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1.
Heliyon ; 10(11): e31920, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38882383

RESUMO

This study conducted experimental analyses on a 280 Ah single lithium iron phosphate battery using an independently constructed experimental platform to assess the efficacy of compressed nitrogen foam in extinguishing lithium-ion battery fires. Based on theoretical analysis, the fire-extinguishing effects of compressed nitrogen foam at different outlet pressures from foam mixture tanks were analyzed, examining factors such as battery surface temperature, flame temperature, and thermal weight loss. The results indicate that the compressed nitrogen foam can extinguish the open flame of the battery in 14 s at 0.7 MPa, with the battery's surface temperature dropping by approximately 11 % before and after the application of the extinguishing agent. Compared with other commonly used extinguishing agents, the compressed nitrogen foam demonstrates superior extinguishing efficiency, but its cooling efficiency is somewhat lower. At pressures ranging from 0.4 to 0.6 MPa, the foam displays prolonged drainage time and sustained cooling effects, rendering it more suitable for lithium-ion battery fire scenarios. To address the issue of reduced cooling performance during later stages of fire suppression by compressed nitrogen foam, an intermittent injection approach has been proposed to effectively preserve its cooling efficacy.

2.
Am J Surg ; 233: 94-99, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38369416

RESUMO

BACKGROUND: Marginal ulcer (MU) is one of the postoperative complications of pancreaticoduodenectomy (PD), which needs particular attention in postoperative treatments. METHODS: The data of 190 patients who underwent PD and follow-up gastroscopic review due to upper GI symptoms within two years were retrospectively analyzed. The incidence of MU and risk factors were analyzed based on personal history, surgical procedure, past medical history, postoperative complications, and other relevant indicators. RESULTS: The proportion of MU in patients who underwent endoscopic follow-up for upper gastrointestinal symptoms in the postoperative period in this cohort was 10.5% (20/190). Advanced age (69y vs. 59y, P â€‹= â€‹0.012), alcohol consumption (20% vs. 8.2%, P â€‹= â€‹0.03), and cigarette smoking (35% vs. 14.7%, P â€‹= â€‹0.022) were associated with an increased incidence of MU. Longer surgery time (276.5min vs. 240min, P â€‹= â€‹0.049), postoperative bleeding (10% vs. 1.8%, P â€‹= â€‹0.030), and failure to take antacid regularly postoperatively (75% vs. 97.1%, P â€‹= â€‹0.000) would increase the risk of MU; taking antacid regularly was an independent protective factor for postoperative anastomotic ulceration (OR: 0.091, CI: 0.022-0.383, P â€‹= â€‹0.001). CONCLUSION: Advanced age, alcohol consumption, smoking, longer operation time, or postoperative extraluminal hemorrhage are associated with MU. Regular use of antacids is an independent protective factor against the development of MU.


Assuntos
Pancreaticoduodenectomia , Complicações Pós-Operatórias , Humanos , Masculino , Pancreaticoduodenectomia/efeitos adversos , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Incidência , Idoso , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Adulto , Úlcera Péptica/epidemiologia , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Úlcera Gástrica/epidemiologia , Úlcera Gástrica/etiologia
3.
Mol Carcinog ; 62(12): 1947-1959, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37642304

RESUMO

Cyclin-dependent kinase subunit 2 (CKS2) has been reported to promote various malignancies. This study investigated the functional role of CKS2 in pancreatic cancer (PC). An analysis of abnormally expressed genes and their prognostic value for PC was performed by using the Gene Expression Profiling Interactive Analysis (GEPIA) database and performing immunohistochemical staining on 64 samples of tumor tissue. CCK-8 assays, EdU staining, colony formation assays, flow cytometry, and a xenograft tumor model were used to analyze the biological function of CKS2 in PC. Our results revealed that CKS2 was expressed at significantly higher levels in PC tissues than in adjacent normal tissues, and a high level of CKS2 expression was associated with a poor prognosis for patients with PC. Moreover, functional assays revealed that CKS2 knockdown suppressed cell proliferation, induced cell cycle S phase, G2/M phase arrest, and apoptosis in vitro, and also reduced tumor growth in vivo. In addition, CKS2 knockdown increased the levels of Bax, caspase-3, P53, P21, and GADD45α expression, but decreased Bcl-2, Cyclin B1, CDK1, Cyclin A, and Cdc25C expression. CKS2 overexpression produced the opposite effects of CKS2 knockdown. Furthermore, we found that ELK1 protein regulated transcription of the CKS2 gene. In conclusion, our findings suggest that CKS2 expression is regulated by ELK1, which could possibly serve as prognostic indicator and therapeutic target for PC.


