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The main mechanism of hyaluronidase 1(HYAL-1) in the development of postoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD) was unknown. In this study, a comprehensive inventory of pre-, intra-, and postoperative clinical and biological data of two cohorts (62 pancreatic cancer [PCa] and 111 pancreatic ductal adenocarcinoma [PDAC]) which could induce POPF were retrospectively analyzed. Then, a total of 7644 genes correlated with HYAL-1 was predicted in PDAC tissues and the enriched pathway, kinase targets and biological process of those correlated genes were evaluated. Finally, a mouse pancreatic fistula (PF) model was first built and in vitro studies were performed to investigate the effects of HYAL-1 on PF progression. Our data indicated that preoperative serum HYAL-1 level, pancreatic fibrosis score, and pancreatic duct size were valuable factors for detecting POPF of Grade B and C. The serum HYAL-1 level of 2.07 mg/ml and pancreatic fibrosis score of 2.5 were proposed as the cutoff values for indicating POPF. The bioinformatic analysis and in vitro and in vivo studies demonstrated that HYAL-1 facilitates pancreatic acinar cell autophagy via the dephosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK) and signal transducers and activators of transcription 3 (STAT3) signaling pathways, which exacerbate pancreatic secretion and inflammation. In summary, the preoperative serum HYAL-1 was a significant predictor for POPF in patients who underwent PD. Tumor-induced HYAL-1 is one of core risk in accelerating PF and then promoting pancreatic secretion and acute inflammation response through the AMPK and STAT3-induced autophagy.
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Autofagia/fisiología , Hialuronoglucosaminidasa/sangre , Fístula Pancreática/patología , Pancreaticoduodenectomía , Adulto , Anciano , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/cirugía , Femenino , Humanos , Intestinos/patología , Masculino , Persona de Mediana Edad , Páncreas/patología , Fístula Pancreática/diagnóstico , Fístula Pancreática/cirugía , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Pancreaticoduodenectomía/métodos , Estudios Retrospectivos , Factores de Riesgo , Neoplasias PancreáticasRESUMEN
BACKGROUND Acute pancreatitis (AP) is a common digestive disorder. Its management depends on the severity; therefore, it is essential to stratify AP patients early. D-dimer, a coagulation indicator, appears to be associated with the pathogenesis of AP. The aim of this study was to evaluate D-dimer as an early predictor of the severity of AP. MATERIAL AND METHODS This was a single-center retrospective study of 1260 patients diagnosed based on the revised Atlanta classification. Only patients hospitalized within 24 h of onset were included, and 334 patients were enrolled. Blood was collected at admission and 3 times within 48 h of admission. Values at admission and average of the 3 blood samples were evaluated by univariate and multivariate analyses. Furthermore, the area under the receiver-operating characteristic curve (AUC) was used to estimate the validity of the predictor and to define optimal cut-off points for prediction. RESULTS We found that 53.3% of the patients had mild AP (MAP), 24.3% had moderately severe AP (MSAP), and 22.4% had severe AP (SAP). D-dimer at admission and the average D-dimer could distinguish MAP patients from MSAP and SAP patients, with cut-off values of 3.355 mg/L and 4.868 mg/L, respectively. No difference in the parameters at admission was observed in multivariate analysis in distinguishing SAP from MSAP, but the average D-dimer level was significantly different with a cut-off value of 7.268 mg/L by comparing Ranson score, APACHE II score, and D-dimer level. CONCLUSIONS The average value of D-dimer levels could be used as a predictor of severity of AP. In general, patients with an average D-dimer level <4.868 could be diagnosed with MAP, >7.268 would develop into SAP, and between 4.868 and 7.268 would be MSAP.
