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Objective: To explore the antiviral activity of the small-molecule compound AM679 in hepatitis B virus (HBV) replication and infection cell models. Methods: The positive regulatory effect of AM679 on EFTUD2 expression was validated by qPCR and Western blotting. HepAD38 and HepG2-NTCP cells were treated with AM679 (0.5, 1, and 2 nmol/L). Negative control, positive control, and AM679 combined with the entecavir group were set up. HBV DNA intra-and extracellularly, as well as the expression levels of intracellular HBV total RNAs and 3.5kb-RNA changes, were detected with qPCR. Hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) levels were measured in the cell supernatant by an enzyme-linked immunosorbent assay (ELISA). The t-test method was used for the statistical analysis of the mean difference between groups. Results: EFTUD2 mRNA and protein expression levels were significantly increased in HepAD38 and HepG2-NTCP cells following AM679 treatment, with a statistically significant difference (Pâ <â 0.001). Intra-and extracellular indicators such as HBV DNA, HBV RNAs, HBV 3.5kb-RNA, HBsAg, and HBeAg were decreased to varying degrees in both cell models, and the decrease in these indicators was more pronounced with the increase in AM679 concentration and prolonged treatment duration, while the combined use of AM679 and entecavir had a more significant antiviral effect. The HBV DNA inhibition rates in the supernatant of HepAD38 cells with the use of 2 nmol/L AM679 were 21% and 48% on days three and nine, respectively. The AM679 combined with the ETV treatment group had the most significant inhibitory effect (62%), with a Pâ <â 0.01. More active HBV replication was observed after silencing EFTUD2, while the antiviral activity of AM679 was significantly weakened. Conclusion: AM679 exerts anti-HBV activity in vitro by targeting the regulation of EFTUD2 expression.
Subject(s)
Antiviral Agents , Hepatitis B virus , Virus Replication , Humans , Antiviral Agents/pharmacology , DNA, Viral , Guanine/analogs & derivatives , Hep G2 Cells , Hepatitis B e Antigens/metabolism , Hepatitis B Surface Antigens/metabolism , Hepatitis B virus/drug effects , Virus Replication/drug effects , Indoles/chemistry , Indoles/pharmacology , Pentanoic Acids/chemistry , Pentanoic Acids/pharmacology , Peptide Elongation Factors/antagonists & inhibitors , Peptide Elongation Factors/metabolism , Ribonucleoprotein, U5 Small Nuclear/antagonists & inhibitors , Ribonucleoprotein, U5 Small Nuclear/metabolismABSTRACT
Objective: To apply artificial intelligence technology in clinical real-world data of patients with primary hepatocellular carcinoma, explore the precise treatment of disease and build up artificial intelligence-based clinical decision support system. Methods: A total of 5 642 patients with primary hepatocellular carcinoma admitted to West China Hospital from July 2004 to June 2016 with complete follow-up records were included in the study. A merged model composed of multiple sub-classifiers was adopted to calculate therapy recommendation coefficient, and receiver operator characteristic curve was analyzed. Survival risk and recurrence risk were predicted by DeepSurv algorithm, and Kaplan-Meier survival curves were further compared among low, middle and high risk groups. Siamese-Net was applied to find similar patients. Results: The Top-1 and Top-2 accuracy of therapy recommendation coefficient reached 82.36% and 94.13% respectively. In internal verification of West China Hospital, the above-mentioned value reached 95.10% in accordance with multi-disciplinary team results. The C-index derived from survival risk model was 0.735 (95%CI:0.70-0.77), and the difference of Kaplan-Meier in pairwise comparison was of statistical significance under log-rank test (P<0.001). Meanwhile, the C-index derived from recurrence risk model was 0.705 (95%CI:0.68-0.73), and the difference of Kaplan-Meier in pairwise comparison was of statistical significance under log-rank test (P<0.001). Conclusions: The artificial intelligence-based clinical decision support system for primary hepatocellular carcinoma has can accurately make therapy recommendation and prognosis prediction for primary hepatocellular carcinoma.
