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1.
Cancer Med ; 13(7): e7186, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38597789

RESUMO

BACKGROUND: The definition of textbook outcome in biliary system cancers is a developing concept in need of expansion and investigation of its association with survival and quality of life. METHODS: In this original research, we developed a novel "all or none" textbook outcome definition which addresses the rapid recovery of post-surgical indexes, in addition to short-term mortality, hospital re-admission, prolonged stay, surgical margin and postoperative complications. Based on the fulfillment of relevant criteria, patients were divided into textbook outcome and non-textbook outcome groups and their characteristics and survival data were analyzed. A customized "quality of life" questionnaire was developed to address short-term recovery and post-discharge life quality of patients. Association with quality of life improvement was then investigated. RESULTS: A total of 129 patients were included. Textbook outcome was achieved in 25.58% of patients (37.04% of gallbladder cancer patients and 17.8% of cholangiocarcinoma patients). Compared to non-textbook outcome group, patients with textbook outcome had lower rate of pre-operative biliary drainage (p = 0.026), higher rate of normal preoperative liver function (p < 0.001) and tumor markers (p = 0.001), reduced perioperative bleeding (p = 0.006) and blood transfusion (p = 0.005), and higher rate of N0 stage cases (p = 0.008). Textbook outcome was also associated with enhanced survival, significantly in older patients (<65 years) (1-year survival rate: 100% vs. 78.57% (p = 0.108), 2-year survival rate: 87.5% vs. 44% (p = 0.046)). Finally, textbook outcome was significantly associated with enhanced basic daily performance (p < 0.001), social life performance (p = 0.033), and personal evaluation (p < 0.001), and thus improved quality of life (p < 0.001). CONCLUSIONS: The novel definition of textbook outcome was able to address the specific nature of recovery after resection of biliary system cancers. Expanding the scope of textbook outcome and addressing the influence on survival and quality of life provides a comprehensive concept able to reflect physical, psychological and functioning enhancements in patients recovery.


Assuntos
Neoplasias dos Ductos Biliares , Neoplasias do Sistema Biliar , Humanos , Idoso , Qualidade de Vida , Assistência ao Convalescente , Alta do Paciente , Neoplasias do Sistema Biliar/cirurgia , Ductos Biliares Intra-Hepáticos
2.
Hepatobiliary Surg Nutr ; 13(1): 3-15, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38322199

RESUMO

Background: We aim to investigate the prevalence, patterns, risk factors, and outcomes of peritoneal metastases (PM) after curative laparoscopic hepatectomy (LH) for hepatocellular carcinoma (HCC). Methods: A multicenter cohort of 2,138 HCC patients who underwent curative LH from August 2010 to December 2016 from seven hospitals in China was retrospectively analyzed. The incidence of PM following LH was evaluated and compared with that in open hepatectomy (OH) after 1:1 propensity score matching (PSM). Results: PM prevalence was 5.1% (15/295) in the early period [2010-2013], 2.6% (47/1,843) in the later period [2014-2016], and 2.9% (62/2,138) in all LH patients, which was similar to 4.0% (59/1,490) in the OH patients. The recurrence patterns, timing, and treatment did not significantly vary between the LH and OH patients (P>0.05). Multivariate logistic regression revealed that tumor diameter >5 cm, non-anatomical resection, presence of microvascular invasion, and lesions <2 cm from major blood vessels were independent risk factors of PM after LH. Of the 62 cases with PM, 26 (41.9%) had PM only, 34 (54.9%) had intrahepatic recurrence (IHR) and PM, and 2 (3.2%) had synchronous extraperitoneal metastases (EPM). Patients with resectable PM had a 5-year overall survival (OS) of 65.0% compared to 9.0% for unresectable PM (P=0.001). Conclusions: The prevalence, patterns and independent risk factors of PM were identified for HCC patients after LH. LH was not associated with increased incidence of PM in HCC patients for experienced surgeons. Surgical re-excision of PM was associated with prolonged survival.