Assuntos
Quinases relacionadas a CDC2 e CDC28 , Neoplasias Pancreáticas , Humanos , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Quinases relacionadas a CDC2 e CDC28/genética , Quinases relacionadas a CDC2 e CDC28/metabolismo , Proliferação de Células/genética , Fase G2 , Apoptose/genética , Neoplasias Pancreáticas/genética , Regulação Neoplásica da Expressão Gênica , Proteínas Elk-1 do Domínio ets/genética , Proteínas Elk-1 do Domínio ets/metabolismo , Proteínas Elk-1 do Domínio ets/farmacologia
4.
J Gastrointest Surg ; 27(10): 2145-2154, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37488423

RESUMO

BACKGROUND: For infected necrotizing pancreatitis (INP), percutaneous catheter drainage (PCD) is now widely acknowledged as the initial intervention in a step-up approach, followed, if necessary, by minimally invasive necrosectomy or even open pancreatic necrosectomy. However, an overemphasis on PCD may cause a patient's condition to deteriorate, leading to missed surgical opportunities or even death. This study aimed to develop a simple and convenient scoring tool for assessing the need for surgery in INP patients who received PCD procedures. METHODS: In an observational study conducted between April 2015 and December 2020, PCD was utilized as the initial step to treat 143 consecutive INP patients. A surgical necrosectomy was performed when the patient failed to respond. Risk factors of PCD failure (i.e., need for surgical necrosectomy) were identified by multivariate logistic regression models. An integer-based risk scoring tool was developed using the ß coefficients derived from the logistic regression model. RESULTS: In 62 (43.4%) patients, PCD was successful, while the remaining 81 (56.6%) individuals required subsequent surgical necrosectomy. In the multivariate model, organ failure, percentage of pancreatic necrosis, extrapancreatic necrosis volume, and mean CT density of extrapancreatic necrosis volume were associated with a need for surgical necrosectomy. A predictive scoring tool based on these four factors demonstrated an area under the receiver operating characteristic curve (AUC) of 0.893. Under the scoring tool, a total score of 4 or more indicates a high possibility of surgical necrosectomy being required (at least 80%). Using the coordinates of the receiver operating characteristic curve (ROC), the sensitivity and specificity at this threshold are 0.802 and 0.903, respectively. CONCLUSIONS: A risk score model integrating organ failure, percentage of pancreatic necrosis, extrapancreatic necrosis volume, and mean CT density of extrapancreatic necrosis volume can identify INP patients at high risk for necrosectomy. The straightforward risk assessment tool assists clinicians in stratifying INP patients and making more judicious medical decisions.


Assuntos
Pancreatite Necrosante Aguda , Humanos , Pancreatite Necrosante Aguda/complicações , Pancreatite Necrosante Aguda/diagnóstico por imagem , Pancreatite Necrosante Aguda/cirurgia , Resultado do Tratamento , Drenagem/métodos , Fatores de Risco , Necrose/cirurgia , Estudos Retrospectivos
5.
World J Surg Oncol ; 21(1): 119, 2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37004027

RESUMO

BACKGROUND/OBJECTIVES: To evaluate perioperative safety and outcome of parenchyma-preserving pancreatectomy and risk factors of metastasis and recurrence for patients with solid pseudopapillary neoplasm (SPN). METHODS: Demographic data, operative and pathological parameter, follow-up data of patients with SPN undergoing their first operation were collected in our single center from May 2016 to October 2021 and compared between regular pancreatectomy group and parenchyma-preserving surgery group. Risk factors for metastasis and recurrence were investigated. RESULTS: A total of 194 patients were included, 154 of whom were female and the average age of all patients was 33 years old. Most patients were asymptomatic, with the most common complaint being abdominal pain or discomfort. Of them, 62 patients underwent parenchyma-preserving pancreatectomy including middle segment pancreatectomy and enucleation, and 132 patients underwent regular pancreatectomy including pancreaticoduodenectomy, distal pancreatectomy and total pancreatectomy. Patients in the parenchyma-preserving surgery group had a shorter duration of operation, less intraoperative bleeding, and decreased risk of combined organ removal and blood transfusion, with no statistical significance yet. The two groups exhibited a similar incidence of postoperative complications including grade B and C pancreatic fistula, delayed gastric emptying, postoperative pancreatic hemorrhage, and other complications, as well as radiological intervention, relaparotomy and the length of postoperative hospital stay. There were no perioperative deaths. All the patients, except 18 of those who discontinued follow-up, were alive with a median follow-up time of 31 months. Three patients in the regular pancreatectomy group were observed to have liver metastasis, and no metastasis was observed in the parenchyma-preserving surgery group. Significant risk factors for tumor metastasis and recurrence were tumor size, angioinvasion, and nerve infiltration. CONCLUSIONS: Parenchyma-preserving surgery did not significantly increase the frequency of perioperative complications or recurrence and might be preferable if comprehensive conditions allow.


