ABSTRACT
Heterogeneous interface construction is of far-reaching significance to optimize the electrochemical performance of electrodes. Herein, a multi-step alternating electrochemical deposition (MAED) method is proposed to alternately deposit Co0.85Se and Ni3S4 nanosheets on a nickel foam (NF), forming a special alternate layer-by-layer structure with multi-layered heterogeneous interfaces. The creation of the multi-layered heterogeneous interfaces provides a large interfacial area for redox reactions with optimum interstitials facilitating ion diffusion, thus greatly improving the electrochemical energy storage efficiency. With the increase in the layer number, the material exhibits increasingly better energy storage performance, and 8L-Co0.85Se@Ni3S4/NF exhibits the highest specific capacitances of 2508 F g-1 and 1558 F g-1 at a scan rate of 2 mV s-1 and a current density of 1 A g-1. The 8L-Co0.85Se@Ni3S4/NF//polypyrrole (PPy)/NF asymmetric supercapacitor provides a maximum operation potential window of 1.55 V and energy densities of 76.98 and 35.74 W h kg-1 when the power densities are 775.0 and 15 500 W kg-1, respectively, superior to most of the related materials reported. Through MAED, the deposited phase and the layer number can be accurately controlled, thus providing an efficient strategy for interface construction so as to increase the electrochemical activity of the energy storage materials.
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This study aims to address the suboptimal performance of conventional denitrifying strains in treating mariculture tail water (MTW) containing inorganic nitrogen (IN). The concentration of inorganic nitrogen in the mariculture tail water is about 5-20 mg·L-1. A biofilm treatment process was developed and evaluated using an anoxic-anoxic-aerobic biofilter composite system inoculated with the denitrifying strain Meyerozyma guilliermondii Y8. The removal effect of total nitrogen (TN), IN, and Chemical Oxygen Demand (CODMn) from MTW was investigated. The results indicate that the A2O composite biological filter has excellent pollutant removal efficiency within 25 days of operation, after the acclimation of the denitrifying microorganisms. The initial concentrations of TN, IN, and CODMn ranged between 10.24 and 12.89 mg·L-1, 7.84-10.49 mg·L-1, and 9.44-11.52 mg·L-1, respectively, and the removal rates of these indexes reached 38-68 %, 45-70 %, and 55-70 %, respectively. The experiments with different hydraulic retention times (HRT = 6 h, 8 h, 10 h) demonstrated that longer HRT was more conducive to the removal of inorganic nitrogen. Moreover, scanning electron microscopy observations revealed that the target strain successfully grew and attached to the filler in large quantities. The findings of this study provide practical guidance for the development of efficient biofilm processes for the treatment of MTW.
Subject(s)
Nitrogen , Water Pollutants, Chemical , Anaerobiosis , Biofilms , Waste Disposal, Fluid/methods , Denitrification , Biological Oxygen Demand Analysis , Aquaculture , Biodegradation, Environmental , Water Purification/methodsABSTRACT
We conducted this study to investigate the radioprotective effects of recombinant human thrombopoietin (rhTPO) on beagle dogs irradiated with 3.0 Gy 60Co gamma rays. Fifteen healthy adult beagles were randomly assigned to a control group with alleviating care, and 5 and 10 µg/kg rhTPO treatment group. All animals received total-body irradiation using 60Co γ-ray source at a dose of 3.0 Gy (dose rate was 69.1 cGy/min). The treatment group received intramuscular injection of rhTPO 5 and 10 µg/kg at 2 h postirradiation, and the control group was administrated the same volume of normal saline. The survival rate, clinical signs, peripheral hemogram, serum biochemistry, and histopathological examination of animals in each group were assessed. Single administration of 10 µg/kg rhTPO at 2 h postirradiation promoted the recovery of multilineage hematopoiesis and improved the survival rate of beagles irradiated with 3 Gy 60Co γ rays. The administration of 10 µg/kg rhTPO alleviated fever and bleeding, reduced the requirement for supportive care, and may have mitigated multiple organ damage.