Subject(s)
Carcinoma, Hepatocellular , Decision Support Systems, Clinical , Liver Neoplasms , Artificial Intelligence , Carcinoma, Hepatocellular/therapy , China , Humans , Kaplan-Meier Estimate , Liver Neoplasms/therapy , Prognosis , Retrospective StudiesABSTRACT
The RRS1 regulator of ribosome synthesis has recently been reported a new target gene linked to cancer development. This study therefore investigates RRS1effectsb on BT549 cell proliferation and apoptosis in breast cancer. Western blot (WB) and real - time quantitative PCR (qPCR) were used to detect the relative expression of RRS1 in breast cancer cells BT-549 and the normal HMEC mammary gland epithelial cells. BT-549 cells were cultured and infected with retroviruses and RRS1 expression was detected by qPCR and WB. The MTT assay, Caspase-3/7 and flow cytometry (FCM) then detected growth and apoptosis in the BT549 breast cancer BT cell. WB detected the expression of Bcl-2 and Bax genes related to apoptosis at the protein level, and MTT assay confirmed that RRS1 knockdown significantly decreased cell viability (p<0.05) and induced apoptosis which was rescued by shRNA-RRS1 expression. The amount of caspase-3 increased significantly and apoptosis was obvious. The apoptotic cells amount analyzed by FCM was significantly increased and RRS1 knockdown also decreased the expression of apoptosis related protein bcl-2 and simultaneously increased the expression of Bax (p<0.05). Finally, the RRS1 gene was highly expressed in breast cancer cell line BT549 and its knockdown significantly reduced proliferation and apoptosis in BT549 cell. These results suggest that RRS1 is a novel gene related to breast cancer and has an important role in breast cancer proliferation and apoptosis.
Subject(s)
Apoptosis , Breast Neoplasms/pathology , Cell Proliferation , Gene Knockdown Techniques , Nuclear Proteins/genetics , Caspases/genetics , Cell Line, Tumor , Humans , Proto-Oncogene Proteins c-bcl-2/genetics , RNA-Binding Proteins , bcl-2-Associated X Protein/geneticsSubject(s)
Bias , Research Design , Humans , Biomedical Research/methods , Biomedical Research/standardsABSTRACT
The stress-induced magnetic anisotropy can significantly affect giant magneto-impedance (GMI) effect of the soft magnetic film. This paper is devoted to the GMI effect of the single layer soft magnetic film implied without and with a stress. By simulating a physical model with MATLAB and COMSOL software, the impedance expression of the single layer soft magnetic film and the relation between external magnetic field and magnetic permeability are deduced. We observed that, without a stress, the sensitive region increased firstly and then decreased with the increasing of the excitation current frequency from 1 MHz to 200 MHz. While the film was subjected to the stress in the direction of the current with one end stressed, the stress on the film was gradually reduced from stressed end to free end. Also, the impedance change rate of the film changed when the stress was added, which is similar to the effect of adding a bias magnetic field on the film. More importantly, the addition of stress σ can induce the bias of the GMI measurement range and improve its sensitivity near zero magnetic fields. This may provide a new way for designing a GMI sensor with higher sensitivity and adjustable measurement range.
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OBJECTIVE: To investigate the effect of high mobility group protein box 1 (HMGB1) on apoptosis of astrocytes after oxygen glucose deprivation/reoxygenation (OGD/R), and to investigate the possible mechanism by evaluating the expression of apoptosis related protein Bcl-2 and Bax. METHODS: The cerebral cortex astrocytes of neonatal rats were divided into normal group, model group, interference group and control group. Lentivirus vector of rat HMGB1 short hairpin RNA (shRNA) was used to suppress the HMGB1 protein expression in the astrocytes. Then the detection was made after astrocytes were deprived of oxygen and glucose 6 h, reoxygenation for 24 h. The effect of RNA interference was evaluated by Western blotting. The cell survival rate was measured by MTT assay. The apoptosis of astrocytes was determined by TUNEL assay. The expressions of Bcl-2 and Bax were detected by Western blotting. RESULTS: Compared with the normal group, the protein expression of HMGB1 was significantly increased in model group after OGD/R (P<0.001), the astrocytes survival rate was decreased (P<0.001), the number of apoptotic cells labeled with TUNEL was increased (P<0.001), and the ratio of Bcl-2/Bax was decreased (P<0.001). Compared with the model group, RNA interference effectively inhibited the expression of HMGB1 in interference group (P<0.001), the astrocytes survival rate was increased (P<0.001), the number of apoptotic cells labeled with TUNEL was reduced (P<0.01), and the ratio of Bcl-2/Bax was increased (P<0.001). CONCLUSION: The apoptosis of astrocytes can be induced by HMGB1 after OGD/R, and the mechanism may be related to regulating the expression of apoptosis related proteins Bcl-2 and Bax.
