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1.
AME Case Rep ; 8: 34, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38711904

RESUMO

Background: Rudimentary horn pregnancy (RHP) is a special type of ectopic pregnancy and its pathophysiological basis is an abnormal fusion of the bilateral accessory mesonephric duct during the embryonic period. If sonographers lack experience to this disease, it is easily to be misdiagnosed in the early period, which often leads to rupture of the pregnant horn and life-threatening bleeding. Therefore, a high index of vigilance is required. Case Description: We present a case of a 27-year-old female who went to the department of emergency due to menopause, pelvic pain and elevated human chorionic gonadotropin (hCG) (above 200,000 IU/L). Sonographic examination showed uterus only had the right horn and endometrium was thickened about 1.7 cm without gestational sac (GS) in the uterine cavity. Besides, a 3.5×3.0 cm GS was found between the left ovary and corpus uteri. RHP was suspected by sonographer, and the patient underwent laparoscopy. Obstetricians and gynecologists removed the rudimentary horn and the left fallopian tube. The patient made a good recovery and was soon discharged home after surgery. Conclusions: This article analyzed one case and summarized ultrasonic characteristics of RHP which may help to improve the early diagnosis of RHP. If necessary, other imaging such as magnetic resonance imaging (MRI) can be combined to make a clear diagnosis and treatment as soon as possible.

2.
ACS Nano ; 18(19): 12401-12411, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38701333

RESUMO

Accurate identification of single nucleotide variants (SNVs) in key driver genes holds a significant value for disease diagnosis and treatment. Fluorescent probes exhibit tremendous potential in specific, high-resolution, and rapid detection of SNVs. However, additional steps are required in most post-PCR assays to convert double-stranded DNA (dsDNA) products into single-stranded DNA (ssDNA), enabling them to possess hybridization activity to trigger subsequent reactions. This process not only prolongs the complexity of the experiment but also introduces the risk of losing target information. In this study, we proposed two strategies for enriching active double-stranded DNA, involving PCR based on obstructive groups and cleavable units. Building upon this, we explored the impact of modified units on the strand displacement reaction (SDR) and assessed their discriminatory efficacy for mutations. The results showed that detection of low variant allele frequencies (VAF) as low as 0.1% can be achieved. The proposed strategy allowed orthogonal identification of 45 clinical colorectal cancer tissue samples with 100% specificity, and the results were generally consistent with sequencing results. Compared to existing methods for enriching active targets, our approach offers a more diverse set of enrichment strategies, characterized by the advantage of being simple and fast and preserving original information to the maximum extent. The objective of this study is to offer an effective solution for the swift and facile acquisition of active double-stranded DNA. We anticipate that our work will facilitate the practical applications of SDR based on dsDNA.


Assuntos
DNA , Polimorfismo de Nucleotídeo Único , Polimorfismo de Nucleotídeo Único/genética , Humanos , DNA/genética , DNA/química , Neoplasias Colorretais/genética , Reação em Cadeia da Polimerase , Corantes Fluorescentes/química , DNA de Cadeia Simples/genética , DNA de Cadeia Simples/química
3.
Orphanet J Rare Dis ; 19(1): 136, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38532506

RESUMO

BACKGROUND: Diffuse sclerosing variant of papillary thyroid carcinoma (DSVPTC) is a rare but high invasive subtype of papillary thyroid carcinoma, which mandates an aggressive clinical strategy. Few studies have focused on the sonographic characteristics of DSVPTC and the role of ultrasound in diagnosis and treatment of this variant remains unknown. This study aimed to identify and understand DSVPTC more accurately under ultrasound in correlation with pathology. METHODS: The ultrasound characteristics and histopathologic sections of 10 lesions in 10 DSVPTC patients who underwent thyroid surgery at our center between 2014 and 2020 were reviewed and compared with 184 lesions in 168 classic variant of papillary thyroid carcinoma (cPTC) patients. RESULTS: 6 DSVPTC cases (60%) showed the "snowstorm" pattern on sonogram and 4 cases (40%) presented hypoechoic solid nodules only. Vague borders (100.0% vs. 18.5%, P = 0.019) and abundant microcalcifications (66.7% vs. 10.9%, P = 0.037) were more common in DSVPTC nodules than in cPTC nodules, corresponding to the infiltrating boundaries and numerous psammoma bodies under the microscope respectively. Most of the DSVPTC cases had a heterogeneous background (80%) and suspicious metastatic cervical lymph nodes (80%) on sonograms. All DSVPTC cases had histopathological metastatic cervical lymph nodes. CONCLUSION: The sonographic "snowstorm" pattern indicated DSVPTC with whole-lobe occupation. Hypoechoic solid nodules with vague borders and abundant microcalcifications on sonogram suggested DSVPTC lesion with an ongoing invasion. Regardless of which of the two sonograms was shown, the corresponding DSVPTC lesions were aggressive and required the same attention from the surgeons.