Subject(s)
Gamma Rays , Hematopoiesis , Radiation-Protective Agents , Recombinant Proteins , Thrombopoietin , Whole-Body Irradiation , Animals , Dogs , Thrombopoietin/pharmacology , Thrombopoietin/administration & dosage , Recombinant Proteins/administration & dosage , Recombinant Proteins/pharmacology , Hematopoiesis/drug effects , Hematopoiesis/radiation effects , Humans , Radiation-Protective Agents/pharmacology , Radiation-Protective Agents/administration & dosage , Male , Cobalt Radioisotopes , Female , Dose-Response Relationship, RadiationABSTRACT
Exposure to medium and high doses of ionizing radiation (IR) can induce long-term bone marrow (BM) suppression. We previously showed that recombinant human thrombopoietin (rhTPO) significantly promotes recovery from hematopoietic-acute radiation syndrome, but its effect on long-term BM suppression remains unknown. C57BL/6 mice were exposed to 6.5 Gy γ-rays of total body irradiation (TBI) at a dose-rate of 63.01 cGy per minute, and the mice were treated with rhTPO (100 µg; intramuscular injection) or vehicle at 2 h after TBI. All mice were killed one or two months after TBI for analysis of peripheral blood cell counts, long-term hematopoietic stem cell (HSC) frequency, and BM-derived clonogenic activity. The HSC self-renewal capacity was analyzed by BM transplantation. The levels of reactive oxygen species (ROS) production and ratios of γH2AX+ and p16, p53, and p21 mRNA in HSCs were measured by flow cytometry and real-time polymerase chain reaction, respectively. Treatment with rhTPO reduced long-term myelosuppression by improving long-term hematopoietic reconstitution (p < 0.05) after transplantation and resting state maintenance of HSCs (p < 0.05). Moreover, rhTPO treatment was associated with a sustained reduction in long-term ROS production, reduction of long-term DNA damage, diminished p53/p21 mRNA expression, and prevention of senescence after TBI. This study suggests rhTPO is an effective agent for treating IR-induced long-term BM injury because it regulates hematopoietic remodeling and HSC cycle disorder through the ROS/p53/p21/p16 pathway long term after IR.
Subject(s)
Radiation Injuries , Thrombopoietin , Animals , Mice , Hematopoietic Stem Cells , Mice, Inbred C57BL , Reactive Oxygen Species/metabolism , Recombinant Proteins/metabolism , RNA, Messenger/metabolism , Tumor Suppressor Protein p53/metabolism , Whole-Body IrradiationABSTRACT
OBJECTIVE: To confirm the therapeutic effect of recombinant human thrombopoietin (rhTPO) on rhesus monkeys irradiated with 5.0 Gy 60Co γ-ray, and provide experimental basis for clinical treatment of similar patients. METHODS: Fourteen adult rhesus monkeys were irradiated with 60Co γ-ray on both sides at the dose of 5.0 Gy (dose rate 69.2 cGy/min) to establish the acute radiation sickness model. The monkeys were divided into irradiation group (n=5), rhTPO 5 µg/kg group (n=4) and rhTPO 10 µg/kg group (n=5). Two hours after irradiation, the three groups of monkeys were injected with saline 0.1 ml/kg, rhTPO 5 µg/kgï¼0.1 ml/kgï¼ and rhTPO 10 µg/kg(0.2 ml/kg), respectively. The general signs, survival, peripheral hemogram and serum biochemistry of rhesus monkeys were observed before and after irradiation, and the differences between rhTPO group and irradiation control group were compared. RESULTS: After total body irradiation with 5.0 Gy60Co γ-ray, rhesus monkeys successively showed fever, hemorrhage, sharp decrease of whole blood cell counts in peripheral blood and disorder of serum biochemical indexes. Compared with the irradiated control group, a single intramuscular injection of rhTPO 5 µg/kg or 10 µg/kg 2 hours after irradiation could improve the symptoms of fever and bleeding, increase the nadir of peripheral red blood cells and platelets counts, shorten the duration of hemocytopenia, and advance the time for blood cells to return to the pre-irradiation level. The serum biochemical results showed that rhTPO could improve the abnormality of serum biochemical indexes in rhesus monkeys induced by 5.0 Gy total body irradiation to some extent. Compared with the two administration groups, the therapeutic effect of rhTPO 10 µg/ kg was better. CONCLUSION: A single injection of rhTPO 5 µg/ kg or 10 µg/ kg 2 hours after irradiation can alleviate the injury of multilineage hematopoiesis and promote the recovery in monkeys irradiated by 5.0 Gy γ-ray. It also improves animal signs and has obvious therapeutic effect on acute radiation sickness.
Subject(s)
Radiation Injuries , Humans , Animals , Macaca mulattaABSTRACT
Medical ultrasound imaging plays an important role in computer-aided diagnosis systems. In many cases, it is the preferred method of doctors for diagnosing diseases. Combined with computer vision technology, segmentation of ovarian ultrasound images can help doctors accurately judge diseases, reduce doctors' workload, and improve doctors' work efficiency. However, accurate segmentation of an ovarian ultrasound image is a challenging task. On the one hand, there is a lot of speckle noise in ultrasound images; on the other hand, the edges of objects are blurred in ultrasound images. In order to segment the target accurately, we propose an ovarian follicles segmentation network combined with edge information. By adding an edge detection branch at the end of the network and taking the edge detection results as one of the losses of the network, we can accurately segment the ovarian follicles in an ultrasound image, making the segmentation results finer on the edge. Experiments show that the proposed network improves the segmentation accuracy of ovarian follicles, and that it has advantages over current algorithms.