3.
Adv Sci (Weinh) ; 11(13): e2309388, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38269649

RESUMO

Cuproptosis, an emerging form of programmed cell death, has received tremendous attention in cancer therapy. However, the efficacy of cuproptosis remains limited by the poor delivery efficiency of copper ion carriers. Herein, copper complex nanoparticles (denoted as Cu(I) NP) are developed that can efficiently deliver copper complex into cancer cells to induce cuproptosis. Cu(I) NP demonstrate stimulus-responsive release of copper complexes, which results in mitochondrial dysfunction and promotes the aggregation of lipoylated dihydrolipoamide S-acetyltransferase (DLAT), leading to cuproptosis. Notably, Cu(I) NP not only induce cuproptosis, but also elicit robust immune responses to suppress tumor growth. Overall, this study provides a promising strategy for cuproptosis-based cancer therapy.


Assuntos
Nanopartículas , Neoplasias , Cobre , Imunoterapia , Apoptose , Neoplasias/terapia
4.
Dig Surg ; 41(1): 42-52, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38295782

RESUMO

INTRODUCTION: This study aimed to evaluate associations between frailty and outcomes in patients with intrahepatic cholangiocarcinoma (ICC) undergoing hepatic lobectomy using a large, nationally representative sample. METHODS: This population-based, retrospective observational study extracted the data of adults ≥20 years old with ICC undergoing hepatic lobectomy from the US Nationwide Inpatient Sample database between 2005 and 2018. Frailty was assessed by the validated Hospital Frailty Risk Score (HFRS). Associations between frailty and surgical outcomes were analyzed using logistic regression analyses. RESULTS: After exclusions, 777 patients were enrolled, including 427 frail and 350 non-frail. Patients' mean age was 64.5 (±0.4) years and the majority were males (51.1%) and whites (76.5%). Frailty was significantly associated with increased odds of in-hospital mortality (aOR: 18.51, 95% CI: 6.70, 51.18), non-home discharge (aOR: 3.58, 95% CI: 2.26, 5.66), prolonged LOS (aOR: 5.56, 95% CI: 3.87, 7.99), perioperative cardiac arrest/stroke (aOR: 5.44, 95% CI: 1.62, 18.24), acute respiratory distress syndrome (ARDS)/respiratory failure (aOR: 3.88, 95% CI: 2.40, 6.28), tracheostomy/ventilation (aOR: 3.83, 95% CI: 2.23, 6.58), bleeding/transfusion (aOR: 1.67, 95% CI: 1.24, 2.26), acute kidney injury (AKI) (aOR: 14.37, 95% CI: 7.13, 28.99), postoperative shock (aOR: 4.44, 95% CI: 2.54, 7.74), and sepsis (aOR: 11.94, 95% CI: 6.90, 20.67). DISCUSSION/CONCLUSION: Among patients with ICC undergoing hepatic lobectomy, HFRS-defined frailty is a strong predictor of worse in-patient outcomes, including in-hospital death, prolonged LOS, unfavorable discharge, and complications (perioperative cardiac arrest/stroke, ARDS/respiratory failure, tracheostomy/ventilation, bleeding/transfusion, AKI, postoperative shock, and sepsis). Study results may help stratify risk in frail patients undergoing hepatic resection for ICC.


Assuntos
Injúria Renal Aguda , Colangiocarcinoma , Fragilidade , Parada Cardíaca , Síndrome do Desconforto Respiratório , Insuficiência Respiratória , Sepse , Acidente Vascular Cerebral , Adulto , Masculino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Feminino , Pacientes Internados , Fragilidade/complicações , Fragilidade/epidemiologia , Mortalidade Hospitalar , Estudos Retrospectivos , Colangiocarcinoma/cirurgia , Fatores de Risco , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Tempo de Internação
5.
Surgery ; 175(4): 1147-1153, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38267341

