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1.
J Nucl Med ; 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34593598

RESUMO

Fibroblast activation protein (FAP) has become an attractive target for diagnosis and therapy, and a series of FAP inhibitor (FAPI) based radiotracers have been developed and performed excellent diagnosis outcome in clinical applications. Yet, their fast clearance and insufficient tumor retention have hampered their further clinical applications for cancer treatment. In this study, we developed two albumin binder-conjugated FAPI radiotracers, TEFAPI-06 and TEFAPI-07. They are derived from FAPI-04, and optimized by conjugating two types of well-studied albumin binders, 4-(p-iodophenyl) butyric acid moiety (TEFAPI-06) and truncated Evans blue moiety (TEFAPI-07), to try to overcome the above limitations at the expense of prolonging the blood circulation. Methods: TEFAPI-06 and TEFAPI-07 were synthesized and labeled with 68Ga, 86Y and 177Lu successfully. A series of cell assays were performed to identify the binding affinity and FAP specificity in vitro. PET imaging, SPECT imaging and biodistribution study were performed to evaluate the pharmacokinetics in the pancreatic cancer patient-derived xenografts (PDX) animal models. The cancer treatment efficacy of 177Lu-TEFAPI-06 and 177Lu-TEFAPI-07 have been evaluated and the comparative study with 177Lu-FAPI-04 has also been performed in pancreatic cancer PDX-bearing mice. Results: The binding affinity (Kd) to FAP of 68Ga-TEFAPI-06 and 68Ga-TEFAPI-07 is 10.16 ± 2.56 nM and 7.81 ± 2.28 nM, respectively, which were comparable with that of 68Ga-FAPI-04. Comparative PET imaging of HT-1080-FAP and HT-1080 tumor-bearing mice and blocking study showed the FAP targeting ability in vivo of these two tracers. Compared with 177Lu-FAPI-04, PET imaging, SPECT imaging and biodistribution studies of TEFAPI-06 and TEFAPI-07 have demonstrated their remarkably enhanced tumor accumulation and retention, respectively. Notable tumor growth inhibitions of 177Lu-TEFAPI-06 and 177Lu-TEFAPI-07 have been observed, while the control groups and the group treated by 177Lu-FAPI-04. Conclusion: Two albumin binder-conjugated FAPI radiopharmaceuticals have been developed and evaluated in vitro and in vivo. Notably improved tumor uptake and retention have been observed compared to the original FAPI tracer. Both 177Lu-TEFAPI-06 and 177Lu-TEFAPI-07 showed remarkable growth inhibition to PDX tumors while the side effect is negligible, showing that they are promising for further clinical translational studies.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34651221

RESUMO

PURPOSE: The aim of this study was to explore the association of cardiac fibroblast activation with clinical parameters and cardiovascular magnetic resonance (CMR) imaging parameters in patients with chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: Thirteen CTEPH patients were prospectively enrolled. All of the patients underwent cardiac 68Gallium-labelled fibroblast activation protein inhibitor (68 Ga-FAPI-04)-positron emission tomography/computed tomography (PET/CT), right heart catheterisation, and echocardiography, and 11 of them additionally underwent CMR. Thirteen control subjects were selected to establish the normal range of cardiac 68 Ga-FAPI-04 uptake. Cardiac 68 Ga-FAPI-04 uptake higher than that in the blood pool was defined as abnormal. The global and segmental maximum standardised uptake values (SUVmax) of the right ventricle (RV) were measured and further expressed as target-to-background ratio (TBRRV) with left ventricular lateral wall activity as background. Late gadolinium enhancement (LGE) was visually evaluated, and native-T1 times, enhanced-T1 times, and extracellular volume (ECV) were quantitatively measured. RESULTS: Ten CTEPH patients (77%) had abnormal 68 Ga-FAPI-04 uptake in RV, mainly located in the free wall, which was significantly higher than that in controls (TBRRV: 2.4 ± 0.9 vs 1.0 ± 0.1, P < 0.001). The TBRRV correlated positively with the thickness of RV wall (r = 0.815, P = 0.001) and inversely with RV fraction area change (RVFAC) (r = - 0.804, P = 0.001) and tricuspid annular plane systolic excursion (TAPSE) (r = - 0.678, P = 0.011). No correlation was found between 68 Ga-FAPI-04 activity and CMR imaging parameters. CONCLUSION: Fibroblast activation in CTEPH, measured by 68 Ga-FAPI-04 imaging, is mainly localised in the RV free wall. Enhanced fibroblast activation reflects the thickening of the RV wall and decreased RV contractile function.

