AIM:To investigate the risk factors and characteristics of hepatocellular carcinoma(HCC) in the patients with drug-resistant chronic hepatitis B(CHB).METHODS:A total of 432 patients with drug-resistant CHB were analyz...AIM:To investigate the risk factors and characteristics of hepatocellular carcinoma(HCC) in the patients with drug-resistant chronic hepatitis B(CHB).METHODS:A total of 432 patients with drug-resistant CHB were analyzed retrospectively from January 2004to December 2012. The patients were divided into two groups:the HCC group(n = 57) and the non-HCC group(n = 375). Two groups compared using logistic regression for various patients and viral characteristics in order to identify associated risk factors for HCC.Secondarily,patient and tumor characteristics of HCC patients with na ve CHB(N group,n = 117) were compared to the HCC group(R group,n = 57) to identify any difference in HCC characteristics between them.RESULTS:A significant difference was found for age,platelet count,alpha-fetoprotein(AFP),positivity of HBeAg,seroconversion rate of HBeAg,virologic response,the Child-Pugh score,presence of rtM204I,and the duration of antiviral treatment in non-HCC and HCC group. Cirrhosis,age(> 50 years),HBeAg(+),virologic non-responder status,and rtM204I mutants were independent risk factors for the development of HCC. The R group had lower serum C-reactive protein(CRP) and AFP levels,earlier stage tumors,and a shorter mean tumor surveillance period than the N group. However,the total follow-up duration was not significantly different between the two groups.CONCLUSION:13.2% of patients with drug-resistant CHB developed HCC. Age,cirrhosis,YIDD status,HBeAg status,and virologic response are associated with risk of HCC. Patients with drug-resistant CHB and these clinical factors may benefit from closer HCC surveillance.展开更多
The FOXO3a and FOXM1 forkhead transcription factors are key players in cancer initiation,progression,and drug resistance.Recent research shows that FOXM1 is a direct transcriptional target of FOXO3a,a vital downstream...The FOXO3a and FOXM1 forkhead transcription factors are key players in cancer initiation,progression,and drug resistance.Recent research shows that FOXM1 is a direct transcriptional target of FOXO3a,a vital downstream effector of the PI3K-AKT-FOXO signaling cascade.In addition,FOXM1 and FOXO3a also antagonize each other's activity by competitively binding to the same target genes,which are involved in chemotherapeutic drug sensitivity and resistance.Understanding the role and regulation of the FOXO-FOXM1 axis will provide insight into chemotherapeutic drug action and resistance in patients,and help to identify novel therapeutic approaches as well as diagnostic and predictive biomarkers.展开更多
Colorectal cancer(CRC) ranked third in cancer related death and its incidence has been increasing worldwide. In recent decades important therapeutic advances have been developed in treatment of metastatic CRC(mCRC), s...Colorectal cancer(CRC) ranked third in cancer related death and its incidence has been increasing worldwide. In recent decades important therapeutic advances have been developed in treatment of metastatic CRC(mCRC), such as monoclonal antibodies against epidermal growth factor receptor(anti-EGFR), which provided additional clinical benefits in mCRC. However, anti-EGFR therapies have limited usage due to approximately 95% of patients with KRAS mutated mCRC do not response to anti-EGFR treatment. Thus, KRAS mutation is predictive of nonresponse to anti-EGFR therapies but it alone is not a sufficient basis to decide who should not be received such therapies because; approximately fifty percent(40%-60%) of CRC patients with wild-type KRAS mutation also have poor response to anti-EGFR based treatment. This fact leads us to suspect that there must be other molecular determinants of response to anti-EGFR therapies which have not been identified yet. Current article summarizes the clinical efficacy of anti-EGFR therapies and also evaluates its resistance mechanisms.展开更多
<strong>Background:</strong><span><span><span style="font-family:""><span style="font-family:Verdana;"> Group B </span><i><span style="f...<strong>Background:</strong><span><span><span style="font-family:""><span style="font-family:Verdana;"> Group B </span><i><span style="font-family:Verdana;">Streptococcus </span></i><span style="font-family:Verdana;">(GBS) is a major cause of bacterial infections in the perinatal period, of which colonization prevalence among Northern-Nigerian pregnant women is scarce. We attempted to determine </span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">1</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">) its prevalence</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">,</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">2</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">) risk factors for GBS colonization and </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">3</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">) drugs-susceptibility.</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><b><span style="font-family:Verdana;">Methodology:</span></b></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> This cross-sectional study involved 185 pregnant women between 35</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">-</span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">37 weeks of gestation at tertiary health center of Sokoto, Nigeria. </span><span style="font-family:Verdana;">Vaginal/rectal swabs were collected, were cultured for GBS and tested for drug-</span><span style="font-family:Verdana;">susceptibilities. The study was conducted between December, 2017 and April, </span><span style="font-family:Verdana;">2018.