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OBJECTIVE: To study the effect of interleukin-6 (IL-6) gene deletion on radiation-induced hematopoietic injury in mice and relative mechanism. METHODS: Before and after whole body 60Co γ-ray irradiation, it was analyzed and compared that the difference of peripheral hemogram, bone marrow hematopoietic stem and progenitor cells conts in IL-6 gene knockout (IL-6-/-) and wild-type (IL-6+/+) mice and serum IL-6 and G-CSF expression levels in above- mentioned mouse were detected. Moreover, 30 days survival rate of IL-6-/- and IL-6+/+ mice after 8.0 Gy γ-ray irradiation were analyzed. RESULTS: IL-6 levels in serum of IL-6+/+ and IL-6-/- mice were respectively (98.95±3.85) pg/ml and (18.36±5.61) pg/ml, which showed a significant statistical differences (P<0.001). There were no significant differences of peripheral blood cell counts and G-CSF level in serum between IL-6+/+ and IL-6-/- mice before irradiation (P>0.05). However, the number of leukocytes, neutrophils, lymphocytes, monocytes, platelets in peripheral blood and G-CSF level in serum of IL-6-/- mice were significantly decreased at 6 h after 8.0 Gy γ-ray irradiation compared with that of IL-6+/+ mice. On days 30 after 8.0 Gy γ-ray irradiation, the survival rate of IL-6+/+ and IL-6-/- mice was 62.5% and 12.5%, and the mean survival time of dead mice was 16.0±1.0 and 10.6±5.3 days, respectively. On days 14 after 6.5 Gy γ-ray irradiation, bone marrow nucleated cells in IL-6+/+ and IL-6-/- mice were respectively (10.0±1.2)×106 and (8.3±2.2)×106 per femur. Compared with IL-6+/+ mice, the proportion of Lin-Sca-1-c-kit+ (LK) in bone marrow of IL-6-/- mice had no significant change (P>0.05), but the proportion of Lin-Sca-1+c-kit+ (LSK) was significantly decreased (P<0.05). CONCLUSION: IL-6 plays an obvious role in regulating hematopoietic radiation injury, and IL-6 deficiency can inhibit the radiation-induced increase of endogenous G-CSF level in serum, aggravates the damage of mouse hematopoietic stem cellsï¼HSCï¼ and the reduction of mature blood cells in peripheral blood caused by ionizing irradiation, resulting in the shortening of the survival time and significant decrease of the survival rate of mice exposed to lethal dose radiation.
Subject(s)
Interleukin-6/metabolism , Radiation Injuries , Animals , Gene Deletion , Granulocyte Colony-Stimulating Factor/pharmacology , Mice , Whole-Body IrradiationABSTRACT
BACKGROUND: Optic nerve sheath diameter (ONSD) is recognized as a surrogate indicator of intracranial pressure (ICP) during surgery. Due to the requirements of surgery, the adjustment to the steep Trendelenburg position and the establishment of CO2 pneumoperitoneum can lead to an increase in ICP, resulting in an increase in the ONSD. Anesthetic agents have different impacts on cerebral blood volume and ICP. The aim of this study was to evaluate the effects of propofol and inhalational anesthetics on the ONSD based on data from randomized controlled trials (RCTs). METHODS: The electronic databases of PubMed, EMBASE, Ovid MEDLINE, the Cochrane Library, and other databases were searched systematically using specified keywords from their inception to June 2021. The Chi-square test and I2 test were used to evaluate the heterogeneity across the studies. The weighted mean difference (WMD) with 95% confidence interval (CI) were adopted to analyze continuous data. RESULTS: A total of 379 patients from 7 studies were involved in this meta-analysis. There were borderline significant differences in the ONSD atT2 between propofol and the control group: T2 (WMD =-0.15, 95% CI: -0.31, -0.00, P=0.005). There were significant differences at T3 (WMD =-0.23,95% CI: -0.42, -0.05, Pâ=0.013) and T4 (WMDâ =-0.18, 95% CI: -0.29, -0.07, Pâ=0â.001). After statistical verification, there was no significant difference in the ONSD at T1 between the 2 groups: T1 (WMD =-0.08, 95% CI: -0.26, 0.10, Pâ=0â.368). There were also no significant differences in mean arterial pressure (MAP) (P=0.654, 0.445, 0.698, and 0.562, respectively) and end tidal CO2 (ETCO2) (P=0.081, 0.506, 0.126, and 0.983, respectively) at T1, T2, T3 and T4 between propofol and inhalational anesthetics. DISCUSSION: The findings in the present study indicated that the ONSD during propofol anesthesia was significantly lower than that during inhalational anesthesia after adopting the Trendelenburg position and CO2 pneumoperitoneum. These analysis results suggest that propofol anesthesia may help to minimize changes in ICP compared to inhalational anesthetics.