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Productos de Degradación de Fibrina-Fibrinógeno/análisis , Pancreatitis/metabolismo , APACHE , Enfermedad Aguda , Adulto , China , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Pancreatitis/clasificación , Plasma/química , Valor Predictivo de las Pruebas , Pronóstico , Curva ROC , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Percutaneous vertebroplasy (PVP) might lead to significant radiation exposure to patients, operators, and operating room personnel. Therefore, radiaton exposure is a concern. The aim of this study was to present a remote control cement delivery device and study whether it can reduce dose exposue to operators. METHODS: After meticulous preoperative preparation, a series of 40 osteoporosis patients were treated with unilateral approach PVP using the new cement delivery divice. We compared levels of fluoroscopic exposure to operator standing on different places during operation. group A: operator stood about 4 meters away from X-ray tube behind the lead sheet. group B: operator stood adjacent to patient as using conventional manual cement delivery device. RESULTS: During whole operation process, radiation dose to the operator (group A) was 0.10 ± 0.03 (0.07-0.15) µSv, group B was 12.09 ± 4.67 (10-20) µSv. a difference that was found to be statistically significant (P < 0.001) between group A and group B. CONCLUSION: New cement delivery device plus meticulous preoperative preparation can significantly decrease radiation dose to operators.
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Cementos para Huesos/uso terapéutico , Sistemas de Liberación de Medicamentos/instrumentación , Exposición Profesional/prevención & control , Dosis de Radiación , Radiografía Intervencional , Vertebroplastia/instrumentación , Anciano , Anciano de 80 o más Años , Diseño de Equipo , Fluoroscopía , Humanos , Inyecciones , Masculino , Exposición Profesional/efectos adversos , Salud Laboral , Traumatismos Ocupacionales/prevención & control , Traumatismos por Radiación/prevención & control , Protección Radiológica , Radiografía Intervencional/efectos adversos , Factores de Riesgo , Dosimetría Termoluminiscente , Vertebroplastia/métodosRESUMEN
In order to understand the composition and accumulation characteristics of phthalates esters (PAEs) in agricultural soils in Gansu province, a total of 41 soil samples from four agricultural soils in Gansu province were collected, and the content of six PAEs compounds was analyzed using a gas chromatography-single quadrupole mass spectrometer (GC-MS). The results showed that the average value of PAEs compounds in agricultural soils in Gansu province was 432.4 µg·kg-1. The detection rates of DMP, DEP, DnBP, DEHP, and DNOP in the soil were 100%, and BBP was not detected. The order of the average value of PAEs content in the four agricultural soils in Gansu province was:greenhouse>farmland (open field)>forest>grassland. The exceeding rates of dibutyl phthalate (DnBP), dimethyl phthalate (DMP), and dimethyl phthalate (DEP) were 94%, 28%, and 27%, and the remaining three did not exceed the standard. The composition of PAEs in different agricultural soils was different due to their different sources. DEHP and DnBP components in the six different PAEs monomers accounted for a higher proportion and were the main pollutants of PAEs in agricultural soils in Gansu province. In this study, the contents of soil PAEs and DEHP were significantly positively correlated with the residual amount of mulch film in the farmland (P<0.05). In general, the content of soil PAEs in the Hexi area of Gansu province was significantly higher than that in the Longdong area.
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Dietilhexil Ftalato , Contaminantes Ambientales , Ácidos Ftálicos , Contaminantes del Suelo , 2,4-Dinitrofenol/análogos & derivados , China , Dibutil Ftalato , Ésteres , Suelo , Contaminantes del Suelo/análisisRESUMEN
A high platform can fix rats without restriction and completely expose the acupoints on the back during acupuncture manipulation. This article describes methods for the fabrication of the high platform, establishes a rat model of asthma and measures changes in respiratory function using a noninvasive and real-time whole-body plethysmography (WBP) system.