</span></span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><b><span style="font-family:Verdana;">Results:</span></b></span></span><span><span><span style="font-family:""> <a name="_Toc14800008"></a><span style="font-family:Verdana;">One hundred and eighty five (185) pregnant women participated </span></span></span></span><span><span><span><span style="font-family:""><span style="font-family:Verdana;">in this study. GBS vaginal-colonization-rate was 3.8% (7/185). A significance relationship was observed between GBS-colonization and socio-economic class, as 57.10% (4/7) of the GBS positive women were of low-socio economic class (</span><i><span style="font-family:Verdana;">p</span></i><span style="font-family:Verdana;"> 0.035). No associations were observed between GBS-colonization and the followings: maternal age, parity, poor obstetric outcome-history. All the 7 GBS positive cultures were sensitive to Clindamycin. One was sensitive to both Clindamycin and Ceftriaxone. None was sensitive to Penicillin. </span><b><span style="font-family:Verdana;">Conclusion</span></b></span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><b><span style="font-family:Verdana;">:</span></b></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> The prevalence of GBS colonization was low in this area. Maternal socio-economic class is found to be a risk of GBS-colonization.</span></span></span>展开更多
The paper examines the effects of grapefruit consumption in relation to drugs, obesity and cardiovascular risk factors. The review includes the most updated studies found in Pub-Med. The grapefruit effect refers to th...The paper examines the effects of grapefruit consumption in relation to drugs, obesity and cardiovascular risk factors. The review includes the most updated studies found in Pub-Med. The grapefruit effect refers to the ability of grapefruit juice and supplements to interact with a wide variety of pharmaceuticals, either enhancing or limiting their systemic availability. Due to altering the active dosage of the pharmaceutical, Grapefruit juice is commonly not allowed to be used alongside with many drugs. Naringin is the most important one, which can inhibit absorption of some drugs but more commonly 6’7’-dihydroxybergamottin, which inhibits CYP3A4. Lately, grapefruit has been found both in rats and adults to reduce body weight, blood pressure, improve lipid and hepatic profile and decrease platelet aggregation. These promising results must be followed by additional studies in order to add to the importance of the role and effects of grapefruit as part of our diet.展开更多
AIM To determine the scope of acute hypoglycemic effects for certain anti-rheumatic medications in a large retrospective observational study. METHODS Patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VAR...AIM To determine the scope of acute hypoglycemic effects for certain anti-rheumatic medications in a large retrospective observational study. METHODS Patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry were selected who, during follow-up, initiated treatment with tumor necrosis factor inhibitors (TNFi's, including etanercept, adalimumab, infliximab, golimumab, or certolizumab), prednisone, or conventional disease-modifying anti-rheumatic drugs(DMARDs), and for whom proximate random blood glucose (RBG) measurements were available within a window 2-wk prior to, and 6 mo following, medication initiation. Similar data were obtained for patients with proximate values available for glycosylated hemoglobin A1C values within a window 2 mo preceding, and 12 mo following, medication initiation. RBG and A1C measurements were compared before and after initiation events using paired t-tests, and multivariate regression analysis was performed including established comorbidities and demographics.RESULTS Two thousands one hundred and eleven patients contributed at least one proximate measurement surrounding the initiation of any examined medication. A significant decrease in RBG was noted surrounding 653 individual hydroxychloroquine-initiation events(-3.68 mg/dL, P = 0.04), while an increase was noted for RBG surrounding 665 prednisone-initiation events(+5.85 mg/d L, P < 0.01). A statistically significant decrease in A1C was noted for sulfasalazine initiation, as measured by 49 individual initiation events(-0.70%, P < 0.01). Multivariate regression analyses, using methotrexate as the referent, suggest sulfasalazine (β =-0.58, P = 0.01) and hydroxychloroquine(β =-5.78, P = 0.01) use as predictors of lower post-medicationinitiation RBG and A1C values, respectively. Analysis by drug class suggested prednisone (or glucocorticoids) as predictive of higher medication-initiation event RBG among all start events as compared to DMARDs, while this analysis did not show any drug class-level effect for TNFi. A diagnosis of congestive heart failure(β = 4.69, P = 0.03) was predictive for higher post-initiation RBG values among all medication-initiation events.CONCLUSION No statistically significant hypoglycemic effects surrounding TNFi initiation were observed in this large cohort. Sulfasalazine and hydroxychloroquine may have epidemiologically significant acute hypoglycemic effects.展开更多
Objective: Discuss impacts of family environment over Hainan province adolescent drug taking behavior.Methods: Adopt "Investigation Questionnaire of Family Environment of Drug Abuse Adolescent in Hainan Province&...Objective: Discuss impacts of family environment over Hainan province adolescent drug taking behavior.Methods: Adopt "Investigation Questionnaire of Family Environment of Drug Abuse Adolescent in Hainan Province" that compiled by self and "Family Environment Scale(FES-CV-Ⅲ)" for research tools.To carry out questionnaire investigation to the 352 drug taking adolescents,who come from "The First Reeducation Through Labor Institute in Hainan Province","The Second Reeducation Through Labor Institute in Hainan Province" and "The Center of Spirit Drug Treated in Hainan Province",then give the data analysis and correlation analysis of the differences.Results: The Cohesion、Intellectual-Cultural orientation、Active-Recreational orientation、Organization、Expressiveness、Independence and Achievement Orientation scores of the drug taking adolescent families in Hainan province were significantly lower than normal samples in China,but the Moral-Religious Emphasis、Conflict and Control scores were significantly higher than the normal samples.Conclusions: The drug taking adolescent not only lack of well-educated families,but also has not been a good school education;most of their families belong to the low social class;adverse family environment is an important reason for drug abuse by adolescent.展开更多
