ABSTRACT
Objective: To investigate the role of an inflammatory microenvironment induced by Porphyromonasgingivalis (P. gingivalis) in the occurrence of esophageal squamous cell carcinoma (ESCC) in mice. Methods: A total of 180 C57BL/6 mice were randomly divided into 6 groups, i.e. control group, P. gingivalis group, 4NQO group, 4NQO + P. gingivalis group, 4NQO + P. gingivalis + celecoxib group, and 4NQO + P. gingivalis + antibiotic cocktail (ABC, including metronidazole, neomycin, ampicillin, and vancomycin) group, with 30 mice in each group, using the random number table. All mice were normalized by treatment with ABC in drinking water for 2 weeks. In the following 2 weeks, the mice in the control group and the P. gingivalis group were given drinking water, while the other 4 groups were treated with 30 µg/ml 4NQO in the drinking water. In weeks 11-12, the mice in the P. gingivalis group, the 4NQO + P. gingivalis group, the 4NQO + P. gingivalis + celecoxib group, and the 4NQO + P. gingivalis + ABC group were subjected to ligation of the second molar in oral cavity followed by oral P. gingivalis infection thrice weekly for 24 weeks in weeks 11-34. In weeks 13-34, the mice in 4NQO + P. gingivalis+celecoxib group and 4NQO + P. gingivalis + ABC group were administered with celecoxib and ABC for 22 weeks, respectively. At the end of 34 weeks, gross and microscopic alterations were examined followed by RT-qPCR and immunohistochemistry to examine the expression profiles of inflammatory- and tumor-molecules in esophagi of mice. Results: At 34 weeks, 4NQO treatment alone did not affect the foci of papillary hyperproliferation, diseased area, and the thickness of the esophageal wall, but significantly enhanced the foci of hyperproliferation (median 1.00, Pï¼0.05) and mild/moderate dysplasia (median 2.00, Pï¼0.01). In addition, the expression levels of IL-6 [8.35(3.45,8.99)], IL-1ß [6.90(2.01,9.72)], TNF-α [12.04(3.31,14.08)], c-myc [2.21(1.80,3.04)], pSTAT3, Ki-67, and pH2AX were higher than those in the control group. The pathological changes of the esophageal mucosa were significantly more overt in the 4NQO + P. gingivalis group in terms of the foci of papillary hyperproliferation (median 2.00), diseased area (median 2.51 mm2), the thickness of the esophageal wall (median 172.52 µm), the foci of hyperproliferation (median 1.00, Pï¼0.05), and mild/moderate dysplasia (median 1.00, Pï¼0.01). In mice of the 4NQO + P. gingivalis group, the expression levels of IL-6 [12.27(5.35,22.08)], IL-1ß [13.89(10.04,15.96)], TNF-α [19.56(6.07,20.36)], IFN-γ [11.37(8.23,20.07)], c-myc [2.62(1.51,4.25)], cyclin D1 [4.52(2.68,7.83)], nuclear pSTAT3, COX-2, Ki-67, and pH2AX were significantly increased compared with the mice in the control group. In mice of the 4NQO + P. gingivalis group, the diseased area, invasive malignant foci as well as pSTAT3 and pH2AX expression were significantly blunted by celecoxib. Treatment with ABC markedly reduced the papillary hyperproliferative foci, invasive malignant foci, and pSTAT3 expression but not pH2AX. Conclusions: P. gingivalis promotes the occurrence of esophageal squamous cell carcinoma in mice by inducing an inflammatory microenvironment primed with 4NQO induced DNA damage. Clearance of P. gingivalis with ABC or anti-inflammatory intervention holds promise for prevention of esophageal squamous cell malignant pathogenesis via blockage of IL-6/STAT3 signaling and amelioration of inflammation.
Subject(s)
4-Nitroquinoline-1-oxide , Celecoxib , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Mice, Inbred C57BL , Porphyromonas gingivalis , Tumor Microenvironment , Animals , Mice , Esophageal Neoplasms/microbiology , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma/microbiology , Esophageal Squamous Cell Carcinoma/metabolism , Esophageal Squamous Cell Carcinoma/pathology , Celecoxib/pharmacology , Inflammation , Bacteroidaceae Infections/microbiology , Interleukin-6/metabolism , Anti-Bacterial Agents/pharmacology , STAT3 Transcription Factor/metabolism , Cyclooxygenase 2/metabolism , Cyclooxygenase 2/genetics , Esophagus/microbiology , Esophagus/pathology , Esophagitis/microbiology , Esophagitis/pathology , Proto-Oncogene Proteins p21(ras)/genetics , Proto-Oncogene Proteins p21(ras)/metabolism , Carcinoma, Squamous Cell/microbiology , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/metabolismABSTRACT
OBJECTIVE: With the help of metrology, we can identify research hotspots and development trends in dynamic electrocardiography, and thereby provide corresponding reference material to aid further theoretical research. MATERIALS AND METHODS: All research data derived from the core collection of Web of Science, and all searches were completed on the same day (February 6, 2022). The obtained data were stored in plain text format and imported into CiteSpace for subsequent analysis. Citation analysis and visualization technology were used to draw a visual map of the research elements, using factors such as annual literature volume, country, journal, author, abstract, keywords, and citation. RESULTS: After screening, 2,937 papers were obtained. Research on ambulatory electrocardiography is increasing worldwide every year. Using research hotspots, keyword-clustering time-zone maps, and high-frequency emerging words, the research in this field was roughly divided into two stages, with 2017 as the divider. The first stage primarily focuses on areas such as atrial fibrillation, stroke, autonomic nerve function, catheter ablation, and T-wave alternation. The second stage saw the focus shift to wearable devices, sudden cardiac death, obstructive sleep apnea, feature extraction, cryptogenic stroke, and similar topics. CONCLUSIONS: With the development of various wearable technologies, the daily monitoring of healthy people engaged in sporting activities and the development of innovative analysis algorithms providing more accurate data may represent the hotspots and direction of future research.