3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1582-1588, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34627444

RESUMO

AbstractObjective: To analyze the liver injury and coagulation dysfunction in COVID-19 severe/critical type patients. METHODS: The clinical data of 53 COVID-19 patients were collected from a single center in Wuhan from February 8, 2020 to March 25, 2020. The patients were divided into severe type group (38 patients) and critical type group (15 patients). The clinical characteristics, indexes of liver function, coagulation function and inflammatory markers were analyzed retrospectively. According to the degree of abnormal liver function in the process of diagnosis and treatment, the patients were divided into three groups: combined liver injury, mild abnormal liver function and normal liver function group. Statistical analysis was performed by using Student t test, Mann-Whitney U test, Kruskal-Wallis test and Chi-square test. RESULTS: Among the 53 patients, 29 were male (54.7%) and 24 were female (45.3%), the median age was 57(27-80) years old. The time from onset to admission was (11.5±7.7) days. The levels of AST, TBIL, DBIL, ALP, GGT, LDH, D-dimer, PCT and hsCRP in critical patients were higher than those in severe patients (P<0.05). The levels of Alb in critical patients was lower than those in severe patients (P<0.05). Among the 53 patients, 34 (64%) patients showed abnormal elevation of ALT, AST or TBIL, while 4 (7.5%) patients showed the criteria of COVID-19 with liver injury. After the patients were grouping according to the degree of liver dysfunction, the levels of ALP, GGT and D-dimer of the patients in the liver injury group were significantly higher than those in the normal liver function group, D-dimer levels of the patients in the liver injury group was significantly higher than those in the mild abnormal liver function group, while the levels of ALP and GGT in the mild abnormal liver function group were significantly higher than those in the normal liver function group, and the differences were statistically significant(P<0.05). CONCLUSION: In this group, the patients with COVID-19 severe/critical type have a certain proportion of liver injury accompanied by significantly increased D-dimer levels, critical type patients have more severe liver function and coagulation dysfunction, which may promote the progression of COVID-19.


Assuntos
Transtornos da Coagulação Sanguínea , COVID-19 , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Fígado , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2
5.
Chem Biol Interact ; 348: 109642, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34509492

RESUMO

Gossypol is a yellow natural polyphenolic compound extracted from the seeds, leaves, stems, and flower buds of the cotton plant. Several studies have shown that exposure to gossypol impacts reproductive health in both humans and animals. However, whether gossypol exposure would influence oocyte quality has not yet been determined. Here, we studied the effects of gossypol on the meiotic maturation of mouse oocytes in vitro. The results revealed that gossypol exposure did not affect germinal vesicle breakdown (GVBD) but significantly reduced polar body extrusion (PBE) rates. Moreover, we observed meiotic spindle organization and chromosome alignment were entirely disturbed after gossypol exposure. Further, gossypol exposure also caused mitochondrial dysfunction and abruptly decreased the levels of cellular ATP, and diminished the mitochondrial membrane potential (MMP). Accordingly, gossypol-induced oxidative stress was confirmed through an increased level of reactive oxygen species (ROS). Early apoptosis incidence also increased as identified by positive Annexin-V signaling. Collectively, the above findings provide evidence that gossypol exposure impaired oocyte meiotic maturation, disturbed spindle structure and chromosome dynamics, disrupted mitochondrial function, induced oxidative stress, and triggered early apoptosis. These findings emphasize gossypol's adverse effects on oocyte maturation and thus on female fertility.