Assuntos
Calcinose , Carcinoma Papilar , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/diagnóstico , Carcinoma Papilar/patologia , Carcinoma Papilar/cirurgia
4.
BMC Med Imaging ; 24(1): 46, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365645

RESUMO

PURPOSE: To study the value of ultrasound in the diagnosis of juxtaglomerular cell tumor (JGCT). METHODS: From January 2005 to July 2020, fifteen patients diagnosed as JGCT by surgical pathology in Peking Union Medical College Hospital were collected. All patients underwent preoperative ultrasound examination. The clinical, laboratory, ultrasound, computed tomography (CT), surgical, and pathological features of the patients were analyzed retrospectively. RESULTS: The 15 patients were 5 males and 10 females with a median age of 29 years (10∼72 years). 14 of them had hypertension and one had normal blood pressure. The tumors were all solitary, with a median diameter of 1.5 cm (0.9-5.9 cm). Among the fifteen patients, eleven were correctly detected by preoperative ultrasound, and four were missed. There was a significant difference in tumor size (2.64 ± 1.48 cm vs. 1.23 ± 0.21 cm) and whether the tumor protruded outward (9/11 vs. 0/4) between the ultrasound-detected group and the ultrasound-missed group (p = 0.010, p = 0.011). Of the 11 tumors detected by ultrasound, four were extremely hypoechoic, two were hypoechoic, three were isoechoic, and two were hyperechoic. Color Doppler showed no blood flow in five tumors with the size range from 0.9 to 2.0 cm, and mild blood flow in six tumors with the size range from 2.8 to 5.9 cm. CONCLUSIONS: JGCT is rare, and has characteristic clinical manifestations. Diagnosis should be suspected in case of secondary hypertension, particularly in young women, if no renal vascular cause was found. Ultrasound, combined with clinical manifestations, was helpful for the diagnosis.


Assuntos
Adenoma , Hipertensão , Neoplasias Renais , Masculino , Humanos , Feminino , Adulto , Estudos Retrospectivos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Ultrassonografia , Hipertensão/diagnóstico por imagem
5.
Theranostics ; 14(4): 1517-1533, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38389853

RESUMO

Rationale: Stem cell-based therapies have emerged as promising tools for tissue engineering and regenerative medicine, but their therapeutic efficacy is largely limited by the oxidative stress-induced loss of transplanted cells at injured tissue sites. To address this issue, we aimed to explore the underlying mechanism and protective strategy of ROS-induced MSC loss. Methods: Changes in TFAM (mitochondrial transcription factor A) signaling, mitochondrial function, DNA damage, apoptosis and senescence in MSCs under oxidative stress conditions were assessed using real-time PCR, western blotting and RNA sequencing, etc. The impact of TFAM or lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) knockdown or overexpression on mitochondrial function, DNA damage repair, apoptosis and senescence in MSCs was also analyzed. The effect of mitochondrion-targeted antioxidant (Mito-TEMPO) on the survival of transplanted MSCs was evaluated in a mouse model of renal ischemia/reperfusion (I/R) injury. Results: Mitochondrial ROS (mtROS) bursts caused defects in TFAM signaling and overall mitochondrial function, which further impaired NEAT1 expression and its mediated paraspeckle formation and DNA repair pathways in MSCs, thereby jointly promoting MSC senescence and death under oxidative stress. In contrast, targeted inhibition of the mtROS bursts is a sufficient strategy for attenuating early transplanted MSC loss at injured tissue sites, and coadministration of Mito-TEMPO improved the local retention of transplanted MSCs and reduced oxidative injury in ischemic kidneys. Conclusions: This study identified the critical role of the mitochondria‒paraspeckle axis in regulating cell survival and may provide insights into developing advanced stem cell therapies for tissue engineering and regenerative medicine.