RESUMO

AIM: To evaluate the efficacy of the application of intraoperative segmental pancreatic occlusion and insulin assay in surgical procedures for pancreatic hypoglycemia. METHODS: We retrospectively analyzed the clinical data of 11 pancreatic hypoglycemia cases treated in the China-Japan Friendship Hospital between September 2015 and August 2021. Intraoperative segmental pancreatic occlusion and insulin assay were used to enhance hypersecretory pancreatic tissues' localization and to achieve a complete resection. Intraoperative testing of insulin levels (peripheral venous blood) was carried out at several time points starting from before the resection of hypersecretory tissues (base value) and at 1 minute, 5 minutes, 15 minutes, 30 minutes, and 60 minutes after resection. Additional testing every 30 minutes until the end of the operation was carried out when necessary. RESULTS: A total of 11 pancreatic hypoglycemia cases were included; 9 cases were insulinomas (all with single pancreatic lesions, with 4 located in the head, 1 in the body, and 4 in the tail), 1 MEN-1, and 1 nesidioblastosis. The insulin assay (30 minutes after the resection of hypersecretory tissues) enhanced the ability to locate target tissues and the accuracy of complete resection to 100%. As for intraoperative blood glucose monitoring, the accuracy 30 minutes after resection was as low as 36.6%. Postoperative levels of insulin and glucose were normal in all patients, with no recurrence of hypoglycemic symptoms during postoperative follow-up visits (9 to 72 months). CONCLUSION: Intraoperative segmental pancreatic occlusion and insulin assay in pancreatic hypoglycemia is a simple, accurate, and fast approach that enhances the localization and complete resection of hypersecretory tissues. Such a combination is highly significant in challenging cases of hypoglycemia.


Assuntos
Hipoglicemia , Insulinoma , Neoplasias Pancreáticas , Humanos , Insulina , Neoplasias Pancreáticas/diagnóstico , Automonitorização da Glicemia , Estudos Retrospectivos , Glicemia , Hipoglicemia/diagnóstico , Hipoglicemia/etiologia , Insulinoma/diagnóstico , Insulinoma/cirurgia , Pancreatectomia/efeitos adversos , Pancreatectomia/métodos
7.
Adv Sci (Weinh) ; 11(2): e2304460, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37973557

RESUMO

Methods accurately predicting the responses of colorectal cancer (CRC) and colorectal cancer liver metastasis (CRLM) to personalized chemotherapy remain limited due to tumor heterogeneity. This study introduces an innovative patient-derived CRC and CRLM tumor model for preclinical investigation, utilizing 3d-bioprinting (3DP) technology. Efficient construction of homogeneous in vitro 3D models of CRC/CRLM is achieved through the application of patient-derived primary tumor cells and 3D bioprinting with bioink. Genomic and histological analyses affirm that the CRC/CRLM 3DP tumor models effectively retain parental tumor biomarkers and mutation profiles. In vitro tests evaluating chemotherapeutic drug sensitivities reveal substantial tumor heterogeneity in chemotherapy responses within the 3DP CRC/CRLM models. Furthermore, a robust correlation is evident between the drug response in the CRLM 3DP model and the clinical outcomes of neoadjuvant chemotherapy. These findings imply a significant potential for the application of patient-derived 3DP cancer models in precision chemotherapy prediction and preclinical research for CRC/CRLM.


Assuntos
Bioimpressão , Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Neoplasias Colorretais/patologia , Prognóstico , Neoplasias Hepáticas/genética
8.
Clin. transl. oncol. (Print) ; 25(10): 2938-2949, oct. 2023. graf
Artigo em Inglês | IBECS | ID: ibc-225075

RESUMO

Renal cell carcinoma (RCC) with poor prognosis and high incidence rate is a common malignant disease. Current therapies could bring little benefit for the patients with advanced-stage RCC. PDIA2 is an isomerase responsible for protein folding and its role in cancer including RCC is under investigation. In this study, we found that PDIA2 was expressed much higher in RCC tissues than the control but the methylation level of PDIA2 promoter was lower based on the TCGA data. Patients with higher PDIA2 expression exerted worse survival. In clinical specimen, PDIA2 expression was correlated to patients’ clinical factors such as TNM stage (I/II vs III/IV, p = 0.025) and tumor size (≤ 7 cm vs > 7 cm, p = 0.004). Moreover, K-M analysis showed that PDIA2 was associated with patients’ survival in RCC. PDIA2 was expressed much higher in cancer cells A498 than 786-O than that in 293 T cells. After PDIA2 was knocked down, cell proliferation, migration and invasion was potently inhibited. But cell apoptotic rate increased reversely. Furthermore, the efficacy of Sunitinib on RCC cells was strengthened after PDIA2 knockdown. In addition, knockdown of PDIA2 gene leaded to downregulation of levels of JNK1/2, phosphorylated JNK1/2, c-JUN, and Stat3. But this inhibition was partially released when JNK1/2 was overexpressed. In consistent, cell proliferation was also partially recovered. In summary, PDIA2 plays important role in progression of RCC and JNK signaling pathway might be regulated by PDIA2. This study suggests PDIA2 as a candidate target for therapy of RCC (AU)