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Terapia por Acupuntura , Asma/terapia , Puntos de Acupuntura , Animales , Asma/fisiopatología , Modelos Animales de Enfermedad , Humanos , Masculino , Nebulizadores y Vaporizadores , Agujas , Pletismografía Total , Ratas , RespiraciónRESUMEN
OBJECTIVES: This study aimed to assess the need of surgical necrosectomy after percutaneous catheter drainage (PCD) for infected necrotizing pancreatitis. METHODS: The clinical data of documented/suspected patients who were treated with a step-up approach were extracted and analyzed. RESULTS: Of the 329 patients enrolled, the initial PCD was performed at 12 (interquartile range, 9-15) days since onset and 35.3% were cured by PCD alone. In the pre-PCD model, mean computed tomographic (CT) density of necrotic fluid collection (NFC; P < 0.001), and multiple-organ failure (MOF; P < 0.001) within 24 hours before the initial PCD were independent risk factors, and a combination of the previously mentioned 2 factors produced an area under the curve of 0.775. In the post-PCD model, mean CT density of NFC (P = 0.041), MOF (P = 0.002), and serum procalcitonin level (P = 0.035) 3 days after the initial PCD were independent risk factors, and a combination of these previously mentioned factors produced an area under the curve of 0.642. CONCLUSIONS: Both mean CT density of NFC and MOF are independent pre- and post-PCD risk factors for the need of necrosectomy after PCD. Post-PCD serum procalcitonin level might be a respondent factor that is correlated with the necessity of necrosectomy.
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Drenaje/métodos , Infecciones/cirugía , Pancreatitis Aguda Necrotizante/cirugía , Adulto , Líquidos Corporales/química , Catéteres , Femenino , Humanos , Infecciones/etiología , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/complicaciones , Insuficiencia Multiorgánica/diagnóstico por imagen , Necrosis , Pancreatitis Aguda Necrotizante/complicaciones , Factores de Riesgo , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Chronic pancreatitis (CP) is described as a progressive fibro-inflammatory disorder of the exocrine disease, which eventually leads to damage of the gland. Excessive activation of pancreatic stellate cells (PSCs) is a critical participant in the initiation of CP. Autophagy is involved in multiple degeneration and inflammation in acute pancreatitis and CP. In our study, we report that retinoblastoma coiled coil protein 1 (RB1CC1) expression and the autophagic level are elevated in activated PSCs. RB1CC1 is positively correlated with pancreatic fibrogenesis in tissues and plasma of CP patients. Knockdown of RB1CC1 restrains alpha smooth muscle actin (α-SMA) and collagen expressions, and autophagy in activated PSCs in vitro. Furthermore, we show that RB1CC1 induces PSC activation via binding to ULK1 promoter and the direct interaction with ULK1 protein. These suppress ULK1 expression and its kinase activity. In mice, knockdown of RB1CC1 blocks autophagy and then inhibits the pancreatic duct ligation-induced pancreatic fibrosis. Consequently, our study highlights that RB1CC1-mediated autophagy is a key event for the activation of PSCs. Inhibition of RB1CC1 alleviates autophagy, which plays a critical role in anti-fibrotic activation in PSCs and CP progression. RB1CC1 could be a novel strategy for the treatment of pancreatic fibrosis.
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Autofagia/fisiología , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Páncreas/metabolismo , Páncreas/patología , Células Estrelladas Pancreáticas/citología , Células Estrelladas Pancreáticas/metabolismo , Pancreatitis Crónica/metabolismo , Pancreatitis Crónica/patología , Proteínas Tirosina Quinasas/metabolismo , Animales , Autofagia/genética , Proteínas Relacionadas con la Autofagia , Western Blotting , Células Cultivadas , Ensayo de Cambio de Movilidad Electroforética , Fibrosis/metabolismo , Fibrosis/patología , Técnica del Anticuerpo Fluorescente , Humanos , Inmunohistoquímica , Péptidos y Proteínas de Señalización Intracelular/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Pancreatitis Crónica/genética , Proteínas Tirosina Quinasas/genéticaRESUMEN
Recently, pancreatic ductal adenocarcinoma (PDAC) has emerged as one of the most aggressive malignant tumors with the worst prognosis. Previous studies have demonstrated that long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is increased in pancreatic cancer and is identified as a diagnostic biomarker. Nonetheless, the molecular mechanism of elevated MALAT1 levels and tumor aggressiveness remains unknown. In this study, MALAT1 was found to be highly expressed in PDAC tissues, and elevated expression was associated with poorer prognoses. In addition, MALAT1 was positively linearly correlated with the expression of LC3B mRNA. Furthermore, several molecules involved in cellular autophagic flux were modulated following the downregulation of MALAT1, including LC3, P62, and LAMP-2. Mechanistically, we found that MALAT1 interacted with RNA binding protein HuR, and silencing of MALAT1 greatly enhanced the posttranscriptional regulation of TIA-1 and had further effects on inhibiting autophagy. MALAT1 was speculated to regulate tumorigenesis via HuR-TIA-1-mediated autophagic activation. Hence, we investigated the biological properties of MALAT1 in terms of tumor proliferation and metastasis by promoting autophagy in vitro In brief, these data demonstrate that MALAT1 could facilitate the advanced progression of tumors in vivo Our study highlights the new roles of MALAT1 on protumorigenic functioning and anticancer therapy via activating autophagy in pancreatic cancer. Mol Cancer Ther; 15(9); 2232-43. ©2016 AACR.