Subject(s)
Apoptosis , Astrocytes , Cell Hypoxia , Glucose , HMGB1 Protein , bcl-2-Associated X Protein , Animals , Cells, Cultured , Glucose/metabolism , HMGB1 Protein/physiology , Oxygen , Proto-Oncogene Proteins c-bcl-2 , Rats , Rats, Sprague-Dawley , bcl-2-Associated X Protein/metabolismABSTRACT
Objective: To evaluate the application and clinical results of two-stage total hip arthroplasty in the treatment of the deep hip infection following the internal fixation of hip fractures. Methods: From May 2007 to November 2014, 21 patients with active hip infection secondary to internal fixation of hip fractures were treated with two-stage total hip arthroplasty using a temporary antibiotic-loaded cement spacers. Of 21 cases, 15 were males and 6 were females, aged from 27 to 64 years (mean, 45); there are 18 cases of femoral neck fractures and 3 cases of intertrochanteric fractures. The serologic examination and X-ray were taken at 1 month, 3 months, 6 months, 12 months and annually thereafter post-operatively to evaluate the clinical results and prosthesis status. Harris hip score system was used to evaluate the joint function. Results: All patients were successfully treated with two stage operations under general anesthesia. The operational interval was 12-44 weeks (mean, 21) and 1 spacer breakage. For the arthroplasty, cementless components were used in 20 cases and cemented component was use in 1 case. The patients were followed up 25-102 months ( mean, 55 ) and infections were eradicated in all hips. The Harris hip score was improved from 23.24±11.81 pre-operatively to 90.24±3.92 post-operatively and the difference was statistically significant (P<0.05). According to this scoring criteria, the excellent and good rate reached up to 95%. At latest fellow-up, the location of prosthesis were well and the function of hip joint was satisfied. All cases had no dislocation, periprosthetic fracture, ectopic ossification or any other complications at the latest fellow-up. Conclusion: By means of an antibiotic-loaded cement spacer, two-stage total hip arthroplasty is an effective salvage procedure eradicating infection and providing functional improvement to the infected internal fixation of hip fractures. The early and mid-term clinical effects are satisfied.
Subject(s)
Arthroplasty, Replacement, Hip , Hip Fractures , Hip Prosthesis , Prosthesis-Related Infections , Adult , Anti-Bacterial Agents , Female , Humans , Male , Middle Aged , Reoperation , Treatment OutcomeABSTRACT
OBJECTIVE: To investigate the knowledge, attitudes and practices surrounding occupational blood-borne pathogen exposure amongst dental students at two Chinese dental schools, as well as important factors that are associated with their career choice and attitudes towards infected patients. SUBJECT AND METHODS: The study was conducted using a student self-administered questionnaire from March to June 2013 at two Chinese dental schools. Chi-square tests and multivariable logistic regression were used to compare the categorical variables and identify the variables related to attitudes. RESULTS: One hundred and seventy-one students answered the questionnaire (response rate 83%). Most participants had incomplete knowledge about occupational exposure and participants' compliance with the infection control programme during routine clinical work was low. Fifty-six participants (34%) experienced at least one occupational exposure, but only one reported the incident. Percutaneous injuries and mucous membrane exposures were the main causes for exposure. Protection of the eyes and post-exposure management were inadequate. According to most participants, they had received insufficient education. Their concerns about the risk of infectious professional exposure would influence their career choice and approach to patients. Only 14% and 26% of the participants were willing to treat human immunodeficiency virus- and hepatitis B virus-infected patients, respectively. CONCLUSIONS: More effective education on prevention and management is required for dental students to reduce the harm caused by occupational exposure. It is important to ensure dental students' knowledge and understanding before allowing them to enter clinical training.