Assuntos
Paraspeckles , Transplantes , Animais , Camundongos , Espécies Reativas de Oxigênio , Transplante de Células-Tronco , Antioxidantes
6.
Cancer Imaging ; 24(1): 13, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38245789

RESUMO

OBJECTIVES: To develop a nomogram using pretreatment ultrasound (US) and contrast-enhanced ultrasound (CEUS) to predict the clinical response of neoadjuvant chemotherapy (NAC) in patients with borderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC). METHODS: A total of 111 patients with pancreatic ductal adenocarcinoma (PDAC) treated with NAC between October 2017 and February 2022 were retrospectively enrolled. The patients were randomly divided (7:3) into training and validation cohorts. The pretreatment US and CEUS features were reviewed. Univariate and multivariate logistic regression analyses were used to determine the independent predictors of clinical response in the training cohort. Then a prediction nomogram model based on the independent predictors was constructed. The area under the curve (AUC), calibration plot, C-index and decision curve analysis (DCA) were used to assess the nomogram's performance, calibration, discrimination and clinical benefit. RESULTS: The multivariate logistic regression analysis showed that the taller-than-wide shape in the longitudinal plane (odds ratio [OR]:0.20, p = 0.01), time from injection of contrast agent to peak enhancement (OR:3.64; p = 0.05) and Peaktumor/ Peaknormal (OR:1.51; p = 0.03) were independent predictors of clinical response to NAC. The predictive nomogram developed based on the above imaging features showed AUCs were 0.852 and 0.854 in the primary and validation cohorts, respectively. Good calibration was achieved in the training datasets, with C-index of 0.852. DCA verified the clinical usefulness of the nomogram. CONCLUSIONS: The nomogram based on pretreatment US and CEUS can effectively predict the clinical response of NAC in patients with BRPC and LAPC; it may help guide personalized treatment.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Terapia Neoadjuvante , Nomogramas , Pâncreas , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/tratamento farmacológico , Estudos Retrospectivos
7.
Small ; 20(1): e2303425, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37649233

RESUMO

Postsurgical adhesion (PA) is a common and serious postoperative complication that affects millions of patients worldwide. However, current commercial barrier materials are insufficient to inhibit diverse pathological factors during PA formation, and thus, highly bioactive materials are needed. Here, this work designs an injectable multifunctional composite hydrogel that can serve as a combination therapy for preventing PA. In brief, this work reveals that multiple pathological events, such as chronic inflammatory and fibrotic processes, contribute to adhesion formation in vivo, and such processes can not be attenuated by barrier material (e.g., hydrogel) alone treatments. To solve this limitation, this work designs a composite hydrogel made of the cationic self-assembling peptide KLD2R and TGF-ß receptor inhibitor (TGF-ßRi)-loaded mesenchymal stem cell-derived nanovesicles (MSC-NVs). The resulting composite hydrogel displays multiple functions, including physical separation of the injured tissue areas, antibacterial effects, and local delivery and sustained release of anti-inflammatory MSC-NVs and antifibrotic TGF-ßRi. As a result, this composite hydrogel effectively inhibited local inflammation, fibrosis and adhesion formation in vivo. Moreover, the hydrogel also exhibits good biocompatibility and biodegradability in vivo. Together, the results highlight that this "all-in-one" composite hydrogel strategy may provide insights into designing advanced therapies for many types of tissue injury.


Assuntos
Hidrogéis , Inflamação , Humanos , Hidrogéis/farmacologia , Aderências Teciduais/prevenção & controle , Aderências Teciduais/patologia
8.
Quant Imaging Med Surg ; 13(12): 8587-8598, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38106337