Assuntos
Neoplasias Pancreáticas , Humanos , Feminino , Adulto , Masculino , Neoplasias Pancreáticas/patologia , Prognóstico , Pancreatectomia/efeitos adversos , Pancreaticoduodenectomia , Hemorragia Pós-Operatória/etiologia , Estudos Retrospectivos , Pâncreas/cirurgia , Pâncreas/patologia , Resultado do Tratamento
6.
Int J Surg ; 109(7): 2096-2119, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37073540

RESUMO

BACKGROUND: Delayed gastric emptying (DGE) is a common complication after pancreaticoduodenectomy (PD) or pylorus-preserving pancreaticoduodenectomy (PPPD). However, its risk factors are still unclear. This meta-analysis aimed to identify the potential risk factors of DGE among patients undergoing PD or PPPD. MATERIALS AND METHODS: We searched PubMed, EMBASE, Web of Science, Cochrane Library, Google Scholar, and ClinicalTrial.gov for studies that examined the clinical risk factors of DGE after PD or PPPD from inception through 31 July 2022. We pooled odds ratios (ORs) with 95% CIs using random-effects or fixed-effects models. We also performed heterogeneity, sensitivity, and publication bias analyses. RESULTS: The study included a total of 31 research studies, which involved 9205 patients. The pooled analysis indicated that out of 16 nonsurgical-related risk factors, three risk factors were found to be associated with an increased incidence of DGE. These risk factors were older age (OR 1.37, P =0.005), preoperative biliary drainage (OR 1.34, P =0.006), and soft pancreas texture (OR 1.23, P =0.04). On the other hand, patients with dilated pancreatic duct (OR 0.59, P =0.005) had a decreased risk of DGE. Among 12 operation-related risk factors, more blood loss (OR 1.33, P =0.01), postoperative pancreatic fistula (POPF) (OR 2.09, P <0.001), intra-abdominal collection (OR 3.58, P =0.001), and intra-abdominal abscess (OR 3.06, P <0.0001) were more likely to cause DGE. However, our data also revealed 20 factors did not support stimulative factors influencing DGE. CONCLUSION: Age, preoperative biliary drainage, pancreas texture, pancreatic duct size, blood loss, POPF, intra-abdominal collection, and intra-abdominal abscess are significantly associated with DGE. This meta-analysis may have utility in guiding clinical practice for improvements in screening patients with a high risk of DGE and selecting appropriate treatment measures.


Assuntos
Abscesso Abdominal , Gastroparesia , Humanos , Pancreaticoduodenectomia/efeitos adversos , Gastroparesia/epidemiologia , Gastroparesia/etiologia , Piloro/cirurgia , Fístula Pancreática/etiologia , Fatores de Risco , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Abscesso Abdominal/epidemiologia , Abscesso Abdominal/etiologia , Esvaziamento Gástrico
7.
Molecules ; 27(19)2022 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-36235164

RESUMO

An effective method for separating and purifying critical saponins (polyphyllin II and polyphyllin VII) from a Paris polyphylla var. yunnanensis extract was developed in this study which was environmentally friendly and economical. Static adsorption kinetics, thermodynamics, and the dynamic adsorption-desorption of macroporous resins were investigated, and then the conditions of purification and separation were optimized by fitting with an adsorption thermodynamics equation and a kinetic equation. Effective NKA-9 resin from seven macroporous resins was screened out to separate and purify the two saponins. The static adsorption and dynamic adsorption were chemical and physical adsorption dual-processes on the NKA-9 resin. Under the optimum parameters, the contents of polyphyllin II and polyphyllin VII in the product were 17.3-fold and 28.6-fold those in plant extracts, respectively. The total yields of the two saponins were 93.16%. This research thus provides a theoretical foundation for the large-scale industrial production of the natural drugs polyphyllin II and polyphyllin VII.


Assuntos
Liliaceae , Melanthiaceae , Saponinas , Adsorção , Liliaceae/química , Melanthiaceae/química , Extratos Vegetais , Resinas Vegetais , Saponinas/química
8.
BMC Surg ; 22(1): 318, 2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-35982438

RESUMO

BACKGROUND: Pancreatojejunostomy stricture (PJS) is a rare long-term complication of pancreaticojejunal anastomosis. This study aimed to investigate the role of surgery in the management of pancreatojejunostomy strictures. METHODS: The database of the Pancreas Center of Nanjing Medical University was retrospectively screened for patients who underwent a surgical revision for PJS between June 2012 and August 2019, and their clinical characteristics and management modalities were reviewed. RESULTS: Fourteen consecutive cases were retrieved, the median age at index operation was 41.1 years (19-71). The average time between the two operations was 70.6 months (8-270 months). Index procedures included pancreaticoduodenectomy (PD) (7/14, 50%), pylorus-preserving PD (4/14, 28.6%), Berger procedure (2/14, 14.3%), and middle pancreatectomy (1/14, 7.1%). The diameter of the main pancreatic duct was < 4 mm in all 14 cases, and nine underwent pancreaticojejunostomy (PJ) stenting during the index operation. The most frequent complaints were abdominal pain (6/14, 42.9%), recurrent acute pancreatitis (6/14, 42.9%), pancreatic fistula (1/14, 7.1%), and abdominal distention (1/14, 7.1%). The diagnosis of PJ stricture was confirmed by computed tomography or magnetic resonance imaging in all cases. All patients had a main duct diameter > 5 mm before surgical revision. All patients underwent wedge excision with interrupted one-layer suturing with absorbable sutures and without stent placement. In this series, only one patient required reoperation. Upon follow-up, 11 of 12 patients had complete resolution of the PJ stricture. CONCLUSION: PJS is a long-term complication of pancreatojejunostomy. Surgical revision of the anastomosis is a safe and effective treatment modality.