Subject(s)
Anesthetics, Inhalation , Laparoscopy , Propofol , Robotic Surgical Procedures , Head-Down Tilt , Humans , Male , Optic Nerve , Propofol/therapeutic use , Prostatectomy , Randomized Controlled Trials as TopicABSTRACT
PURPOSE: Recombinant human thrombopoietin (rhTPO) has been evaluated as a therapeutic intervention for radiation-induced myelosuppression. However, the immunogenicity induced by a repeated-dosing strategy raises concerns about the therapeutic use of rhTPO. In this study, single-dose administration of rhTPO was evaluated for efficacy in the hematopoietic response and survival effect on mice and nonhuman primates exposed to total body irradiation (TBI). METHODS AND MATERIALS: Survival of lethally (9.0 Gy) irradiated C57BL/6J male mice was observed for 30 days after irradiation. Hematologic evaluations were performed on C57BL/6J male mice given a sublethal dose of radiation (6.5 Gy). Furthermore, in sublethally irradiated mice, we performed bone marrow (BM) histologic evaluation and evaluated BM-derived clonogenic activity. Next, the proportion and number of hematopoietic stem cells (HSCs) were analyzed. Competitive repopulation experiments were conducted to assess the multilineage engraftment of irradiated HSCs after BM transplantation. Flow cytometry was used to evaluate DNA damage, cell apoptosis, and cell cycle stage in HSCs after irradiation. Finally, we evaluated the efficacy of a single dose of rhTPO administered after 7 Gy TBI in male and female rhesus monkeys. RESULTS: A single administration of rhTPO 2 hours after irradiation significantly mitigated TBI-induced death in mice. rhTPO promoted multilineage hematopoietic recovery, increasing peripheral blood cell counts, BM cellularity, and BM colony-forming ability. rhTPO administration led to an accelerated recovery of BM HSC frequency and multilineage engraftment after transplantation. rhTPO treatment reduced radiation-induced DNA damage and apoptosis and promoted HSC proliferation after TBI. Notably, a single administration of rhTPO significantly promoted multilineage hematopoietic recovery and improved survival in nonhuman primates after TBI. CONCLUSIONS: These findings indicate that early intervention with a single administration of rhTPO may represent a promising and effective radiomitigative strategy for victims of radiation disasters.
Subject(s)
Bone Marrow/radiation effects , Radiation Injuries, Experimental/prevention & control , Thrombopoietin/administration & dosage , Whole-Body Irradiation/adverse effects , Animals , Apoptosis , Blood Cell Count , Bone Marrow/drug effects , Bone Marrow/injuries , Bone Marrow/pathology , Bone Marrow Cells/drug effects , Bone Marrow Cells/radiation effects , Cell Cycle , DNA Damage/drug effects , Female , Hematopoietic Stem Cells/drug effects , Hematopoietic Stem Cells/radiation effects , Hematopoietic System/drug effects , Hematopoietic System/injuries , Hematopoietic System/pathology , Hematopoietic System/radiation effects , Humans , Macaca mulatta , Male , Mice , Mice, Inbred C57BL , Recombinant Proteins/administration & dosage , Time FactorsABSTRACT
BACKGROUND: To provide an overview of systematic reviews and meta-analyses (SRs/MAs) of the correlation between genetic polymorphisms and blood concentrations of calcineurin inhibitors (CNIs) in recipients of renal transplant. METHODS: Databases including Medline, EMBase, The Cochrane Library (Issue 7, 2016), the Chinese Biomedical Literature Database, the China National Knowledge Infrastructure, the China Science and Technology Journal Database, and the Wan Fang Database were searched for SRs/MAs of the correlation between genetic polymorphisms and blood concentrations of CNIs in renal transplant recipients from inception to July 2016. Two reviewers independently screened the literatures and extracted data, then the AMSTAR measurement tool was used to assess the methodological quality of SRs/Mas included in the overview. RESULTS: Fourteen SRs/MAs met the inclusion criteria. The most commonly reported genotype was CYP3A53/3, which was strongly associated with cyclosporine A (CsA) and tacrolimus (FK506). MDR1 C3435T CC was also associated with CNI use, especially with CsA therapy. Other less commonly reported genotypes such as CYP3A41B, MDR1 C1236T CC, and MDR1 G2677T/A GG also affected the blood concentrations of CNIs. CONCLUSIONS: Our overview showed that polymorphisms influence the blood concentrations of CNIs, which suggests the necessity to monitor these concentrations in patients with genotypes that affect dose-adjusted trough concentrations (C0/D) or dose-adjusted peak concentrations (C2/D) to regulate the dosage for individual administration. Because of the limited number of included studies, these findings should be verified in more high-quality studies.