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Autofagia/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , ARN Largo no Codificante/genética , Animales , Línea Celular Tumoral , Proliferación Celular , Modelos Animales de Enfermedad , Proteína 1 Similar a ELAV/genética , Femenino , Silenciador del Gen , Humanos , Ratones , Metástasis de la Neoplasia , Neoplasias Pancreáticas/mortalidad , Proteínas de Unión a Poli(A)/genética , Pronóstico , Interferencia de ARN , Antígeno Intracelular 1 de las Células T , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Long intergenic non-protein coding RNA, p53 induced transcript (Linc-pint) is a long noncoding RNA (lncRNA) that regulates tumor cell viability and proliferation. We used qRT-PCR and RNA FISH analysis to evaluate Linc-pint levels in the plasma and tumor tissues of pancreatic cancer (PCa) patients. Our data demonstrate that Linc-pint expression is lower in plasma samples from PCa patients than from healthy individuals, and indicate that plasma Linc-pint levels are more sensitive than CA19-9 for detecting PCa. Our data also show that Linc-pint levels are lower in PCa tumors than in adjacent tissues, carcinoma of the ampulla of Vater (CAV) and cholangiocarcinoma (CCA), and suggest that Linc-pint could be used for distinguishing the cause of malignant obstructive jaundice. Low plasma Linc-pint levels correlate with tumor recurrence, while low tumor Linc-pint levels correlate with poor prognosis for PCa patients after pancreatectomy. These results thus indicate that low plasma Linc-pint expression could serve as a minimally invasive biomarker for early PCa detection, and that low Linc-pint levels in PCa tumors could be used for predicting patient prognosis.
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Biomarcadores de Tumor/análisis , Neoplasias Pancreáticas/diagnóstico , ARN Largo no Codificante/análisis , Adulto , Anciano , Antígeno CA-19-9/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Pronóstico , ARN Largo no Codificante/sangreRESUMEN
BACKGROUND: Post traumatic osteonecrosis of a vertebral body occurring in a delayed fashion was first described by the German doctor Kümmell in 1895. Several studies have reported percutaneous vertebroplasty (PVP), or percutaneous kyphoplasty (PKP) for Kümmell's disease achieves good outcomes. However, it is unknown whether a technique is superior for the treatment of this disease. The objective of the study is to compare the efficacy of PVP and PKP for the treatment of Kümmell's disease. MATERIALS AND METHODS: A retrospective review was conducted for 73 patients with Kümmell's disease. PVP was performed in 38 patients and PKP in 35 patients. Visual analogue score (VAS) was used to evaluate pain. The anterior vertebral height was measured. The operative time, the incidence of cement leakage and the costs were recorded. RESULTS: In both PVP group and PKP group, the VAS and anterior vertebral height significantly improved at 1-day postoperatively (P < 0.05), and the improvement sustained at the final followup (P > 0.05). Between the PVP and PKP groups, there were no significant differences in VAS and the anterior vertebral height at 1-day postoperatively and at the final followup (P > 0.05). The operating time and expense in the PKP group were higher than the PVP group (P < 0.001). Cement leakages in the PKP group were fewer than PVP group (P < 0.05). CONCLUSIONS: PVP is a faster, less expensive option that still provides a comparable pain relief and restoration of vertebral height to PKP for the treatment of Kümmell's disease. PKP has a significant advantage over PVP in term of the fewer cement leakages.