Besides their possible effects on the development of inflammatory bowel disease(IBD),some environmental factors can modulate the clinical course of both ulcerative colitis(UC) and Crohn's disease(CD).This review i...Besides their possible effects on the development of inflammatory bowel disease(IBD),some environmental factors can modulate the clinical course of both ulcerative colitis(UC) and Crohn's disease(CD).This review is mainly devoted to describing the current knowledge of the impact of some of these factors on the outcome of IBD,with special emphasis on smoking and diet.Although the impact of smoking on the susceptibility to develop CD and UC is firmly established,its influence on the clinical course of both diseases is still debatable.In CD,active smoking is a risk factor for postoperative recurrence.Beyond this clinical setting,smoking cessation seems to be advantageous in those CD patients who were smokers at disease diagnosis,while smoking resumption may be of benefit in ex-smokers with resistant UC.The role of dietary habits on the development of IBD is far from being well established.Also,food intolerances are very frequent,but usually inconsistent among IBD patients,and therefore no general dietary recommendations can be made in these patients.In general,IBD patients should eat a diet as varied as possible.Regarding the possible therapeutic role of some dietary components in IBD,lessons should be drawn from the investigation of the primary therapeutic effect of enteral nutrition in CD.Low-fat diets seem to be particularly useful.Also,some lipid sources,such as olive oil,medium-chain triglycerides,and perhaps omega-3 fatty acids,might have a therapeutic effect.Fermentable fiber may have a role in preventing relapses in inactive UC.展开更多
Objective:To describe the prescribing behavior of the physician in Kerala,and to describe types and number of medicine prescribed by doctors so as to rationalize the prescription writing habits of physician.Methods: A...Objective:To describe the prescribing behavior of the physician in Kerala,and to describe types and number of medicine prescribed by doctors so as to rationalize the prescription writing habits of physician.Methods: A six month study was done to define the pattern of drug use in Medical college hospital,Calicut. The data and the other important aspects of study were collected by personal interview,questionnaires meant for doctors and prescription monitoring Performa for the patients issued by WHO. The findings of survey were critically analyzed.Results: The results indicated that majority of doctors prescribed on the basis of patient's history,patient's feed back report,drug availability,brand cost,quality of drug and ADRs. All the interviewed doctors looked upon the side effects. It was found that individual drugs were prescribed more than fixed dose combinations (85.6%). Out of these 71.5% were prescribed as branded and 28.5% as generic. The demographic data,like name,age,sex,disease diagnosis were available on all the patient health care cards and these constituted an essential part of the prescription particularly age and sex being an important in deciding the dose preference for patients. Socio economically most patients were found to be in the grade ⅡI (Population below poverty line). During the study of drug related parameters,doses were mentioned only in 80% of the prescription. But duration of the drug therapy was found to be only 30%.These indicated the irrational use of prescription. Branded drugs prescribed were found to be 71.5%,which showed a trend towards a good prescription habit. The results indicated the rational use of drug.Conclusion: The survey reveales that most of the doctors in Medical college hospital,Calicut are maintaining rational use of drugs and their prescription writing habits was found to be good.展开更多
AIM To investigate potential triggering factors leading to acute liver failure(ALF) as the initial presentation of autoimmune hepatitis(AIH).METHODS A total of 565 patients treated at our Department between 2005 and 2...AIM To investigate potential triggering factors leading to acute liver failure(ALF) as the initial presentation of autoimmune hepatitis(AIH).METHODS A total of 565 patients treated at our Department between 2005 and 2017 for histologically-proven AIH were retrospectively analyzed. However, 52 patients(9.2%) fulfilled the criteria for ALF defined by the "American Association for the Study of the Liver(AASLD)". According to this definition, patients with "acute-on-chronic" or "acute-on-cirrhosis" liver failure were excluded. Following parameters with focus on potential triggering factors were evaluated: Patients' demographics, causation of liver failure, laboratory data(liver enzymes, MELD-score, autoimmune markers, virus serology), liver histology, immunosuppressive regime, and finally, outcome of our patients.RESULTS The majority of patients with ALF were female(84.6%) and mean age was 43.6 ± 14.9 years. Interestingly, none of the patients with ALF was positive for antiliver kidney microsomal antibody(LKM). We could identify potential triggering factors in 26/52(50.0%) of previously healthy patients presenting ALF as their first manifestation of AIH. These were drug-induced ALF(57.7%), virus-induced ALF(30.8%), and preceding surgery in general anesthesia(11.5%), respectively. Unfortunately, 6 out of 52 patients(11.5%) did not survive ALF and 3 patients(5.7%) underwent liver transplantation(LT). Comparing data of survivors and patients with non-recovery following treatment, MELDscore(P < 0.001), age(P < 0.05), creatinine(P < 0.01), and finally, ALT-values(P < 0.05) reached statistical significance. CONCLUSION Drugs, viral infections, and previous surgery may trigger ALF as the initial presentation of AIH. Advanced age and high MELD-score were associated with lethal outcome.展开更多
