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1.
J Investig Med ; 71(7): 782-790, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37477004

ABSTRACT

Prediction of prognosis after radical resection of gastric cancer has not been well established. Therefore, we aimed to establish a prognostic model based on a new score system of patients with gastric cancer. A total of 1235 patients who underwent curative gastrectomy at our hospital from October 2015 to April 2017 were included in this study. Univariate and multivariate analyses were used to screen for prognostic risk factors. Construction of the nomogram was based on Cox proportional hazard regression models. The construction of the new score models was analyzed by the receiver operating characteristic curve (ROC curve), calibration curve, and decision curve. Multivariate analysis showed that tumor size, T, N, carcinoembryonic antigen, CA125, and CA19-9 were independent prognostic factors. The new score model had a greater AUC (The area under the ROC curve) than other systems, and the C-index of the nomogram was highly reliable for evaluating the survival of patients with gastric cancer. Based on the tumor markers and other clinical indicators, we developed a precise model to predict the prognosis of patients with gastric cancer after radical surgery. This score system can be helpful to both surgeons and patients.

2.
World J Gastrointest Oncol ; 15(4): 665-676, 2023 Apr 15.
Article in English | MEDLINE | ID: mdl-37123061

ABSTRACT

BACKGROUND: For the prognosis of patients with early gastric cancer (EGC), lymph node metastasis (LNM) plays a crucial role. A thorough and precise evaluation of the patient for LNM is now required. AIM: To determine the factors influencing LNM and to construct a prediction model of LNM for EGC patients. METHODS: Clinical information and pathology data of 2217 EGC patients downloaded from the Surveillance, Epidemiology, and End Results database were collected and analyzed. Based on a 7:3 ratio, 1550 people were categorized into training sets and 667 people were assigned to testing sets, randomly. Based on the factors influencing LNM determined by the training sets, the nomogram was drawn and verified. RESULTS: Based on multivariate analysis, age at diagnosis, histology type, grade, T-stage, and size were risk factors of LNM for EGC. Besides, nomogram was drawn to predict the risk of LNM for EGC patients. Among the categorical variables, the effect of grade (well, moderate, and poor) was the most significant prognosis factor. For training sets and testing sets, respectively, area under the receiver-operating characteristic curve of nomograms were 0.751 [95% confidence interval (CI): 0.721-0.782] and 0.786 (95%CI: 0.742-0.830). In addition, the calibration curves showed that the prediction model of LNM had good consistency. CONCLUSION: Age at diagnosis, histology type, grade, T-stage, and tumor size were independent variables for LNM in EGC. Based on the above risk factors, prediction model may offer some guiding implications for the choice of subsequent therapeutic approaches for EGC.

3.
World J Gastrointest Surg ; 15(3): 430-439, 2023 Mar 27.
Article in English | MEDLINE | ID: mdl-37032799

ABSTRACT

BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors. After resection, one of the major problems is its peritoneal dissemination and recurrence. Some free cancer cells may still exist after resection. In addition, the surgery itself may lead to the dissemination of tumor cells. Therefore, it is necessary to remove residual tumor cells. Recently, some researchers found that extensive intraoperative peritoneal lavage (EIPL) plus intraperitoneal chemotherapy can improve the prognosis of patients and eradicate peritoneal free cancer for GC patients. However, few studies explored the safety and long-term outcome of EIPL after curative gastrectomy. AIM: To evaluate the efficacy and long-term outcome of advanced GC patients treated with EIPL. METHODS: According to the inclusion and exclusion criteria, a total of 150 patients with advanced GC were enrolled in this study. The patients were randomly allocated to two groups. All patients received laparotomy. For the non-EIPL group, peritoneal lavage was washed using no more than 3 L of warm saline. In the EIPL group, patients received 10 L or more of saline (1 L at a time) before the closure of the abdomen. The surviving rate analysis was compared by the Kaplan-Meier method. The prognostic factors were carried out using the Cox appropriate hazard pattern. RESULTS: The basic information in the EIPL group and the non-EIPL group had no significant difference. The median follow-up time was 30 mo (range: 0-45 mo). The 1- and 3-year overall survival (OS) rates were 71.0% and 26.5%, respectively. The symptoms of ileus and abdominal abscess appeared more frequently in the non-EIPL group (P < 0.05). For the OS of patients, the EIPL, Borrmann classification, tumor size, N stage, T stage and vascular invasion were significant indicators. Then multivariate analysis revealed that EIPL, tumor size, vascular invasion, N stage and T stage were independent prognostic factors. The prognosis of the EIPL group was better than the non-EIPL group (P < 0.001). The 3-year survival rate of the EIPL group (38.4%) was higher than the non-EIPL group (21.7%). For the recurrence-free survival (RFS) of patients, the risk factor of RFS included EIPL, N stage, vascular invasion, type of surgery, tumor location, Borrmann classification, and tumor size. EIPL and tumor size were independent risk factors. The RFS curve of the EIPL group was better than the non-EIPL group (P = 0.004), and the recurrence rate of the EIPL group (24.7%) was lower than the non-EIPL group (46.4%). The overall recurrence rate and peritoneum recurrence rate in the EIPL group was lower than the non-EIPL group (P < 0.05). CONCLUSION: EIPL can reduce the possibility of perioperative complications including ileus and abdominal abscess. In addition, the overall survival curve and RFS curve were better in the EIPL group.