Subject(s)
Blood-Borne Pathogens , Education, Dental , Health Knowledge, Attitudes, Practice , Occupational Exposure , Schools, Dental , Students, Dental/statistics & numerical data , Attitude of Health Personnel , Career Choice , Chi-Square Distribution , China , Dental Clinics , Disease Transmission, Infectious/prevention & control , Female , HIV Infections/prevention & control , HIV Infections/transmission , Hepatitis B/prevention & control , Hepatitis B/transmission , Humans , Immunization , Infection Control, Dental , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Logistic Models , Male , Mandatory Reporting , Multivariate Analysis , Odds Ratio , Risk Factors , Surveys and Questionnaires , Vaccination , Wounds and Injuries/prevention & controlABSTRACT
Objective: To explore the clinical and perfusion weighted imaging (PWI) characteristics of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) in order to improve the early diagnosis rate. Methods: Clinical and imaging data of 46 patients with final diagnosis of MELAS treated in Henan Province People's Hospital from January 2012 to June 2016 were collected. Results: Patients presented with symptoms of epilepsy, hemiplegia, language disorders, and decreased visual acuity and so on. Diffusion-weighted imaging (DWI) of the lesion area showed a high signal, apparent diffusion coefficient (ADC) chart with the course of disease development can be a high signal, low signal, high and low signal. Vascular stenosis was not seen in all the patients by magnetic resonance angiography (MRA). PWI perfusion increased in acute phase and was normal or decreased in the chronic phase. Conclusions: The clinical manifestations of MELAS patients are complex and various, and lack of specificity. Routine MRI examination is of great significance for the screening of the lesion, which has a characteristic performance and is helpful to improve the early diagnosis rate of the disease.
Subject(s)
Acidosis, Lactic , MELAS Syndrome , Hemiplegia , Humans , Magnetic Resonance Imaging , Perfusion Imaging , StrokeABSTRACT
Dentition defects damage the integrity of the dental arch, affecting smile esthetics and oral function. Compared to restorative treatment, pre-restoration orthodontic treatment overcomes the limitations of a single method, effectively avoiding excessive wear of natural teeth, reducing the number of units for restorative production to a certain extent, and potentially improving facial shape and occlusal relationship, which maximizes the therapeutic effect. This article explores the key points of pre-restoration orthodontic treatment for different types of dentition defects in terms of malocclusion manifestations, treatment objectives, treatment methods, and maintenance recommendations from the perspective of combined orthodontic restoration treatment.
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Malocclusion is an oral disease with a high prevalence. The goal of orthodontic treatment is health, aesthetics, function and stability. The transmission straight wire appliance and technique is an innovative orthodontic system with independent intellectual property rights invented by Professor Jiuxiang Lin's team based on decades of clinical experience, which provides a new solution for the non-surgical correction of skeletal malocclusions, especially class â ¢ malocclusion, and it is also a good carrier for the implementation of the concept of healthy orthodontics. Due to the lack of guidelines, how to implement standardized application of transmission straight wire technique remains a problem to be solved. This technical specification was formed by combining the guidance from Professor Jiuxiang Lin and joint revision by a number of authoritative experts from the Orthodontic Special Committee, Chinese Stomatological Association, with reference to relevant literatures, and combined with abundant clinical experience of many experts. This specification aims to provide reference to standardize the clinical application of transmission straight wire technique, so as to reduce the risk and complications, and finally to improve the clinical application level of this technique.
Subject(s)
Malocclusion, Angle Class III , Malocclusion , Humans , Esthetics, Dental , Malocclusion/therapy , Orthodontic Wires , Prevalence , Orthodontics, Corrective/methodsABSTRACT
AIMS: To develop a gold immunochromatographic test strip for on-site rapid detection of lymphocystis disease virus (LCDV). METHODS AND RESULTS: Monodispersional colloidal gold and gold-labelled anti-LCDV monoclonal antibody (McAb) 2D11 were prepared and characterized by UV-visible spectroscopy and transmission electron microscopy. Gold-labelled probe was used as the detection antibody, and goat anti-mouse IgG at the control line and anti-LCDV McAb 1A8 at the test line of the test strip served as the capture antibody. The positive results could be easily judged by the presence of a red test line with naked eye within 10 min. The test strip, in good agreement with enzyme-linked immunosorbent assay and dot-blotting in sensitivity and LCDV detection, gave a detection limit of 1 µg ml(-1) of LCDV and was stable for 6 months at room temperature and 12 months at 4°C. CONCLUSIONS: The test strip was specific, simple and convenient for rapid detection of LCDV presenting good stability and reproducibility. SIGNIFICANCE AND IMPACT OF THE STUDY: This ready-to-use test strip allows on-site rapid detection of LCDV in fish without the requirement of specialized equipments and professional personnel, which could augment the practical application for diagnosis of LCDV even in disadvantage areas.