RESUMO

Background: Ultrasonography of the uterine artery (UtA) in the first and second trimesters of pregnancy can assess uterine-placental blood perfusion and guide early clinical prevention. Establishing normal ranges of the UtA pulsatility index (UtA-PI) at 11-14 weeks of pregnancy is helpful for the early identification of high-risk pregnant women and improving the prognosis. This study aimed to establish a reference range of UtA-PI based on crown-rump length (CRL) for spontaneous and in vitro fertilization (IVF) singleton pregnancy during 11-14 weeks, respectively. Methods: A prospective study was performed at Peking Union Medical College Hospital. Healthy, low-risk women with a singleton pregnancy at 11-14 gestational weeks were consecutively recruited for this study from December 2017 to December 2020. All participants underwent routine prenatal ultrasound examination. The CRL of the fetus and the UtA-PI were measured in both uterine arteries, and average values were calculated. The LMS method was used to fit the percentile (P)5, P10, P25, P50, P75, P90, and P95 curves of the UtA-PI value of spontaneous and IVF singleton pregnancy with CRL changes, respectively. Results: A total of 1,962 pregnant women with normal fetuses were included in this study, including 1,792 pregnancies conceived naturally and 170 IVF fetuses. The UtA-PI reference range in the spontaneous pregnancy group was consistently higher than that in the IVF group during 11-14 weeks, and showed a statistically significant difference in UtA-PI for spontaneous and IVF pregnancies (P<0.001). According to the LMS method, each percentile curve of UtA-PI decreased with the increase of CRL in both the natural pregnancy group and the IVF group. The P95 range of UtA-PI for pregnant women with naturally conceived and IVF pregnancy was 2.74 to 2.11 and 2.50 to 1.94, respectively. The overall change of UtA-PI differentials of the two groups showed a downward trend and decreased slightly with the increase of CRL. Conclusions: This study provided a single-center, large sample of data and constructed a CRL-based reference value of UtA-PI for spontaneous and IVF singleton pregnancy, which provides a reliable basis for early UtA evaluation and early clinical decision-making during 11-14 gestational weeks.

9.
J Cancer Res Clin Oncol ; 149(19): 17189-17197, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37783929

RESUMO

PURPOSE: There were limited data on the diagnostic efficacy of liquid-based cytology (LBC) for pancreatic tissues acquired by percutaneous ultrasound-guided fine-needle aspiration (US-FNA). This study aimed to evaluate the diagnostic value of LBC acquired via percutaneous US-FNA for pancreatic tumors compared with LBC combined with smear cytology (SC). METHODS: A retrospective database search (January 2014 and February 2022) was performed for patients who underwent percutaneous US-FNA with both LBC and SC. Clinical and pathological data were collected from 298 patients; eventually, 251 cases met the inclusion criteria. Diagnostic accuracy, sensitivity (SEN), specificity (SPE), positive predictive value (PPV) and negative predictive value (NPV) were compared. Rapid on-site evaluation (ROSE) was not available in all cases. RESULTS: Based on the pancreaticobiliary cytology guidelines published by the Papanicolaou Society of Cytopathology, 224 (89.2%), 13 (5.2%) and 14 (5.6%) cases were diagnosed as malignant, pre-malignant and benign lesions, respectively. The diagnostic accuracy of the LBC + SC (88.5%) was better than that of LBC (87.3%) but without statistical significance (P = 0.125). The SEN, SPE, PPV and NPV were 87.5%, 85.2%, 98.0% and 45.1%, respectively, in the LBC group and 88.8%, 85.2%, 98.0% and 47.9%, respectively, in the LBC + SC group. According to univariate and multivariate analyses, there were no factors have significant association with the diagnostic sensitivity of LBC. CONCLUSIONS: LBC obtained via percutaneous US-FNA provides good diagnostic value for pancreatic lesions and there was no significant difference between the diagnostic accuracy of LBC and LBC + SC when ROSE was unavailable.


Assuntos
Neoplasias Pancreáticas , Humanos , Biópsia por Agulha Fina , Estudos Retrospectivos , Sensibilidade e Especificidade , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Ultrassonografia de Intervenção
10.
Neuroimage ; 281: 120370, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37716591