4.
Virus Res ; 331: 199111, 2023 07 02.
Article in English | MEDLINE | ID: mdl-37062496

ABSTRACT

Pseudorabies (PR) and classical swine fever (CSF) are economically important infectious diseases in pigs. Most pig farms in China are vaccinated against these two diseases. Gene-deleted pseudorabies virus (PRV) can be used to develop promising and economical multivalent live attenuated viral vector vaccines. It has been reported that recombinant PRV can express a truncated E2 protein (1-338 aa), but it has not been reported that recombinant PRV can express a full-length E2 protein. We constructed nine groups of E2 proteins with different expression forms and found that the E2 protein could be expressed in vitro only when the transmembrane region of E2 was removed and the signal peptide was added. Analysis of the transmembrane region of E2 revealed that the high hydrophobicity of the E2 transmembrane region was the main reason for its inability to express. By mutating an amino acid to reduce the hydrophobicity of the transmembrane region, it was found that the full-length mutant of E2 (E2FL-muta3 or E2FL-muta4) could be expressed. The expressed full-length mutant E2 could also localize to the cell membrane. Mice immunized with a PRV vector vaccine expressing E2FL-muta3 or E2FL-muta4 developed specific cellular immunity to the E2 protein and stimulated higher levels of E2 antibody than mice immunized with a PRV vector expressing truncated E2. After immunizing the rabbits, the lethal challenge by PRV-ZJ2013 and the febrile response elicited by CSFV were simultaneously prevented. These results suggest that rPRV-dTK/gE-E2FL-muta4 is a promising bivalent vaccine against CSFV and PRV infections.


Subject(s)
Classical Swine Fever Virus , Classical Swine Fever , Herpesvirus 1, Suid , Pseudorabies , Swine Diseases , Viral Vaccines , Animals , Swine , Mice , Rabbits , Herpesvirus 1, Suid/genetics , Classical Swine Fever Virus/genetics , Amino Acids/genetics , Viral Vaccines/genetics , Antibodies, Viral , Immunization , Pseudorabies/prevention & control , Mutation , Viral Envelope Proteins/genetics
5.
World J Gastrointest Surg ; 15(1): 49-59, 2023 Jan 27.
Article in English | MEDLINE | ID: mdl-36741063

ABSTRACT

BACKGROUND: Nearly 66% of occurrences of gastric cancer (GC), which has the second-highest death rate of all cancers, arise in developing countries. In several cancers, the predictive significance of inflammatory markers has been established. AIM: To identify clinical characteristics and develop a specific nomogram to determine overall survival for GC patients. METHODS: Nine hundred and four GC patients treated at the First Affiliated Hospital of Anhui Medical University between January 2010 and January 2013 were recruited. Prognostic risk variables were screened for Cox analysis. The C index, receiver operator characteristic (ROC) curve, and decision curve analysis were used to evaluate the nomogram. RESULTS: Tumor node metastasis stage, carcinoembryonic antigen, systemic immune-inflammation index, and age were identified as independent predictive variables by multivariate analysis. Systemic immune-inflammation index value was superior to that of other inflammatory indicators. The ROC indicated the nomogram had a higher area under the curve than other factors, and its C-index for assessing the validation and training groups of GC patients was extremely reliable. CONCLUSION: We created a novel nomogram to forecast the prognosis of GC patients following curative gastrectomy based on blood markers and other characteristics. Both surgeons and patients can benefit significantly from this new scoring system.