Subject(s)
Bibliometrics , Publications , Cluster Analysis , Electrocardiography , Electrocardiography, Ambulatory , HumansABSTRACT
Objective: BMI may play a protective role in reducing the mortality rate of patients with chronic obstructive pulmonary disease (COPD), but its effect on acute exacerbation of COPD remain unclear. Methods: Subjects were selected from the COPD patients registration system established in 2014 in Pudong new district, Shanghai. COPD patients from 8 communities were selected by cluster sampling and follow up was conducted prospectively for 18 months. Basic information and BMI were obtained from baseline survey, and acute exacerbations were collected during follow-up. The association between BMI and risk of acute exacerbation was evaluated by using multiple negative binomial regression. Results: Among 328 community COPD patients, 295 who completed the follow up were included in the analysis, in whom 96.3% (284/295) were mild COPD patients. During the follow-up, 11.1% (33/295) of the patients reported acute exacerbation. The results of multiple negative binomial regression suggested that, the risk for acute exacerbation decreased with the increase of BMI (IRR=0.85, 95%CI:0.73-0.98), overweight patients with BMI ≥25.0 kg/m2 (IRR=0.36, 95%CI:0.13-0.91) or moderate BMI (T2 vs. T1, IRR=0.31, 95%CI:0.11-0.77) had lower risk for acute exacerbation compared with the patients with normal or low BMI. BMI had a linear correlation with the risk of acute exacerbation. Conclusion: The risk for acute exacerbation in patients with mild or moderate COPD in communities decreased with the increase of BMI, and being overweight might be a protective factor for the acute exacerbation of COPD.
Subject(s)
Overweight , Pulmonary Disease, Chronic Obstructive , Body Mass Index , China/epidemiology , Disease Progression , Humans , Overweight/complications , Prospective Studies , Pulmonary Disease, Chronic Obstructive/complicationsABSTRACT
Reservoir computing (RC) is a recently introduced bio-inspired computational framework capable of excellent performances in the temporal data processing, owing to its derivation from the recurrent neural network (RNN). It is well-known for the fast and effective training scheme, as well as the ease of the hardware implementation, but also the problematic sensitivity of its performance to the optimizable architecture parameters. In this article, a particular time-delayed RC with a single clamped-clamped silicon beam resonator that exhibits a classical Duffing nonlinearity is presented and its optimization problem is studied. Specifically, we numerically analyze the nonlinear response of the resonator and find a quasi-linear bifurcation point shift of the driving voltage with the driving frequency sweeping, which is called Bifurcation Point Frequency Modulation (BPFM). Furthermore, we first proposed that this method can be used to find the optimal driving frequency of RC with a Duffing mechanical resonator for a given task, and then put forward a comprehensive optimization process. The high performance of RC presented on four typical tasks proves the feasibility of this optimization method. Finally, we envision the potential application of the method based on the BPFM in our future work to implement the RC with other mechanical oscillators.
ABSTRACT
OBJECTIVE: Renal injury caused by sepsis is a difficult point in the field of critical care medicine today, which seriously endangers the health of patients. The aim of our paper was to study the role of irisin in the inflammation and apoptosis of renal injury caused by sepsis and its potential mechanism of action. MATERIALS AND METHODS: Lipopolysaccharide (LPS) was utilized to establish an acute kidney injury model. HK-2 cells were divided into 3 groups: control group, LPS group, LPS+irisin group. The expression of TNF-α, IL-1ß, Bcl-2, and Bax were detected using Western blot. Commercial enzyme-linked immunosorbent assay (ELISA) kits were used to detect the levels of TNF-α, IL-6, and IL-1ß in the cell supernatant. The LDH content was detected to observe cell damage. TUNEL staining and flow cytometry were to investigate the apoptosis in three groups. The viability of HK-2 cells was detected using Cell Counting Kit-8 (CCK-8) assay. RESULTS: After HK-2 cells were treated with LPS, the LDH content in the cell supernatant was greatly increased, and the expression of TNF-α, IL-6, and IL-1ß was also significantly increased. However, after treatment with irisin, LDH content and expression of inflammatory factors were significantly suppressed. Similarly, LPS treatment greatly elevated the levels of TNF-α, IL-1ß, Bax, p65 and IκKα, as well as inhibited the expression of Bcl-2 and IκB-α. However, irisin treatment reversed these situations. In addition, the number of TUNEL-positive cells and the apoptotic rate were also greatly decreased in LPS+irisin group compared with those in LPS group. CONCLUSIONS: Irisin could inhibit inflammation and apoptosis of HK-2 cells treated with LPS via the NF-κB pathway.