Assuntos
Humanos , Sistema de Sinalização das MAP Quinases/genética , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/genética , Neoplasias Renais/patologia , Neoplasias Renais/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Prognóstico
9.
Molecules ; 28(17)2023 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-37687239

RESUMO

Bilobalide exhibits numerous beneficial bioactivities, including neuroprotective, anti-inflammatory, and antioxidant activity. Our previous study demonstrated that bilobalide inhibits adipogenesis and promotes lipolysis. The dose-dependent cytotoxicity was found to be specific to the mature adipocytes only, indicating the potential for regulating apoptosis in them. Herein, we aimed to investigate the apoptotic effects of bilobalide on 3T3-L1 mature adipocytes and elucidate the underlying mechanisms thereof. Flow cytometry analysis (FACS) revealed the pro-apoptotic effects of bilobalide on these cells. Bilobalide induced early apoptosis by reducing the mitochondrial membrane potential (MMP). DNA fragmentation was confirmed using TUNEL staining. Additionally, bilobalide increased the intracellular reactive oxygen species (ROS) levels and activities of Caspases 3/9. Pre-treatment with NAC (an ROS scavenger) confirmed the role of ROS in inducing apoptosis. Moreover, bilobalide up- and down-regulated the expression of Bax and Bcl-2, respectively, at the mRNA and protein expression levels; upregulated the Bax/Bcl-2 ratio; triggered the release of cytochrome c from the mitochondria; and increased the protein expression of cleaved Caspase 3, cleaved Caspase 9, and PARP cleavage. These results support the conclusion that bilobalide induces apoptosis in mature 3T3-L1 adipocytes through the ROS-mediated mitochondrial pathway, and offers potential novel treatment for obesity.


Assuntos
Bilobalídeos , Camundongos , Animais , Espécies Reativas de Oxigênio , Células 3T3-L1 , Proteína X Associada a bcl-2 , Apoptose , Mitocôndrias , Adipócitos
10.
Med Oncol ; 40(8): 235, 2023 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-37432515

RESUMO

To analyse the effect of POFUT1 (Protein O-Fucosyltransferase 1) on the proliferation, migration and apoptosis of colorectal cancer (CRC) cells and to explore its potential mechanism. The effects of POFUT1 silencing in vitro on the proliferation, migration, and apoptosis of CRC cells were investigated using the SW480 and RKO cell lines. The effect of POFUT1 expression on cell phenotype was detected by cell proliferation assay (CCK8), colony formation assay, flow cytometry, wound healing assay, transwell assay, cell apoptosis assay, etc. In vitro, silencing of POFUT1 resulted in decreased proliferation, cell cycle arrest, reduced migration and increased apoptosis of CRC cells. In CRC cells, POFUT1 plays a tumour-promoting role by promoting cell proliferation and migration and inhibiting apoptosis.


