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1.
Zhonghua Wei Chang Wai Ke Za Zhi ; 27(4): 395-402, 2024 Apr 25.
Article in Chinese | MEDLINE | ID: mdl-38644245

ABSTRACT

Objective: To explore the efficacy of immune checkpoint inhibitors combined with adjuvant chemotherapy in patients with phase III gastric cancer and esophagogastric junction cancer. Methods: This study used a retrospective cohort study method based on real-world data. Clinical data of 403 patients with stage III gastric/esophagogastric junction cancer who underwent gastrectomy followed by adjuvant therapy in the Department of Gastric Surgery at Sun Yat-sen University Cancer Center from January 2020 to December 2023 were retrospectively collected. The study cohort comprised 147 (36.5%) patients with stage IIIA, 130 (32.3%) with stage IIIB, and 126 (31.3%) with stage IIIC gastric/esophagogastric junction cancer. Of them, 15 (3.7%) were HER-2 positive, 25 (6.2%) dMMR, and 22 (5.5%) patients Epstein-Barr virus encoding RNA (EBER) positive. Based on treatment plans, the patients were divided into immune checkpoint inhibitor combined with chemotherapy group (immune therapy group, n=110, 71 males and 39 females, median age 59 years old) and chemotherapy alone group (chemotherapy group, n=293, 186 males and 107 females, median age 60 years old). All patients in the immunotherapy group received immune checkpoint inhibitors targeting the programmed cell death protein-1 (PD-1) and its ligand (PD-L1). Of them, 85 received pembrolizumab, 10 received sintilimab, 8 received tislelizumab, 4 received camrelizumab, 2 received toripalimab, and 1 received pabocizumab. The adjuvant chemotherapy regimens used among the chemotherapy alone group includes SOX regimen (132 cases), XELOX (102 cases), S-1 monotherapy (44 cases), and other regimens (15 cases). The 3-year DFS rate of the two groups was compared, and subgroup analysis was conducted based on different ages, molecular phenotypes, pTNM staging, extranodal infiltration, and tumor length. Results: The median follow-up was 20.5 months (range 3.1~46.3), with a 3-year overall DFS rate of 61.4% for the entire 403 patients. The 3-year DFS rate for the immunotherapy group was 82.7%, higher than the chemotherapy alone group (58.8%), with a statistically significant difference (P=0.021). Multivariate analysis showed that postoperative immunotherapy was a protective factor for DFS (HR=0.352, 95%CI: 0.180~0.685). Subgroup analysis showed that stage IIIC (HR=0.416, 95%CI: 0.184~0.940), aged ≥60 years (HR=0.336, 95%CI: 0.121~0.934) and extranodal invasion (HR=0.378, 95%CI: 0.170~0.839) were associated with benefit from the combined immune adjuvant chemotherapy, while no association was observed for MMR, HER-2 or EBER status. Conclusion: Stage III gastric/esophagogastric junction cancer patients may benefite from postoperative immune checkpoint inhibitor combined with adjuvant chemotherapy in real-world settings.


Subject(s)
Esophagogastric Junction , Gastrectomy , Immune Checkpoint Inhibitors , Neoplasm Staging , Stomach Neoplasms , Humans , Male , Female , Retrospective Studies , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Middle Aged , Immune Checkpoint Inhibitors/therapeutic use , Chemotherapy, Adjuvant , Esophagogastric Junction/pathology , Aged , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use
2.
Nat Commun ; 14(1): 3437, 2023 Jun 10.
Article in English | MEDLINE | ID: mdl-37301861

ABSTRACT

Recent works in metamaterials and transformation optics have demonstrated exotic properties in a number of open systems, including perfect absorption/transmission, electromagnetically induced transparency, cloaking or invisibility, etc. Meanwhile, non-Hermitian physics framework has been developed to describe the properties of open systems, however, most works related to this focus on the eigenstate properties with less attention paid to the reflection characteristics in complex frequency plane, despite the usefulness of zero-reflection (ZR) for applications. Here we demonstrate that the indirectly coupled two-magnon system not only exhibits non-Hermitian eigenmode hybridization, but also ZR states in complex frequency plane. The observed perfect-ZR (PZR) state, i.e., ZR with pure real frequency, is manifested as infinitely narrow reflection dips (~67 dB) with infinite group delay discontinuity. This reflection singularity of PZR distinguishes from the resonant eigenstates but can be adjusted on or off resonance with the eigenstates. Accordingly, the absorption and transmission can be flexibly tuned from nearly full absorption (NFA) to nearly full transmission (NFT) regions.