Subject(s)
Acute Kidney Injury/metabolism , Fibronectins/metabolism , NF-kappa B/metabolism , Sepsis/metabolism , Acute Kidney Injury/chemically induced , Acute Kidney Injury/pathology , Animals , Apoptosis/drug effects , Cells, Cultured , Disease Models, Animal , Dose-Response Relationship, Drug , Humans , Lipopolysaccharides , Sepsis/chemically induced , Sepsis/pathology , Signal TransductionABSTRACT
Porphyromonas gingivalis has been linked to the development and progression of oesophageal squamous cell carcinoma (ESCC), and is considered to be a high-risk factor for ESCC. Currently, the commonly used methods for P. gingivalis detection are culture or DNA extraction-based, which are either time and labour intensive especially for high-throughput applications. We aimed to establish and evaluate a rapid and sensitive direct quantitative polymerase chain reaction (qPCR) protocol for the detection of P. gingivalis without DNA extraction which is suitable for large-scale epidemiological studies. Paired gingival swab samples from 192 subjects undergoing general medical examinations were analysed using two direct and one extraction-based qPCR assays for P. gingivalis. Tris-EDTA buffer-based direct qPCR (TE-direct qPCR), lysis-based direct qPCR (lysis-direct qPCR) and DNA extraction-based qPCR (kit-qPCR) were used, respectively, in 192, 132 and 60 of these samples for quantification of P. gingivalis. The sensitivity and specificity of TE-direct qPCR was 95.24% and 100% compared with lysis-direct qPCR, which was 100% and 97.30% when compared with kit-qPCR; TE-direct qPCR had an almost perfect agreement with lysis-direct qPCR (κ = 0.954) and kit-qPCR (κ = 0.965). Moreover, the assay time used for TE-direct qPCR was 1.5 h. In conclusion, the TE-direct qPCR assay is a simple and efficient method for the quantification of oral P. gingivalis and showed high sensitivity and specificity compared with routine qPCR.
Subject(s)
Polymerase Chain Reaction/methods , Porphyromonas gingivalis/isolation & purification , Bacteriological Techniques , Humans , Sensitivity and SpecificityABSTRACT
Objective: To analyze the relationship of body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) with diabetes mellitus in community residents aged ≥15 years in Pudong new district of Shanghai, and provide evidence for the prevention and treatment of diabetes mellitus. Methods: Using multi-stage stratified cluster sampling method, a total of 7 194 community residents aged ≥15 years were surveyed by using questionnaire, physical examination and laboratory tests in 2016. The relationship of BMI, waist circumference and waist-hip ratio with diabetes mellitus was analyzed by χ(2) test, single factor linear correlation and logistic regression analyses. Results: In 2016, the crude prevalence rate of diabetes mellitus in Pudong was 27.37%, which was 12.75% after standardization. The prevalence rate of diabetes mellitus was slightly higher in men than in women and was increased with age. The levels of FPG, 2 h plasma glucose and HbA1c were positively correlated with BMI, WC and WHR. After adjusting the confounding factors, multiple logistic regression analysis showed that obesity (OR=1.351, P<0.01), excessive waist circumference (OR=1.255, P<0.01) and high WHR (OR=1.291, P<0.01) were risk factors for diabetes mellitus. Conclusions: The increase of obesity, WC and WHR will increase the risk for diabetes mellitus. It is important to maintain healthy weight, especially the control of WC and WHR, reduce the accumulation of abdominal fat to reduce the risk for diabetes mellitus.