Assuntos
Apoptose , Neoplasias Colorretais , Humanos , Linhagem Celular , Proliferação de Células , Neoplasias Colorretais/genética , Citometria de Fluxo
11.
J Agric Food Chem ; 71(31): 12004-12014, 2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37523494

RESUMO

Umami peptides are small molecular weight oligopeptides that play a role in umami taste attributes. However, the identification of umami peptides is easily limited by environmental conditions, and the abundant source and high chromatographic separation efficiency remain difficult. Herein, we report a robust strategy based on a phage random linear heptapeptide library that targets the T1R1-Venus flytrap domain (T1R1-VFT). Two candidate peptides (MTLERPW and MNLHLSF) were readily identified with high affinity for T1R1-VFT binding (KD of MW-7 and MF-7 were 790 and 630 nM, respectively). The two peptides exhibited umami taste and significantly enhanced the umami intensity when added to the monosodium glutamate solution. Overall, this strategy shows that umami peptides could be developed via phage display technology for the first time. The phage display platform has a promising application to discover other taste peptides with affinity for taste receptors of interest and has more room for improvement in the future.


Assuntos
Peptídeos , Receptores Acoplados a Proteínas G , Receptores Acoplados a Proteínas G/metabolismo , Peptídeos/química , Glutamato de Sódio , Paladar
12.
Anal Chem ; 95(27): 10390-10397, 2023 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-37358224

RESUMO

Oxidation and protein phosphorylation are critical mechanisms involved in regulating various cellular activities. Increasing research has suggested that oxidative stress could affect the activities of specific kinases or phosphatases, leading to alterations in the phosphorylation status of certain proteins. Ultimately, these alterations can affect cellular signaling pathways and gene expression patterns. However, the relationship between oxidation and protein phosphorylation remains complex and not yet fully understood. Therefore, the development of effective sensors capable of detecting both oxidation and protein phosphorylation simultaneously presents an ongoing challenge. To address this need, we introduce a proof-of-concept nanochannel device that is dual-responsive to both H2O2 and phosphorylated peptide (PP). Specifically, we design a peptide GGGCEG(GPGGA)4CEGRRRR, which contains an H2O2-sensitive unit CEG, an elastic peptide fragment (GPGGA)4, and a phosphorylation site recognition fragment RRRR. When the peptides are immobilized on the inner walls of conical nanochannels in a polyethylene terephthalate membrane, this peptide-modified nanochannel device exhibits a sensitive response to both H2O2 and PPs. The peptide chains undergo a random coil-to-α-helix transition in response to H2O2, which leads to a close-to-open transition of the nanochannel, accompanied with a remarkable increase in the transmembrane ionic current. In contrast, binding of the peptides with PPs shields the positive charge of the RRRR fragments, causing a decrease of the transmembrane ionic current. These unique features enable the sensitive detection of reactive oxygen species released by 3T3-L1 cells stimulated by platelet-derived growth factor (PDGF) as well as PDGF-induced change in the PP level. Real-time kinase activity monitoring further confirms the device's potential utility for kinase inhibitor screening.


Assuntos
Peróxido de Hidrogênio , Peptídeos , Peróxido de Hidrogênio/farmacologia , Peptídeos/metabolismo , Fator de Crescimento Derivado de Plaquetas/metabolismo , Fosforilação , Estresse Oxidativo
13.
Front Bioeng Biotechnol ; 11: 1168086, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37101750

RESUMO

Accurate blood glucose determination is essential to the clinical diagnosis and management of diabetes. This work establishes an inner filter effect (IFE) strategy between upconversion nanoparticles (UCNPs) and quinone-imine complex for glucose monitoring in human serum simply and efficiently. In this system, the enzyme glucose oxidase (GOx) catalyzes the reaction of glucose into hydrogen peroxide (H2O2) and gluconic acid when compulsion by oxygen. In the presence of horseradish peroxidase (HRP), the produced H2O2 can catalytically oxidize phenol and 4-amino antipyrine (4-AAP) to generate quinone-imine products. The purple-colored quinone-imine complex effectively absorbed the fluorescence of NaYF4:Yb3+, Er3+ UCNPs, leading to the strong fluorescence quenching of UCNPs through IFE. Thus, a new approach was established for glucose monitoring by determining the fluorescence intensity. Under the optimal condition, this approach shows better linearity to glucose from 2-240 µmol/L with a low detection limit at 1.0 µmol/L. Owing to the excellent fluorescence property and background-free interference of the UCNPs, the biosensor was applied for glucose measurements in human serum and got a satisfactory result. Furthermore, this sensitive and selective biosensor revealed great potential for the quantitative analysis of blood glucose or different kinds of H2O2-involved biomolecules for the application of clinical diagnosis.