Assuntos
Gossipol/efeitos adversos , Técnicas de Maturação in Vitro de Oócitos , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Mitocôndrias/metabolismo , Oócitos/citologia , Oócitos/efeitos dos fármacos
7.
Chem Commun (Camb) ; 57(71): 8953-8956, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34486586

RESUMO

A reliable copper-mediated nucleophilic radiosynthesis of the PET imaging probe [18F]FBPA was developed using novel aryldiboron precursors. The carrier-free [18F]FBPA with radiochemical purity >99% was prepared routinely via the two-step synthesis with an automatic module and can be used for clinical PET imaging of tumours.


Assuntos
Compostos de Boro/química , Fenilalanina/análogos & derivados , Compostos Radiofarmacêuticos/química , Animais , Compostos de Boro/síntese química , Radioisótopos de Flúor/química , Fenilalanina/síntese química , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/síntese química
8.
Mikrochim Acta ; 188(10): 355, 2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34585278

RESUMO

A novel strategy for microRNAs (miRNAs) detection has been developed utilizing duplex-specific nuclease-assisted signal amplification (DSNSA) and guanine-rich DNA-enhanced fluorescence of DNA-templated silver nanoclusters (AgNCs). The combination between target miRNA, DSNSA, and AgNCs is achieved by the unique design of DNA sequences. Target miRNA opens the hairpin structure of the Hairpin DNA probe (HP) by hybridizing with the HP and initiates the duplex-specific nuclease-assisted signal amplification (DSNSA) reaction. The DSNSA reaction generates the release of the guanine-rich DNA sequence, which can turn on the fluorescence of the dark AgNCs by hybridizing with the DNA template of the dark AgNCs. The fluorescence intensity of AgNCs corresponds to the dosage of the target miRNA. This is measured at 630 nm by exciting at 560 nm. The constructed method exhibits a low detection limit (~8.3 fmol), a great dynamic range of more than three orders of magnitude, and excellent selectivity. Moreover, it has a good performance for miR-21 detection in complex biological samples. A novel strategy for microRNAs (miRNAs) detection has been developed utilizing duplex-specific nuclease-assisted signal amplification (DSNSA) and guanine-rich DNA-enhanced fluorescence of DNA-templated silver nanoclusters (AgNCs).

9.
Environ Toxicol ; 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34558770

RESUMO

Benzophenone-3 (BP-3), one of the most commonly utilized ultraviolet filters in personal care products, has aroused public concern in recent years for its high chances of human exposure. Previous studies have found that BP-3 can impair testes development and spermatogenesis, but the targets of BP-3 are still unknown. In this study, primary Sertoli cells from 20-day-old mice were treated in vitro with 0-100 µM BP-3 for 24 h to identify its toxicity on Sertoli cells and Sertoli cell barrier. Results demonstrated that BP-3 could induce a notable change in cell morphology and impair Sertoli cell viability. The analysis of transepithelial electrical resistance showed that the integrity of the Sertoli cell barrier was destroyed by BP-3 (100 µM). Some structural proteins of the barrier including ZO-1, Occludin, and Connexin43 were lower expressed and the localization of basal ectoplasmic specializations protein ß-catenin was altered because of BP-3 treatment. Further exploration suggested that BP-3 led to Sertoli cell F-actin disorganization by affecting the expression of Rictor, a key component of the mTORC2 complex. Moreover, although increased DNA damage marker γH2A.X was observed in the treatment group, the cell apoptosis rate was changeless which was further confirmed by increased BAX and stable Bcl-2 (two primary apoptosis regulating proteins). In conclusion, this study revealed that BP-3 had the potential to perturb the Sertoli cell barrier through altered junction proteins and disorganized F-actin, but it could hardly evoke Sertoli cell apoptosis.