6.
Antiviral Res ; 211: 105548, 2023 03.
Article in English | MEDLINE | ID: mdl-36702445

ABSTRACT

Pseudorabies (PR) and classical swine fever (CSF) are economically important infectious diseases of pigs. Most pig farms in China are immunized against these two diseases. Here, we describe a stabilized E2 protein as an immunogen inserted into the PRV genome as a bivalent live virus-vectored vaccine. The E2 protein has 48 variant sites, there are 2-5 candidate amino acids per variant site, and the relative energy contribution of each amino acid to E2 energy was calculated. Combined substitutions of amino acids at the neighbor variant site (neighbor substitution) were performed to obtain the E2 protein sequence with the lowest energy (stabilized E2). Multiple amino acid substitutions at 48 variant sites were performed, and the results were consistent with neighbor substitutions. The stabilized E2 sequence was obtained, and its energy decreased by 22 Rosetta Energy Units (REUs) compared with the original sequence. After the recombinant PRV expressing stabilized E2 of CSFV was constructed, the secretion efficiency of stabilized E2 was increased by 2.97 times, and the thermal stability was increased by 10.5 times. Immunization of mice resulted in a 2-fold increase in antibody production, and a balanced antibody level against subtype 1.1 and subtype 2.1d E2 was achieved. In rabbits immunized, the lethal challenge of PRV-ZJ and the fever response induced by CSFV could be prevented simultaneously. These findings suggest that rPRV-muta/287aaE2 is a promising bivalent vaccine against CSFV and PRV infections.


Subject(s)
Classical Swine Fever Virus , Classical Swine Fever , Herpesvirus 1, Suid , Pseudorabies , Viral Vaccines , Rabbits , Animals , Swine , Mice , Classical Swine Fever Virus/genetics , Herpesvirus 1, Suid/genetics , Pseudorabies/prevention & control , Amino Acids , Viral Envelope Proteins/genetics , Antibodies, Viral
7.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1003956

ABSTRACT

【Objective】 To develop a mobile software application named " Component Assistant" and test for its performance in practical work, so as to address the difficulties and problems encountered during the management process of blood component preparation, such as communication and coordination in the workflow, personnel scheduling and workload arrangements. 【Methods】 The software was developed based on the daily work requirements and processes using Java language, and foreground-background separation technologies were employed to provide secure and reliable data support. 【Results】 The results of practical work verification showed that through this software, component preparation managers were able to real-time monitor blood collection situations, blood transfusion details, manage inventory levels, and summarize and review the details of the preparation process. Comparison of the usage sequence of this software, the average amount of blood prepared of employees has increased(198 bloodbag, /M), the workload of employees has increased(3.5, /M) and the rest time has been shortened(1 h, /M). 【Conclusion】 The innovation of this software lies in providing effective data support for matching the workload and personnel in component preparation operations, meeting the needs of blood component preparation management, and greatly improving work efficiency in this field.

8.
World J Diabetes ; 14(12): 1824-1838, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-38222783

ABSTRACT

BACKGROUND: Fibroblast growth factor 21 (FGF21), primarily secreted by the pancreas, liver, and adipose tissues, plays a pivotal role in regulating glucose and lipid metabolism. Acute pancreatitis (AP) is a common inflammatory disease with specific clinical manifestations. Many patients with diabetes present with concurrent inflammatory symptoms. Diabetes exacerbates intestinal permeability and intestinal inflammation, thus leading to the progression to AP. Our previous study indicated that FGF21 significantly attenuated susceptibility to AP in mice. AIM: To investigate the potential protective role of FGF21 against AP in diabetic mice. METHODS: In the present study, a mouse model of AP was established in diabetic (db)/db diabetic mice through ceruletide injections. Thereafter, the protective effects of recombinant FGF21 protein against AP were evaluated, with an emphasis on examining serum amylase (AMS) levels and pancreatic and intestinal inflammatory cytokines [interleukin (IL)-6, tumor necrosis factor-alpha (TNF-), and intestinal IL-1ß]. Additionally, the impact of this treatment on the histopathologic changes of the pancreas and small intestinal was examined to elucidate the role of FGF21 in diabetic mice with AP. An antibiotic (Abx) cocktail was administered in combination with FGF21 therapy to investigate whether the effect of FGF21 on AP in diabetic mice with AP was mediated through the modulation of the gut microbiota. Subsequently, the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt), a bioinformatics software package, was used to predict different pathways between the groups and to explore the potential mechanisms by which the gut microbiota influenced the protective effect of FGF21. RESULTS: The results indicated that FGF21 notably diminished the levels of serum AMS (944.5 ± 15.9 vs 1732 ± 83.9, P < 0.01) and inflammatory factors including IL-6 (0.2400 ± 0.55 vs 1.233 ± 0.053, P < 0.01), TNF- (0.7067 ± 0.22 vs 1.433 ± 0.051, P < 0.01), and IL-1ß (1.377 ± 0.069 vs 0.3328 ± 0.02542, P < 0.01) in diabetic mice with AP. Moreover, notable signs of recovery were observed in the pancreatic structure of the mice. The histologic evidence of inflammation in the small intestine, including edema and villous damage, was significantly alleviated. FGF21 also significantly altered the composition of the gut microbiota, reestablishing the Bacteroidetes/Firmicutes ratio. Upon treatment with an Abx cocktail to deplete the gut microbiota, the FGF21 + Abx group showed lower levels of serum AMS (0.9328 ± 0.075 vs 0.2249 ± 0.023, P < 0.01) and inflammatory factors (1.083 ± 0.12 vs 0.2799 ± 0.032, p < 0.01) than the FGF21 group. Furthermore, the FGF21 + Abx group exhibited diminished injury to the pancreatic and small intestinal tissues, accompanied by a significant decrease in blood glucose levels (17.50 ± 1.1 vs 9.817 ± 0.69 mmol/L, P < 0.001). These findings underscored the superior protective effects of the combination therapy involving an Abx cocktail with FGF21 over the FGF21 treatment alone in diabetic mice with AP. The gut microbiota composition across different groups was further characterized, and a differential expression analysis of gene functions was undertaken using the PICRUSt2 prediction method. These findings suggested that FGF21 could potentially confer therapeutic effects on diabetic mice with AP by modulating the sulfate reduction I pathway and the superpathway of n-acetylceramide degradation in the gut microbiota. CONCLUSION: This study reveals the potential of FGF21 in improving pancreatic and intestinal damage recovery, reducing blood glucose levels, and reshaping gut microbiota composition in diabetic mice with AP. Notably, the protective effects of FGF21 are augmented when combined with the Abx cocktail.