14.
Clin Transl Oncol ; 25(10): 2938-2949, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37017923

RESUMO

Renal cell carcinoma (RCC) with poor prognosis and high incidence rate is a common malignant disease. Current therapies could bring little benefit for the patients with advanced-stage RCC. PDIA2 is an isomerase responsible for protein folding and its role in cancer including RCC is under investigation. In this study, we found that PDIA2 was expressed much higher in RCC tissues than the control but the methylation level of PDIA2 promoter was lower based on the TCGA data. Patients with higher PDIA2 expression exerted worse survival. In clinical specimen, PDIA2 expression was correlated to patients' clinical factors such as TNM stage (I/II vs III/IV, p = 0.025) and tumor size (≤ 7 cm vs > 7 cm, p = 0.004). Moreover, K-M analysis showed that PDIA2 was associated with patients' survival in RCC. PDIA2 was expressed much higher in cancer cells A498 than 786-O than that in 293 T cells. After PDIA2 was knocked down, cell proliferation, migration and invasion was potently inhibited. But cell apoptotic rate increased reversely. Furthermore, the efficacy of Sunitinib on RCC cells was strengthened after PDIA2 knockdown. In addition, knockdown of PDIA2 gene leaded to downregulation of levels of JNK1/2, phosphorylated JNK1/2, c-JUN, and Stat3. But this inhibition was partially released when JNK1/2 was overexpressed. In consistent, cell proliferation was also partially recovered. In summary, PDIA2 plays important role in progression of RCC and JNK signaling pathway might be regulated by PDIA2. This study suggests PDIA2 as a candidate target for therapy of RCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/patologia , Sistema de Sinalização das MAP Quinases , Prognóstico
15.
Plant Physiol Biochem ; 196: 965-973, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36889235

RESUMO

Lilacs have high ornamental value due to their strong aroma. However, the molecular regulatory mechanisms of aroma biosynthesis and metabolism in lilac were largely unclear. In this study, two varieties with distinct aroma, Syringa oblata 'Zi Kui' (faint aroma) and Syringa vulgaris 'Li Fei' (strong aroma), were used for exploring the regulation mechanism of aroma difference. Via GC-MS analysis, a total of 43 volatile components were identified. Terpene volatiles was the most abundant volatiles constituting the aroma of two varieties. Notably, 3 volatile secondary metabolites were unique in 'Zi Kui' and 30 volatile secondary metabolites were unique in 'Li Fei'. Then, a transcriptome analysis was performed to clarify the regulation mechanism of aroma metabolism difference between these two varieties, and identified 6411 differentially expressed genes (DEGs). Interestingly, ubiquinone and other terpenoid-quinone biosynthesis genes were significantly enriched in DEGs. We further conducted a correlation analysis between the volatile metabolome and transcriptome and found that TPS, GGPPS, and HMGS genes might be the key contributors to the differences in floral fragrance composition between the two lilac varieties. Our study improves the understanding in the regulation mechanism of Lilac aroma and would help improve the aroma of ornamental crops by metabolic engineering.


Assuntos
Syringa , Syringa/genética , Syringa/metabolismo , Odorantes , Perfilação da Expressão Gênica , Metaboloma , Transcriptoma/genética , Terpenos/metabolismo
16.
Cancer Med ; 12(10): 11672-11685, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36999792