Subject(s)
Hybridization, Genetic , Physics , Vibration
3.
Zhonghua Liu Xing Bing Xue Za Zhi ; 44(4): 581-586, 2023 Apr 10.
Article in Chinese | MEDLINE | ID: mdl-37147829

ABSTRACT

Objective: To forecast mortality, age-standardized mortality, and probability of premature mortality from diabetes, and to simulate the impact of controlling risk factors by 2030 in China. Methods: We simulated the burden of disease from diabetes in six scenarios according to the development goals of risk factors control by the WHO and Chinese government. Based on the theory of comparative risk assessment and the estimates of the burden of disease for China from the Global Burden of Disease Study 2015, we used the proportional change model to project the number of deaths, age-standardized mortality, and probability of premature mortality from diabetes under different scenarios of risk factors control in 2030. Results: If the trends in exposures to risk factors from 1990 to 2015 continued. Mortality, age-standardized mortality, and probability of premature mortality from diabetes would increase to 32.57/100 000, 17.32/100 000, and 0.84% by 2030, respectively. During that time, mortality, age-standardized mortality and probability of premature mortality for males would all be higher than for females. If the goals of controlling risk factors were all achieved, the number of deaths from diabetes in 2030 would decrease by 62.10% compared to the predicted numbers based on the historical trends in exposure to risk factors, and the probability of premature mortality would drop to 0.29%. If only the exposure to a single risk factor were achieved by 2030, high fasting plasma glucose control would have the greatest impact on diabetes, resulting in a 56.00% reduction in deaths compared to the predicted numbers based on the historical trends, followed by high BMI (4.92%), smoking (0.65%), and low physical activity (0.53%). Conclusions: Risk factors control plays an important role in reducing the number of deaths, age-standardized mortality rate, and probability of premature mortality from diabetes. We suggest taking comprehensive measures to control relevant risk factors for certain populations and regions, to achieve the goal of reducing the burden of disease from diabetes as expected.


Subject(s)
Diabetes Mellitus , Male , Female , Humans , Risk Factors , Diabetes Mellitus/epidemiology , Mortality, Premature , Smoking , Cost of Illness , China/epidemiology , Global Burden of Disease
4.
Zhonghua Yu Fang Yi Xue Za Zhi ; 56(5): 567-573, 2022 May 06.
Article in Chinese | MEDLINE | ID: mdl-35644969

ABSTRACT

Objective: Predictive models were used to evaluate the impact of common risk factors on the number of cardio-cerebrovascular deaths and the probability of premature death. Methods: Using the data for China estimated by the Global Burden of Disease study 2015 (GBD 2015), we calculated the population attribution fraction (PAF) of risk factors. The proportional change model was used to estimate the number of unattributable deaths by 2030, and to predict the number of deaths, mortality, standardized mortality and probability of premature death by 2030. Results: According to the natural change trend of risk factors from 1990 to 2015, the number of deaths and mortality would reach 6.12 million and 428.53/100 000 by 2030, with an increase of 59.92% and 52.87%. By 2030, the probability of premature death from cardio-cerebrovascular diseases among Chinese aged 30-70 years old would continue to decline, from 11.43% to 11.28% for men, and from 5.79% to 4.43% for women. If the goals of all included risk factors were reached by 2030, 2 289 200 cardio-cerebrovascular deaths would be avoided. If only the exposure to a single risk factor was achieved by 2030, blood pressure, total cholesterol, and fine particulate matter exposure were the three most important factors affecting cardio-cerebrovascular deaths, which would reduce 1 332 800, 609 100 and 306 800 deaths, respectively. Among the involved risk factors, the control of blood pressure would mostly decrease the number of deaths due to ischemic heart disease and hemorrhagic stroke, about 677 300 and 391 100 deaths, accordingly. Conclusion: The control of risk factors is of great significance in reducing deaths and probability of premature death due to cardio-cerebrovascular diseases. If the control targets of all risk factors could be achieved by 2030, the burden of cardio-cerebrovascular diseases would be reduced greatly.


Subject(s)
Cerebrovascular Disorders , Mortality, Premature , Adult , Aged , Blood Pressure , Cerebrovascular Disorders/epidemiology , China/epidemiology , Female , Humans , Male , Middle Aged , Risk Factors
5.
Zhonghua Liu Xing Bing Xue Za Zhi ; 43(2): 201-206, 2022 Feb 10.
Article in Chinese | MEDLINE | ID: mdl-35184485

