Bevacizumab, has recently achieved promising outcome in unresectable HCC patients. Other immunotherapy, such as chimeric antigen receptor T (CAR-T) cell therapy has achieved an evolutional success in hematologic malignancies, and has extended its use in deadly solid tumors, such as HCC. Although there exist various barriers, novel approaches are developed to move potential adoptive T cell therapy strategies, including cytokine-induced killer (CIK) cells, tumor-infiltrating lymphocytes (TIL), T cell receptor (TCR) T cells, CAR-T cells, to clinical application.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Carcinoma Hepatocelular/imunologia , Ensaios Clínicos como Assunto , Terapia Combinada , Humanos , Imunoterapia , Imunoterapia Adotiva , Neoplasias Hepáticas/imunologia , Resultado do Tratamento
18.
Ann Palliat Med ; 9(5): 2886-2894, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32921078

RESUMO

BACKGROUND: The total survival rate in patients with acute aortic dissection (AAD) has been greatly improved because of surgical technique advances. However, the pre-operative mortality rate remained high. In this study, we sought to evaluate the effects of dexmedetomidine (DEX) on heart rate control and preoperative outcome in AAD. METHODS: Retrospectively enrolled 461 patients who were diagnosed with AAD during the first 7-day after admission and divided into two groups according to the use of intravenous DEX: DEX group (91 patients) and Control group (370 patients). The heart rate and systolic blood pressure (SBP) level in both groups were recorded, and the incidence of aortic dissection rupture and pre-operative survival rates within 7 days were considered as the primary clinical outcomes. RESULTS: Compared to the Control group, heart rate of DEX group in the early 3 hours was significantly higher (P=0.009), and the 24-hour heart rate fluctuation was smaller (P=0.012). There was no difference in the systolic blood pressure (SBP) between the two groups, but the 24-hour fluctuation of SBP in DEX group was less (P=0.003). We performed a propensity-matched analysis to minimize selection bias and found that there were 7 (7.9%) patients in the DEX group occurred acute pulmonary edema, 17 (19.1%) patients in the Control group (P=0.047). And the pre-operative survival rates within 7 days were significantly improved in DEX group (P=0.004). And the pre-operative survival rates within 7 days were significantly improved in DEX group (P=0.004). CONCLUSIONS: DEX can be beneficial to facilitate heart rate control, keep SBP more steady, and reduce the incidence of pre-operative aortic rupture in patients with AAD.


Assuntos
Aneurisma Dissecante , Dexmedetomidina , Aneurisma Dissecante/tratamento farmacológico , Aneurisma Dissecante/cirurgia , Pressão Sanguínea , Dexmedetomidina/uso terapêutico , Frequência Cardíaca , Humanos , Estudos Retrospectivos
20.
Ann Palliat Med ; 9(5): 3018-3027, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32787354

RESUMO

BACKGROUND: Platinum-based chemotherapy (PBCT) has gained an important position as a first-line treatment for metastatic triple-negative breast cancer (mTNBC). We assessed whether maintenance chemotherapy maintenance was superior to observation after first-line PBCT in patients with mTNBC. METHODS: A total of 265 patients with mTNBC who had exhibited non-PD after 4-6 cycles of firstline PBCT at the Fudan University Shanghai Cancer Center from January 2008 to April 2019 were retrospectively analyzed. 107 patients who did not receive additional treatment were defined as the control observation group, and the remaining 158 patients who continued to receive maintenance therapy were defined as the maintenance treatment group. RESULTS: The median progression-free survival (PFS) time in the maintenance group was 9.63 months, which was significantly longer than the PFS time of 7.47 months in the observation group (HR 0.49, 95% CI: 0.37-0.67, P<0.0001). The median overall survival (OS) of the observation group and the maintenance group was 25.37 months and 31.27 months, respectively (HR 0.65, 95% CI: 0.44-0.95, P=0.019). The survival benefit was still present after adjusting baseline characteristics. Moreover, multivariate analyses suggested that maintenance chemotherapy is an independent predictive factor for both PFS and OS. Interaction and stratified analyses showed no difference in the PFS with between the single-drug maintenance strategy, single agent or doublet group and the doublet-drug maintenance group. The most common adverse event in this study was hematologic toxicity. Except for hand-foot syndrome (0 vs. 7.6%, P=0.004), the incidence of other adverse events was not significantly different between the observation and maintenance groups. CONCLUSIONS: After achieving non-PD with the first-line PBCT in mTNBC patients, chemotherapy maintenance may provide OS benefit prior to the era of biologicals.


Assuntos
Neoplasias de Mama Triplo Negativas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , China , Intervalo Livre de Doença , Humanos , Quimioterapia de Manutenção , Platina/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
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