RESUMO

BACKGROUND: Approximately 90% of pancreatic ductal adenocarcinoma (PDAC) cases are driven by the untargetable non-G12C KRAS mutations, and only a small subset of patients are eligible for FDA-approved precision therapies. The practice of precision therapy in pancreatic cancer was limited by the paucity of targetable genetic alterations, especially in the Asian population. METHODS: To explore therapeutic targets in 499 Chinese PDAC patients, a deep sequencing panel (OncoPanscan™, Genetron health) was used to characterize somatic alterations including point mutations, indels, copy number alterations, gene fusions as well as pathogenic germline variants. RESULTS: We performed genomic profiling in 499 Chinese PDAC patients, which revealed somatic driver mutations in KRAS, TP53, CDKN2A, SMAD4, ARID1A, RNF43, and pathogenic germline variants (PGVs) in cancer predisposition genes including BRCA2, PALB2, and ATM. Overall, 20.4% of patients had targetable genomic alterations. About 8.4% of patients carried inactivating germline and somatic variants in BRCA1/2 and PALB2, which were susceptible to platinum and PARP inhibitors therapy. Patients with KRAS wild-type disease and early-onset pancreatic cancer (EOPC) harbored actionable mutations including BRAF, EGFR, ERBB2, and MAP2K1/2. Compared to PGV-negative patients, PGV-positive patients were younger and more likely to have a family history of cancer. Furthermore, PGVs in PALB2, BRCA2, and ATM were associated with high PDAC risk in the Chinese population. CONCLUSIONS: Our results demonstrated that a genetic screen of actionable genomic variants could facilitate precision therapy and cancer risk reduction in pancreatic cancer patients of Asian ethnicity.


Assuntos
Carcinoma Ductal Pancreático , População do Leste Asiático , Neoplasias Pancreáticas , Humanos , Proteína BRCA1/genética , Proteína BRCA2/genética , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , População do Leste Asiático/genética , Genômica , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/epidemiologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias Pancreáticas
17.
BMC Musculoskelet Disord ; 24(1): 159, 2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-36864407

RESUMO

BACKGROUND: Preoperative expectations of total knee arthroplasty (TKA) outcomes are important determinants of patient satisfaction. However, expectations of patients in different countries are affected by cultural background. The general goal of this study was to describe Chinese TKA patients' expectations. METHODS: Patients scheduled for TKA were recruited in a quantitative study(n = 198). The Hospital for Special Surgery Total Knee Replacement Expectations Survey Questionnaire was used for survey TKA patients' expectations. Descriptive phenomenological design was used for the qualitative research. Semi-structured interviews were conducted with 15 TKA patients. Colaizzi's method was used for interview data analysis. RESULTS: The mean expectation score of Chinese TKA patients was 89.17 points. The 4 highest score items were walk short distance, remove the need for walker, relieve pain and make knee or leg straight. The 2 lowest score items were employed for monetary reimbursement and sexual activity. Five main themes and 12 sub-themes emerged from the interview data, including multiple factors raised expectations, expectations of physical comfort, expect various activities back to normal, hope for a long joint lifespan, and expect a better mood. CONCLUSIONS: Chinese TKA patients reported a relatively high level of expectations, and differences across cultures result in different expectation points than other national populations, requiring adjustment of items when using assessment tools across cultures. Strategies for expectation management should be further developed. LEVEL OF EVIDENCE: Level IV.


Assuntos
Artroplastia do Joelho , Humanos , Motivação , População do Leste Asiático , Povo Asiático , Articulação do Joelho/cirurgia
18.
Artigo em Inglês | MEDLINE | ID: mdl-36763789

RESUMO

Aggregation-induced emission (AIE) is a unique photophysical process, and its emergence brings a revolutionary change in luminescence. However, AIE-based research has been limited to a few classical molecular skeletons, which is unfavorable for in-depth studies of the photophysical characteristics of AIE and the full exploitation of their potential values. There is an urgent need to develop new skeletons to rise to the challenges of an insufficient number of AIE core structures and difficult modification. Here, we report a novel dumbbell AIE skeleton, in which two phenyls are connected through (E)-3-iminoprop-1-en-1-amine. This skeleton shows extremely strong solid-state emission with an absolute quantum yield up to 69.5%, a large Stokes shift, and typical AIE characteristics, which well resolves the challenge of difficult modification and low luminous efficiency of the traditional AIE skeletons. One-step reaction, high yield, and diversified modification endow the skeleton with great scalability from simple to complicated, or from symmetrical to asymmetrical structures, which establishes the applicability of the skeleton in various scenarios. These molecules self-assemble into highly ordered layer-, rod-, petal-, hollow pipe-, or helix-like nanostructures, which contribute to strong AIE emission. Crystallographic data reveal the highly ordered layer structures of the aggregates with different substituents, and a novel halogen bond-driven self-assembly mechanism that restricts intramolecular motion is clearly discovered. Taking advantage of these merits, a full-band emission system from green to red is successfully established, which displays great potential in the construction of light-emitting films and advanced light-emitting diodes. The discovery of this AIE skeleton may motivate a huge potential application value in luminescent materials and lead to hitherto impossible technological innovations.