ABSTRACT

Objective: To forecast the burden of chronic obstructive pulmonary disease (COPD) in China by 2030 and evaluate the effectiveness of controlling risk factors based on the predictive model. Methods: Based on the relationship between the death of COPD and exposure to risk factors and the theory of comparative risk assessment, we used the estimates of the Global Burden of Disease Study 2015 (GBD2015) for China, targets for controlling risk factors, and proportion change model to project the number of deaths, standardized mortality rate, and probability of premature mortality from chronic respiratory diseases by 2030 in different scenarios and to evaluate the impact of controlling the included risk factors to the disease burden of COPD in 2030. Results: If the trends in exposure to risk factors from 1990 to 2015 continued, the number of deaths and the mortality for COPD would be 1.06 million and 73.85 per 100 000 population in China by 2030, respectively, with an increase of 15.81% and 10.69% compared to those in 2015. Compared to 2015, the age-standardized mortality rate would decrease by 38.88%, and the premature mortality would reduce by 52.73% by 2030. If the smoking rate and fine particulate matter (PM2.5) concentration separately achieve their control targets by 2030, there would be 0.34 and 0.27 million deaths that could be avoided compared to the predicted numbers based on the natural trends in exposure to risk factors and the probability of premature death would reduce to 0.59% and 0.52%, respectively. If the control targets of all included risk factors were achieved by 2030, a total of 0.53 million deaths would be averted, and the probability of premature death would decrease to 0.44%. Conclusions: If the exposures to risk factors continued as showed from 1990 to 2015, the number of deaths and mortality for COPD would increase by 2030 compared to 2015, and the standardized mortality and the probability of premature death would decrease significantly, which would achieve the targets of preventing and controlling COPD. If the exposure to the included risk factors all achieved the targets by 2030, the burden of COPD would be reduced, suggesting that the control of tobacco use and air pollution should be enhanced to prevent and control COPD.


Subject(s)
Air Pollutants , Air Pollution , Pulmonary Disease, Chronic Obstructive , Air Pollutants/analysis , Air Pollution/analysis , Air Pollution/prevention & control , China/epidemiology , Cost of Illness , Environmental Exposure , Humans , Particulate Matter/analysis , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/prevention & control , Risk Factors
6.
Zhonghua Liu Xing Bing Xue Za Zhi ; 43(1): 37-43, 2022 Jan 10.
Article in Chinese | MEDLINE | ID: mdl-35130650

ABSTRACT

Objective: To predict the number of deaths, standardized mortality and probability of premature mortality caused by malignant cancer in the context of risk factor control at different levels in China in 2030, and assess the possibility of achieving the target of reducing the probability of premature mortality of malignant cancer. Methods: According to the risk factor control standard for malignant cancer used both at home and abroad, the results of China from Global Burden of Disease Study 2015 were used to calculate the population attributable fraction of the risk factors. Based on the comparative risk assessment theory, the deaths of malignant cancer were classified as attributable deaths and un-attributable deaths. Proportional change model was used to predict risk factor exposure and un-attributable deaths of malignant cancer in the future, then the number of deaths, standardized mortality rate and probability of premature mortality of malignant cancer in 2030 was estimated. Data analyses were performed by using software R 3.6.1. Results: If the risk factor exposure level during 1990-2015 remains, the number of deaths, standardized mortality rate, and probability of premature mortality of malignant cancer would increase to 3.62 million, 153.96/100 000 and 8.92% by 2030, respectively. If the risk factor exposure control level meets the requirement, the probability of premature mortality from cancer in people aged 30-70 years would drop to 7.57% by 2030. Conclusions: The control of risk factor exposure will play an important role in reducing deaths, standardized mortality rate and probability of premature mortality of malignant cancer. But more efforts are needed to achieve the goals of Health China Action.


Subject(s)
Mortality, Premature , Neoplasms , Adult , Aged , China/epidemiology , Cost of Illness , Humans , Middle Aged , Neoplasms/epidemiology , Risk Factors
7.
Int J Dermatol ; 57(4): 449-457, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29417554

ABSTRACT

BACKGROUND: Myiasis induced by the sheep blowfly, Lucilia sericata, represents a public health problem widely distributed throughout the world. L. sericata larval stages feed on both humans and animals. L. sericata adults and larvae can play a role in spreading agents of mycobacterial infections. OBJECTIVES: It is critical to establish new and safe alternative methods of controlling L. sericata. METHODS: The insecticidal effectiveness and growth inhibition potential of three commercially available essential oils (EOs), vetiver (Chrysopogon zizanioides), cinnamon (Cinnamomum zeylanicum), and lavender (Lavandula angustifolia), as well as their blends, were tested against the second (L2) and third (L3) larval stages of L. sericata. Sunflower (Helianthus annuus) oil was used as a carrier and tested on L2 and L3 larvae. To the best of our knowledge, all applied essential oils, except lavender, and oil blends were tested against L. sericata for the first time. RESULTS: All applied oils did not repel L2 from the treated liver but adversely affected their development. Contact treatments on L. sericata L3 indicated that vetiver and cinnamon oils significantly affected treated larvae. Total mortality rates were 93.33 and 95.56%, respectively. Furthermore, oil blends tested through contact assays killed larvae when used at higher concentrations; adult emergence was eliminated post-treatment with doses >30% for oil blend 1 and >10% for oil blend 2. CONCLUSION: Overall, cinnamon and vetiver oils (5%) were selected as reliable and cheap biopesticides for controlling larvae of L. sericata. The tested oils are inexpensive and represent new promising botanical insecticides in the fight against blowflies causing myiasis.