Assuntos
Pancreaticojejunostomia , Pancreatite , Doença Aguda , Anastomose Cirúrgica/efeitos adversos , Constrição Patológica/complicações , Constrição Patológica/cirurgia , Humanos , Fístula Pancreática , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/métodos , Pancreaticojejunostomia/efeitos adversos , Pancreaticojejunostomia/métodos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Reoperação/efeitos adversos , Estudos Retrospectivos
9.
Cancer Manag Res ; 14: 1409-1419, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35431580

RESUMO

Background: Undifferentiated carcinoma of pancreas with osteoclast-like giant cells is an extremely rare tumor in pancreas. It is relatively difficult to have preoperative diagnosis due to the lack of specific tumor markers and pre-operative images. Methods: In the present study, database of the pancreas center in the First Affiliated Hospital of Nanjing Medical University was retrospectively screened. A total of thirteen cases diagnosed as undifferentiated carcinoma of pancreas with osteoclast-like giant cells were included. Their clinical data and treatments were collected. Results: Thirteen patients include eight males and five females, and the median age was 67 (60-72) years old. The lesions were found in more than half patients through health examination with no symptoms. NSE was elevated in eight cases (66%). CT scan revealed that cystic and solid lesions often had thick (4/5), contrast-enhanced (5/5) wall with smooth edges (5/5) and the boundary of lesions mainly with solid composition (4/10) is not well demarcated with normal pancreatic parenchyma. All patients received surgical resection. Eight patients had adjuvant chemotherapy and only one patient had adjuvant radiotherapy. The median survival time was 13 months. Five patients had postoperative metastasis or recurrence of tumor and four of them had died of this disease during follow-up. Conclusion: Our data showed that elevated level of NSE and characteristic pre-operative images might provide aid with the pre-operative diagnosis for undifferentiated carcinoma of pancreas with osteoclast-like giant cells. Patients with suspected diagnosis should receive surgical intervention as soon as possible, supplemented with postoperative chemotherapy, in order to prolong the survival of patients.

10.
Gland Surg ; 11(1): 42-55, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35242668

RESUMO

BACKGROUND: Postoperative pancreatic fistula (POPF) is the major complication following pancreaticoduodenectomy (PD). We sought to develop and validate a risk prediction model for POPF after PD with the aim of determining personal risk probability and proposing a novel strategy for intraoperative placement and/or early-removal of prophylactic drainage. METHODS: Data from 993 patients undergoing PD from January 2012 to December 2016 were retrospectively analyzed. Patients were randomly assigned to either training cohort or validation cohort. A nomogram was formulated based on the results from multivariable regression model for prediction of POPF. Internal and external validation were carried out with calibration plot respectively. RESULTS: POPF occurred in 162 (16.3%) patients. The final pre-/intra-operative prediction model included alanine transaminase level [odds ratio (OR) 1.00, 95% confidence interval (CI): 1.00-1.00, P=0.023], combined portal-superior mesenteric vein resection (OR 0.22, 95% CI: 0.05-0.95, P=0.043), pancreatic duct diameter (OR 1.48, 95% CI: 1.11-1.96, P=0.007), intraoperative colloid infusion (OR 1.00, 95% CI: 1.00-1.00, P=0.001), pathology (OR 1.71, 95% CI: 1.09-2.66, P=0.018). The area under the curve (AUC) was 0.667 in the training cohort and 0.621 in the validation cohort. The final postoperative prediction model included pancreatic duct diameter (OR 1.58, 95% CI: 1.14-2.19, P=0.006), intraoperative colloid infusion (OR 2.52, 95% CI: 1.26-5.06, P=0.009), drainage fluid amylase on postoperative day 3 (POD3) (OR 4.70, 95% CI: 3.30-6.70, P<0.001), and neutrophil count on POD3 (OR 2.83, 95% CI: 1.63-4.93, P<0.001). The AUC was 0.809 in the training cohort and 0.797 in the validation cohort. Based on these variables, two nomogram prediction models were developed respectively. The calibration plot of the two models showed a good correlation between the expected risk and the actual risk in the low-risk range. Our risk-stratified strategy for drain management according to nomograms may be beneficial for 34.5% of patients. CONCLUSIONS: Our study formulated and validated two nomogram models for predicting POPF that performed particularly well in the low-risk range. This tool may allow surgeons to propose a risk stratified strategy for intraoperative drain placement and early drain removal, which may be beneficial for a substantial proportion of patients.