AIM:To establish a rabbit model with chronic condition of retinal neovascularization(RNV)induced by intravitreal(IVT)injection of DL-2-aminoadipic acid(DL-AAA),a retinal glial(Mül er)cell toxin,extensive characte...AIM:To establish a rabbit model with chronic condition of retinal neovascularization(RNV)induced by intravitreal(IVT)injection of DL-2-aminoadipic acid(DL-AAA),a retinal glial(Mül er)cell toxin,extensive characterization of DL-AAA induced angiographic features and the suitability of the model to evaluate anti-angiogenic and anti-inflammatory therapies for ocular vascular diseases.METHODS:DL-AAA(80 mmol/L)was administered IVT into both eyes of Dutch Belted rabbit.Post DL-AAA delivery,clinical ophthalmic examinations were performed weekly following modified Mc Donald-Shadduck Scoring System.Color fundus photography,fluorescein angiography(FA),and optical coherence tomography(OCT)procedures were performed every 2 or 4 wk until stable retinal vascular leakage was observed.Once stable retinal leakage(12 wk post DL-AAA administration)was established,anti-vascular endothelial growth factor(VEGF)(bevacizumab,ranibizumab and aflibercept)and anti-inflammatory(triamcinolone,TAA)drugs were tested for their efficacy after IVT administration.Fluorescein angiograms were scored before and after treatment following a novel grading system,developed for the DL-AAA rabbit model.RESULTS:Post DL-AAA administration,eyes were presented with moderate to severe retinal/choroidal inflammation which was accompanied by intense vitreous flare and presence of inflammatory cells in the vitreous humor.Retinal hemorrhage was restricted to the tips of neo-retinal vessels.FA revealed maximum retinal vascular leakage at 2 wk after DL-AAA injection and then persisted as evidenced by stable mean FA scores in weeks 8 and 12.Retinal vascular angiographic and tomographic features were stable and consistent up to 36 mo among two different staggers induced for RNV at two different occasions.Day 7,mean FA scores showed that 1μg/eye of bevacizumab,ranibizumab,aflibercept and 2μg/eye of TAA suppress 65%,90%,100%and 50%retinal vascular leakage,respectively.Day 30,bevacizumab and TAA continued to show 66%and 44%suppression while ranibizumab effect was becoming less effective(68%).In contrast,aflibercept was still able to fully(100%)suppress vascular leakage on day 30.On day 60,bevacizumab,ranibizumab and TAA showed suppression of 7%,12%,and 9%retinal vascular leakage,respectively,however,aflibercept continued to be more effective showing 50%suppression of vascular leakage.CONCLUSION:The DL-AAA rabbit model mimics RNV angiographic features like RNV and chronic retinal leakage.Based on these features the DL-AAA rabbit model provides an invaluable tool that could be used to test the therapeutic efficacy and duration of action of novel anti-angiogenic formulations,alone or in combination with anti-inflammatory compounds.展开更多
Clostridium difficile associated disease (CDAD) is the most common hospital acquired infection, due to exposure to various drugs. C. difficile toxins influence barrier function in intestinal epithelium. Biotherapeutic...Clostridium difficile associated disease (CDAD) is the most common hospital acquired infection, due to exposure to various drugs. C. difficile toxins influence barrier function in intestinal epithelium. Biotherapeutic approaches, employing probiotic and epidermal growth factor (EGF) could help in barrier protein protection and aid in CDAD management. A preliminary investigation on the effect of Lactobacillus acidophilus and EGF on tight junction proteins in experimentally induced C. difficile infection was done. BALB/mice were divided into 5 groups. Group 1 was comprised of healthy controls, whereas animals in Groups 2 - 5 were sub-divided into 3 subgroups (a, b and c) each. Animals in Groups 2 - 5 received C. difficile inoculum either on day 1 (Group 2) or after pretreatment with ampicillin (Group 3), cyclosporine (Group 4) or lansoprazole (Group 5). Additionally animals in subgroups “b” and “c” also received L. acidophilus and EGF inocula respectively after C. difficile challenge. All animals were investigated for the presence of tight junction proteins (occludin, α-actinin and zonula occludens) in their colonic segments. Data were analyzed using the SPSS version 10 software. These three proteins were present in significantly less (P < 0.05) number of animals in the drug receiving animals, whereas they were found in significantly more (P < 0.05) number of animals receiving L. acidophilus and EGF after challenge with ampicillin, cyclosporine and lansoprazole, suggesting their role in protecting intestinal barrier function.展开更多
Platelet-derived growth factors (PDGFs) and their receptors were identified and purified decades ago. PDGFs are important during normal development and in human cancers. In particular, autocrine PDGF signaling has bee...Platelet-derived growth factors (PDGFs) and their receptors were identified and purified decades ago. PDGFs are important during normal development and in human cancers. In particular, autocrine PDGF signaling has been implicated in various types of malignancies such as gliomas and leukemia. In contrast, paracrine signaling was found in cancers that originate from epithelial cells, where it may be involved in stromal cell recruitment, metastasis, and epithelial-mesenchymal transition. This editorial briefly discusses autocrine and paracrine PDGF signaling and their roles in human cancers, and introduces a series of review articles in this issue that address the possible roles of PDGFs in various processes involved in different types of cancers.展开更多