9.
Vet Immunol Immunopathol ; 253: 110501, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36332427

ABSTRACT

Fowl typhoid is an important disease of chickens and turkeys, which is caused by Salmonella Gallinarum (S. Gallinarum). Vaccines with high levels of protective effects against fowl typhoid need to be developed for the poultry industry. In this study, a S. Gallinarum strain, named SG01, was isolated from a poultry farm in Mashan region of Wuxi City, China, and identified through biochemical tests and specific PCR amplifications. Then, safety evaluations of the SG01 strain were performed in young chickens. No clinical symptom including depression and diarrhea and gross lesion involved in the cardiac nodule, hepatic necrotic lesion and splenic necrotic lesion, was determined on fifteen-day-old chickens after immunization with 1 × 1010 CFU of the SG01 strain through the oral route. However, diarrhea symptoms and hepatic lesions were identified from chickens immunized with the commercial vaccine strain SG9R by the same dose and route. At 14 days post inoculation, SG01 strain was eliminated in the liver and spleen from SG01-immunized chickens, while the SG9R strain still could be identified from SG9R-immunized chickens. After challenge with the virulent S. Gallinarum strain, significant reduction of the morbidity rate was found in the SG01 immunized group (20 %) compared to the challenge group (100 %) according to signs scoring systems for clinical symptoms and gross lesions. Additionally, immunization with the SG01 strain could provide more than 8 weeks of protection periods against fowl typhoid. These results demonstrate the SG01 strain is avirulent to young chickens and might be safer compared to the SG9R strain. In addition, SG01 strain is a potential vaccine candidate against fowl typhoid in young chickens.


Subject(s)
Poultry Diseases , Salmonella Infections, Animal , Salmonella Vaccines , Typhoid Fever , Animals , Chickens , Salmonella Infections, Animal/prevention & control , Poultry Diseases/prevention & control , Typhoid Fever/prevention & control , Typhoid Fever/veterinary , Salmonella , Vaccines, Attenuated , Poultry , Diarrhea/veterinary
10.
World J Clin Cases ; 10(36): 13250-13263, 2022 Dec 26.
Article in English | MEDLINE | ID: mdl-36683638

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of liver cancer and has a high risk of invasion and metastasis along with a poor prognosis. AIM: To investigate the independent predictive markers for disease-free survival (DFS) in patients with HCC and establish a trustworthy nomogram. METHODS: In this study, 445 patients who were hospitalized in The First Affiliated Hospital of Anhui Medical College between December 2009 and December 2014 were retrospectively examined. The survival curve was plotted using the Kaplan-Meier method and survival was determined using the log-rank test. To identify the prognostic variables, multivariate Cox regression analyses were carried out. To predict the DFS in patients with HCC, a nomogram was created. C-indices and receiver operator characteristic curves were used to evaluate the nomogram's performance. Decision curve analysis (DCA) was used to evaluate the clinical application value of the nomogram. RESULTS: Longer DFS was observed in patients with the following characteristics: elderly, I-II stage, and no history of hepatitis B. The calibration curve showed that this nomogram was reliable and had a higher area under the curve value than the tumor node metastasis (TNM) stage. Moreover, the DCA curve revealed that the nomogram had good clinical applicability in predicting 3- and 5-year DFS in HCC patients after surgery. CONCLUSION: Age, TNM stage, and history of hepatitis B infection were independent factors for DFS in HCC patients, and a novel nomogram for DFS of HCC patients was created and validated.