Subject(s)
Chromatography, Affinity/methods , DNA Virus Infections/veterinary , Fish Diseases/diagnosis , Flounder/virology , Iridoviridae/isolation & purification , Animals , Antibodies, Monoclonal , DNA Virus Infections/diagnosis , Enzyme-Linked Immunosorbent Assay , Female , Fish Diseases/virology , Gold Colloid , Mice , Mice, Inbred BALB C , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
Most HIV-1 infections of children result from mother-to-infant transmission, which may occur perinatally or postnatally, as a consequence of breast feeding. In this study, the influence of maternal viral load on transmission of infection to infants from non-breast-feeding mothers was examined using samples of plasma and peripheral blood mononuclear cells (PBMCs) collected at several time points during pregnancy and the 6-month period after delivery. These samples were analyzed by several quantitative methods, including virus cultures of PBMCs and polymerase chain reaction (PCR) assays for HIV-1 RNA in plasma and DNA in PBMCs. The risk of transmission increased slightly with a higher viral load, but transmission and nontransmission occurred over the entire range of values for each assay. No threshold value of virus load was identified which discriminated between transmitters and nontransmitters. We also noted a significant rise in viral load and a decline in CD4+ lymphocytes in the six months after delivery. These findings suggest that a high maternal viral load is insufficient to fully explain vertical transmission of HIV-1. Additional studies are needed to examine the post-partum increase in viremia.
Subject(s)
HIV Infections/prevention & control , HIV Infections/transmission , HIV-1 , Viral Load , Anti-HIV Agents/therapeutic use , CD4 Lymphocyte Count , Cohort Studies , DNA, Viral/blood , Female , HIV Infections/drug therapy , HIV Infections/immunology , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Pregnancy , Pregnancy Complications, Infectious/drug therapy , RNA, Viral/blood , Twins , Zidovudine/therapeutic useABSTRACT
Objective: To understand the current status of anti-hypertensive drug use in patients with hypertension in the Southwest areas of China. Methods: Based on the Program of Screening and Intervention Subjects with High Risk Cardiovascular Diseases, this study presented information on adults aged 35-75 in Southwest China by convenient sampling method, from January 2016 to November 2018. Basic information and cardiovascular related data were collected. Data on hypertensive patients were recorded, including names, doses and frequency of anti-hypertensive drugs they used. Information on the use of anti-hypertensive drugs among different hypertension subgroups, potential related characteristics, types and combination patterns of drugs, etc., were analyzed. Results: A total of 394 957 subjects were included in the study, with 159 014 identified as being hypertensive [mean age (58.8±9.5) years, 40.2% male]. 29.8% of them ever received antihypertensive drugs. A total of 30 445 of the patients reported detailed information of the drugs they ever used and 22.5% of them received therapy of combined drugs. Rates of using combination therapy were consistent among subgroups with different age, gender, blood pressure level and history of cardiovascular and cerebrovascular diseases. Results from the multivariate logistic regression analysis showed that patients with previous cardiovascular and cerebrovascular events, obesity or diabetes were more likely to have received combined therapy, while patients with less education or lower income were in the opposite. Calcium antagonists (58.6%) were the main drugs being used in single drug therapy, while traditional fixed-dose combination drugs (31.4%) were the most common ones in the drug-combination therapy, followed by angiotensin converting enzyme inhibitor/angiotensin receptor blocker combined with calcium antagonists (22.4%). Angiotensin converting enzyme inhibitor/angiotensin receptor blocker combined with beta blocker was the main drug used in patients with coronary heart disease. Conclusions: Treatment programs using the antihypertensive drugs for hypertensive patients in Southwest China needs to be improved, since the irrational use of antihypertensive drugs still exists. However, we would encourage the use of combination therapy for hypertensive patients.