<strong>Objective:</strong> The study was conducted to understand the situation of patients with inflammatory bowel disease (IBD) to participant clinical trials and to analyze the factors affecting the cli...<strong>Objective:</strong> The study was conducted to understand the situation of patients with inflammatory bowel disease (IBD) to participant clinical trials and to analyze the factors affecting the clinical trial participation of patients with IBD. A clinical experiment guidance will be proved by this study to maximized the benefits to patients and to help the clinical trial to conduct successfully. <strong>Method: </strong>An anonymous questionnaire was designed and was administrated to the patients with IBD who were randomly delivered in the inpatient or outpatient departments. The survey result was analyzed. <strong>Result:</strong> Total 372 available questionnaires were returned. Among these patients, 26.3% patients with IBD indicated willingness to participate, 57.3% indicated a situation dependence, and 41.04% indicated unwillingness. Among the potential factors that may influence the patient’s willingness to participate the clinical, trusted physician’s recommendation, no proved drugs to use and accessing to free medication to release financial burden were statistically significant. <strong>Conclusion:</strong> The overall willingness of IBD patients to participate in drug clinical trials is not high. Among the patients who are willing to participate in clinical trials, the main reasons for their participation are that they trust doctors’ recommendation, can get free medication and examination, and can reduce the economic burden. Efficacy and safety were the main influencing factors in patients who were case-dependent and unwilling to participate in clinical trials.展开更多
To establish a cytologic expressing system of rat glutathione S-transferase pi (GST-pi) cDNA for detecting the resistance of HeLa cells to anticancer drugs. Methods The assessment was made with various anticancer dr...To establish a cytologic expressing system of rat glutathione S-transferase pi (GST-pi) cDNA for detecting the resistance of HeLa cells to anticancer drugs. Methods The assessment was made with various anticancer drugs (adriamycin, mitomycin, cisplatinum and vincristine) that showed different cytotoxicities in transfectant HeLa cells with pSV-GT containing rat GST-pi cDNA (HeLa/pSV-GT) or control pSV-neo (HeLa/pSV-neo). Expression levels of GST-pi mRNA in HeLa/pSV-GT and HeLa/pSV-neo were measured by in situ hybridization using Digoxin-labelled cDNA probe. Results HeLa/pSV-GT expressed significantly high degree of GST-pi mRNA, whereas both HeLa/pSV-neo and HeLa cells had very low expression. Cytotoxicities of HeLa/pSV-GT and HeLa/pSV-neo with 4 anticancer drugs were measured by MTT assay. Drug concentrations for yielding 50% inhibition (IC50) in HeLa/pSV-GT by adriamycin, mitomycin and cisplatinum were 70.13 靏/mL, 10.95 靏/mL and 16.52 靏/mL, respectively. In contrast, IC50 in HeLa/pSV-neo was 10.34 靏/mL, 7.48 靏/mL and 13.70 靏/mL, respectively. The cytotoxicities of vincristine on both HeLa/pSV-GT and HeLa/pSV-neo were not significantly different. Conclusions Our findings suggest that HeLa/pSV-GT containing rat GST-pi cDNA is resistant to some anticancer drugs due to overexpression of GST-pi. Also, HeLa/pSV-GT cell line could serve as a useful cytogenetic model for further research.展开更多
基金Supported by Grants from Chonnam National University Hospital 42,Jaebong-ro,Dong-Ku,Gwangju,501-757,South Korea
文摘AIM:To investigate the risk factors and characteristics of hepatocellular carcinoma(HCC) in the patients with drug-resistant chronic hepatitis B(CHB).METHODS:A total of 432 patients with drug-resistant CHB were analyzed retrospectively from January 2004to December 2012. The patients were divided into two groups:the HCC group(n = 57) and the non-HCC group(n = 375). Two groups compared using logistic regression for various patients and viral characteristics in order to identify associated risk factors for HCC.Secondarily,patient and tumor characteristics of HCC patients with na ve CHB(N group,n = 117) were compared to the HCC group(R group,n = 57) to identify any difference in HCC characteristics between them.RESULTS:A significant difference was found for age,platelet count,alpha-fetoprotein(AFP),positivity of HBeAg,seroconversion rate of HBeAg,virologic response,the Child-Pugh score,presence of rtM204I,and the duration of antiviral treatment in non-HCC and HCC group. Cirrhosis,age(> 50 years),HBeAg(+),virologic non-responder status,and rtM204I mutants were independent risk factors for the development of HCC. The R group had lower serum C-reactive protein(CRP) and AFP levels,earlier stage tumors,and a shorter mean tumor surveillance period than the N group. However,the total follow-up duration was not significantly different between the two groups.CONCLUSION:13.2% of patients with drug-resistant CHB developed HCC. Age,cirrhosis,YIDD status,HBeAg status,and virologic response are associated with risk of HCC. Patients with drug-resistant CHB and these clinical factors may benefit from closer HCC surveillance.
文摘The FOXO3a and FOXM1 forkhead transcription factors are key players in cancer initiation,progression,and drug resistance.Recent research shows that FOXM1 is a direct transcriptional target of FOXO3a,a vital downstream effector of the PI3K-AKT-FOXO signaling cascade.In addition,FOXM1 and FOXO3a also antagonize each other's activity by competitively binding to the same target genes,which are involved in chemotherapeutic drug sensitivity and resistance.Understanding the role and regulation of the FOXO-FOXM1 axis will provide insight into chemotherapeutic drug action and resistance in patients,and help to identify novel therapeutic approaches as well as diagnostic and predictive biomarkers.
文摘Colorectal cancer(CRC) ranked third in cancer related death and its incidence has been increasing worldwide. In recent decades important therapeutic advances have been developed in treatment of metastatic CRC(mCRC), such as monoclonal antibodies against epidermal growth factor receptor(anti-EGFR), which provided additional clinical benefits in mCRC. However, anti-EGFR therapies have limited usage due to approximately 95% of patients with KRAS mutated mCRC do not response to anti-EGFR treatment. Thus, KRAS mutation is predictive of nonresponse to anti-EGFR therapies but it alone is not a sufficient basis to decide who should not be received such therapies because; approximately fifty percent(40%-60%) of CRC patients with wild-type KRAS mutation also have poor response to anti-EGFR based treatment. This fact leads us to suspect that there must be other molecular determinants of response to anti-EGFR therapies which have not been identified yet. Current article summarizes the clinical efficacy of anti-EGFR therapies and also evaluates its resistance mechanisms.