RESUMO

The goal of this work was to explore the total iron burden of cerebral microbleeds (CMBs) using a semi-automatic quantitative susceptibility mapping and to establish its effect on brain atrophy through the mediating effect of white matter hyperintensities (WMH). A total of 95 community-dwelling people were enrolled. Quantitative susceptibility mapping (QSM) combined with a dynamic programming algorithm (DPA) was used to measure the characteristics of 1309 CMBs. WMH were evaluated according to the Fazekas scale, and brain atrophy was assessed using a 2D linear measurement method. Histogram analysis was used to explore the distribution of CMBs susceptibility, volume, and total iron burden, while a correlation analysis was used to explore the relationship between volume and susceptibility. Stepwise regression analysis was used to analyze the risk factors for CMBs and their contribution to brain atrophy. Mediation analysis was used to explore the interrelationship between CMBs and brain atrophy. We found that the frequency distribution of susceptibility of the CMBs was Gaussian in nature with a mean of 201 ppb and a standard deviation of 84 ppb; however, the volume and total iron burden of CMBs were more Rician in nature. A weak but significant correlation between the susceptibility and volume of CMBs was found (r = -0.113, P < 0.001). The periventricular WMH (PVWMH) was a risk factor for the presence of CMBs (number: ß = 0.251, P = 0.014; volume: ß = 0.237, P = 0.042; total iron burden: ß = 0.238, P = 0.020) and was a risk factor for brain atrophy (third ventricle width: ß = 0.325, P = 0.001; Evans's index: ß = 0.323, P = 0.001). PVWMH had a significant mediating effect on the correlation between CMBs and brain atrophy. In conclusion, QSM along with the DPA can measure the total iron burden of CMBs. PVWMH might be a risk factor for CMBs and may mediate the effect of CMBs on brain atrophy.

11.
Diagnostics (Basel) ; 13(13)2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37443577

RESUMO

Contrast-enhanced ultrasound (CEUS) is a promising imaging modality in predicting the efficacy of neoadjuvant chemotherapy for pancreatic cancer, a tumor with high mortality. In this study, we proposed a deep-learning-based strategy for analyzing CEUS videos to predict the prognosis of pancreatic cancer neoadjuvant chemotherapy. Pre-trained convolutional neural network (CNN) models were used for binary classification of the chemotherapy as effective or ineffective, with CEUS videos collected before chemotherapy as the model input, and with the efficacy after chemotherapy as the reference standard. We proposed two deep learning models. The first CNN model used videos of ultrasound (US) and CEUS (US+CEUS), while the second CNN model only used videos of selected regions of interest (ROIs) within CEUS (CEUS-ROI). A total of 38 patients with strict restriction of clinical factors were enrolled, with 76 original CEUS videos collected. After data augmentation, 760 and 720 videos were included for the two CNN models, respectively. Seventy-six-fold and 72-fold cross-validations were performed to validate the classification performance of the two CNN models. The areas under the curve were 0.892 and 0.908 for the two models. The accuracy, recall, precision and F1 score were 0.829, 0.759, 0.786, and 0.772 for the first model. Those were 0.864, 0.930, 0.866, and 0.897 for the second model. A total of 38.2% and 40.3% of the original videos could be clearly distinguished by the deep learning models when the naked eye made an inaccurate classification. This study is the first to demonstrate the feasibility and potential of deep learning models based on pre-chemotherapy CEUS videos in predicting the efficacy of neoadjuvant chemotherapy for pancreas cancer.

12.
Quant Imaging Med Surg ; 13(6): 3902-3914, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37284072

RESUMO

Background: Contrast-enhanced ultrasound (CEUS) has proven valuable in diagnosing benign and malignant pancreatic diseases, but its value in evaluating hepatic metastasis remains to be further explored. This study investigated the relationship between CEUS features of pancreatic ductal adenocarcinoma (PDAC) and concomitant or recurrent liver metastases after treatment. Methods: This retrospective study included 133 participants with PDAC who were diagnosed with pancreatic lesions with CEUS at Peking Union Medical College Hospital from January 2017 to November 2020. According to the CEUS classification methods in our center, all the pancreatic lesions were classified as either with rich or poor blood supply. Additionally, quantitative ultrasonographic parameters were measured in the center and periphery of all pancreatic lesions. CEUS modes and parameters of the different hepatic metastasis groups were compared. The diagnostic performance of CEUS was calculated for diagnosing synchronous and metachronous hepatic metastasis. Results: The proportions of rich blood supply and poor blood supply were 46% (32/69) and 54% (37/69), respectively, in the no hepatic metastasis group; 42% (14/33) and 58% (19/33), respectively, in the metachronous hepatic metastasis (MHM) group; and 19% (6/31) and 81% (25/31), respectively, in the synchronous hepatic metastasis (SHM) group. The wash-in slope ratio (WIS ratio) between the center of the lesion and around the lesion and peak intensity ratio (PI ratio) between the center of the lesion and around the lesion had higher values in the negative hepatic metastasis group (P<0.05). In predicting synchronous and metachronous hepatic metastasis, the WIS ratio had the best diagnostic performance. The sensitivity (SEN), specificity (SPE), accuracy (ACC), positive predictive value (PPV), and negative predictive value (NPV) were 81.8%, 95.7%, 91.2%, 90.0%, and 91.7%, respectively, for MHM; and 87.1%, 95.7%, 93.0%, 90.0%, and 94.3%, respectively, for SHM. Conclusions: CEUS would be helpful in image surveillance for synchronous or metachronous hepatic metastasis of PDAC.