Subject(s)
Chrysopogon , Cinnamomum zeylanicum , Diptera/drug effects , Larva/drug effects , Oils, Volatile/pharmacology , Plant Oils/pharmacology , Animals , Biological Control Agents/pharmacology , Diptera/growth & development , Insect Control/methods , Insect Repellents/pharmacology , Larva/growth & development , Lavandula , Pupa/drug effects , Sunflower Oil/pharmacology
8.
Transplant Proc ; 49(6): 1244-1248, 2017.
Article in English | MEDLINE | ID: mdl-28735988

ABSTRACT

BACKGROUND: Laparoscopic donor nephrectomy (LDN) has gradually become the main approach to obtain live donor kidneys. However, the shorter right renal vein limits its wider application. The aim of this study was to compare the outcomes of left- and right-side retroperitoneal LDN. METHODS: We reviewed the perioperative data of 527 consecutive donors receiving retroperitoneal pure LDN with a new method at our center between April 2009 and April 2014. The patients were divided into group A (the first 100 patients) and group B (the remaining 427 patients). A total of 423 cases of left donor surgery and 104 cases of right donor surgery were compared. The comparison of the laterality of LDN was also performed between group A and group B. RESULTS: This is currently the largest case series of LDN in our country. Although right-side LDN patients had longer operation time and a slightly higher incidence of intraoperative complications compared with left-side LDN patients, the operation time was shorter in both the groups compared with previous reports. In group B, patients undergoing right-side LDN had longer operation time and more frequent complications. Once the learning curve of 100 cases was completed, the incidence of complications and operation time were greatly reduced in both sides for LDN. There was no significant difference in the serum creatinine levels in recipients at 6 months of follow-up. CONCLUSIONS: Despite a slightly higher incidence of complications and longer operation time, right-side LDN can achieve equally safe and effective transplantation outcomes. This expands the source of potential donor kidneys.


Subject(s)
Kidney Transplantation/methods , Laparoscopy/methods , Living Donors , Nephrectomy/methods , Tissue and Organ Harvesting/methods , Adult , China/epidemiology , Female , Humans , Incidence , Kidney/surgery , Laparoscopy/adverse effects , Male , Middle Aged , Nephrectomy/adverse effects , Operative Time , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retroperitoneal Space/surgery , Tissue and Organ Harvesting/adverse effects
9.
J Appl Microbiol ; 122(1): 119-128, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27797429

ABSTRACT

AIMS: 3-ketosteroid-Δ1 -dehydrogenase (KSDD), a flavin adenine dinucleotide (FAD)-dependent enzyme involved in sterol metabolism, specifically catalyses the conversion of androst-4-ene-3,17-dione (AD) to androst-1,4-diene-3,17-dione (ADD). However, the low KSDD activity and the toxic effects of hydrogen peroxide (H2 O2 ) generated during the biotransformation of AD to ADD with FAD regeneration hinder its application on AD conversion. The aim of this work was to improve KSDD activity and eliminate the toxic effects of the generated H2 O2 to enhance ADD production. METHODS AND RESULTS: The ksdd gene obtained from Mycobacterium neoaurum JC-12 was codon-optimized to increase its expression level in Bacillus subtilis, and the KSDD activity reached 12·3 U mg-1 , which was sevenfold of that of codon-unoptimized gene. To improve AD conversion, catalase was co-expressed with KSDD in B. subtilis 168/pMA5-ksddopt -katA to eliminate the toxic effects of H2 O2 generated during AD conversion. Finally, under optimized bioconversion conditions, fed-batch strategy was carried out and the ADD yield improved to 8·76 g l-1 . CONCLUSIONS: This work demonstrates the potential to improve enzyme activity by codon-optimization and eliminate the toxic effects of H2 O2 by co-expressing catalase. SIGNIFICANCE AND IMPACT OF THE STUDY: This study showed the highest ADD productivity ever reported and provides a promising strain for efficient ADD production in the pharmaceutical industry.