11.
Eur J Cancer ; 165: 58-70, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35219024

RESUMO

BACKGROUND: BRAF and MEK inhibitors significantly prolonged the progression-free survival of patients with BRAF mutant melanoma, but their long-term efficacy was limited by drug resistance. Our previous studies found that targeted inhibition of the mitogen-activated protein kinases (MAPK) pathway promotes the activation of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway in BRAF-mutant melanoma cells. Whether dual inhibition of MAPK and JAK2/STAT3 pathways can reverse drug resistance in melanoma remains unclear. METHODS: This study verified whether morusin could enhance the inhibitory effect of MAPK pathway inhibitors on BRAF mutant melanoma by inhibiting the feedback activation of STAT3 at the cellular and animal levels. RESULTS: We demonstrated that morusin could enhance the inhibitory effect of MAPK pathway inhibitors on BRAF mutant melanoma cells by inhibiting the feedback activation of the STAT3/SOX2 pathway. Moreover, our study showed morusin combined with MAPK pathway inhibitors specifically inhibited BRAF-mutant melanoma cells to a greater extent than wild-type cells. Our results also showed that the combination of morusin and BRAF inhibitors could jointly inhibit BRAF mutant melanoma in vivo. Finally, our experiment also revealed that the combination therapy of morusin and MAPK pathway inhibitors jointly inhibited drug-resistant melanoma in vitro and in vivo. CONCLUSION: Our results suggested that the combination of morusin and MAPK pathway inhibitors may be a more effective treatment strategy for BRAF-mutant melanoma than MAPK pathway inhibitors alone.


Assuntos
Melanoma , Proteínas Proto-Oncogênicas B-raf , Animais , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Retroalimentação , Flavonoides , Humanos , Sistema de Sinalização das MAP Quinases , Melanoma/tratamento farmacológico , Melanoma/genética , Melanoma/patologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Mutação , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Fator de Transcrição STAT3/metabolismo
12.
JAMA Netw Open ; 5(2): e2148721, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35171259

RESUMO

Importance: A higher incidence of pancreatic cancer has been reported in the Chinese population compared with the White population, but genetic differences are unknown to date. Large-sample germline testing for both familial and sporadic pancreatic cancers has been conducted predominantly in White populations, whereas similar studies in Chinese populations are limited. Objective: To assess the prevalence of germline sequence variations in patients with pancreatic diseases in China. Design, Setting, and Participants: This genetic association study was a case series that included genetic data from patients with pancreatic ductal adenocarcinoma (PDAC) or non-PDAC pancreatic diseases seen at The First Affiliated Hospital of Nanjing Medical University in Nanjing, China, between January 2006 and December 2017 (Nanjing cohort). Comparator group data were obtained for a US cohort from Johns Hopkins Hospital (JHH), a population from East Asia from the Exome Aggregation Consortium (ExAC) database, and the larger population from China from the ChinaMAP database. Data were updated and analyzed in July 2021. Main Outcomes and Measures: Next-generation sequencing technology was used to examine the prevalence of deleterious variations in 59 genes of the included Chinese patients with DNA extracted from peripheral blood samples. The Fisher exact test was used to assess differences among the frequencies of germline variations in the study patients vs the comparator groups. Results: A total of 1009 patients with PDAC (627 [62.1%] male; mean [SD] age, 62.8 [10.2] years) and 885 with non-PDAC diseases (477 [53.9%] male; mean [SD] age, 52.0 [15.9] years) from the Nanjing cohort were included for genetic analysis; all were Han Chinese individuals. Pathogenic variations were detected in 63 patients with PDAC (6.2%; 95% CI, 4.7%-7.7%). Variations in BRCA2 (odds ratio [OR], 3.2; 95% CI, 1.4-7.7; P = .008) and PALB2 (OR, 5.2; 95% CI, 1.6-17.0; P = .007) were significantly associated with pancreatic risk in the Nanjing cohort. Pathogenic variants of genes associated with homologous recombination DNA damage repair, including ATM, BRCA1/2, PALB2, BRIP1, FANCA, FANCC, RAD51D, and XRCC2, were found in 34 patients with PDAC (3.4%). No Ashkenazi Jewish-specific BRCA2 variation (p.Ser1982fs) was detected. The odds ratio of a SPINK1 variation in patients with PDAC was 3.2 (95% CI, 1.8-5.7; P < .001) in the Nanjing cohort compared with the ExAC cohort. Variations in the pancreatic secretory enzyme genes CPA1 and CPB1 were not detected in the Nanjing cohort. Conclusions and Relevance: In this genetic association study, sporadic pancreatic cancer was associated with pathogenic germline variations in a cohort from China. These findings provide insights into the genetic background of pancreatic cancer in the Han Chinese population with PDAC.