文摘<strong>Background:</strong><span><span><span style="font-family:""><span style="font-family:Verdana;"> Group B </span><i><span style="font-family:Verdana;">Streptococcus </span></i><span style="font-family:Verdana;">(GBS) is a major cause of bacterial infections in the perinatal period, of which colonization prevalence among Northern-Nigerian pregnant women is scarce. We attempted to determine </span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">1</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">) its prevalence</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">,</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">2</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">) risk factors for GBS colonization and </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">3</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">) drugs-susceptibility.</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><b><span style="font-family:Verdana;">Methodology:</span></b></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> This cross-sectional study involved 185 pregnant women between 35</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">-</span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">37 weeks of gestation at tertiary health center of Sokoto, Nigeria. </span><span style="font-family:Verdana;">Vaginal/rectal swabs were collected, were cultured for GBS and tested for drug-</span><span style="font-family:Verdana;">susceptibilities. The study was conducted between December, 2017 and April, </span><span style="font-family:Verdana;">2018.</span></span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><b><span style="font-family:Verdana;">Results:</span></b></span></span><span><span><span style="font-family:""> <a name="_Toc14800008"></a><span style="font-family:Verdana;">One hundred and eighty five (185) pregnant women participated </span></span></span></span><span><span><span><span style="font-family:""><span style="font-family:Verdana;">in this study. GBS vaginal-colonization-rate was 3.8% (7/185). A significance relationship was observed between GBS-colonization and socio-economic class, as 57.10% (4/7) of the GBS positive women were of low-socio economic class (</span><i><span style="font-family:Verdana;">p</span></i><span style="font-family:Verdana;"> 0.035). No associations were observed between GBS-colonization and the followings: maternal age, parity, poor obstetric outcome-history. All the 7 GBS positive cultures were sensitive to Clindamycin. One was sensitive to both Clindamycin and Ceftriaxone. None was sensitive to Penicillin. </span><b><span style="font-family:Verdana;">Conclusion</span></b></span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><b><span style="font-family:Verdana;">:</span></b></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> The prevalence of GBS colonization was low in this area. Maternal socio-economic class is found to be a risk of GBS-colonization.</span></span></span>
文摘The paper examines the effects of grapefruit consumption in relation to drugs, obesity and cardiovascular risk factors. The review includes the most updated studies found in Pub-Med. The grapefruit effect refers to the ability of grapefruit juice and supplements to interact with a wide variety of pharmaceuticals, either enhancing or limiting their systemic availability. Due to altering the active dosage of the pharmaceutical, Grapefruit juice is commonly not allowed to be used alongside with many drugs. Naringin is the most important one, which can inhibit absorption of some drugs but more commonly 6’7’-dihydroxybergamottin, which inhibits CYP3A4. Lately, grapefruit has been found both in rats and adults to reduce body weight, blood pressure, improve lipid and hepatic profile and decrease platelet aggregation. These promising results must be followed by additional studies in order to add to the importance of the role and effects of grapefruit as part of our diet.
基金Supported by VA HSR&D MERIT Award IIR,No.14-048-3 for Dr Caplansupported by a VA GME Enhancement Award
文摘AIM To determine the scope of acute hypoglycemic effects for certain anti-rheumatic medications in a large retrospective observational study. METHODS Patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry were selected who, during follow-up, initiated treatment with tumor necrosis factor inhibitors (TNFi's, including etanercept, adalimumab, infliximab, golimumab, or certolizumab), prednisone, or conventional disease-modifying anti-rheumatic drugs(DMARDs), and for whom proximate random blood glucose (RBG) measurements were available within a window 2-wk prior to, and 6 mo following, medication initiation. Similar data were obtained for patients with proximate values available for glycosylated hemoglobin A1C values within a window 2 mo preceding, and 12 mo following, medication initiation. RBG and A1C measurements were compared before and after initiation events using paired t-tests, and multivariate regression analysis was performed including established comorbidities and demographics.RESULTS Two thousands one hundred and eleven patients contributed at least one proximate measurement surrounding the initiation of any examined medication. A significant decrease in RBG was noted surrounding 653 individual hydroxychloroquine-initiation events(-3.68 mg/dL, P = 0.04), while an increase was noted for RBG surrounding 665 prednisone-initiation events(+5.85 mg/d L, P < 0.01). A statistically significant decrease in A1C was noted for sulfasalazine initiation, as measured by 49 individual initiation events(-0.70%, P < 0.01). Multivariate regression analyses, using methotrexate as the referent, suggest sulfasalazine (β =-0.58, P = 0.01) and hydroxychloroquine(β =-5.78, P = 0.01) use as predictors of lower post-medicationinitiation RBG and A1C values, respectively. Analysis by drug class suggested prednisone (or glucocorticoids) as predictive of higher medication-initiation event RBG among all start events as compared to DMARDs, while this analysis did not show any drug class-level effect for TNFi. A diagnosis of congestive heart failure(β = 4.69, P = 0.03) was predictive for higher post-initiation RBG values among all medication-initiation events.CONCLUSION No statistically significant hypoglycemic effects surrounding TNFi initiation were observed in this large cohort. Sulfasalazine and hydroxychloroquine may have epidemiologically significant acute hypoglycemic effects.
文摘Objective: Discuss impacts of family environment over Hainan province adolescent drug taking behavior.Methods: Adopt "Investigation Questionnaire of Family Environment of Drug Abuse Adolescent in Hainan Province" that compiled by self and "Family Environment Scale(FES-CV-Ⅲ)" for research tools.To carry out questionnaire investigation to the 352 drug taking adolescents,who come from "The First Reeducation Through Labor Institute in Hainan Province","The Second Reeducation Through Labor Institute in Hainan Province" and "The Center of Spirit Drug Treated in Hainan Province",then give the data analysis and correlation analysis of the differences.Results: The Cohesion、Intellectual-Cultural orientation、Active-Recreational orientation、Organization、Expressiveness、Independence and Achievement Orientation scores of the drug taking adolescent families in Hainan province were significantly lower than normal samples in China,but the Moral-Religious Emphasis、Conflict and Control scores were significantly higher than the normal samples.Conclusions: The drug taking adolescent not only lack of well-educated families,but also has not been a good school education;most of their families belong to the low social class;adverse family environment is an important reason for drug abuse by adolescent.