Subject(s)
Androstadienes/metabolism , Bacillus subtilis/genetics , Bacillus subtilis/metabolism , Bacterial Proteins/genetics , Catalase/genetics , Nontuberculous Mycobacteria/enzymology , Oxidoreductases/genetics , Bacterial Proteins/metabolism , Biotransformation , Catalase/metabolism , Metabolic Engineering , Nontuberculous Mycobacteria/genetics , Oxidoreductases/metabolism , Polyenes/metabolism
10.
Transplant Proc ; 47(10): 2952-6, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26707320

ABSTRACT

OBJECTIVE: Conversion from calcineurin inhibitors (CNIs) to mammalian target-of-rapamycin inhibitors (mTORi) was systematically evaluated in heart transplant recipients (HTRs) for the first time. METHODS: MEDLINE (PUBMED), EMBASE, Cochrane Library, and clinical trial registries were searched comprehensively. After screening for eligibility, the randomized controlled trials (RCTs) comparing continuation of CNI with conversion to mTORi therapy underwent review, quality assessment, and data extraction. Outcomes analyzed including creatinine clearance, serum creatinine level, rejection, adverse effects, and triglyceride levels were expressed as mean differences (MDs) or as risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: This is the first systematic review evaluating converting from CNI to mTORi therapy in HTRs. A total of 4 RCTs (231 HTRs, 117 vs 114) were included in our analysis. Patients converted to mTORi had a higher creatinine clearance (MD, 19.31; 95% CI [11.16, 27.46]; P < .00001) and lower serum creatinine levels (MD, -0.15; 95% CI [-0.25, -0.05]; P = .002). Patients converted to mTORi had a significantly higher occurrence of adverse effects, which included skin diseases, gastrointestinal side effects, bone marrow suppression, and infections. There was no significant difference between the 2 groups regarding graft rejection and triglyceride levels (RR, 2.61; 95% CI [0.08, 81.25]; P = .58; MD, 22.89; 95% CI [-21.86, 67.63]; P = .32). CONCLUSIONS: Conversion from CNI to mTORi therapy may improve the renal function in HTRs, but the patients may suffer from a high incidence of mTORi-associated adverse events. Therefore, conversion to mTORi must be carefully assessed for the benefits and risks.


Subject(s)
Calcineurin Inhibitors/therapeutic use , Drug Substitution , Graft Rejection/prevention & control , Heart Transplantation/adverse effects , Protein Kinase Inhibitors/therapeutic use , TOR Serine-Threonine Kinases/antagonists & inhibitors , Calcineurin Inhibitors/adverse effects , Drug-Related Side Effects and Adverse Reactions/epidemiology , Drug-Related Side Effects and Adverse Reactions/etiology , Humans , Incidence , Randomized Controlled Trials as Topic
11.
Lett Appl Microbiol ; 61(6): 573-9, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26393961

ABSTRACT

UNLABELLED: Acetoin and 2,3-butanediol are widely used in the chemical and pharmaceutical industries. The enzyme, 2,3-butanediol dehydrogenase/acetoin reductase (2,3-BDH/AR), plays a significant role in the microbial production of acetoin and 2,3-butanediol by catalysing a reversible reaction between acetoin and 2,3-butanediol. To date, a 2,3-BDH has not been characterized from Corynebacterium crenatum. 2,3-BDH was cloned from Coryne. crenatum SYPA5-5 and expressed in Escherichia coli BL21. Sequence analysis suggested that the 2,3-BDH from Coryne. crenatum SYPA5-5 belongs to the short-chain dehydrogenase/reductase superfamily. Its maximum specific activity was obtained at 35°C, however, it became very unstable when the temperature was above 35°C. Its optimal pH was 4·0 for reduction reaction and 10·0 for oxidation reaction. The 2,3-BDH activity was increased to some extent by Ca(2+) , Mg(2+) , Zn(2+) and Mn(2+) ions. In particular, Ca(2+) induced about 1·5-fold increase. The value of kcat /Km for diacetyl and acetoin are higher than for 2,3-butanediol indicating that 2,3-BDH can easily reduce diacetyl or acetoin to 2,3-butanediol under lower pH conditions. The characteristics of 2,3-BDH from Coryne. crenatum SYPA5-5 will give guide to further studies for the production of acetoin and 2,3-butanediol with engineered Coryne. crenatum SYPA5-5. SIGNIFICANCE AND IMPACT OF THE STUDY: Acetoin and 2,3-butanediol are commonly used as platform chemicals and widely used in pharmaceutical industries. 2,3-butanediol dehydrogenase/acetoin reductase (2,3-BDH/AR) plays a significant role in the microbial production of acetoin and 2,3-butanediol. In this study, 2,3-BDH was cloned from Corynebacterium crenatum SYPA5-5, was expressed in Escherichia coli BL21 and characterized with respect to the optimal temperature, pH, substrate specificity and kinetics. The results will guide further studies in Coryne. crenatum SYPA5-5 for the production of acetoin and 2,3-butanediol.