Subject(s)
Angiotensin II Type 1 Receptor Blockers/therapeutic use , Antihypertensive Agents/therapeutic use , Calcium Channel Blockers/therapeutic use , Hypertension/drug therapy , Adult , Aged , Blood Pressure , China/epidemiology , Drug Therapy, Combination , Female , Humans , Hypertension/epidemiology , Male , Middle Aged , Treatment OutcomeABSTRACT
OBJECTIVE: To explore the biological function of microRNA-373 (miR-373) in regulating the progression of oral squamous cell carcinoma (OSCC) and the related mechanism. PATIENTS AND METHODS: 50 patients who were diagnosed as OSCC in the Department of Stomatology of the Stomatological Hospital of Chongqing Medical University were enrolled as the cancer group. 20 healthy oral mucosa specimens were obtained as the control group. The miR-373 level in both OSCC clinical samples and cell lines was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The binding relationship between speckle-type POZ protein (SPOP) and miR-373 was detected through online prediction software and luciferase reporter assay. RESULTS: MiR-373 was upregulated in OSCC samples and cell lines. It could negatively regulate the protein expression of SPOP. However, it did not affect the mRNA expression of SPOP. The up-regulation of miR-373 promoted proliferation, invasion, and migration ability of the OSCC cells. However, the effects of miR-373 were abolished by the over-expression of SPOP in cells. CONCLUSIONS: Up-regulated miR-373 promotes proliferation, invasion, and migration of OSCC by targeting SPOP. MiR-373/SPOP axis could be a potential therapeutic target for OSCC.
Subject(s)
Gene Expression Regulation, Neoplastic , MicroRNAs/metabolism , Mouth Neoplasms/genetics , Nuclear Proteins/genetics , Repressor Proteins/genetics , Squamous Cell Carcinoma of Head and Neck/genetics , Apoptosis/genetics , Cell Line , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Disease Progression , Down-Regulation , Humans , Keratinocytes , Mouth Mucosa/cytology , Mouth Mucosa/pathology , Mouth Mucosa/surgery , Mouth Neoplasms/pathology , Mouth Neoplasms/surgery , Neoplasm Invasiveness/genetics , Neoplasm Metastasis/genetics , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/surgery , Up-RegulationABSTRACT
This study investigated the impact of electrode materials on HfO2-based RRAM devices. The research includes three types of electrode materials: (1) the electrodes with strong ability of oxygen reservoirs; (2) the electrode with poor ability of oxygen reservoirs; (3) the active electrode with injection ability. Through implementing different combinations of electrodes, three types of switching modes were obtained and the relative conduction mechanism was analyzed, as well as conduction model. Those studies may offer ways of using electrodes to control the resistive switching processes and fabricating the RRAM devices with good performance.
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Whether anatomic resection (AR) achieves better outcomes than nonanatomic resection (NAR) in patients with primary intrahepatic cholangiocarcinoma (ICC) is unclear. Data were retrieved for all consecutive patients who underwent liver resection for primary ICC from January 2007 to July 2017. The prognoses of the patients without direct invasion to contiguous organs or extrahepatic metastasis who underwent AR or NAR were compared. 85 patients underwent AR, and 65 patients underwent NAR. operation time were slightly decreased in the NAR group. The risk of Clavien-Dindo classification (CDC) IV in the AR group was significant higher than that in the NAR group. Cox regression analysis showed lymph node metastasis and adjuvant therapy were significant prognostic factors for overall survival (OS) and disease-free survival (DFS), respectively. After 1:1 propensity score matching (PSM), 29 pairs of patients were compared. The survival curves showed the NAR group had slightly improved DFS and OS than the AR group before and after matching. Thus, we conclude NAR was not inferior to AR in improving the survival outcomes for patients with primary solitary ICC lesions without direct invasion to contiguous organs or extrahepatic metastasis. Furthermore, patients may benefit from NAR.