Subject(s)
Body Mass Index , Diabetes Mellitus/epidemiology , Waist Circumference , Waist-Hip Ratio , Adolescent , Adult , China/epidemiology , Female , Humans , Male , Risk FactorsABSTRACT
OBJECTIVE: The aim of this study was to investigate the effect of dexmedetomidine (DEX) on kidney injury in sepsis rats through the Toll-like receptor 4 (TLR4)/myeloid differential protein-88 (MyD88)/nuclear factor-κB (NF-κB)/inducible nitric oxide synthase (iNOS) signaling pathway. MATERIALS AND METHODS: A total of 30 Sprague-Dawley (SD) rats were randomly divided into three groups, including the control group (n=10), lipopolysaccharide (LPS)-induced acute kidney injury (AKI) group (model group, n=10) and DEX treatment group (DEX group, n=10). The model of sepsis was successfully established in rats. The levels of serum creatinine (Cr), blood urea nitrogen (BUN), serum interleukin-6 (IL-6), IL-1ß, IL-10 and tumor necrosis factor-α (TNF-α) were detected via enzyme-linked immunosorbent assay (ELISA). The pathological changes in kidney tissues were detected via hematoxylin-eosin (HE) staining. Furthermore, the mRNA and protein expressions of TLR4, MyD88, NF-κB, and iNOS in the kidney were detected via fluorescence quantitative Polymerase Chain Reaction (PCR) and Western blotting, respectively. RESULTS: Compared with the control group, rats in the model group showed significant kidney injury, markedly increased levels of serum Cr, BUN and pro-inflammatory cytokines, remarkably decreased the level of IL-10 (p<0.05), and significantly increased mRNA and protein expressions of TLR4, MyD88, NF-κB, and iNOS. In the DEX group, AKI was markedly improved, while the expressions of inflammatory cytokines were remarkably declined. Furthermore, the mRNA and protein expressions of TLR4, MyD88, NF-κB, and iNOS decreased significantly. CONCLUSIONS: DEX has a protective effect on LPS-induced AKI, whose mechanism may be related to the inhibition of the TLR4/MyD88/NF-κB/iNOS pathway.
Subject(s)
Acute Kidney Injury/drug therapy , Adrenergic alpha-2 Receptor Agonists/pharmacology , Dexmedetomidine/pharmacology , Sepsis/complications , Signal Transduction/drug effects , Acute Kidney Injury/immunology , Acute Kidney Injury/pathology , Administration, Oral , Adrenergic alpha-2 Receptor Agonists/therapeutic use , Animals , Dexmedetomidine/therapeutic use , Disease Models, Animal , Humans , Kidney/drug effects , Kidney/immunology , Kidney/pathology , Lipopolysaccharides/administration & dosage , Lipopolysaccharides/immunology , Male , Myeloid Differentiation Factor 88/metabolism , NF-kappa B/metabolism , Nitric Oxide Synthase Type II/metabolism , Rats , Sepsis/drug therapy , Sepsis/immunology , Signal Transduction/immunology , Specific Pathogen-Free Organisms , Toll-Like Receptor 4/metabolismABSTRACT
Precision breeding is an approach to grapevine genetic improvement that transfers only specific traits among sexually compatible species via the relatively stable mitotic cell division pathway in order to avoid the significant disruption imposed upon conventional breeding by meiosis. Factors enabling precision breeding include the availability of the Vitis genome sequence combined with highly optimized gene insertion and plant regeneration protocols. A protocol for the production of grapevine embryogenic cultures and their genetic transformation is described. Embryogenic cultures are produced from either leaf or floral explants. Somatic embryos at the cotyledonary stage of development are used for Agrobacterium-mediated transformation. Following co-cultivation with Agrobacterium containing the genes of interest, modified embryos are selected on the basis of anthocyanin pigmentation and antibiotic resistance. Somatic embryos are then germinated to produce modified plants that are hardened and transferred to a greenhouse. The presence of the genes of interest is confirmed by PCR.
Subject(s)
Plant Breeding/methods , Plant Somatic Embryogenesis Techniques/methods , Plants, Genetically Modified/genetics , Transformation, Genetic , Vitis/genetics , Agrobacterium/genetics , Cotyledon , Gene Editing/methods , Genome, Plant/genetics , Plant Somatic Embryogenesis Techniques/instrumentation , SeedsABSTRACT
The present study aimed to investigate the mechanisms by which mannose protects the lung injury induced in rats with acute pancreatitis (AP). An AP combined with Acute Lung Injury (ALI) model was established. A total of 90 healthy adult male Sprague-Dawley rats (300±50g weight) were randomly divided into three groups: sham operation group (SO group), severe acute pancreatitis lung injury group (SAP group), and mannose intervention group (MT group). Subsequently, each group was divided into two subgroups based on the time passed from intervention, namely 6 and 12 h. Each subgroup comprised 15 rats. The ratio of wet/dry weight of the lung tissue exhibited no significant change at different time points in the SO group. This parameter was significantly increased in the SAP group compared with the SO group at each time point of the treatment (P less than 0.05) and it was significantly lower in the MT group than that in the AP group (P less than 0.05) and it was significantly increased in the AP group at each time (P less than 0.05) compared with the SO group. The levels of TNF-α in the lung tissue in the SO group exhibited no significant change at different time points, but they were significantly decreased in the MT group at each time point (P less than 0.05) compared with the SAP group. The mannose receptor (MR) mRNA and protein levels in the lung tissues exhibited no significant change at different time points. The mRNA and protein levels of MR in the SAP group were significantly decreased at each time point (P less than 0.05) compared with the SO group. The mRNA and protein levels of MR, in the lung tissue of the MT group were significantly increased at each time point compared with the SAP group (P less than 0.05). Mannose could reduce the injury caused to the lung tissue of rats with severe acute pancreatitis by up-regulation of the expression of MR mRNA and protein.