Subject(s)
Acetoin/metabolism , Alcohol Oxidoreductases/genetics , Alcohol Oxidoreductases/isolation & purification , Butylene Glycols/metabolism , Corynebacterium/enzymology , Alcohol Oxidoreductases/metabolism , Amino Acid Sequence , Cloning, Molecular , Corynebacterium/genetics , Escherichia coli/genetics , Escherichia coli/metabolism , Kinetics , Molecular Sequence Data , Sequence Alignment , Substrate Specificity , Temperature
12.
Eur Rev Med Pharmacol Sci ; 18(20): 3056-62, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25392105

ABSTRACT

OBJECTIVE: Osteoarthritis (OA) is a most common chronic degenerative joint lesion, which affects both cartilage and bone. A better understanding of the gene expression profiling of OA may help understanding the pathogenesis of OA and finding the therapy targets for OA treatment. MATERIALS AND METHODS: GSE8077 was downloaded from Gene Expression Omnibus (GEO) including 5 OA rats induced by anterior cruciate ligament transection and partial medial meniscectomy and 5 rats that were performed sham surgery as control. Differentially expressed genes (DEGs) between OA group and control group were identified by t-test with p < 0.05 and the coding genes that transcription factors corresponded were screened by TRANSFAC. Then Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for DEGs and transcription factors were performed. The DEGs and transcription factors were integrated with information from STRING database to construct PPI network. RESULTS: A total of 119 up-regulated genes, 39 down-regulated genes and 9 transcription factors were identified in OA sample. The GO enrichment analysis showed that 119 up-regulated genes were significantly enriched in blood vessel development and KEGG pathway enrichment showed that genes were involved in circadian rhythm pathway. In the PPI network, Cd44, Mmp13, Timp1 and Igf1 showed higher degrees. CONCLUSIONS: The screened genes could provide a new and comprehensive view for treatment of OA.


Subject(s)
Gene Expression Profiling/methods , Gene Expression Regulation , Osteoarthritis/genetics , Osteoarthritis/metabolism , Animals , Down-Regulation/physiology , Gene Regulatory Networks/physiology , Matrix Metalloproteinase 13/biosynthesis , Matrix Metalloproteinase 13/genetics , Microarray Analysis/methods , Osteoarthritis/pathology , Rats , Transcription Factors/genetics , Up-Regulation/physiology
13.
Transpl Infect Dis ; 16(5): 760-6, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25092411

ABSTRACT

BACKGROUND: The role of therapeutic drug monitoring (TDM) of mycophenolic acid (MPA) in kidney transplant recipients (KTRs) is not clear. We performed a prospective cohort study to evaluate the efficiency of MPA TDM in the Chinese population. METHODS: A total of 183 living-related KTRs were studied; 101 KTRs received controlled-dose mycophenolate mofetil (MMF) (the CD group), and 82 patients received fixed-dose MMF (the FD group). MPA exposure was measured at days 3, 7, 14, and 30 in the CD group, and at day 30 in the FD group. The primary endpoint was treatment failure (a composite of acute rejection, graft loss, death, or MMF discontinuation) at 12 months post transplantation. RESULTS: In the CD group, with a starting MMF dose of 2 g/day, approximately 35% of patients had high MPA levels, which were >60 mg × h/L, and mean MPA levels were 59.17 mg × h/L and 61.38 mg × h/L for the CD and FD groups, respectively (P = 0.588). After adjusting MMF dose, MPA exposures in the CD group at day 30 were lower than those in the FD group at day 30 (54.06 vs. 61.38, P = 0.004). At month 12, the CD group had fewer infections (16.8% vs. 31.7%, P = 0.018) with no difference in treatment failure, acute rejection, diarrhea, or anemia. CONCLUSIONS: KTRs can benefit from short-term TDM of MPA in reducing infection, without increasing acute rejection.


Subject(s)
Drug Monitoring , Immunosuppressive Agents/administration & dosage , Kidney Transplantation/adverse effects , Mycophenolic Acid/analogs & derivatives , Mycophenolic Acid/blood , Adult , Area Under Curve , Bacterial Infections/prevention & control , China , Female , Graft Survival , Humans , Immunosuppressive Agents/pharmacokinetics , Longitudinal Studies , Male , Mycophenolic Acid/administration & dosage , Mycophenolic Acid/pharmacokinetics , Mycoses/prevention & control , Prospective Studies , Survival Rate , Time Factors , Treatment Failure , Young Adult
14.
Vet Parasitol ; 205(1-2): 169-74, 2014 Sep 15.
Article in English | MEDLINE | ID: mdl-25086494

ABSTRACT

Sera from calves originating on a 17,000 ha ranch in southeastern Alberta, were collected over three consecutive years (2008-2010) at weaning and analysed for the presence of anti-Ostertagia antibodies using the SVANOVIR(®)Ostertagia ostertagi-Ab ELISA kit. Faecal samples taken at the same time were analysed for presence of nematode eggs using the modified Wisconsin faecal flotation technique. Mean optical density ratio (ODR) values for all calves were similar in 2008 and 2010 while the 2009 values were significantly higher. Similar cumulative frequency distribution profiles were found for 2008 and 2010 while the 2009 profile had an increased number of values in the higher bin categories. This pattern indicates higher nematode transmission on pasture in 2009. There was no significant difference in ODR values between egg positive and egg-negative calves and no significant correlation was detected between individual ODR values and faecal egg output. Significantly higher ODR values in 2009 appear contradictory to general assumptions about the ecological requirements of larval development, as 2009 was a relatively dry year. However, examination of weather data identified 5-6 rainfall events that may have resulted in episodic enhanced survival of nematode larvae.