11.
BMC Pulm Med ; 21(1): 203, 2021 Jun 23.
Article in English | MEDLINE | ID: mdl-34162374

ABSTRACT

BACKGROUND: Invasive and non-invasive mechanical ventilation (MV) have been combined as sequential MV in the treatment of respiratory failure. However, the effectiveness remains unclear. Here, we performed a randomized controlled study to assess the efficacy and safety of sequential MV in the treatment of tuberculosis with respiratory failure. METHODS: Forty-four tuberculosis patients diagnosed with respiratory failure were randomly divided into sequential MV group (n = 24) and conventional MV group (n = 20). Initially, the patients in both groups received invasive positive pressure ventilation. When the patients' conditions were relieved, the ventilation modality in sequential MV group was switched to oronasal face mask continuous positive airway pressure until weaning. RESULTS: After treatment, the patients in sequential MV group had similar respiratory rate, heart rate, oxygenation index, alveolo-arterial oxygen partial pressure difference (A-aDO2), blood pH, PaCO2 to those in conventional MV group (all P value > 0.05). There was no significant difference in ventilation time and ICU stay between the two groups (P > 0.05), but sequential MV group significantly reduced the time of invasive ventilation (mean difference (MD): - 36.2 h, 95% confidence interval (CI) - 53.6, - 18.8 h, P < 0.001). Sequential MV group also reduced the incidence of ventilator-associated pneumonia (VAP; relative risk (RR): 0.44, 95% CI 0.24, 0.83, P = 0.006) and atelectasis (RR:0.49, 95% CI 0.24,1.00, P = 0.040). CONCLUSIONS: Sequential MV was effective in treating tuberculosis with respiratory failure. It showed advantages in reducing invasive ventilation time and ventilator-associated adverse events. REGISTRATION NUMBER FOR CLINICAL TRIAL: Chinese Clinical Trial Registry ChiCTR2000032311, April 21st, 2020.


Subject(s)
Pneumonia, Ventilator-Associated/etiology , Respiration, Artificial/methods , Respiratory Insufficiency/therapy , Tuberculosis/complications , Adult , Aged , Female , Humans , Male , Masks/adverse effects , Middle Aged , Prospective Studies , Respiration, Artificial/adverse effects , Treatment Outcome
12.
Sci Rep ; 11(1): 8741, 2021 Apr 22.
Article in English | MEDLINE | ID: mdl-33888811

ABSTRACT

When operating within the environments rich with sodium chloride, steel bars of reinforced concrete structures are often subject to corrosion caused by surrounding erosive materials, and the associated rust expansion force due to corrosion takes a critical role in determining the durability of relevant reinforced concrete structures. By investigating the corrosion course of steel reinforcement with theory of elasticity, a numerical rust expansion model is established for the moment of concrete surface rupture based on non-uniform sin function. Cuboid reinforced concrete specimen with squared cross sections is tested to analyze the rust expansion when concrete cracks due to corrosive forces. The utility of the established expansion model is validated by numerical simulation with Abaqus through the comparison between the associated outcomes. The impacts of steel bar diameter and concrete cover thickness on the magnitude of rust expansion force are discussed.

13.
Clin Lab ; 66(11)2020 Nov 01.
Article in English | MEDLINE | ID: mdl-33180422

ABSTRACT

BACKGROUND: The lack of effective means for the early diagnosis of non-small cell lung cancer (NSCLC) is the leading cause of the high mortality of NSCLC. This study aims to evaluate the clinical significance of serum mannan-binding lectin associated serine protease (MASP)-2 and isocitrate dehydrogenase 1 (IDH1) in the early diagnosis of NSCLC. METHODS: The serum levels of MASP-2 and IDH1 were detected in 139 NSCLC patients, 46 patients with benign lung diseases and 61 healthy controls, using an enzyme linked immunosorbent method. The diagnostic significance in NSCLC of the two tumor markers were analyzed by receiver operating characteristic (ROC) curves. In addition, we compared the two markers with the current commonly used tumor marker cytokeratin 19 fragment (Cy¬fra21-1). RESULTS: The serum levels of MASP-2 and IDH1 in the NSCLC patients were significantly higher than those of healthy controls and patients with benign lung diseases. The differences were statistically significant (p < 0.01). The combined sensitivity of MASP-2, IDH1, and Cyfra21-1 in the NSCLC was 68.3%, which was significantly higher than that of the single tumor marker (p < 0.01). The sensitivities of MASP-2 and IDH1 in detecting early NSCLC (stage I and stage II) were 39.0% and 41.5%, which were significantly higher than that of Cyfra21-1 (p < 0.05). The area under the ROC curves (AUCs) of MASP-2 and IDH1 in the diagnosis of NSCLC were 0.621, and 0.840, which were higher than that of Cyfra21-1 (AUC = 0.606). CONCLUSIONS: Serum MASP-2 and IDH1 may be used as potential tumor markers for the auxiliary diagnosis and early diagnosis of NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Antigens, Neoplasm , Biomarkers, Tumor , Carcinoma, Non-Small-Cell Lung/diagnosis , Early Detection of Cancer , Humans , Isocitrate Dehydrogenase/genetics , Keratin-19 , Lung Neoplasms/diagnosis , Mannose-Binding Protein-Associated Serine Proteases
14.
Int J Mol Med ; 45(6): 1888-1908, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32236591