Assuntos
Povo Asiático/genética , Carcinoma/genética , Carcinoma/fisiopatologia , Mutação em Linhagem Germinativa , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/fisiopatologia , População Branca/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/epidemiologia , China/epidemiologia , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/epidemiologia , Prevalência , Análise de Sequência , Estados Unidos/epidemiologia , Adulto Jovem
13.
Ann Hepatol ; 27(1): 100552, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34614432

RESUMO

INTRODUCTION AND OBJECTIVES: Optimal treatment of hepatocellular carcinoma (HCC) involving portal vein tumor thrombus (PVTT) remains controversial. MATERIALS AND METHODS: A total of 627 HCC patients with PVTT after initial treatment with one of the following at Affiliated Tumor Hospital of Guangxi Medical University: liver resection (LR, n = 225), transarterial chemoembolization (TACE, n = 298) or sorafenib (n = 104) were recruited and randomly divided into the training cohort (n = 314) and internal validation cohort (n = 313). Survival analysis were repeated after stratifying patients by Cheng PVTT type. RESULTS: Resection led to significantly higher OS than the other two treatments among patients with type I or II PVTT. TACE worked significantly better than the other two treatments for patients with type III. All three treatments were associated with similar OS among patients with type IV. These findings were supported by the internal validation cohort. CONCLUSIONS: Our results suggest that the optimal treatment for HCC involving PVTT depends on the type of PVTT. LR may be more appropriate for type I or II PVTT; TACE, for type III Sorafenib may be more appropriate than invasive treatments for patients with type IV PVTT.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Hepatectomia/métodos , Neoplasias Hepáticas/terapia , Veia Porta , Sorafenibe/administração & dosagem , Trombose Venosa/etiologia , Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/diagnóstico , Feminino , Seguimentos , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Trombose Venosa/diagnóstico , Trombose Venosa/terapia
14.
Front Oncol ; 11: 656332, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33996579

RESUMO

OBJECTIVE: The aim of this study was to test the hypothesis that early oral feeding (EOF) is superior to early nasojejunal nutrition (ENN) after pylorus-preserving pancreaticoduodenectomy (PPPD) in terms of delayed gastric emptying (DGE). BACKGROUND: DGE is a common complication after PPPD. Although EOF after PPPD is recommended by several international guidelines, there is no randomized trial to support this recommendation. METHODS: From September 2016 to December 2017, a total of 120 patients undergoing PPPD were randomized into the ENN, EOF, or saline groups at a 1:1:1 ratio (40 patients in each group). The primary endpoint was the rate of clinically relevant DGE. Secondary endpoints included overall morbidity, postoperative pancreatic fistula, post-pancreatectomy hemorrhage, abdominal infection, length of hospital stay, reoperation rate, and in-hospital mortality. RESULTS: The baseline characteristics and operative parameters were comparable between the groups. The incidence of clinically relevant DGE varied significantly among the three groups (ENN, 17.5%; EOF, 10.0%; saline, 32.5%; p =0.038). The saline group had a higher clinically relevant DGE rate than the EOF group (p = 0.014). The saline group also had greater overall morbidities than the ENN and EOF groups (p = 0.041 and p = 0.006, respectively). There were no significant differences in other surgical complication rates or postoperative hospital stay. No mortality was observed in any of the groups. CONCLUSIONS: Nutritional support methods were not related to DGE after PPPD. EOF was feasible and safe after PPPD, and additional ENN should not be routinely administered to patients after PPPD. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT03150615.

15.
Langenbecks Arch Surg ; 406(3): 691-701, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33507403

RESUMO

PURPOSE: To introduce sub-adventitial divestment technique (SDT), a procedure to remove the tumor while preserving the artery during curative pancreatectomy. Peri-operative safety profile was also evaluated. METHODS: In a single center consecutive series of pancreatectomy for pancreatic cancer, the outcome of patients who had pancreatectomy with SDT was compared to standard pancreatic surgery. RESULTS: From June 2014 to June 2016, 72 patients had pancreatectomy with SDT and 235 had standard surgery. Tumor stage was T4 in all 72 (100%) tumors removed using SDT compared to four (2%) with standard pancreatectomy (p < 0.001). All 72 (100%) tumors in the SDT group were stage III compared to 24 (10%) in the standard surgery group (p < 0.001). Both groups had a high proportion of poorly differentiated tumors (52 (72%) and 163 (69%) respectively) and perineural tumor invasion (62 (86%) and 186 (79%) respectively). R1 (< 1 mm) was found in 24 (86%) of 28 tumors in the SDT group, and in 72 (60%) out of 120 standard pancreatectomy tumors (p = 0.01). Complications occurred in 29 (40%) of the SDT group and in 88 (37%) of the standard group. The in-hospital mortality was four (6%) in the SDT group and one (0.4%) in the standard group (p = 0.01), with a 90-day mortality of 5 (8%)/60 and 6 (3%)/209 (p = 0.07) respectively. CONCLUSIONS: The sub-adventitial divestment technique appeared to be an effective surgical technique to remove the tumor while preserving the artery. This approach warrants further validation in prospective studies.