Subject(s)
Antibodies, Helminth/blood , Cattle Diseases/parasitology , Gastrointestinal Diseases/veterinary , Nematode Infections/veterinary , Animals , Canada/epidemiology , Cattle , Cattle Diseases/epidemiology , Ecosystem , Gastrointestinal Diseases/blood , Gastrointestinal Diseases/epidemiology , Gastrointestinal Diseases/parasitology , Nematode Infections/blood , Nematode Infections/epidemiology , Nematode Infections/parasitology , Time
15.
Vet Parasitol ; 203(1-2): 6-20, 2014 Jun 16.
Article in English | MEDLINE | ID: mdl-24709006

ABSTRACT

Cattle ticks are an important constraint on livestock production, particularly in tropical and subtropical areas. Use of synthetic acaricides is the primary method of tick control; therefore, it would be imperative to develop strategies to preserve the efficacy of existing acaricides. This paper summarizes the status of acaricide resistance in cattle ticks from different parts of the world and reviews modes of action of currently used acaricides, mechanism of resistance development, contributory factors for the development and spread of resistance, management of resistant strains and strategies to prolong the effect of the available acaricides. Use of vaccines, synthetic and botanical acaricides and educating farmers about recommended tick control practices are discussed, along with the integration of currently available options for the management of drug resistance and, ultimately, the control of cattle ticks.


Subject(s)
Acaricides/pharmacology , Cattle Diseases/parasitology , Rhipicephalus/drug effects , Tick Control , Tick Infestations/veterinary , Animals , Cattle , Cattle Diseases/drug therapy , Cattle Diseases/prevention & control , Insecticide Resistance/genetics , Tick Infestations/drug therapy , Tick Infestations/parasitology , Tick Infestations/prevention & control , Vaccination
16.
Neoplasma ; 60(3): 254-61, 2013.
Article in English | MEDLINE | ID: mdl-23373994

ABSTRACT

The purpose of this study was to evaluate the association of expression level of α5ß1-integrin and MMP-14 with clinicopathologic features and prognosis in colorectal cancer (CRC). The expressions of α5ß1-integrin and MMP-14 in normal colorectal mucosa and CRC tissue were detected with immunohistochemistry. We estimated the five-year survival rate by the Kaplan-Meier method. The positive expressions rates of α5ß1-integrin and MMP-14 in CRC tissue were 60.6% and 63.3% respectively, and there were significant differences on their positive expression rates between in CRC tissue and in normal colorectal mucosa(P<0.05). The expression rates of α5ß1-integrin and MMP-14 in patients with poor histological differentiation, lymph node metastasis and high clinical staging were heightened. There was a significant difference (P<0.05) on the five-year survival rate for α5ß1-integrin expression, which was 44.6% in positive groups and 75.5% in negative groups. And there was a significant difference (P<0.05) on the five-year survival rate for MMP-14 expression, which was 48.2% in positive group and 73.1% in negative group. The expression of α5ß1-integrin and MMP-14 is correlated with the progression and metastasis of CRC, and α5ß1-integrin and MMP-14 may be used as prognostic markers in CRC.


Subject(s)
Adenocarcinoma/mortality , Biomarkers, Tumor/metabolism , Colorectal Neoplasms/mortality , Integrin alpha5beta1/metabolism , Matrix Metalloproteinase 14/metabolism , Adenocarcinoma/metabolism , Adenocarcinoma/secondary , Colon/metabolism , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Disease Progression , Female , Humans , Immunoenzyme Techniques , Lymphatic Metastasis , Male , Middle Aged , Prognosis , Rectum/metabolism , Survival Rate
17.
Curr Oncol ; 19(6): 324-8, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23300358

ABSTRACT

The ubiquitin-proteasome pathway is a common cellular process in eukaryotic tissue. Ubiquitin binds to proteins and tags them for destruction; this tagging directs proteins to the proteosome in the cell that degrades and recycles unneeded proteins. The ubiquitin-proteasome pathway plays an important role in the regulation of cellular proteins with respect to cell cycle control, transcription, apoptosis, cell adhesion, angiogenesis, and tumour growth. This review article discusses the various ways that the ubiquitin pathway is involved in ovarian cancer, such as modulating the ovarian-cancer-related gene BRCA1 and tumour suppressor p53, and interfering with the erk pathway, the cyclin-dependent cell cycle regulation process, and ERBB2 gene expression.