14.
Eur J Trauma Emerg Surg ; 49(4): 1665-1672, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35972516

RESUMO

Fibrinogen is the substrate of plasma coagulation. It plays an important role in the formation of reticular network, which is crucial to the strength and stability of blood clots. In addition to directly participating in coagulation, fibrinogen also participates in the destruction of blood-brain barrier and neuroinflammation. This article reviews the pathophysiological changes of fibrinogen after traumatic brain injury. Considerable efforts have been made to understand the mechanisms by which fibrinogen damages the central nervous system. Combined with the latest research hotspots, potentially promising treatment strategies at the molecular level were discussed. We believe that understanding the role of fibrinogen-mediated damage in nerve and blood-brain barrier function will enable timely intervention in patients with nerve damage, and guide the development of novel targeted therapeutics.


Assuntos
Lesões Encefálicas Traumáticas , Hemostáticos , Humanos , Fibrinogênio/farmacologia , Fibrinogênio/fisiologia , Lesões Encefálicas Traumáticas/terapia , Coagulação Sanguínea/fisiologia , Plasma
15.
Front Oncol ; 12: 1013017, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36531064

RESUMO

Neuroendocrine neoplasms (NENs) comprise a heterogeneous collection of tumors derived from various neuroendocrine cells and are divided into functioning NEN and non-functioning NEN. Some NENs present with mild symptoms and can secrete somatostatin. These neoplasms are known as somatostatin-producing oligosymptomatic NENs. In this report, we describe a case of metastatic somatostatin-producing oligosymptomatic NEN with peritumoral hepatic steatosis and review the relevant literature. The patient was a 45-year-old woman who presented with mild steatorrhea and melena. A computed tomography scan revealed an enlarged pancreas protruding into the duodenum. Pathology after total pancreatectomy showed a grade 2 pancreatic NEN with positive somatostatin immunostaining. Enlarging masses on the liver were observed after the operation. Ultrasound examination revealed several lesions in the liver, with inner hypoechoic areas that showed rapid enhancement and fast washout on contrast-enhanced ultrasonography and with outer hyperechoic areas with continuous iso-enhancement. Therefore, the inner hypoechoic areas seen on contrast-enhanced ultrasonography were suspected to be true metastases. A biopsy confirmed this suspicion and indicated that the outer areas were peritumoral liver steatosis. This case highlights the importance of the imaging pattern described in this report for accurate diagnosis of metastatic NEN to avoid incorrect estimation of tumor size or a missed diagnosis on biopsy.

16.
J Control Release ; 352: 1009-1023, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36375619

RESUMO

Kidney diseases are a serious health issue worldwide, and novel therapeutics are urgently needed. Extracellular vesicles (EVs) have emerged as potent drug delivery systems (DDSs), but their therapeutic potential is limited by short circulation times and insufficient renal retention. Here, we report that endogenous ligand (albumin, ALB) binding is an efficient modification strategy to improve the therapeutic potency of EV-based DDSs for kidney diseases. Surface albumin-binding peptide (ABP)-displayed EVs (ABP-EVs) were produced by transfecting parent cells with the ABP-Lamp2b fusion plasmid. Compared with unmodified EVs (NC-EVs), ABP-EVs showed increased binding to ALB in vitro and elevated circulation time and multiple organ retention in vivo after systemic (iv) injection. Moreover, ABP-EVs had higher renal retention than NC-EVs in mice with acute kidney injury through a complex mechanism involving microvascular injury and megalin-mediated endocytosis. As a result, delivery of small molecule drugs (e.g., curcumin) or proteins (e.g., hepatocyte growth factor) by ABP-EVs had superior therapeutic (e.g., anti-apoptotic, antioxidant, anti-inflammatory) effects in vitro and in vivo. This study highlights that ABP-EVs are versatile DDSs for kidney diseases and provides insights into the new strategies of engineering EVs for drug delivery.