10.
J Nucl Med ; 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34531265

RESUMO

Increased expression of fibroblast activating protein (FAP) in fibrous caps may contribute to progression of atherosclerotic plaques. Methods: Forty-one patients who underwent gallium-68-conjugated quinoline-based FAP inhibitor (68Ga-FAPI-04) PET/CT for non-cardiovascular indications were retrospectively analyzed. Correlations were assessed between the uptake of 68Ga-FAPI-04 in large arterial walls (SUVmax and target-to-background ratio, TBR) and degree of calcification and cardiovascular risk factors. Results: Focal arterial uptake of 68Ga-FAPI-04 or calcification was detected in 1,177 arterial segments in all 41 patients. TBR was negatively correlated with the degree of calcification (HU) (r = -0.27, P < 0.01). Mean TBR in higher-risk patients was greater than lower-risk patients (2.2 ± 0.3 vs. 1.8 ± 0.3, P < 0.01). Immunohistochemical labeling of carotid plaques exhibited prominent FAP expression in a thin fibrous cap and moderate FAP expression in a thick cap. Conclusion: 68Ga-FAPI-04 PET/CT might have potential for imaging fibroblastic activation in the arterial wall.

11.
Trials ; 22(1): 553, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34419124

RESUMO

BACKGROUND: With the increased understanding of heart disease, microvascular angina (MVA) is receiving greater attention from clinicians. Studies have shown that patients with MVA have significantly higher major cardiovascular events and all-cause mortality than the control population, and the search for effective treatments is of great clinical importance. Both basic and clinical studies have shown that Qi-Jing Hui-Xin Decoction (QJHX) can relieve angina symptoms and improve clinical efficacy, but there is a lack of high-quality clinical studies to provide a research basis. This article introduces the evaluation protocol of QJHX for the adjunctive treatment of MVA. METHODS/DESIGN: This is a prospective randomized controlled trial. The trial will enroll 150 patients with MVA. On the basis of Western drug treatment, patients will be randomized into two groups, and the experimental group will receive QJHX treatment for 12 weeks and follow-up at 24 week. The primary indicators are the clinical efficacy of angina pectoris and the evidence of traditional Chinese medicine (TCM) efficacy. Secondary indicators are the Seattle Angina Scale score, serum lipid levels, electrocardiogram, and echocardiogram diagnosis. Additional indicators are endothelial function and immunoinflammatory factors. Adverse events will be monitored throughout the trial. DISCUSSION: Integrated traditional Chinese and Western medicine is commonly used for angina in China. This study will evaluate the clinical effectiveness and safety of adding QJHX based on standardized Western medications. The results of the trial will provide high-level clinical research-based evidence for the application of QJHX in MVA. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900027015 . Registered on 28 October 2019.


Assuntos
Medicamentos de Ervas Chinesas , Angina Microvascular , Medicamentos de Ervas Chinesas/efeitos adversos , Coração , Humanos , Medicina Tradicional Chinesa , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Breast ; 59: 124-134, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34229127

RESUMO

PURPOSE: The aim of this study was to establish individualized nomograms to predict survival outcomes in older female patients with stage IV breast cancer who did or did not undergo local surgery, and to determine which patients could benefit from surgery. METHODS: A total of 3,129 female patients with stage IV breast cancer aged ≥70 years between 2010 and 2015 were included in the Surveillance, Epidemiology, and End Results program. Multivariate Cox regression analysis was used to identify risk factors for overall survival (OS) and breast cancer-specific survival (BCSS). Survival analysis was performed using the Kaplan-Meier plot and log-rank test. Nomograms and risk stratification models were constructed. RESULTS: Patients who underwent surgery had better OS (HR = 0.751, 95% CI [0.668-0.843], P < 0.001) and BCSS (HR = 0.713, 95% CI [0.627-0.810], P < 0.001) than patients who did not undergo surgery. Patients with human epidermal growth factor receptor 2-positive, lung or liver metastases may not benefit from surgery. In the stratification model, low-risk patients benefited from surgery (OS, HR = 0.688, 95% CI [0.568-0.833], P < 0.001; BCSS, HR = 0.632, 95% CI [0.509-0.784], P < 0.001), while patients in the high-risk group had similar outcomes (OS, HR = 0.920, 95% CI [0.709-1.193], P = 0.509; BCSS, HR = 0.953, 95% CI [0.713-1.275], P = 0.737). CONCLUSION: Older female patients with stage IV breast cancer who underwent surgery had better OS and BCSS than those who did not in each specific subgroup. Patients in low- or intermediate-risk group benefit from surgery while those in the high-risk group do not.