19.
J Clin Med ; 12(2)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36675372

RESUMO

BACKGROUNDS: Concomitant abdominal aortic aneurysms (AAA) and gastrointestinal malignancies are uncommon. Endovascular repair (EVAR) is widely used to treat AAA. However, no consensus exists on the optimal strategy for treating AAA when associated with pancreatic adenocarcinoma. In addition, only few reports of pancreaticoduodenectomy (PD) after EVAR exist. PRESENTATION OF CASE: A pancreatic tumor was detected during follow-up after EVAR for AAA in an 83-year-old female patient. The diagnosis was high-grade intraepithelial neoplasia. Modified pylorus-preserving pancreaticoduodenectomy was safely performed. The patient recovered moderately and was discharged two weeks after surgery. The pathological diagnosis was middle-grade pancreatic ductal adenocarcinoma. The patient survived for 24 months with no recurrence or cardiovascular complications. CONCLUSIONS: Conducting periodic follow-ups after AAA surgery is helpful for the early discovery of gastrointestinal tumors. EVAR surgery is safe and feasible and thus recommended for AAA patients with pancreatic cancer, although it may increase the risk of cancer. The stage of malignancy and post-EVAR medical history can be valuable in evaluating the benefits of pancreatic surgery for such cases.

20.
Chin J Integr Med ; 29(1): 3-9, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35915317

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of Cidan Capsule combined with adjuvant transarterial chemoembolization (TACE) in patients with a high risk of early recurrence after curative resection of hepatocellular carcinoma (HCC). METHODS: A multicenter, randomized controlled trial was conducted in patients with high-risk recurrence factors after curative resection of HCC from 9 medical centers between July 2014 and July 2018. Totally 249 patients were randomly assigned to TACE with or without Cidan Capsule administration groups by stratified block in a 1:1 ratio. Postoperative adjuvant TACE was given 4-5 weeks after hepatic resection in both groups. Additionally, 125 patients in the TACE plus Cidan group were administrated Cidan Capsule (0.27 g/capsule, 5 capsules every time, 4 times a day) for 6 months with a 24-month follow-up. Primary endpoints included disease-free survival (DFS) and tumor recurrence rate (TRR). Secondary endpoint was overall survival (OS). Any drug-related adverse events (AEs) were observed and recorded. RESULTS: As the data cutoff in July 9th, 2018, the median DFS was not reached in the TACE plus Cidan group and 234.0 days in the TACE group (hazard ratio, 0.420, 95% confidence interval, 0.290-0.608; P<0.01). The 1- and 2-year TRR in the TACE plus Cidan and TACE groups were 31.5%, 37.1%, and 60.8%, 63.4%, respectively (P<0.01). Median OS was not reached in both groups. The 1- and 2-year OS rates in TACE plus Cidan and TACE groups were 98.4%, 98.4%, and 89.5%, 87.9%, respectively (P<0.05). The most common grade 3-4 AEs included fatigue, abdominal pain, lumbar pain, and nausea. One serious AE was reported in 1 patient in the TACE plus Cidan group, the death was due to retroperitoneal mass hemorrhage and hemorrhagic shock, and was not related to study drug. CONCLUSIONS: Cidan Capsule in combination with TACE can reduce the incidence of early recurrence in HCC patients at high-risk of recurrence after radical hepatectomy and may be an appropriate option in postoperative anti-recurrence treatment. (Registration No. NCT02253511).


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Quimioembolização Terapêutica/efeitos adversos , Hepatectomia , Intervalo Livre de Doença , Resultado do Tratamento , Estudos Retrospectivos
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