ABSTRACT

Heat shock protein 90 (Hsp90) is associated with resisting heat­stress injury to the heart, particularly in myocardial mitochondria. However, the mechanism underlying this effect remains unclear. The present study was based on the high expression of Hsp90 during heat stress (HS) and involved inducing higher expression of Hsp90 using aspirin in mouse hearts. Higher Hsp90 levels inhibited HS­induced myocardial damage and apoptosis, and mitochondrial dysfunction, by stimulating Akt (protein kinase B) activation and PKM2 (pyruvate kinase M2) signaling, and subsequently increasing mitochondrial Bcl­2 (B­cell lymphoma 2) levels and its phosphorylation. Functional inhibition of Hsp90 using geldanamycin verified that reducing the association of Hsp90 with Akt and PKM2 caused the functional decline of phosphorylated (p)­Akt and PKM2 that initiate Bcl­2 to move into mitochondria, where it is phosphorylated. Protection by Hsp90 was weakened by blocking Akt activation using Triciribine, which could not be recovered by normal initiation of the PKM2 pathway. Furthermore, increased Hsp70 levels induced by Akt activation in myocardial cells may flow into the blood to resist heat stress. The results provided in vivo mechanistic evidence that in myocardial cells, Hsp90 resists heat stress via separate activation of the Akt­Bcl­2 and PKM2­Bcl­2 signaling pathways, which contribute toward preserving cardiac function and mitochondrial homeostasis.


Subject(s)
HSP90 Heat-Shock Proteins/metabolism , Heat-Shock Response/physiology , Myocytes, Cardiac/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Pyruvate Kinase/metabolism , Signal Transduction/physiology , Animals , Apoptosis/drug effects , Benzoquinones/pharmacology , Heat-Shock Response/drug effects , Lactams, Macrocyclic/pharmacology , Male , Mice , Mice, Inbred C57BL , Mitochondria/drug effects , Mitochondria/metabolism , Myocardium/metabolism , Myocytes, Cardiac/drug effects , Phosphorylation/drug effects , Signal Transduction/drug effects
15.
J Cancer ; 10(15): 3543-3552, 2019.
Article in English | MEDLINE | ID: mdl-31293659

ABSTRACT

Purpose: Aldo-keto reductase family 1, member C2 (AKR1C2) gene encodes for a member of the AKR superfamily and participates in the metabolism of various drugs. Moreover, tumor and normal tissues exhibit an evident difference in the expression level of this gene. Methods: We downloaded and analyzed AKR1C2 expression level and the data consisting of the clinicopathological features of 490 papillary thyroid carcinoma (PTC) tumor tissues and 59 normal thyroid tissues from The Cancer Genome Atlas (TCGA) cohort. Diverse statistical methods, such Chi-square test, univariate and multivariate Cox regression analyses, and Kaplan-Meier survival curves were used. We down-/up-regulated the expression of AKR1C2 and explored its specific role in thyroid cancer cell lines by utilizing the si-RNA and plasmid. Results: We divided all patients who were collected in TCGA data sets into under-expressed (n = 245) and over-expressed groups (n = 245). We subsequently analyzed the data and obtained the following findings: (a) AKR1C2 is down-regulated in papillary thyroid carcinoma (PTC) (p<0.001), (b) Kaplan-Meier result revealed that high expression level of AKR1C2 are correlated with favorable survival in PTC (p = 0.043), and (c) factors independently associated with recurrence-free survival are AKR1C2 expression (hazard ratio (HR 0.819) and American Joint Committee on Cancer (AJCC) stage (HR 1.534). We also analysed the relationship between AKR1C2 expression and clinicopathological features in the validated cohort. AKR12C under-expression correlated with lymph node metastasis (p = 0.009) and AJCC stage (p= 0.001) which might indicate AKR12C as a prognostic factor in PTC. The cell line experiment results showed that the knockdown and overexpression of AKR1C2 significantly enhance and weaken the abilities of migration and invasion in papillary thyroid carcinoma cell. Conclusion: Our results indicated that AKR1C2 exerts inhibitory effects on PTC oncogenesis and elevated AKR1C2 expression is associated with the favorable prognostic factors and recurrence free survival.