Subject(s)
Calcineurin Inhibitors/blood , Kidney Transplantation , Pharmacogenomic Variants , Calcineurin Inhibitors/therapeutic use , Humans , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/genetics , Kidney Failure, Chronic/surgery , Meta-Analysis as Topic , Systematic Reviews as TopicABSTRACT
Herein, we found ARHGAP25 was down-regulated in colon biopsies of patients with colorectal cancer (CRC). Gene set enrichment analysis (GSEA) also showed that ARHGAP25 was negatively correlated with Wnt/ß-catenin activation. To study the role of ARHGAP25 in CRC and its possible mechanism, we established lentiviral-mediated ARHGAP25 overexpression in HCT116 and RKO cells along with siRNA-mediated ARHGAP25 knockdown in SW620â¯cells. The metastatic capacity of the CRC cell lines in vitro was assessed by measuring cell proliferation, migration and invasion. Additionally, expression of matrix metalloproteinases (MMP2, MMP7 and MMP9), EMT-associated factors (E-cadherin, ZEB1, Snail and Twist1) and ß-catenin (a core part of Wnt/ß-catenin signaling) was determined. XAV939, a Wnt/ß-catenin inhibitor, was used for treatment. Our data suggests that ARHGAP25 overexpression significantly inhibits CRC cell growth, suppresses cell migration and invasion, and reduces expression of MMPs, EMT-associated factors and ß-catenin. Our results suggest not only that ARHGAP25 has an anti-metastatic role in CRC cells, but also that the inactivation of the Wnt/ß-catenin pathway is important in this process. Accordingly, siRNA-ARHGAP25 resulted in the opposite effect, favoring CRC metastasis in vitro, and activating the Wnt/ß-catenin pathway in CRC cells. In addition, the siRNA-ARHGAP25 induced changes on cell proliferation, migration, and invasion were significantly reversed with XAV939 treatment. Importantly, the anti-metastatic effects of ARHGAP25 were further substantiated in a CRC lung metastasis xenograft model. We conclude that ARHGAP25 negatively regulates the metastatic potential of CRC cells via the Wnt/ß-catenin pathway. Thus, our findings implicate ARHGAP25 as a potential therapeutic target in CRC metastasis.
Subject(s)
Colorectal Neoplasms/pathology , GTPase-Activating Proteins/metabolism , Wnt Signaling Pathway , Aged , Animals , Cell Line, Tumor , Cell Movement , Cell Transformation, Neoplastic , Down-Regulation , Epithelial-Mesenchymal Transition , Female , GTPase-Activating Proteins/genetics , Humans , Male , Matrix Metalloproteinases/metabolism , Mice , Middle Aged , Neoplasm Metastasis , beta Catenin/metabolismABSTRACT
Evidence suggests that Weichang'an (WCA) inhibited the metastasis of colorectal cancer (CRC) in vitro and downregulates oncogenic ß-catenin; more intriguingly, we also found an upregulation of ARHGAP25 in this process. This study aimed to investigate the mechanisms by which WCA regulated CRC metastasis in vitro. Here, HCT116 cells were transfected with siRNAs to interfere ARHGAP25 expression. WCA decoction, XAV939 (a specific Wnt/ß-catenin pathway inhibitor), and LiCl (an activator for Wnt/ß-catenin pathway) were used for treatment. Cell migratory and invasive capacities were determined using Transwell chamber. The activation of Wnt/ß-catenin pathway was assessed by determining the expression of MMP7, MMP9, ZEB1, and ß-catenin. The study suggests that WCA inhibited the migration and invasion of HCT116 cells and suppressed the activation of Wnt/ß-catenin pathway, as evidenced by retarding MMP7, MMP9, ZEB1, and ß-catenin. However, siRNA-ARHGAP25 resulted in the opposite. In siRNA-ARHGAP25-transfected HCT116 cells, WCA (0.4 mg/mL) induced the antimetastatic effects and the inactivation of Wnt/ß-catenin pathway was remarkably reversed with additional LiCl treatment. Our study concludes that inhibiting Wnt/ß-catenin pathway while promoting ARHGAP25 was the mechanism, whereby WCA retarded migration and invasion of CRC in vitro.
Subject(s)
Cell Movement/drug effects , Drugs, Chinese Herbal/pharmacology , GTPase-Activating Proteins/metabolism , Up-Regulation/drug effects , Wnt Signaling Pathway/drug effects , beta Catenin/antagonists & inhibitors , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drugs, Chinese Herbal/chemistry , GTPase-Activating Proteins/genetics , HCT116 Cells , Heterocyclic Compounds, 3-Ring/chemistry , Heterocyclic Compounds, 3-Ring/pharmacology , Humans , Structure-Activity Relationship , beta Catenin/metabolismABSTRACT
OBJECTIVES: To investigate the risk factors in the development of pneumonia and its impact on outcome after primary intraventricular hemorrhage (PIVH). METHODS: This is a single-center retrospective study including consecutive patients with PIVH admitted to West China Hospital from 2010 to 2016. Pneumonia was defined according to the modified Centers for Disease Control and Prevention criteria within 7 days after PIVH onset. Poor outcome (modified Rankin score ≥3) and mortality at discharge and at 90 days were analyzed. RESULTS: Among the included 174 patients, pneumonia occurred in 13 (7.5%) patients. Patients with pneumonia had lower Glasgow Coma Scale (GCS) score (P = 0.001) and greater Graeb score (P = 0.001) at admission, presented more often with acute hydrocephalus (P = 0.04) and greater rates with stroke history (P = 0.002), and harbored greater admission blood glucose (P = 0.01) and absolute neutrophil counts (P = 0.02). In a multivariable analysis, only GCS score and stroke history were independent predictors of pneumonia after PIVH. The patients with pneumonia had longer duration of hospital stay (P = 0.002) and poorer outcome (P = 0.02) at 90 days. However, after adjustment for confounders, pneumonia after PIVH was not an independent predictor of poor outcome at 90 days. CONCLUSIONS: GCS score and stroke history were independent predictors of pneumonia development after PIVH. Pneumonia after PIVH was associated with longer duration of hospital stay and poorer outcome at 90 days.