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One of the most important theories of the traditional Chinese medicine is the exterior-interior relationship between the lung and the large intestine; so far, little direct experimental evidence has been reported to support such relationship. Here we for the first time investigated the mutual interactions between the lung and the large intestine by examining the relevancies between the pulmonary functions and the rectal resting pressure in the rat models of asthma and constipation. We also evaluated the effects of the lung homogenate and the large intestine homogenate on the isolated large intestine muscle strip and the isolated tracheal spiral, respectively. Our results showed that the pulmonary resistance and pulmonary compliance were closely related to the rectal resting pressure in the asthmatic rat model, while the rectal resting pressure was much correlated with the pulmonary resistance in the rat model of constipation. Moreover, it was shown that the lung homogenate could specifically contract the isolated large intestine muscle strip. Overall, this study provided new lines of evidence for the theory and highlighted the potential application in the treatment of the corresponding diseases.
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The aim of this study was to investigate the treatment of Kümmell's disease with neurological deficits and to determine whether intravertebral clefts are a pathognomonic sign of Kümmell's disease. A total of 17 patients who had initially been diagnosed with Kümmell's disease were admitted, one patient was excluded from this study. Posterior decompression and vertebroplasty for the affected vertebrae were conducted. Pedicle screw fixation and posterolateral bone grafts were performed one level above and one level below the affected vertebrae. Vertebral tissue was extracted for histopathological examination. The mean time of follow-up was 22 months (range, 18 to 42 months). The anterior and middle vertebral heights were measured on standing lateral radiographs prior to surgery, one day postoperatively and at final follow-up. The Cobb angle, the visual analog scale (VAS) and the Frankel classification were used to evaluate the effects of the surgery. The VAS, anterior and middle vertebral heights and the Cobb angle were improved significantly one day postoperatively and at the final follow-up compared with the preoperative examinations (P<0.05). No significant differences were observed between the one-day postoperative results and those at final follow-up (P>0.05). The neurological function of all patients was improved by at least one Frankel grade. All patients in this study exhibited intravertebral clefts, and postoperative pathology revealed bone necrosis. One patient (not included in this study) showed an intravertebral cleft, but the pathology report indicated a non-Hodgkin's lymphoma. The intravertebral cleft sign is not pathognomonic of Kümmell's disease. Posterior decompression with short-segment fixation and fusion combined with vertebroplasty is an effective treatment for Kümmell's disease with neurological deficits.
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OBJECTIVE: To investigate the influence of continuous high-volume hemofiltration (CHVHF) on interleukin 1 receptor-associated kinase-4 (IRAK-4) and tumor necrosis factor-alpha (TNF-alpha) levels in patients with severe acute pancreatitis (SAP). METHODS: Forty-one patients with SAP were randomly divided into two groups to receive treatment with CHVHF plus conventional therapy (21 patients) and conventional therapy only (20 patients). Venous blood samples were taken before and 12, 24, and 72 h after the treatment for evaluation of APACHE II scores. The mRNA and protein levels of IRAK-4 in the monocytes were determined by real-time PCR and Western blotting, respectively, and serum TNF-alpha levels was detected using enzyme-linked immunosorbent assay (ELISA). RESULTS: Among the 21 patients receiving CHVHF, 18 survived and 3 died, and in the conventional therapy group, death occurred in 5 cases. In the surviving patients of CHVHF group, the APACHE II scores, IRAK-4 mRNA and protein levels and TNF-alpha levels were all significantly lowered after the treatment, and these indices were also significantly lower than those in the conventional group after treatment (P<0.05). CONCLUSION: CHVHF is effective in reducing monocyte IRAK-4 levels and serum TNF-alpha level in SPA patients, and thus alleviates the symptoms and improves the prognosis of SAP, possibly by reducing the level of the activators that induce monocyte activation via the Toll-like receptor.