16.
Clin Genet ; 96(5): 418-428, 2019 11.
Article in English | MEDLINE | ID: mdl-31334828

ABSTRACT

The mechanism of papillary thyroid cancer (PTC) has shown numerous recurrently mutated genes, but the discovery of abnormal expression of novel tumor suppressor genes has been slow. The aim of our study is to explore the biological functions of SDPR in thyroid cancer. We reanalyzed the RNA-Seq data of PTC from The Cancer Genome Atlas (TCGA) database and found that serum deprivation response (SDPR) was significantly downregulated in PTC. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was performed to assess the expression of SDPR. Both loss- and gain-of-function experiments, and flow cytometry were performed to investigate the functions. SDPR was significantly downregulated in PTC. Reduced expression of SDPR was associated with larger tumor size, more serious lymph node metastasis, and advanced American Joint Committee on Cancer (AJCC) stage. Patients with lower SDPR expression had a shorter recurrence-free survival. SDPR expression and AJCC stage were independent predictors of poor recurrence-free survival (RFS). Moreover, cell proliferation, colony formation, and migration were inhibited after SDPR overexpression, whereas knockdown of SDPR exerted an oncogenic effect. SDPR induction also initiated the mesenchymal-epithelial transition, alongside suppressing AKT signaling and cyclin family expression. Apart from DNA methylation, LOC105373813, may also co-regulate SDPR expression by forming a stable hybrid with SDPR messenger RNA. Our study indicated that SDPR may function as a potential prognostic marker in PTC.


Subject(s)
Biomarkers, Tumor/genetics , DNA Methylation/genetics , Phosphate-Binding Proteins/genetics , Thyroid Cancer, Papillary/genetics , Cell Proliferation/genetics , Female , Gain of Function Mutation/genetics , Gene Expression Regulation, Neoplastic/genetics , Humans , Lymphatic Metastasis , Male , Middle Aged , RNA-Seq , Thyroid Cancer, Papillary/pathology
17.
Cancer Manag Res ; 10: 1351-1358, 2018.
Article in English | MEDLINE | ID: mdl-29881305

ABSTRACT

AIM: To investigate the clinical effects of MUC1 on papillary thyroid cancer (PTC) and explore the relationship between MUC1 expression and BRAF mutation. METHODS: The data of 69 patients subjected to fine-needle aspiration biopsy in our hospital and 486 patient data downloaded from The Cancer Genome Atlas (TCGA) database were used. Univariate and multivariate analyses were performed. RESULTS: The results on the 486 patients recorded in the TCGA indicated that high MUC1 expression was independently related to BRAF mutation, lymph node metastasis (LNM), and unifocal type. In the 69 fine-needle aspiration biopsy patients with PTC, high MUC1 expression was significantly related to LNM and extrathyroid extension (ETE). The result of Pearson's correlation coefficient showed that BRAF mutation and MUC1 expression were moderately correlated. Moreover, in the subgroup with low MUC1 expression, the patients with BRAF mutation had higher ETE frequency and LNM than those without BRAF mutation. In the subgroup with BRAF mutation, patients with high MUC1 expression exhibited higher ETE frequency than those with low MUC1 expression, and high MUC1 expression occurred in older patients. In the subgroup with BRAF wild-type mutation, patients with high MUC1 expression had a higher incidence of ETE and LNM than those with low expression. CONCLUSION: We demonstrated that the MUC1 is an important oncogene in PTC and may have great significance on therapeutic cancer vaccine development.

18.
Ann Clin Lab Sci ; 48(1): 40-44, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29530995

ABSTRACT

BACKGROUND: Among all kinds of breast cancer, triple-negative breast cancer (TNBC) is the most aggressive, with the poorest prognosis and highest mortality rates. Thus, novel biomarkers that personalize the therapeutic regimen and evaluate prognosis for TNBC patients should be determined. METHODS: We analyzed the cystatin E/M (CST6) expression profiles of 161 TNBC tissues and 14 noncancerous tissues through multiple statistical analyses. We also investigated the relationship of CST6 expression with clinical parameters and evaluated the prognostic value of CST6 in 161 TNBC patients. RESULTS: CST6, a member of the cystatin superfamily, was remarkably more up-regulated in TNBC tissues than in adjacent normal breast tissues. High CST6 expression was frequently observed in white people and associated with a high risk of lymph-node metastasis. Cox regression analysis confirmed that the high CST6 expression was an independent predictor of disease-free survival in TNBC. Kaplan-Meier analysis further revealed that high CST6 expression caused a low disease-free survival rate. CONCLUSION: CST6 is involved in the progression of TNBC and may act as a tumor-promoter gene. A systematic literature review shows that our study is the first to explore the relationship between CST6 and TNBC.


Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Ductal, Breast/secondary , Carcinoma, Lobular/secondary , Carcinoma, Medullary/secondary , Cystatin M/metabolism , Triple Negative Breast Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Carcinoma, Ductal, Breast/metabolism , Carcinoma, Lobular/metabolism , Carcinoma, Medullary/metabolism , Case-Control Studies , Female , Follow-Up Studies , Humans , Lymphatic Metastasis , Middle Aged , Prognosis , Survival Rate , Triple Negative Breast Neoplasms/metabolism
19.
Int J Syst Evol Microbiol ; 68(1): 204-210, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29139349

ABSTRACT

A Gram-stain-positive, rod-shaped, non-motile bacterial strain, designated JW-1T, was isolated from activated sludge collected from the outlet of an aeration tank in a prometryn-manufacturing plant, located in Binzhou City, Shandong province, PR China. Phylogenetic analysis, based on 16S rRNA gene sequences, indicated that strain JW-1T belongs to the genus Leucobacter and its closest neighbours are 'Leucobacter kyeonggiensis' F3-P9 (98.95 % similarity), Leucobacter celer subsp. astrifaciens CBX151T (98.62 %), Leucobacter celer subsp. celer NAL101T (98.53 %), Leucobacter chromiiresistens JG31T (97.86 %) and Leucobacter chironomi DSM 19883T (97.37 %). DNA-DNA hybridization values with the above strains were <55 %. The DNA G+C content of strain JW-1T was 72.6 mol%. The major fatty acids of strain JW-1T were iso-C16 : 0, anteiso-C15 : 0, anteiso-C17 : 0 and iso-C15 : 0. The predominant polar lipids were diphosphatidylglycerol, phosphatidylglycerol and glycolipid. The predominant menaquinone was MK-11. The cell wall amino acids were 2,4-diaminobutyric acid, alanine, glutamic acid, glycine and threonine. Based on the molecular and chemotaxonomic data, as well as the physiological and biochemical characteristics, strain JW-1T is considered to represent a novel species of the genus Leucobacter, for which the name Leucobacter triazinivorans is proposed. The type strain is JW-1T (=DSM 105188T=LMG 30083T).


Subject(s)
Actinomycetales/classification , Herbicides/metabolism , Phylogeny , Prometryne/metabolism , Sewage/microbiology , Actinomycetales/genetics , Actinomycetales/isolation & purification , Aminobutyrates , Bacterial Typing Techniques , Base Composition , Cell Wall/chemistry , China , DNA, Bacterial/genetics , Fatty Acids/chemistry , Glycolipids/chemistry , Nucleic Acid Hybridization , Phospholipids/chemistry , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Vitamin K 2/chemistry
20.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-698400

ABSTRACT

BACKGROUND: Iliac screw implantation has no unified standard. Because of the large individual differences, preoperative pelvic three-dimensional (3D) CT reconstruction can measure the diameter, depth and angle of the screws, which increases the placement accuracy. OBJECTIVE: To measure the screw placement-related data by pelvic 3D CT reconstruction, so as to guide the screw placement and improve its accuracy. METHODS: Fifty patients with pelvic lesions or fractures admitted in Shandong Provincial Third Hospital from January 2013 to December 2016 were selected, and the pelvis was scanned with CT and then was reconstructed. The point A (the intersection of S1posterior sacral posterior wall and posterior superior iliac spine) was as the screw placement point, and three paths were measured on the point: posterior superior iliac spine path (AD path); anterior inferior iliac spine path (AC path); top of greater sciatic notch to the acetabular roof (AB path). On the plane of these three pathes, the section was made on the iliac bone, respectively; in each section, the channel for iliac nail was designed. RESULTS AND CONCLUSION: (1) In the same path, there was no significant difference in the path length of the screw between male and female patients (P > 0.05). Paired t test showed that the diameter and length depth and angle of the screws were significantly different between AD and AC paths, AC and AD (P < 0.05). (2) There was no significant difference in the inclination angle of the spiral channel between male and female patients (P > 0.05). The inclination angle of the spiral channel and lateral angle at different paths showed significant difference between male and female patients (P < 0.05). (3) To conclude, 3D reconstruction of pelvis CT can be used to measure the length, diameter and angle of the iliac screw, and to guide the surgical treatment.

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