Assuntos
Vesículas Extracelulares , Nefropatias , Camundongos , Animais , Ligantes , Vesículas Extracelulares/metabolismo , Rim , Nefropatias/tratamento farmacológico , Nefropatias/metabolismo , Peptídeos/metabolismo , Albuminas/metabolismo
17.
Transl Cancer Res ; 11(10): 3645-3656, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36388042

RESUMO

Background: Pancreatic carcinoma is a highly fatal disease, and early diagnosis is of vital importance. This meta-analysis aimed to compare the diagnostic performances of contrast-enhanced ultrasonography (CEUS) against contrast-enhanced computed tomography (CECT) for pancreatic carcinoma, using pathological results or alternative imaging modality as the gold standard. Methods: A thorough search was conducted in PubMed, EMBASE, Web of Science and Cochrane Library databases. Two investigators selected the studies and extracted the data independently. A bivariate mixed-effects regression model was used to calculate the pooled data. Subgroup analysis and meta-regression were performed to explore the causes of heterogeneity. Results: A total of 1,227 records were identified, of which 7 articles with 588 patients were assessed for eligibility. The overall sensitivity, specificity of CEUS and CECT with their 95% confidential intervals (95% CI) were 0.91 (0.85-0.94) and 0.88 (0.81-0.92), 0.83 (0.70-0.91) and 0.87 (0.73-0.94), respectively. The area under curve (AUC) of CEUS and CECT were 0.94 and 0.93. Subgroup analysis showed CEUS may be good at diagnosing lesions with diameters less than 2 cm. Tumor features, region and study type were the main causes of heterogeneity. Conclusions: CEUS has a satisfying diagnostic performance for pancreatic carcinoma and it has high sensitivity for small pancreatic carcinomas (≤2 cm); besides, it performs well in discriminating pancreatic cancer from chronic pancreatitis. Therefore, CEUS can be a useful supplement to CECT.

18.
Environ Pollut ; 315: 120234, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36195197

RESUMO

Asthma is a respiratory disease that can be exacerbated by certain environmental factors. Both formaldehyde (FA) and PM2.5, the most common indoor and outdoor air pollutants in mainland China, are closely associated with the onset and development of asthma. To date, however, there is very little report available on whether there is an exacerbating effect of combined exposure to FA and PM2.5 at ambient concentrations. In this study, asthmatic mice were exposed to 1 mg/m3 FA, 1 mg/kg PM2.5, or a combination of 0.5 mg/m3 FA and 0.5 mg/kg PM2.5, respectively. Results demonstrated that both levels of oxidative stress and inflammation were significantly increased, accompanied by an obvious decline in lung function. Further, the initial activation of p38 MAPK and NF-κB that intensified the immune imbalance of asthmatic mice were found to be visibly mitigated following the administration of SB203580, a p38 MAPK inhibitor. Noteworthily, it was found that combined exposure to the two at ambient concentrations could significantly worsen asthma than exposure to each of the two alone at twice the ambient concentration. This suggests that combined exposure to formaldehyde and PM2.5 at ambient concentrations may have a synergistic effect, thus causing more severe damage in asthmatic mice. In general, this work has revealed that the combined exposure to FA and PM2.5 at ambient concentrations can synergistically aggravate asthma via the p38 MAPK pathway in mice.


Assuntos
Poluentes Atmosféricos , Asma , Camundongos , Animais , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Formaldeído/toxicidade , Asma/metabolismo , Inflamação/induzido quimicamente , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Material Particulado/toxicidade
19.
Curr Med Sci ; 42(5): 1022-1032, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36255661