Subject(s)
Acute Lung Injury , Lung , Mannose/pharmacology , Pancreatitis , Acute Lung Injury/drug therapy , Acute Lung Injury/etiology , Acute Lung Injury/metabolism , Acute Lung Injury/pathology , Animals , Lectins, C-Type/metabolism , Lung/metabolism , Lung/pathology , Male , Mannose Receptor , Mannose-Binding Lectins/metabolism , Pancreatitis/complications , Pancreatitis/drug therapy , Pancreatitis/metabolism , Pancreatitis/pathology , Rats , Rats, Sprague-Dawley , Receptors, Cell Surface/metabolism , Respiratory Function Tests , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Embryo cryopreservation is important for long-term preservation of germplasm and assisted reproduction. However, it is still very difficult to obtain viable embryos from cryopreserved fish embryos. In this study, embryos of Epinephelus moara were used to investigate the effects of various cryopreservation methods. Embryos in stages 10 pairs somite (10S), 18 pairs somite (18S), 22 pairs somite (22S), tail-bud (TB), embryo twitching (ET) and pre-hatch (PH) were treated with five-step equilibrium penetration in 40% PMG3T vitrification solution, which contained 15.75% 1,2-propylene glycol, 10.50% Methanol, 8.75% Glycerol and 5.00% Trehalose. We found that 18S, 22S, TB and ET stage embryos had higher survival rates and were more tolerant to the vitrification solution. Five-step equilibrium treatments on the embryos at the tail-bud stage were performed using two vitrification solutions: 40% PMG3T and 40% PMG3S, which consisted of 15.75% 1,2-propylene glycol, 10.50% Methanol, 8.75% Glycerol and 5.00% Sucrose. The embryonic survival rate under PMG3S treatment (63.36%) was significantly higher than PMG3T treatment (43.93%) (Pâ¯<â¯0.05). PMG3S and PMG3T with concentrations of 35%, 40% and 45% were tested on tail-bud stage embryos. Higher concentration of the vitrification solution led to significantly lower embryonic survival rate (Pâ¯<â¯0.05). The survival rate was 36.79-72.05% in PMG3S, and 37.11-55.18% in PMG3T, and there were non-significant differences in embryonic development and malformation rates among the groups treated with different concentrations. The embryonic normal development rates in PMG3S and PMG3T were 21.27% and 11.04%, and the malformation rates were 36.13% and 31.04%, respectively. The optimum treatment condition was 40â¯min using 40% PMG3S on embryos at the tail-bud stage. Both PMG3S and PMG3T were used for cryopreserving embryos at 16 pairs somite, tail-bud and ET stage in liquid nitrogen, where we obtained 190 surviving embryos, and 44 fishes underwent normal development and hatched. The survival rate of cryopreserved embryos was 5.15%, the normal development rate was 1.31%, and the malformation rate was 3.66%. We found that PMG3S and PMG3T were effective for cryopreservation of Epinephelus moara embryos. The results provide a foundation for further explorations of fish embryo cryopreservation techniques.
Subject(s)
Cryopreservation/veterinary , Cryoprotective Agents/pharmacology , Embryo, Nonmammalian/physiology , Perciformes/embryology , Vitrification , Animals , Embryo, Nonmammalian/drug effects , Survival RateABSTRACT
The aim of this study was to evaluate the therapeutic effect of rhubarb extract on acute pancreatitis. Ninety-six healthy Sprague Dawley rats, weighing 301±5.12 g were randomly divided into 4 groups: sham surgery (group A), acute pancreatitis model (group B), acute pancreatitis with normal saline (group C), and acute pancreatitis model with rhubarb (group D). The levels of serum amylase (AMY) and TNF-α were measured at 1st, 6th, 12th and 24th hour after modeling, and the pancreatic tissue were used to observe the pathologic changes. Compared to the sham group, the serum AMY and serum tumor necrosis factor (TNF-α) levels were significantly increased in the other groups (p <0.05). Compared to the model group and the saline group, the serum AMY, serum TNF-α level and pathological changes of rats in the rhubarb group were significantly lower (p <0.05). The serum AMY and TNF-α levels increased in acute pancreatitis. The rhubarb reduced the serum AMY and TNF-α level in rats with acute pancreatitis and reduced the pathological changes of pancreas and other tissues.