Subject(s)
Cerebral Hemorrhage/complications , Cerebral Hemorrhage/diagnostic imaging , Glasgow Coma Scale/trends , Length of Stay/trends , Pneumonia/diagnostic imaging , Pneumonia/etiology , Adult , Aged , Cerebral Ventricles/diagnostic imaging , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors , Treatment OutcomeABSTRACT
AIM: To examine the effect of Weichang'an (WCA) and 5-fluorouracil (5-FU) on colorectal tumor and hepatic metastasis in a mouse model. METHODS: Quantitative determination of hesperidin, the effective component in WCA decoction, was performed using HPLC. In vitro cytotoxicity of WCA was determined by treating HCT-116 cells with WCA diluents or serum extracted from rats that received WCA by oral gavage for 1 wk and MTT assays. Forty-eight nude mice received cecum implantation with tumor blocks subcutaneously amplified from human colon cancer cell line HCT-116. Mice were randomly divided into four treatment groups: control (CON), WCA, 5-FU and combination (WCA+5-FU). Pathological examination of tumors consisted of tissue sectioning and hematoxylin and eosin staining. Tumor weight and size were measured, and the number of metastatic lesions was counted. Serum carcinoembryonic antigen (CEA) level was determined by ELISA. The expression levels of tumor genesis and metastasis-related proteins ß-catenin and matrix metalloproteinase (MMP)-7 were measured by real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR), immunohistochemistry and immunoblotting. Cell fractionation was used to investigate intracellular distribution of ß-catenin. RESULTS: Parenchymal tumors were palpable in the abdomens of nude mice 2 wk post-implantation and orthotopic tumor formation rate was 100% in all groups. 5-FU treatment alone significantly decreased tumor weight compared to the CON group (1.203±0.284 g vs 1.804±0.649 g, P<0.01). WCA treatment alone reduced the rate of metastasis (50% vs 100%, P<0.05). Combination treatment of WCA+5-FU was the most effective, reducing the tumor weight (1.140±0.464 g vs 1.804±0.649 g, P<0.01) and size (1493.438±740.906 mm3 vs 2180.259±816.556 mm3, P<0.05), the rate of metastases (40% vs 100%, P<0.01), and serum CEA levels (31.263±7.421 µg/L vs 43.040±11.273 µg/L, P<0.05). Expression of ß-catenin and MMP-7 was decreased in drug-treated groups compared to controls, as detected using real-time quantitative RT-PCR, immunohistochemistry and immunoblotting, respectively. Cell fractionation assays revealed that nuclear translocation of ß-catenin was reduced by WCA and/or 5-FU treatments. CONCLUSION: Combination of WCA with 5-FU significantly inhibited colon tumor growth and hepatic metastases. Decreased expression of ß-catenin and MMP-7 may be important.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Colorectal Neoplasms/drug therapy , Liver Neoplasms/prevention & control , Animals , Antimetabolites, Antineoplastic/administration & dosage , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/analysis , Cell Proliferation/drug effects , Cell Survival/drug effects , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Dose-Response Relationship, Drug , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/analysis , Fluorouracil/administration & dosage , HCT116 Cells , Hesperidin/administration & dosage , Hesperidin/analysis , Humans , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Liver Neoplasms/secondary , Male , Matrix Metalloproteinase 7/genetics , Matrix Metalloproteinase 7/metabolism , Mice, Inbred BALB C , Mice, Nude , RNA, Messenger/metabolism , Rats , Time Factors , Tumor Burden/drug effects , Xenograft Model Antitumor Assays , beta Catenin/genetics , beta Catenin/metabolismABSTRACT
BACKGROUND: In China, traditional Chinese herbal medicine (TCHM) has been widely used for pancreatic cancer. This retrospective, matched case-control study aimed to assess factors affecting the survival time of patients with pancreatic cancer. METHODS: From 2004 to 2012, a total of 411 patients with pathologically confirmed pancreatic cancer were enrolled, and 272 patients were matched and divided into TCHM and non-TCHM groups (control group) based on received TCHM or not. The match was according to gender, age of onset, radiotherapy, and chemotherapy. Both groups received comprehensive treatments, the TCHM group simultaneously received the TCHM spleen-invigorating compound for more than 3 months. The Cox model was used for prognostic factor analysis and the Kaplan-Meier method for estimating median overall survival (OS) and disease-free survival (DFS). RESULTS: In 130 patients with advanced pancreatic cancer, COX analysis showed the Karnofsky Performance Scale (KPS; P = .000), radiotherapy (P = .003), and TCHM (P = .001) were independent prognostic factors for OS, with median OS of 12.7 and 9.9 months in TCHM and non-TCHM groups, respectively (hazard ratio [HR] = 0.520; 95% confidence interval [CI] = 0.353-0.766; P = .033). In 142 patients undergoing radical surgery, KPS (P = .000) and TCHM (P = .000) were independent prognostic factors for OS and DFS, median OS was 23.8 and 12.4 months in TCHM and non-TCHM groups, respectively (HR = 0.373; 95% CI = 0.251-0.554; P = .000), and the median DFS was 21.5 and 10.2 months in TCHM and non-TCHM groups, respectively (HR = 0.352; 95% CI = 0.237-0.522; P = .000). CONCLUSIONS: KPS was an important prognostic factor of pancreatic cancer. Spleen-invigorating compounds could have an effect on improving the prognosis of pancreatic cancer patients.