Assuntos
Pancreatectomia , Neoplasias Pancreáticas , Artérias , Humanos , Neoplasias Pancreáticas/cirurgia , Estudos Prospectivos , Estudos Retrospectivos
16.
Sci Rep ; 11(1): 1522, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33452316

RESUMO

Modification of outer membrane proteins (OMPs) is the first line of Gram-negative bacteria defence against antimicrobials. Here we point to Proteus mirabilis OMPs and their role in antibiotic and phage resistance. Protein profiles of amikacin (AMKrsv), phage (Brsv) and amikacin/phage (AMK/Brsv) resistant variants of P. mirabilis were compared to that obtained for a wild strain. In resistant variants there were identified 14, 1, 5 overexpressed and 13, 5, 1 downregulated proteins for AMKrsv, Brsv and AMK/Brsv, respectively. Application of phages with amikacin led to reducing the number of up- and downregulated proteins compared to single antibiotic treatment. Proteins isolated in AMKrsv are involved in protein biosynthesis, transcription and signal transduction, which correspond to well-known mechanisms of bacteria resistance to aminoglycosides. In isolated OMPs several cytoplasmic proteins, important in antibiotic resistance, were identified, probably as a result of environmental stress, e.g. elongation factor Tu, asparaginyl-tRNA and aspartyl-tRNA synthetases. In Brsv there were identified: NusA and dynamin superfamily protein which could play a role in bacteriophage resistance. In the resistant variants proteins associated with resistance mechanisms occurring in biofilm, e.g. polyphosphate kinase, flagella basal body rod protein were detected. These results indicate proteins important in the development of P. mirabilis antibiofilm therapies.


Assuntos
Amicacina/farmacologia , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Proteus mirabilis/metabolismo , Amicacina/metabolismo , Antibacterianos/farmacologia , Infecções Bacterianas , Proteínas da Membrana Bacteriana Externa/efeitos dos fármacos , Proteínas da Membrana Bacteriana Externa/metabolismo , Bacteriófagos/patogenicidade , Bacteriófagos/fisiologia , Biofilmes/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Proteínas de Membrana/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Proteus mirabilis/efeitos dos fármacos , Proteus mirabilis/virologia
17.
Front Oncol ; 11: 832315, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35155218

RESUMO

PURPOSE: This study aims to integrate pancreatic cancer TCGA, GEO, and single-cell RNA-sequencing (scRNA-seq) datasets, and explore the potential prognostic markers and underlying mechanisms of the immune microenvironment of pancreatic cancer through bioinformatics methods, in vitro and in vivo assays. METHODS: Expression data and clinicopathological data of pancreatic cancer TCGA, GEO (GSE131050), single cell sequencing (PAAD_CRA001160) dataset were downloaded. We used R/Bioconductor edgeR for differential expression analysis. ClusterProfiler was utilized to perform GO enrichment analysis on differentially expressed genes. The online software CIBERSORT was used to reanalyze the mRNA expression data of pancreatic cancer. CellRanger, RunPCA, FindNeighbors, FindClusters, RunTSNE and RunUMAP were used to perform preprocessing, cell clustering and expression profile analysis on single-cell sequencing data sets. We analyzed intracellular pH with or without CA9 inhibitor SLC-0111. Indirect co-culture model of human pancreatic cancer cell lines and healthy individual-derived PBMCs were used to determine the effect of CA9-related Acidic Microenvironment on CD8+ T cells. RESULTS: The CIBERSORT analysis of TCGA pancreatic cancer transcriptome sequencing data showed that among the 22 immune microenvironment components, CD8+ T cell infiltration was significantly correlated with the prognosis of pancreatic cancer patients. The differential expression analysis of the TCGA data grouped by the level of CD8+ T cell infiltration indicates that the expression of carbonic anhydrase 9 (CA9) is the most significant, and the survival analysis suggests that CA9 is associated with the overall survival of pancreatic cancer. TCGA data and GEO data set GSE131050 expression correlation analysis suggests that CA9 and CD8 expression are closely related. Pancreatic cancer single-cell sequencing data set PAAD_CRA001160 analysis results show that CA9 is mainly expressed in pancreatic cancer cell clusters, and the expression of the cancer cell subgroup CA9 in the single-cell data set is correlated with CD8+ T cell infiltration. CONCLUSION: Pancreatic cancer cells may inhibit the infiltration of CD8+ T cells through CA9. Further exploration of its related mechanisms can be used to explore the immune escape pathway of pancreatic cancer and provides new perspectives immune targeted therapy.