Subject(s)
Amylases/blood , Pancreatitis/blood , Pancreatitis/drug therapy , Plant Extracts/pharmacology , Rheum/chemistry , Tumor Necrosis Factor-alpha/blood , Acute Disease , Animals , Disease Models, Animal , Pancreatitis/chemically induced , Plant Extracts/chemistry , Rats , Rats, Sprague-DawleyABSTRACT
OBJECTIVE: Our study aimed to compare the chemoradiotherapeutic regimens of carboplatin and paclitaxel with or without bevacizumab for stage III non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: From July 2010 to December 2016, 102 patients with inoperable stage III NSCLC were finally included and divided randomly into two groups. Patients in the CP group received the treatment of carboplatin (area under the curve of 6) on day 1 and paclitaxel (80 mg/m2) on days 1, 8, and 15. Patients in the CPB group received the treatment of carboplatin (area under the curve of 6) on day 1, paclitaxel (80 mg/m2) on days 1, 8, and 15 plus bevacizumab (15 mg/kg) on day 1. The two chemotherapy regimens were repeated every 4 weeks. Patients were treated for about 4-6 cycles until the occurrence of toxicity or patient refusal, or progressive disease. RESULTS: The median overall survival (OS) and progression-free survival (PFS) in the CPB treated group were significantly higher than that in the CP treated group (OS: p<0.01; PFS: p<0.01; respectively). The rates of response and disease control were higher in the CPB treated group (77%, 98%, respectively) compared to the CP treated group (59%, 94%, respectively), although there was no statistical significance. Regarding the toxicities of chemotherapy, we found higher rates of leukopenia and neutropenia in the CPB group, while frequent occurrence of esophagitis, eruption and thrombocytopenia in the CP group. CONCLUSIONS: The carboplatin plus paclitaxel plus bevacizumab regimen was more effective and well tolerated in patients with unresectable stage III NSCLC compared with the carboplatin plus paclitaxel regimen. The CPB regimen may be a better alternative to the current standard regimen.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Adult , Aged , Bevacizumab/administration & dosage , Carboplatin/administration & dosage , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Female , Humans , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Paclitaxel/administration & dosageABSTRACT
Nucleotide-binding oligomerization domain-like receptors (NLRs) play a key role in the innate immune response as pattern-recognition receptors. However, the role of NLRC5, which is a member of the NLR family, in NF-κB activation and MHC-I expression remains debatable. Infection with the J group avian leukosis virus (ALV-J) can result in immunosuppression and a subsequent increase in susceptibility to secondary infection. This results in huge economic losses to the poultry industry worldwide. Using quantitative real-time polymerase chain reaction (qRT-PCR), we investigated the mRNA expression levels of NLRC5 signal pathway-related genes in secondary chicken embryo fibroblasts 7 days after infection with ALV-J. The results indicated that, compared with the control groups, the expression levels of TLR7, MHC-I, and IL-18 increased significantly in the infected groups at 7 days post-infection (d.p.i.). The expression levels of NLRC5 and IL-6 were conspicuously downregulated at 7 d.p.i., but the expression levels of NF-κB, STAT1, and STAT3 were not significantly altered. These results suggest that NLRC5 and some genes involved in the NLRC5 pathway play a key role in antiviral immunity, typically the response to ALV-J infection. Moreover, MHC-I expression levels vary between different cell types.
Subject(s)
Avian Leukosis/metabolism , NLR Proteins/metabolism , Signal Transduction , Up-Regulation , Animals , Avian Leukosis/genetics , Cells, Cultured , Chick Embryo , Cytokines , Fibroblasts/metabolism , Histocompatibility Antigens Class I/genetics , Histocompatibility Antigens Class I/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , NF-kappa B/genetics , NF-kappa B/metabolism , NLR Proteins/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , STAT1 Transcription Factor/genetics , STAT1 Transcription Factor/metabolism , STAT3 Transcription Factor/metabolism , Toll-Like Receptor 7/genetics , Toll-Like Receptor 7/metabolismABSTRACT
OBJECTIVES: This study aims to explore the relationships among components of the Health Belief Model, tuberculosis (TB) preventive behavior, and intention of seeking TB care. STUDY DESIGN: Cross section study. METHODS: Using convenience sampling, 1154 rural-to-urban migrant workers were selected between the ages of 18-50 years in six urban areas of three provinces in China. The survey was conducted by individual, face-to-face interviews with a standardized questionnaire. Lisrel 8.7 was used to conduct path analysis. RESULTS: The knowledge and benefits components of the Health Belief Model predicted preventive behaviors: cover nose/mouth when coughing or sneezing (ß = 0.24, 0.33 respectively), evade others' coughs (ß = 0.13, 0.25) and also predicted seeking TB care (ß = 0.27, 0.19). Susceptibility and severity also predicted seeking TB care (ß = 0.12, 0.16). There were also important relationships among model components. Knowledge of TB predicted both susceptibility (ß = 0.32-0.60) and severity (ß = 0.41-0.45). Further, each of susceptibility (ß = 0.30) and severity (ß = 0.41) predicted perceived benefits of preventive care. CONCLUSION: Thus, a path from knowledge, through severity and susceptibility, and then through benefits predicted prevention and TB care seeking behaviors.