13.
Trials ; 22(1): 466, 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34281600

RESUMO

BACKGROUND: Coronary heart disease (CHD) has become one of the biggest health problems in the world. Stable angina is a common clinical type of CHD with poor prognosis and high mortality. Although there are various interventions for stable angina, none of them can significantly reduce mortality. Both basic and clinical research have shown that Suxiao Jiuxin Pill (SJP) can relieve the symptoms of angina pectoris and improve the clinical efficacy, but there is a lack of high-quality clinical research to provide research-based evidence. We design a randomized, double-blind, placebo-controlled trial to evaluate the efficacy of SJP for stable angina. METHODS/DESIGN: This is a prospective, randomized, double-blind, placebo-controlled, and multicenter trial. The trial will enroll 324 participants with chronic stable angina (Qi Stagnation and Blood Stasis syndrome). All participants will have received the conventional therapy of chronic stable angina. Participants will be randomized into two groups, conventional therapy plus SJP group and conventional therapy plus placebo group. Eligible participants will receive either SJP or placebo (five pills administered orally, three times daily) in addition to conventional treatment for 24 weeks. The primary outcomes are the symptom improvement rate of angina from baseline to 4 weeks after inclusion and major adverse cardiovascular events (MACE). The secondary outcomes are angina classification (CCS), improvement of traditional Chinese medicine (TCM) syndromes, Seattle Angina Scale score, the dosage of emergency drugs and the stopping rate, and electrocardiogram (EKG) efficacy. Adverse events will be monitored throughout the trial. DISCUSSION: Integrated traditional Chinese and Western Medicine is commonly used for angina in China. This study will evaluate the clinical effectiveness and safety of SJP for angina. The results of the trial will provide high-level clinical research-based evidence for the application of SJP instable angina. TRIAL REGISTRATION: This study protocol was registered on 14 March 2019. The registration number is ChiCTR1900021876 on the Chinese Clinical Trial Registry.


Assuntos
Angina Estável , Medicamentos de Ervas Chinesas , Angina Estável/diagnóstico , Angina Estável/tratamento farmacológico , China , Método Duplo-Cego , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Qi , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
14.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(3): 429-434, 2021 Jun 30.
Artigo em Chinês | MEDLINE | ID: mdl-34238420

RESUMO

Objective To design a novel automatic dispensing and injecting system of positron radiopharmaceuticals,for precise dose dispensing,simplified operation,and reduction of occupational radiation exposure. Methods The automatic dispensing and injecting system was fabricated with tungsten alloy as the shielding material.The performance and radiation protection of the device were assessed. Results The total time of injection using the automatic dispensing and injecting system was about 60 s.The ratio of successful injection in stability test was 100%.The deviation of the dispensing dose with the system was ≤3%.With the tungsten alloy shield(40 mmPb of the cabinet,60 mmPb of the countertop,15 mmPb of the protective shield,and 50 mmPb of the inbuilt jar for radiopharmaceuticals),the average dose rate at 30 cm from the device was 1.44 µSv/h,and the radiation dose at the operator's extremity was reduced by 99%. Conclusions This automatic dispensing and injecting system of positron radiopharmaceuticals is easy to operate with precise dispensing dose.It is safe and meets the requirements of radiation protection.