Subject(s)
Bile Duct Neoplasms/pathology , Cholangiocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Bile Ducts, Intrahepatic/pathology , Disease-Free Survival , Female , Humans , Lymphatic Metastasis/pathology , Male , Middle Aged , Prognosis , Propensity ScoreABSTRACT
Objective: To explore the prognostic value of the international prognostic index (IPI), the national comprehensive cancer network IPI(NCCN-IPI)and the age-adjusted IPI (aa-IPI) in diffuse large B cell lymphoma. Methods: A total of 311 patients with de novo diffuse large B-cell lymphoma (DLBCL) diagnosed from 2003 to 2012 in Nanfang hospital were included. All patients were divided into CHOP (cyclophosphamide, vincristine, doxorubicin, and prednisone) and R-CHOP (rituximab, CHOP) groups. Survival analysis was compared among IPI, NCCN-IPI and aa-IPI models. Discrimination of three different prognostic models was assessed using the Harrell's C statistic. Results: A total of 311 patients were analyzed. Among them, 128 patients were treated with CHOP regimen and other 183 patients were treated with R-CHOP regimen. In CHOP groups, both NCCN-IPI (5-year OS: 59.7% vs 26.8%, P<0.001) and aa-IPI (5-year OS: 71.0% vs 25.0%, P<0.001) showed better risk stratification for low-intermediate and high-intermediate group than the IPI (5-year OS: 47.6% vs 36.6%, P=0.003). However, in the patients treated with R-CHOP, NCCN-IPI showed better risk stratification in low, low-intermediate, high-intermediate groups (5-year OS: 96.0% vs 83.0% vs 66.5%, P=0.009). According to the Harrell's C statistic, C-index of IPI, NCCN-IPI and aa-IPI for overall survival (OS) were 0.546, 0.667, 0.698 in CHOP group and 0.611,0.654, 0.695 in R-CHOP group respectively. In patients younger than 60 years old, C-index of IPI, NCCN-IPI and aa-IPI for OS were 0.534, 0.675, 0.698 in CHOP group and 0.584, 0.648, 0.695 in R-CHOP respectively. Conclusion: The NCCN-IPI is more powerful than IPI and aa-IPI in DLBCL patients receiving R-CHOP. aa-IPI is a preferable model in predicting prognosis than IPI and NCCN-IPI in anthracycline-based chemotherapy without rituximab.
Subject(s)
Lymphoma, Large B-Cell, Diffuse , Antibodies, Monoclonal, Murine-Derived , Antineoplastic Combined Chemotherapy Protocols , Cyclophosphamide , Doxorubicin , Humans , Middle Aged , Prednisone , Prognosis , Retrospective Studies , VincristineABSTRACT
Objective: To analyze whether heat-shock protein 90 (HSP90) be involved in a permanently abnormal activated JAK/STAT signaling in ATL cells in vitro. Methods: The effect of 17-AAG on proliferation of ATL cell lines HUT-102 was assessed using CCK8 at different time points. Cell apoptosis was measured by flow cytometry. The specific proteins HSP90, STAT5, p-STAT5 and JAK3 were detected by Western blotting. Results: Overexpression of HSP90 in HUT-102 cell lines was disclosed (P<0.05) , and constitutive activation of JAK3/STAT5 signaling was observed in HTLV-1-infected T-cell lines but not in normal PBMCs; Treatment of ATL cell lines with 17-AAG led to reduced cell proliferation, but there was no significant change in terms of cell proliferation when the concentration of 17-AAG between 2 000-8 000 nmol/L (P>0.05) . 17-AAG induced cell apoptosis in different time-points and concentrations. 17-AAG don't affect the expression of JAK3 gene. Conclusion: This study indicated that JAK3 as HSP90 client protein was aberrantly activated in HTLV-1-infected T-cell lines, leading to constitutive activation of p-STAT5 in JAK/STAT signal pathway, which demonstrated that HSP90-inhibitors 17-AAG inhibited the growth of HTLV-1-infected T-cell lines by reducing cell proliferation and inducing cell apoptosis.
Subject(s)
Human T-lymphotropic virus 1 , Apoptosis , Benzoquinones , Cell Line, Tumor , Cell Proliferation , HSP90 Heat-Shock Proteins , Humans , Janus Kinase 3 , Lactams, Macrocyclic , STAT5 Transcription Factor , Signal TransductionABSTRACT
The microstructure of a high-pressure die-cast hypereutectic A390 alloy, including PSPs, pores, α-Al grains and Cu-rich phases, was characterized using synchrotron X-ray tomography, together with SEM, TEM and EBSD. The Cu-rich phases exhibited a net morphology and distributed at the boundaries of the α-Al grains, which in turn surrounded the PSPs. Statistical analysis of the reconstructed 1000 PSPs showed that both equivalent diameter and shape factor of the PSPs exhibited a unimodal distribution with peaks corresponding to 25 µm and 0.78, respectively.) PSPs morphology with multiple twinning were observed and morphological or growth transition of the PSPs from regular octahedral shape (with a shape factor of 0.85 was mainly caused by the constraint of the Cu-rich phases. In particular, the presence of the Cu-rich phases restricted the growth of the α-Al grains, inducing stress on the internal silicon particles, which caused multiple twinning occurrence with higher growth potential and consequently led to growth transitions of the PSPs.