18.
Surg Infect (Larchmt) ; 22(3): 299-304, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32697624

RESUMO

Background: Abdominal tuberculosis (TB) remains an issue as it masquerades as many malignant or benign abdominal conditions. Objective: To analyze the clinical and laboratory features of abdominal TB retrospectively and discuss its management. Methods: The data of patients with a histopathologic diagnosis of abdominal TB seen from January 1, 2008, to February 1, 2019 were collected in The First Affiliated Hospital of Nanjing Medical University. Nodal, visceral, peritoneal, and mixed TB cases were included while excluding other forms of extra-pulmonary TB (EPTB). Results: A total of 21 patients presented having a median age of 49 years (interquartile range 33-57 years) with 12 females and 9 males. Ten presented with abdominal pain, whereas four had abdominal pain and distention. Weight loss was present in five and type 2 diabetes mellitus (DM) in three. Every patient received contrast-enhanced computed tomography (CE-CT) with positive results in all the cases. Seven patients received endoscopic ultrasound-guided fine-needle aspiration cytology examination (EUS-FNAC) and five had results positive for TB. Pre-operative diagnosis of abdominal TB was possible in seven; however, the majority (n = 14) underwent exploratory laparotomy, and all obtained a definitive diagnosis of TB. No deaths occurred. Conclusions: Both CE-CT and EUS-FNAC can aid in the timely diagnosis. Laparotomy is an invasive but efficient tool for the final diagnosis of abdominal TB.


Assuntos
Diabetes Mellitus Tipo 2 , Tuberculose , Abdome , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Tuberculose/diagnóstico
19.
Cancer Med ; 9(24): 9632-9640, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33128354

RESUMO

Pancreatic cancer (PC) is one of the most malignant gastrointestinal tumors and the 5-year survival is only 9%. The expression of miRNAs in serum has been proved to be related to tumorigenesis and development of cancers. The miRNA targets and gene targets were predicted in microRNA.org, miRDB, TargetScan, and RNAInter. The expression data of STK31 (Serine/Threonine Kinase 31) and miRNAs generated from PC samples was from TCGA and the relationship of expression of STK31 and miR-543 was confirmed in PC samples from our center. Double luciferase reporter gene assay was used to demonstrate the direct binding between miR-543 and STK31. The effect of expression level of miRNAs on survival time was assessed by Kaplan-Meier curves. The Go Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of miR-543-related genes were performed. The results showed that miR-543 had a statistically significant correlation with the expression of STK31 and contained the direct binding site with STK31. The expression level of miR-543 may affect the survival of PC. The results of GO and KEGG pathway analysis showed that miR-543 might play a key role in Insulin signaling pathway. MiR-543 could be combined with STK31 and affect the expression of STK31. The expression of miR-543 could also predict the survival of patients with PC, which suggested that miR-543 might play an important role in PC. The GO and KEGG pathway analysis also displayed that miR-543 was involved in several other pathways of pancreas.


Assuntos
Biologia Computacional/métodos , MicroRNAs/metabolismo , Neoplasias Pancreáticas/metabolismo , Proteínas Serina-Treonina Quinases/biossíntese , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Bases de Dados Genéticas , Feminino , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Proteínas Serina-Treonina Quinases/metabolismo , Taxa de Sobrevida
20.
Biomed Pharmacother ; 125: 109972, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32036221

RESUMO

Ephrin-2 (EFNB2) is expressed at abnormally high levels in some neoplasms, such as squamous cell carcinoma of the head and neck and colorectal cancer. Its overexpression is associated with the malignant progression of tumors. However, the expression of EFNB2 in pancreatic ductal adenocarcinoma (PDAC) has not been thoroughly studied. EFNB2 expression was evaluated by quantitative real-time PCR, immunohistochemistry, and western blotting. Furthermore, the association between its expression levels and the clinicopathological features of PDAC patients was explored. To determine the underlying mechanisms of EFNB2, we transfected PDAC cells with small interfering RNA and performed in vitro and in vivo experiments. EFNB2 expression levels were significantly increased in cancer tissues and were associated with PDAC clinical stage and Ki67 expression. The down-regulation of EFNB2 inhibited cell proliferation by up-regulating p53/p21-mediated G0/G1 phase blockade. Knockdown of EFNB2 decreased the migration and invasion of PDAC cells by blocking epithelial-mesenchymal transition. These results suggested that EFNB2 may participate in the development of PDAC by promoting cell proliferation, migration, and invasion. Thus, EFNB2 is a potential target for the diagnosis and treatment of PDAC.


Assuntos
Adenocarcinoma/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Efrina-B2/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Quinases Ativadas por p21/metabolismo , Adenocarcinoma/genética , Carcinoma Ductal Pancreático/genética , Movimento Celular , Proliferação de Células , Efrina-B2/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Proteína Supressora de Tumor p53/genética , Quinases Ativadas por p21/genética
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