Assuntos
Exposição Ocupacional , Proteção Radiológica , Elétrons , Exposição Ocupacional/análise , Doses de Radiação , Compostos Radiofarmacêuticos
15.
J Nucl Med ; 2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34301781

RESUMO

Purpose: We aimed to investigate the diagnostic and prognostic value of 68Ga-pentixafor positron emission tomography (PET)/computed tomography (CT) imaging in non-cancer patients with suspected adrenal masses. Methods: Sixty-four patients who had benign adrenal masses on CT were retrospectively included in our study. All patients underwent 68Ga-pentixafor PET/CT scans, and 56 of these patients subsequently underwent adrenalectomy. The subtypes of 81 adrenal tumors including 14 nonfunctioning adrenal nodules, 4 cortisol-producing adenomas, 41 aldosterone-producing adenomas, 5 suspected unilateral adrenal hyperplasia, 15 idiopathic aldosterone hyperplasia and 2 pheochromocytomas, were determined by histology or follow-up evaluations. The functional lateralization diagnosis efficiency was calculated by visual analysis. Semi-quantitative parameters of these lesions including maximum standardized uptake value (SUVmax), the ratio of lesional SUVmax to normal liver SUVmean (LLR), and the ratio of lesional SUVmax to contralateral adrenal tissue SUVmean (LCR) have also been calculated. Dynamic analysis has also been performed on fifteen patients. Besides, clinical outcomes were assessed and compared in patients who underwent adrenalectomy. Results: The sensitivity and specificity of 68Ga-pentixafor PET for functional lateralization of patients with adrenocortical lesions were 97.8% (45/46) and 87.5% (14/16) respectively. The two pheochromocytoma lesions had lower pentixafor uptake compared to the normal adrenal glands. Functioning (active) adrenocortical adenomas showed an elevated SUVmax of 16.3±7.9 in comparison to 4.4±1.7 in nonfunctioning (inactive) adenomas and 5.5±2.7 in hyperplasia lesions (P<0.0001). To identify active adrenocortical adenomas, a cutoff value of 7.1 for SUVmax showed a sensitivity of 90.9% and a specificity of 85.3% (AUC=0.96, P<0.0001); a cutoff value of 2.5 for LLR showed a sensitivity of 95.5% and a specificity of 88.2% (AUC=0.97, P<0.0001); and a cutoff value of 2.4 for LCR showed a sensitivity of 88.6% and a specificity of 91.8% (AUC=0.95, P<0.0001). The graphical Ki of active adrenocortical adenomas was significantly higher than in-active adenomas. Uptake values for 68Ga-pentixafor were significantly higher in patients with preferable outcomes (cured/improved) (SUVmax=15.5±8.0, LLR=6.5±4.3, LCR=6.2±5.0) than in patients with nonpreferable outcomes (no improvement) (SUVmax=4.2±0.5, LLR=1.3±0.2, LCR =1.5±0.6, all P<0.0001). Conclusion: 68Ga-pentixafor PET/CT imaging exhibits great potential for noninvasive functional lateralization and characterization of patients with adrenocortical masses.

16.
Cancer Discov ; 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193438

RESUMO

Natural killer (NK) cells and T cells are key effectors of anti-tumor immune responses and major targets of checkpoint inhibitors. In multiple cancer types, we find that the expression of Wnt signaling potentiator R-spondin genes (e.g. RSPO3) is associated with favorable prognosis and is positively correlated with gene signatures of both NK cells and T cells. While endothelial cells and cancer-associated fibroblasts comprise the R-spondin3-producing cells, NK cells and T cells correspondingly express the R-spondin3 receptor LRG6 within the tumor microenvironment. Exogenous expression or intratumor injection of R-spondin3 in tumors enhanced the infiltration and function of cytotoxic effector cells, which led to tumor regression. NK cells and CD8+ T cells independently and cooperatively contributed to R-spondin3-induced control of distinct tumor types. The effect of R-spondin3 was mediated in part through upregulation of MYC and ribosomal biogenesis. Importantly, R-spondin3 expression enhanced tumor sensitivity to anti-PD1 therapy, thereby highlighting new therapeutic avenues.