文摘Besides their possible effects on the development of inflammatory bowel disease(IBD),some environmental factors can modulate the clinical course of both ulcerative colitis(UC) and Crohn's disease(CD).This review is mainly devoted to describing the current knowledge of the impact of some of these factors on the outcome of IBD,with special emphasis on smoking and diet.Although the impact of smoking on the susceptibility to develop CD and UC is firmly established,its influence on the clinical course of both diseases is still debatable.In CD,active smoking is a risk factor for postoperative recurrence.Beyond this clinical setting,smoking cessation seems to be advantageous in those CD patients who were smokers at disease diagnosis,while smoking resumption may be of benefit in ex-smokers with resistant UC.The role of dietary habits on the development of IBD is far from being well established.Also,food intolerances are very frequent,but usually inconsistent among IBD patients,and therefore no general dietary recommendations can be made in these patients.In general,IBD patients should eat a diet as varied as possible.Regarding the possible therapeutic role of some dietary components in IBD,lessons should be drawn from the investigation of the primary therapeutic effect of enteral nutrition in CD.Low-fat diets seem to be particularly useful.Also,some lipid sources,such as olive oil,medium-chain triglycerides,and perhaps omega-3 fatty acids,might have a therapeutic effect.Fermentable fiber may have a role in preventing relapses in inactive UC.
文摘Objective:To describe the prescribing behavior of the physician in Kerala,and to describe types and number of medicine prescribed by doctors so as to rationalize the prescription writing habits of physician.Methods: A six month study was done to define the pattern of drug use in Medical college hospital,Calicut. The data and the other important aspects of study were collected by personal interview,questionnaires meant for doctors and prescription monitoring Performa for the patients issued by WHO. The findings of survey were critically analyzed.Results: The results indicated that majority of doctors prescribed on the basis of patient's history,patient's feed back report,drug availability,brand cost,quality of drug and ADRs. All the interviewed doctors looked upon the side effects. It was found that individual drugs were prescribed more than fixed dose combinations (85.6%). Out of these 71.5% were prescribed as branded and 28.5% as generic. The demographic data,like name,age,sex,disease diagnosis were available on all the patient health care cards and these constituted an essential part of the prescription particularly age and sex being an important in deciding the dose preference for patients. Socio economically most patients were found to be in the grade ⅡI (Population below poverty line). During the study of drug related parameters,doses were mentioned only in 80% of the prescription. But duration of the drug therapy was found to be only 30%.These indicated the irrational use of prescription. Branded drugs prescribed were found to be 71.5%,which showed a trend towards a good prescription habit. The results indicated the rational use of drug.Conclusion: The survey reveales that most of the doctors in Medical college hospital,Calicut are maintaining rational use of drugs and their prescription writing habits was found to be good.
文摘AIM To investigate potential triggering factors leading to acute liver failure(ALF) as the initial presentation of autoimmune hepatitis(AIH).METHODS A total of 565 patients treated at our Department between 2005 and 2017 for histologically-proven AIH were retrospectively analyzed. However, 52 patients(9.2%) fulfilled the criteria for ALF defined by the "American Association for the Study of the Liver(AASLD)". According to this definition, patients with "acute-on-chronic" or "acute-on-cirrhosis" liver failure were excluded. Following parameters with focus on potential triggering factors were evaluated: Patients' demographics, causation of liver failure, laboratory data(liver enzymes, MELD-score, autoimmune markers, virus serology), liver histology, immunosuppressive regime, and finally, outcome of our patients.RESULTS The majority of patients with ALF were female(84.6%) and mean age was 43.6 ± 14.9 years. Interestingly, none of the patients with ALF was positive for antiliver kidney microsomal antibody(LKM). We could identify potential triggering factors in 26/52(50.0%) of previously healthy patients presenting ALF as their first manifestation of AIH. These were drug-induced ALF(57.7%), virus-induced ALF(30.8%), and preceding surgery in general anesthesia(11.5%), respectively. Unfortunately, 6 out of 52 patients(11.5%) did not survive ALF and 3 patients(5.7%) underwent liver transplantation(LT). Comparing data of survivors and patients with non-recovery following treatment, MELDscore(P < 0.001), age(P < 0.05), creatinine(P < 0.01), and finally, ALT-values(P < 0.05) reached statistical significance. CONCLUSION Drugs, viral infections, and previous surgery may trigger ALF as the initial presentation of AIH. Advanced age and high MELD-score were associated with lethal outcome.
文摘AIM:To establish a rabbit model with chronic condition of retinal neovascularization(RNV)induced by intravitreal(IVT)injection of DL-2-aminoadipic acid(DL-AAA),a retinal glial(Mül er)cell toxin,extensive characterization of DL-AAA induced angiographic features and the suitability of the model to evaluate anti-angiogenic and anti-inflammatory therapies for ocular vascular diseases.METHODS:DL-AAA(80 mmol/L)was administered IVT into both eyes of Dutch Belted rabbit.Post DL-AAA delivery,clinical ophthalmic examinations were performed weekly following modified Mc Donald-Shadduck Scoring System.Color fundus photography,fluorescein angiography(FA),and optical coherence tomography(OCT)procedures were performed every 2 or 4 wk until stable retinal vascular leakage was observed.Once stable retinal leakage(12 wk post DL-AAA administration)was established,anti-vascular endothelial growth factor(VEGF)(bevacizumab,ranibizumab and aflibercept)and anti-inflammatory(triamcinolone,TAA)drugs were tested for their efficacy after IVT administration.Fluorescein angiograms were scored before and after treatment following a novel grading system,developed for the DL-AAA rabbit model.RESULTS:Post DL-AAA administration,eyes were presented with moderate to severe retinal/choroidal inflammation which was accompanied by intense vitreous flare and presence of inflammatory cells in the vitreous humor.Retinal hemorrhage was restricted to the tips of neo-retinal vessels.FA revealed maximum retinal vascular leakage at 2 wk after DL-AAA injection and then persisted as evidenced by stable mean FA scores in weeks 8 and 12.Retinal vascular angiographic and tomographic features were stable and consistent up to 36 mo among two different staggers induced for RNV at two different occasions.Day 7,mean FA scores showed that 1μg/eye of bevacizumab,ranibizumab,aflibercept and 2μg/eye of TAA suppress 65%,90%,100%and 50%retinal vascular leakage,respectively.Day 30,bevacizumab and TAA continued to show 66%and 44%suppression while ranibizumab effect was becoming less effective(68%).In contrast,aflibercept was still able to fully(100%)suppress vascular leakage on day 30.On day 60,bevacizumab,ranibizumab and TAA showed suppression of 7%,12%,and 9%retinal vascular leakage,respectively,however,aflibercept continued to be more effective showing 50%suppression of vascular leakage.CONCLUSION:The DL-AAA rabbit model mimics RNV angiographic features like RNV and chronic retinal leakage.Based on these features the DL-AAA rabbit model provides an invaluable tool that could be used to test the therapeutic efficacy and duration of action of novel anti-angiogenic formulations,alone or in combination with anti-inflammatory compounds.