RESUMO

OBJECTIVE: While the upregulation of cytochrome P450 family 24 subfamily A member 1 (CYP24A1) gene expression has been reported in colon cancer, its role in tumorigenesis remains largely unknown. In this study, we aimed to investigate the involvement of CYP24A1 in Wnt pathway regulation via the nuclear factor kappa B (NF-κB) pathway. METHODS: The human colon cancer cell lines HCT-116 and Caco-2 were subjected to stimulation with interleukin-6 (IL-6) as well as tumor necrosis factor alpha (TNF-α), with subsequent treatment using the NF-κB pathway-specific inhibitor ammonium pyrrolidinedithiocarbamate (PDTC). Furthermore, CYP24A1 expression was subjected to knockdown via the use of small interfering RNA (siRNA). Subsequently, NF-κB pathway activation was determined by an electrophoretic mobility shift assay, and the transcriptional activity of ß-catenin was determined by a dual-luciferase reporter assay. A mouse ulcerative colitis (UC)-associated carcinogenesis model was established, wherein TNF-α and the NF-κB pathway were blocked by anti-TNF-α monoclonal antibody and NF-κB antisense oligonucleotides, respectively. Then the tumor size and protein level of CYP24A1 were determined. RESULTS: IL-6 and TNF-α upregulated CYP24A1 expression and activated the NF-κB pathway in colon cancer cells. PDTC significantly inhibited this increase in CYP24A1 expression. Additionally, knockdown of CYP24A1 expression by siRNA could partially antagonize Wnt pathway activation. Upregulated CYP24A1 expression was observed in the colonic epithelial cells of UC-associated carcinoma mouse models. Anti-TNF-α monoclonal antibody and NF-κB antisense oligonucleotides decreased the tumor size and suppressed CYP24A1 expression. CONCLUSION: Taken together, this study suggests that inflammatory factors may increase CYP24A1 expression via NF-κB pathway activation, which in turn stimulates Wnt signaling.


Assuntos
Compostos de Amônio , Neoplasias do Colo , Camundongos , Animais , Humanos , NF-kappa B/genética , NF-kappa B/metabolismo , Via de Sinalização Wnt , beta Catenina/genética , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/genética , Vitamina D3 24-Hidroxilase/metabolismo , RNA Interferente Pequeno , Células CACO-2 , Inibidores do Fator de Necrose Tumoral , Proteínas I-kappa B/metabolismo , Neoplasias do Colo/genética , Luciferases/metabolismo , Anticorpos Monoclonais , Oligonucleotídeos Antissenso
20.
Front Endocrinol (Lausanne) ; 13: 935559, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046785

RESUMO

The aim of this study was to investigate the factors related to large-volume central cervical lymph node metastasis (LNM) in papillary thyroid carcinoma. A retrospective study of 340 patients with 642 papillary thyroid carcinoma nodules who underwent thyroidectomy in Peking Union Medical College Hospital between 2011 and 2015 was conducted. These nodules were divided into two groups by the number of central cervical lymph node metastases: large-volume central cervical LNM (>5 metastatic lymph nodes, n = 129) and no central cervical LNM (n = 211). We evaluated the correlations between gender, age, chronic lymphocytic thyroiditis, thyroid ultrasonographic features, and large-volume central cervical LNM. We found that younger age (≤40 years) (OR = 3.796, 95% CI = 2.842, 5.070), male gender (OR = 4.005, 95% CI = 2.858, 5.61), and ultrasonographic features such as tumor macroaxis size (OR = 2.985, 95% CI = 1.581, 5.633), tumor located in the isthmus (OR = 7.578, 95% CI = 4.863, 11.810), ill-defined margin (OR = 3.008, 95% CI = 1.986, 4.556), microcalcification (OR = 2.155, 95% CI = 1.585, 2.929), and abnormal cervical lymph nodes (OR = 13.753, 95% CI = 9.278, 20.385) were independent risk factors for large-volume central cervical LNM in papillary thyroid carcinoma, while chronic lymphocytic thyroiditis (OR = 0.248, 95% CI = 0.172, 0.358) was a protective factor. Younger age (≤40 years), male sex, and ultrasonographic features such as tumor macroaxis size, tumor located in the isthmus, ill-defined margin, microcalcification, and abnormal cervical lymph nodes were independent risk factors for large-volume central cervical LNM in papillary thyroid carcinoma, while chronic lymphocytic thyroiditis can be considered a protective factor. Our results provide a reference for adjusting clinical treatment approaches.


Assuntos
Calcinose , Carcinoma Papilar , Doença de Hashimoto , Neoplasias da Glândula Tireoide , Adulto , Calcinose/patologia , Carcinoma Papilar/patologia , Carcinoma Papilar/cirurgia , Análise Fatorial , Doença de Hashimoto/patologia , Humanos , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática/patologia , Masculino , Estudos Retrospectivos , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia
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