Subject(s)
Medicine, Chinese Traditional/methods , Pancreatic Neoplasms/therapy , Aged , Case-Control Studies , China , Combined Modality Therapy , Disease-Free Survival , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Karnofsky Performance Status , Male , Middle Aged , Pancreatic Neoplasms/pathology , Prognosis , Proportional Hazards Models , Retrospective Studies , Survival Analysis , Survival Rate , Treatment OutcomeABSTRACT
Objective. We evaluated the efficiency of traditional Chinese herbal medicine (a compound herbal formula for invigorating spleen) as a complementary and alternative therapy for gastric cancer patients with peritoneal metastasis. Methods. Between 2001 and 2012, 93 gastric cancer patients with peritoneal metastasis were enrolled in this study. The effect of traditional Chinese herbal medicine on their long-term outcome was investigated. Kaplan-Meier method was used to assess the difference in survival time, and Cox proportional hazards regression analysis was performed to identify independent prognostic factors. Result. First-line palliative chemotherapy plus traditional Chinese herbal medicine was performed in 47 patients and the other 46 patients received chemotherapy alone. The overall survival was different between patients with and without traditional Chinese herbal medicine (12.0 versus 10.5 months; P = 0.046). According to the Cox proportional hazard model, first-line chemotherapy cycle (hazards ratio [HR] = 0.527; 95% CI = 0.323~0.860) and TCHM (hazards ratio [HR] = 0.644; 95% CI = 0.481~0.992) were selected as independent prognostic factors for survival. Conclusion. The results suggest that traditional Chinese herbal medicine could improve the prognosis of the gastric cancer patients with peritoneal metastasis.
ABSTRACT
BACKGROUND: The incidence of colorectal cancer is high among the elderly. Traditional Chinese medicine (TCM) has been widely used in the treatment for colorectal cancer of old people. However, controlled trials with large sample size evaluating the effect of TCM are rare. OBJECTIVE: This research aimed to evaluate the survival benefit of using TCM syndrome differentiation treatment for elderly patients with stage II or III colorectal cancer. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A total of 78 patients over 70 with resected stage II or III colorectal cancer were selected from the First Department of Oncology, Longhua Hospital of Shanghai University of Traditional Chinese Medicine, and Department of Anorectal Surgery, Changhai Hospital of Second Military Medical University. Patients were assigned to either integrated treatment group or Western medicine group by their own wills. MAIN OUTCOME MEASURES: Cox regression analysis was performed to determine all the potential factors which may affect prognosis such as gender, primary site, pathological type, TNM stage, chemotherapy period, radiotherapy and TCM therapy. RESULTS: A total of 78 cases were included in this study with 37 cases in integrated treatment group and 41 cases in Western medicine group. Cox regression analysis suggested that the TNM stage (P=0.001) and TCM therapy (P=0.021) were independent prognostic factors. The hazard ratio [Exp(ß)] of TCM therapy was 0.393, and 95% confidence interval (CI) was 0.178-0.870. Median disease-free survival (DFS) of Western medicine group was 41.293 months. DFS of integrated treatment group did not reach the median at the time of analysis. There was significant difference between the two groups (P=0.012). The 1-, 2-, 3-, 4-, and 5-year DFS rates of Western medicine group were 87.7 %, 69.6%, 63.4%, 46.5%, and 29.6%, respectively. The 1-, 2-, 3-, 4-, and 5-year DFS rates of integrated therapy group were 100%, 86.3%, 74.6%, 74.6%, and 74.6%, respectively. CONCLUSION: TCM syndrome differentiation and treatment is important for improving the prognosis of stage II or III colorectal cancer in elderly patients. Integrated treatment shows benefit for reducing relapse and metastasis rates, and prolonging survival for elderly patients. The influence of integrated treatment needs to be further evaluated.