17.
Orphanet J Rare Dis ; 16(1): 279, 2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-34134735

RESUMO

BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare multisystem disease characterized by cystic lung disease and extrapulmonary manifestations, including lymphatic system disorder. The objective of this study was to investigate the findings of 68Ga-NOTA-Evans Blue (NEB) PET/CT in LAM and compare it with that of 99mTc-ASC lymphoscintigraphy. METHODS: Ten patients diagnosed with LAM according to the American Thoracic Society/Japanese Respiratory Society guidelines for LAM were recruited in this study. PET/CT acquisition was performed at 20 to 40 min after subcutaneous injection of 68Ga-NEB into the first interdigital spaces of both feet (0.3 ml, 37 MBq/foot). All subjects also underwent 99mTc-antimony sulfide colloid (ASC) lymphoscintigraphy within a week for comparison. RESULTS: 68Ga-NEB PET/CT displayed various lymphatic system abnormalities in 10 (100%) of 10 patients. These included pulmonary lymphatic abnormalities in 10 (100%) of 10 patients, enlarged lymph nodes in 5 (50%), lymphangioleiomyomas in 2 (20%), dilation of the lumbar trunk and/or iliac lymph vessels in 5 (50%), thoracic duct dilation in 2 (20%), chylous effusion in 1 (10%). For pulmonary lymphatic abnormalities, the positive rates of 68Ga-NEB PET/CT and 99mTc-ASC lymphoscintigraphy were 100% (10/10) and 10% (1/10), respectively (P < 0.001). As for the 7 patients with extrapulmonary lymphatic manifestations, 68Ga-NEB PET/CT also presented more information than 99mTc-ASC lymphoscintigraphy. CONCLUSION: 68Ga-NEB PET/CT visualized pulmonary lymphatic abnormality and displayed extrapulmonary lymphatic system disorders of LAM, and might play a role in the diagnosis and evaluation of the disease. 68Ga-NEB PET/CT is advantageous over conventional 99mTc-ASC lymphoscintigraphy in LAM by providing more detailed information of lymphatic dysfunction.


Assuntos
Linfangioleiomiomatose , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Azul Evans , Radioisótopos de Gálio , Compostos Heterocíclicos com 1 Anel , Humanos , Linfocintigrafia , Estudos Prospectivos
18.
Zhongguo Gu Shang ; 34(6): 568-72, 2021 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-34180180

RESUMO

OBJECTIVE: To explore the clinical effect of manual reduction combined with homemade splint external fixation in the treatment of metacarpal fractures. METHODS: A retrospective analysis was performed in 126 patients with metacarpal fracture treated by manual reduction and homemade splint external fixation in the emergency department of our hospital from January 2018 to December 2018, including 102 male, 24 female, ranging in age from 9 to 73 year old, with an average of (33.2±14.3)years old. During the treatment, the X-ray was re-examined regularly, and the external fixation was continued or adjusted according to the X-ray situation. The X-ray showed callus growth. After the fracture was stable, the external fixation was removed to continue functional exercise. The TAM scoring standardwas used to evaluate the hand function, and the fracture healing and complications were summarized. RESULTS: Of the 126 patients, 6 patients were treated with operation because of fracture displacement during the treatment. The other 120 patients were treated with this method and all of them got bony healing. The healing time was (6.3±1.8) weeks. The follow up time ranged from 2 to 12 months, with a mean of (4.4±2.2) months. At the latest follow up, TAM score was used to evaluate the hand function:excellent in 105 cases, good in 13 cases, fair in 2 cases and poor in 0 case. Shortening deformity was found in 7 cases and angulation deformity in 3 cases. CONCLUSION: Manual reduction combined with homemade splint external fixation in the treatment of metacarpal fractures can achieve good clinical results. Homemade splint is easy to obtain materials and low cost, and it is an effective method worthy of clinical promotion.