文摘Clostridium difficile associated disease (CDAD) is the most common hospital acquired infection, due to exposure to various drugs. C. difficile toxins influence barrier function in intestinal epithelium. Biotherapeutic approaches, employing probiotic and epidermal growth factor (EGF) could help in barrier protein protection and aid in CDAD management. A preliminary investigation on the effect of Lactobacillus acidophilus and EGF on tight junction proteins in experimentally induced C. difficile infection was done. BALB/mice were divided into 5 groups. Group 1 was comprised of healthy controls, whereas animals in Groups 2 - 5 were sub-divided into 3 subgroups (a, b and c) each. Animals in Groups 2 - 5 received C. difficile inoculum either on day 1 (Group 2) or after pretreatment with ampicillin (Group 3), cyclosporine (Group 4) or lansoprazole (Group 5). Additionally animals in subgroups “b” and “c” also received L. acidophilus and EGF inocula respectively after C. difficile challenge. All animals were investigated for the presence of tight junction proteins (occludin, α-actinin and zonula occludens) in their colonic segments. Data were analyzed using the SPSS version 10 software. These three proteins were present in significantly less (P < 0.05) number of animals in the drug receiving animals, whereas they were found in significantly more (P < 0.05) number of animals receiving L. acidophilus and EGF after challenge with ampicillin, cyclosporine and lansoprazole, suggesting their role in protecting intestinal barrier function.
文摘Platelet-derived growth factors (PDGFs) and their receptors were identified and purified decades ago. PDGFs are important during normal development and in human cancers. In particular, autocrine PDGF signaling has been implicated in various types of malignancies such as gliomas and leukemia. In contrast, paracrine signaling was found in cancers that originate from epithelial cells, where it may be involved in stromal cell recruitment, metastasis, and epithelial-mesenchymal transition. This editorial briefly discusses autocrine and paracrine PDGF signaling and their roles in human cancers, and introduces a series of review articles in this issue that address the possible roles of PDGFs in various processes involved in different types of cancers.
文摘<strong>Objective:</strong> The study was conducted to understand the situation of patients with inflammatory bowel disease (IBD) to participant clinical trials and to analyze the factors affecting the clinical trial participation of patients with IBD. A clinical experiment guidance will be proved by this study to maximized the benefits to patients and to help the clinical trial to conduct successfully. <strong>Method: </strong>An anonymous questionnaire was designed and was administrated to the patients with IBD who were randomly delivered in the inpatient or outpatient departments. The survey result was analyzed. <strong>Result:</strong> Total 372 available questionnaires were returned. Among these patients, 26.3% patients with IBD indicated willingness to participate, 57.3% indicated a situation dependence, and 41.04% indicated unwillingness. Among the potential factors that may influence the patient’s willingness to participate the clinical, trusted physician’s recommendation, no proved drugs to use and accessing to free medication to release financial burden were statistically significant. <strong>Conclusion:</strong> The overall willingness of IBD patients to participate in drug clinical trials is not high. Among the patients who are willing to participate in clinical trials, the main reasons for their participation are that they trust doctors’ recommendation, can get free medication and examination, and can reduce the economic burden. Efficacy and safety were the main influencing factors in patients who were case-dependent and unwilling to participate in clinical trials.
基金the National Natural Science Foundation of China.
文摘To establish a cytologic expressing system of rat glutathione S-transferase pi (GST-pi) cDNA for detecting the resistance of HeLa cells to anticancer drugs. Methods The assessment was made with various anticancer drugs (adriamycin, mitomycin, cisplatinum and vincristine) that showed different cytotoxicities in transfectant HeLa cells with pSV-GT containing rat GST-pi cDNA (HeLa/pSV-GT) or control pSV-neo (HeLa/pSV-neo). Expression levels of GST-pi mRNA in HeLa/pSV-GT and HeLa/pSV-neo were measured by in situ hybridization using Digoxin-labelled cDNA probe. Results HeLa/pSV-GT expressed significantly high degree of GST-pi mRNA, whereas both HeLa/pSV-neo and HeLa cells had very low expression. Cytotoxicities of HeLa/pSV-GT and HeLa/pSV-neo with 4 anticancer drugs were measured by MTT assay. Drug concentrations for yielding 50% inhibition (IC50) in HeLa/pSV-GT by adriamycin, mitomycin and cisplatinum were 70.13 靏/mL, 10.95 靏/mL and 16.52 靏/mL, respectively. In contrast, IC50 in HeLa/pSV-neo was 10.34 靏/mL, 7.48 靏/mL and 13.70 靏/mL, respectively. The cytotoxicities of vincristine on both HeLa/pSV-GT and HeLa/pSV-neo were not significantly different. Conclusions Our findings suggest that HeLa/pSV-GT containing rat GST-pi cDNA is resistant to some anticancer drugs due to overexpression of GST-pi. Also, HeLa/pSV-GT cell line could serve as a useful cytogenetic model for further research.