Subject(s)
Intention , Patient Acceptance of Health Care/psychology , Population Dynamics , Tuberculosis/prevention & control , Adolescent , Adult , China , Cough , Cross-Sectional Studies , Female , Health Behavior , Health Knowledge, Attitudes, Practice , Humans , Interviews as Topic , Male , Middle Aged , Rural Population , Socioeconomic Factors , Surveys and Questionnaires , Transients and Migrants , Urban Population , Young AdultABSTRACT
BACKGROUND: Mucinous epithelial ovarian cancer (mEOC) may exhibit a distinct biological behavior in epithelial ovarian cancer (EOC). The role of secondary cytoreductive surgery was evaluated in patients with recurrent mEOC, and the prognosis was assessed. METHODS: Twenty-one patients with stages IIc to IV mEOC who experienced disease recurrence and received secondary cytoreductive surgery at Fudan University Cancer Hospital between Jan. 1997 and Dec. 2005 were retrospectively reviewed. Survival curves were generated using the Kaplan-Meier method and the significant comparison of survival rate was estimated by the log-rank test. RESULTS: The median progression-free interval (PFI) was 14 months (range, 5-46 months) after the first cytoreduction. Seven patients (33%) who received secondary cytoreductive surgery were optimally cytoreduced with residual disease less than or equal 1cm, and the other 14 patients (67%) underwent suboptimal surgical cytoreduction. The overall median survival time was 27 months (range, 8-64 months). The median survival time after recurrence was 10 months (range, 3-32 months). There was no significant statistical difference in median survival between patients with optimal and suboptimal secondary surgical cytoreduction, with an estimated survival of 10 months and 9.8 months, respectively (P>0.05). CONCLUSION: Optimal primary cytoreductive surgery for advanced mEOC was very important. Once it recurs, the prognosis is very poor. Patients with recurrent mEOC should be carefully assessed before performing secondary cytoreductive surgery, as this may have limited impact on the overall survival rates.
Subject(s)
Adenocarcinoma, Mucinous/surgery , Neoplasm Recurrence, Local/surgery , Ovarian Neoplasms/surgery , Salvage Therapy , Adenocarcinoma, Mucinous/drug therapy , Adenocarcinoma, Mucinous/pathology , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemotherapy, Adjuvant , China , Disease-Free Survival , Female , Humans , Middle Aged , Neoplasm Recurrence, Local/pathology , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/pathology , Retrospective Studies , Survival AnalysisABSTRACT
A method to produce transgenic plants of Vitis rotundifolia was developed. Embryogenic cultures were initiated from leaves of in vitro grown shoot cultures and used as target tissues for Agrobacterium-mediated genetic transformation. A green fluorescent protein/neomycin phosphotransferase II (gfp/nptII) fusion gene that allowed for simultaneous selection of transgenic cells based on GFP fluorescence and kanamycin resistance was used to optimize parameters influencing genetic transformation. It was determined that both proembryonal masses (PEM) and mid-cotyledonary stage somatic embryos (SE) were suitable target tissues for co-cultivation with Agrobacterium as evidenced by transient GFP expression. Kanamycin at 100 mg l(-1) in the culture medium was effective in suppression of non-transformed tissue and permitting the growth and development of transgenic cells, compared to 50 or 75 mg l(-1), which permitted the proliferation of more non-transformed cells. Transgenic plants of "Alachua" and "Carlos" were recovered after secondary somatic embryogenesis from primary SE explants co-cultivated with Agrobacterium. The presence and stable integration of transgenes in transgenic plants was confirmed by PCR and Southern blot hybridization. Transgenic plants exhibited uniform GFP expression in cells of all plant tissues and organs including leaves, stems, roots, inflorescences and the embryo and endosperm of developing berries.