Assuntos
Ossos Metacarpais , Contenções , Adolescente , Adulto , Idoso , Criança , Fixadores Externos , Feminino , Fixação de Fratura , Fixação Interna de Fraturas , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
19.
Mikrochim Acta ; 188(7): 234, 2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34160693

RESUMO

Coral-like Ag-Mo2C/C-I and blocky Ag-Mo2C/C-II composites were obtained from one-step in situ calcination of [Ag(HL)3(Mo8O26)]n·nH2O [L: N-(pyridin-3-ylmethyl) pyridine-2-amine] under N2/H2 and N2 atmospheres, respectively. The coral-like morphology of Ag-Mo2C/C-I is composed of interwoven nanorods embedded with small particles, and the nano-aggregate of Ag-Mo2C/C-II is formed by cross-linkage of irregular nanoparticles. The above composites are decorated on glassy carbon electrode (GCE) drop by drop to generate two enzyme-free electrochemical sensors (Ag-Mo2C/C/GCE) for amperometric detection of H2O2. In particular, the coral-like Ag-Mo2C/C-I/GCE sensor possesses rapid response (1.2 s), high sensitivity (466.2 µA·mM-1·cm-2), and low detection limit (25 nM) towards trace H2O2 and has wide linear range (0.08 µM~4.67 mM) and good stability. All these sensing performances are superior to Ag-Mo2C/C-II/GCE, indicating that the calcining atmosphere has an important influence on microstructure and electrochemical properties. The excellent electrochemical H2O2 sensing performance of Ag-Mo2C/C-I/GCE sensor is mainly attributed to the synergism of unique microstructure, platinum-like electron structure of Mo2C, strong interaction between Mo and Ag, as well as the increased active sites and conductivity caused by co-doped Ag and carbon. Furthermore, this sensor has been successfully applied to the detection of H2O2 in human serum sample, contact lens solution, and commercial disinfector, demonstrating the potential in related fields of environment and biology. Graphical abstract.

20.
Exp Cell Res ; 405(2): 112657, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34081985

RESUMO

Checkpoint kinases (Chk) 1/2 are known for DNA damage checkpoint and cell cycle control in somatic cells. According to recent findings, the involvement of Chk1 in oocyte meiotic resumption and Chk2 is regarded as an essential regulator for progression at the post metaphase I stage (MI). In this study, AZD7762 (Chk1/2 inhibitor) and SB218078 (Chk1 inhibitor) were used to uncover the joint roles of Chk1/2 and differentiate the importance of Chk1 and Chk2 during oocyte meiotic maturation. Inhibition of Chk1/2 or Chk1 alone had no significant effect on germinal vesicle breakdown (GVBD) but significantly inhibited the first polar body (PB1). Interestingly, inhibition of Chk1 alone could not increase or completely block the extrusion of PB1 like Chk1/2 inhibition. Also, Chk1/2 inhibition resulted in defective meiotic spindle organization and chromosome condensation both in MI and metaphase II (MII) stages of oocytes. The location of γ-tubulin and Securin were abnormal or missing, while P38 MAPK was activated by Chk1/2 inhibition. Meanwhile, Chk1/2 inhibition reduced the percentage of the second polar body extrusion and pronuclear formation. In conclusion, our results further understand the functions and regulatory mechanism of Chk1/2 during oocyte meiotic maturation.


Assuntos
Cromossomos/metabolismo , Meiose/fisiologia , Metáfase/fisiologia , Oócitos/metabolismo , Animais , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Feminino , Camundongos , Securina/metabolismo , Tubulina (Proteína)/metabolismo
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