18.
Parasitology ; 139(2): 237-43, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22018334

ABSTRACT

The objective of the present study was to evaluate the anticoccidial effect of different concentrations of the herbal complex of 4 plants (leaves of Azadirachta indica and Nicotiana tabacum, flowers of Calotropis procera and seeds of Trachyspermum ammi) in broiler chickens in comparison with amprolium anticoccidial. Three concentrations (2 g, 4 g and 6 g) of herbal complex were given to the experimental groups once a day and amprolium (at the dose rate of 125 ppm) was given orally in drinking water from the 14th to the 21st days of age. One group was kept as infected, non-medicated control and one as non-infected, non-medicated control. All groups were inoculated orally with 75,000 sporulated oocysts on the 14th day of age except the non-infected, non-medicated control. Among herbal complex medicated groups, the maximum anticoccidial effect was seen in the group medicated with 6 g herbal complex followed by 4 g and 2 g herbal complex medicated groups. Treatment with 6 g of the herbal complex significantly reduced the negative performance and pathogenic effects associated with Eimeria tenella challenge at a level that was comparable with amprolium when using a largely susceptible recent field isolate. In summary, concentration-dependent anticoccidial activity of the studied herbal complex suggests its use as an alternative anticoccidial agent to chemotherapeutic drugs for Eimeria tenella control.


Subject(s)
Chickens , Coccidiosis/veterinary , Eimeria tenella , Plant Preparations/therapeutic use , Plants, Medicinal , Poultry Diseases/drug therapy , Animal Feed , Animals , Coccidiosis/drug therapy , Coccidiostats/chemistry , Coccidiostats/therapeutic use , Diet/veterinary , Plant Preparations/administration & dosage
19.
Pesqui. vet. bras ; 31(5): 425-429, May 2011. tab
Article in English | LILACS | ID: lil-589080

ABSTRACT

The present study was planned to evaluate the anticoccidial activity of the different concentrations of the HCl against Eimeria tenella infection in broiler chickens in comparison with the amprolium anticoccidial. For this purpose, a total of 198 chicks were placed 11 per pen with three pens per treatment. The different concentrations of HCl (1000ppm, 2000ppm and 3000ppm) and amproilum (at the dose rate of 125ppm) were given to the experimental groups in drinking water from 10 to 19th days of age. One group was kept as infected non medicated control and one as non infected non medicated control. At the 12th day of age, all the groups were inoculated orally with 75,000 sporulated oocysts except non infected non medicated control. Anticoccidial activity was evaluated on the basis of performance (weight gain, feed conversion ratio) and pathogenic (oocyst score, lesion score and mortality percentage) parameters. Among HCl medicated groups, the maximum anticoccidial effect was seen in the group medicated with 1000ppm HCl followed by 2000ppm and 3000ppm HCl medicated groups. Amprolium and 1000ppm HCl were almost equivalent in suppressing the negative performance and pathogenic effects associated with coccidiosis (Eimeria tenella) challenge. In summary, the lower doses of HCl have the potential to be used as alternative to chemotherapeutic drugs for Eimeria tenella control. It is therefore suggested that further studies should be carried out to determine the possible minimum safe levels of HCl with least toxic effects to be used as anticoccidial.


Subject(s)
Animals , Coccidiosis , Coccidiostats , Eimeria tenella
20.
Pesqui. vet. bras ; 31(2): 99-103, Feb. 2011. tab
Article in English | LILACS | ID: lil-578901

ABSTRACT

The objective of the present study was to evaluate the anticoccidial effect of the different concentrations of the acetic acid in the broiler chickens in comparison with the amprolium anticoccidial. A total of 198 chicks were placed 11 per pen with three pens per treatment. The different concentrations (1 percent, 2 percent and 3 percent) of acetic acid and amproilum (at the dose rate of 125ppm) were given to the experimental groups in drinking water from 10-19th days of age. One group was kept as infected non medicated control and one as non infected non medicated control. All the groups were inoculated orally with 75,000 sporulated oocysts at the 12th day of age except non infected non medicated control. Anticoccidial effect was evaluated on the basis of performance (weight gain, feed conversion ratio) and pathogenic (oocyst score, lesion score and mortality percentage) parameters. Among acetic acid medicated groups, the maximum anticoccidial effect was seen in the group medicated with 3 percent acetic acid followed by 2 percent and 1 percent acetic acid medicated groups. Amprolium and 3 percent acetic acid were almost equivalent in suppressing the negative performance and pathogenic effects associated with coccidiosis (Eimeria tenella) challenge. In summary, acetic acid has the potential to be used as alternative to chemotherapeutic drugs for Eimeria tenella control. Concentration-dependent anticoccidial effect of acetic acid suggests that further studies should be carried out to determine the possible maximum safe levels of acetic acid with least toxic effects to be used as anticoccidial.


Subject(s)
Animals , Birds , Coccidiosis/veterinary
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