Subject(s)
Colorectal Neoplasms/drug therapy , Drugs, Chinese Herbal/therapeutic use , Phytotherapy , Aged , Aged, 80 and over , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Disease-Free Survival , Female , Humans , Male , Medicine, Chinese Traditional , Neoplasm Staging , Prognosis , Survival RateABSTRACT
BACKGROUND: Advanced gastric cancer has a low survival rate while traditional Chinese medicine (TCM) therapy has effects in inhibiting tumor growth, lengthening survival time and improving the quality of life. OBJECTIVE: To analyze the effects of integrated traditional Chinese and Western medicine therapy on the survival time and quality of life of advanced gastric cancer patients. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A total of 95 advanced gastric cancer patients were enrolled and divided into comprehensive group (48 cases) and control group (47 cases). The patients in the comprehensive group from the First Department of Oncology, Longhua Hospital, were treated with TCM therapy and chemotherapy based on the gastric cancer treatment guidelines made by the First Department of Oncology of Longhua Hospital, and the patients in the control group from Renji Hospital and Ruijin Hospital in Shanghai were treated with chemotherapy only. MAIN OUTCOME MEASURES: The survival time in the two groups were observed and compared. The Karnofsky score, body weight, the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) score, response rate and chemotherapy-related adverse events in the comprehensive group were observed. RESULTS: The estimated median survival time in the comprehensive group was 16.12 months, longer than 9.64 months in the control group (P<0.05). The scores of function and symptom of EORTC QLQ-C30 in the comprehensive group decreased, while the overall health status increased, and the results indicated that the quality of life of the patients in the comprehensive group was improved. In the comprehensive group, the body weight after treatment was higher than that before treatment (P=0.037), while there was no difference in Karnofsky scores between that before and after treatment (P=0.061). All the patients in the comprehensive group were assessable. The complete response rate was 0, 3 cases had a partial response, 34 cases had stable disease, and 11 cases had disease progression. The overall response rate was 6.25% (3/48), and the disease control rate was 77.08% (37/48). No patient withdrew because of severe adverse events and there was no chemotherapy-related death. CONCLUSION: Integrated traditional Chinese and Western medicine can prolong the survival time and improve the quality of life of advanced gastric cancer patients, and enhance the comprehensive effects.
Subject(s)
Drugs, Chinese Herbal/therapeutic use , Stomach Neoplasms/drug therapy , Stomach Neoplasms/mortality , Female , Humans , Male , Medicine, Chinese Traditional/methods , Middle Aged , Neoplasm Staging , Stomach Neoplasms/pathology , Survival Rate , Treatment OutcomeABSTRACT
AIM: To investigate the expression of multiple genes in Chinese jianpi herbal recipe Wei Chang An (WCA) in human gastric cancer cell line SGC-7901. METHODS: A human gastric adenocarcinoma cell line SGC-7901 grafted onto nude mice was used as the animal model. The mice were randomly divided into 3 groups, one control and the two representing experimental conditions. Animals in the two experimental groups received either WCA over a 34-d period or 5-fluorouracil (5-FU) over 6-d period starting at 8th d after grafting. Control animals received saline on an identical schedule. Animals were killed 41 d after being grafted. The expression profiles in paired WCA treated gastric cancer samples and the N.S. control samples were studied by using a cDNA array representing 14181 cDNA clusters. The alterations in gene expression levels were confirmed by Real-time Quantitative polymerase chain reaction (qPCR). RESULTS: When compared with controls, the average tumor inhibitory rate in WCA group was 44.32% +/- 5.67% and 5-FU 47.04% +/- 11.33% (P < 0.01, respectively). The average labeling index (LI) for PCNA in WCA group and 5-FU group was significantly decreased compared with the control group. Apoptotic index (AI) was significantly increased to 9.72% +/- 4.51% using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate fluorescence nick end labeling (TUNEL) method in WCA group compared with the controls 2.45% +/- 1.37%. 5-FU group was also found to have a significantly increased AI compared with the controls. The expression of cleaved Caspase-3 in WCA group and 5-FU group was significantly increased compared with the control group respectively. There were 45 different expressed sequence tags (ESTs) among the control sample pool and WCA sample pool. There were 24 ESTs up-regulated in WCA samples and 21 ESTs down-regulated. By using qPCR, the expression level of Stat3, rap2 interacting protein x (RIPX), regulator of differentiation 1 (ROD1) and Bcl-2 was lower in WCA group than that in control group respectively. By using SP immunohistochemical method the expression of Phospho-Stat3 (Tyr705) and Bcl-2 in WCA group and 5-FU group was significantly decreased compared with the control group respectively. CONCLUSION: WCA could inhibit gastric cancer cell SGC-7901 growth in vivo. WCA could induce gastric cancer cell apoptosis and suppress proliferation. Its mechanisms might be involved in the down-regulation of Stat3, RIPX, ROD1 and Bcl-2 gene.