Subject(s)
Plants, Genetically Modified/genetics , Regeneration/genetics , Rhizobium/genetics , Vitis/genetics , Blotting, Southern , Cells, Cultured , Kanamycin/pharmacology , Kanamycin Kinase/genetics , Kanamycin Kinase/metabolism , Plants, Genetically Modified/drug effects , Plants, Genetically Modified/physiology , Polymerase Chain Reaction , Regeneration/drug effects , Regeneration/physiology , Transformation, Genetic , Vitis/cytology , Vitis/embryologyABSTRACT
The purpose of this retrospective study was to report our experience with concurrent chemotherapy and adjuvant extended field irradiation after radical surgery for cervical carcinoma patients with common iliac node and/or multiple pelvic lymph nodes metastases. We studied 25 patients with FIGO stage IB-IIB (IB, 3; IIA, 15; and IIB, 7) cervical carcinoma who underwent radical surgery and had histologically confirmed involvement of common iliac nodes and/or multiple (>or=2) pelvic lymph nodes. These patients received the first cycle of systemic chemotherapy 2 weeks after radical surgery. Then, they received pelvic and extended field irradiation (40-45 Gy) with weekly cisplatinum (30 mg/m(2)). They were then given five more cycles of consolidation chemotherapy. Survival curves were generated by the Kaplan-Meier method. The 3-year progression-free survival (PFS) and overall survival rates were 63% and 76%, respectively. The PFS rates with multiple pelvic node and common iliac node metastases were 69% and 61%, respectively. The pelvic recurrence rate was 8% (2/25) and that for distant metastases was 32% (8/25). No patient's treatment failed in the para-aortic region. The median interval from the surgery to the recurrence was 14 months (range, 5-29 months). Nineteen (76%) patients experienced grades 1-2 and four (16%) experienced grades 3-4 neutropenia. Fifteen patients (60%) experienced grades 1-2 and one (4%) experienced grades 3-4 gastrointestinal toxicity. Concurrent chemotherapy and adjuvant extended field irradiation after radical surgery achieved good local control with acceptable toxicity. However, subsequent distant metastasis was still the predominant form of treatment failure even after consolidation chemotherapy.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma/drug therapy , Carcinoma/radiotherapy , Hysterectomy , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/radiotherapy , Adult , Brachytherapy/methods , Carcinoma/pathology , Carcinoma/surgery , Chemotherapy, Adjuvant/adverse effects , Combined Modality Therapy , Disease-Free Survival , Female , Humans , Lymph Nodes/pathology , Lymphatic Metastasis , Middle Aged , Radiotherapy, Adjuvant/adverse effects , Recurrence , Retrospective Studies , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/surgeryABSTRACT
Shoot apical meristem explants of Vitis vinifera "Thompson Seedless" were used for Agrobacterium-mediated genetic transformation. It was determined that the meristems had to be subjected to a dark growth phase then wounded to obtain transgenic plants. Morphological and histological studies illustrated the role of wounding to expose apical meristem cells for transformation. A bifunctional egfp/nptII fusion gene was used to select kanamycin resistant plants that expressed green fluorescent protein (GFP). Kanamycin at a concentration of 16 mg L(-1) in selection medium resulted in recovery of non-chimeric transgenic plants that uniformly expressed GFP, whereas 8 mg L(-1) kanamycin allowed non-transgenic and/or chimeric plants to develop. Polymerase chain reaction (PCR) and Southern blot analyses confirmed the presence of transgenes and their stable integration into the genome of regenerated plants. Up to 1% of shoot tips produced stable transgenic cultures within 6 weeks of treatment, resulting in a total of 18 independent lines.
Subject(s)
Meristem/genetics , Plant Shoots/genetics , Plants, Genetically Modified/genetics , Vitis/genetics , Blotting, Southern , Drug Resistance/genetics , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Kanamycin/pharmacology , Meristem/drug effects , Meristem/ultrastructure , Microscopy, Electron, Scanning , Plant Shoots/drug effects , Plant Shoots/ultrastructure , Plants, Genetically Modified/drug effects , Plants, Genetically Modified/ultrastructure , Polymerase Chain Reaction , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Rhizobium/genetics , Tissue Culture Techniques , Transformation, Genetic , Transgenes/genetics , Vitis/drug effects , Vitis/ultrastructureABSTRACT
The objective of this paper is to clarify the role of cytoreductive surgery and salvage chemotherapy in the management of recurrent advanced epithelial ovarian carcinoma (RAEOC) and to identify factors affecting disease recurrence. One hundred sixty seven patients with RAEOC treated at the Cancer Hospital of Fudan University between January 1986 and December 1997 were retrospectively reviewed. Survival was calculated by Kaplan-Meier method with difference in survival estimated by the log-rank test. Independent prognostic factors were identified by the Cox stepwise regression model and variants associated with disease recurrence were determined using logistic stepwise regression methods. The median age was 52 (range 27-72) years. Sixty (35.9%) patients underwent re-debulking surgery, 23 of them with residual disease =1 cm. There was a significant difference in survival between optimal and suboptimal groups, with an estimated median survival of 18 and 13 months, respectively (P = 0.021, chi2 = 9.42). When patients with suboptimal surgical results were compared to those with chemotherapy alone, there was a significant difference in median survival, 13 vs. 16 months (P = 0.0364, chi2 = 4.38). Residual disease after primary surgery, neoadjuvant chemotherapy, and salvage chemotherapy was a predictor of survival identified by Cox regression analysis, but secondary cytoreductive surgery did not reach a level of statistical significance (P = 0.0561). Logistic stepwise regression analysis showed that age, first-line chemotherapy, neoadjuvant chemotherapy, and the size of residual disease after primary surgical cytoreduction were factors affecting disease recurrence. We conclude that patients with RAEOC benefit from optimal secondary surgical cytoreduction. Should the recurrence not be optimally cytoreduced by surgery, alternative salvage chemotherapy is best for RAEOC.