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Pyroptosis is a pro-inflammatory programmed cell death, and its role in cardiac inflammatory response has become a hot topic. The activation of nucleotide binding oligomerization domain like receptor protein 3(NLRP3) inflammasome is an important mechanism for pyroptosis induced by cysteinyl aspartate specific proteinase 1(caspase-1). The existing studies have shown that cardiomyocyte pyroptosis participates in the pathogenesis of different cardiovascular diseases and the NLRP3 inflammasome-mediated cardiomyocyte pyroptosis has been most widely studied. Also, the intervention in NLRP3 inflammasome activation and cardiomyocyte pyroptosis contributes to ameliorating myocardial injury, which may be the main mechanism of many traditional Chinese medicines in exerting the cardio-protective effects. Therefore, this paper reviewed the studies on cardiomyocyte pyroptosis mediated by NLRP3 inflammasome and put forward the importance of exploring traditional Chinese medicine intervention in the activation of NLRP3 inflammasome.
Subject(s)
Inflammasomes , Medicine, Chinese Traditional , Myocytes, Cardiac , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , PyroptosisABSTRACT
Neuropsychiatric disorders are the leading cause of mental and intellectual disabilities worldwide. Current therapies against neuropsychiatric disorders are very limited, and very little is known about the onset and development of these diseases, and their most effective treatments. MIR137 has been previously identified as a risk gene for the etiology of schizophrenia, bipolar disorder, and autism spectrum disorder. Here we generated a forebrain-specific MIR137 knockout mouse model, and provided evidence that loss of miR-137 resulted in impaired homeostasis of potassium in mouse hippocampal neurons. KCC2, a potassium-chloride co-transporter, was a direct downstream target of miR-137. The KCC2 specific antagonist VU0240551 could balance the current of potassium in miR-137 knockout neurons, and knockdown of KCC2 could ameliorate anxiety-like behavior in MIR137 cKO mice. These data suggest that KCC2 antagonists or knockdown might be beneficial to neuropsychiatric disorders due to the deficiency of miR-137.
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Objective To designe, synthesize a series of chlorin p6 ether photosensitizers and preliminarily investigate their photodynamic antitumor activity based on previous research results that alkoxyl ether derivatives of 3-vinyl on chlorin f exhibited stronger photosensitive antitumor activity than parent compound. Methods Purpurin-18 (4) was obtained by oxidative degradation with air and alkali on pheophorbide a (5) which was prepared through acid hydrolysis of chlorophyll a from crude chlorophyll extracts in Chinese traditional herb named Silkworm excrement. Then, chlorin p6 trimethylester (2) were formed via basic hydrolysis of internal anhydride ring for lead compound 3 and following immediately methylation with CH2N2. The intermediate 2 reacted with 33% HBr, following nucleophilic substitution with various alkoxyl alcohol to get six title compounds (1). All title compounds were subjected to photodynamic antitumor activity screening for melanoma B16-F10 cell in vitro. Results All title compounds showed much higher phototoxicity against melanoma B16-F10 cells than talaporfin and verteporfin. Their structures were confirmed by 1H-NMR, 13C-NMR, ESI-MS and ESI-HRMS spectra. Conclusion Chlorin p6 ether compounds were promising candidate photosensitizers for PDT applications due to theirs high dark toxicity/phototoxicity ratio and excellent phototoxicity, which were worthy of further research and development.
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Objective To explore the application of 3D printing technology in surgical approach choice for cervical vertebra dumbbell tumor.Methods Retrospectively analyzed the clinical data of 17 patients with cervical vertebra dumbbell tumor who were admitted into our hospital from August 2012 and February 2017 and recieved 3D model printing.Three director surgeons chosen surgical approach for each pa-tient with or without 3D printing models.The surgical approach,combined with 3D printing and chosen by most surgeons,was selected as final surgical approach for patients.All the patients were evaluated by JOA score and Frankel grade before and after operation.Results The tumor of patients who selected surgical approach with 3D printing was completely resected.Without 3D printing models in preoperation,3 surgeons selected the same surgical approach for 8 patients,2 surgeons selected the same surgical approach for 9 patients.Compared with those who se-lected surgical approach with 3D printing models in preoperation,the 3 surgeons changed surgical approach in a total of 13 times.The surgical approach of 5 patients were changed,including 2 cases changed from posterior approach to lateral approach,2 cases changed from lateral ap-proach to posterior approach,and 1 case changed from lateral approach to anterior approach.Eventually,11 cases underwent posterior ap-proach,1 case underwent anterior approach,3 cases underwent lateral approach and 2 cases underwent far lateral approach.Conclusion Ap-plied of 3D printing in treatment of cervical vertebra dumbbell tumor can rebuild and print local anatomy by digitizing method.It can excel-lently show the tumor form,relationship of tumor and vertebrae,tumor and foramen intervertebrale,tumor and vessel.3D printing technology could help surgeon precisely and directly understand the operation area and select advanced surgical approach to reduce surgical risk and in -crease the resection rate of tumor.And it has an excellent display effect especially for complex tumors and abnormal blood vessels.
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Objective To study the alteration of blood flow indexes of ophthalmic artery (OA),central retinal artery (CRA) and posterior ciliary artery (PCA) of the patients with cone-rod dystrophy (CRD).Methods The color doppler flow imaging was used in 50 CRD patients (100 eyes,CRD group) and 90 controls (180 eyes,control group) to measure the peak systolic velocity (PSV),end diastolic velocity (EDV),timeaveraged maximum velocity (TAMV),pulsatility index (PI) and resistance index (RI)in OA,CRA and PCA,respectively,and the data was obtained and analyzed statistically by one-sample t test to compare the alteration of these parameters between the CRD group and control group.Results The TAMV of OA was (14.29 ±3.88)cm · s-1 in CRD group and (12.44 ± 3.64) cm · s-1 in the control group,and the difference was statistically significant (P ＜0.05);meanwhile,the PI was 1.75 ±0.42 in CRD group and 2.02 ±0.71 in the control group,and the difference was statistically significant (P ＜0.05).Moreover,the PSV,EDV,TAMV and PI,RI of CRA was (4.60 ± 1.29) cm · s-1,(1.61 ±0.41)cm · s-1,(2.59 ±0.67)cm · s-1 and 1.11 ±0.31,0.63 ±0.10 in CRD group,respectively,and (10.82 ± 2.97) cm · s-1,(3.28 ± 1.11) cm · s-1,(5.50 ± 2.06)cm · s-1 and 1.48 ±0.49,0.71 ±0.08,in the control group,accordingly,and the differences were statistically significant (all P ＜ 0.05).Furthermore,the PSV,EDV,TAMV and PI,RI of PCA was (7.36 ± 2.18) cm · s-1,(2.28 ± 0.82) cm · s-1,(3.99 ± 1.22)cm · s-1 and 1.28 ± 0.37,0.68 ± 0.09 in CRD group,respectively,and (11.61 ± 3.41)cm · s-1,(3.34±1.25)cm · s-1,(5.83 ±1.91)cm · s-1 and 1.49 ±0.43,0.70 ±0.09 in the control group,accordingly,and the differences were statistically significant (all P ＜0.05).Conclusion Hemodynamic unusual alterations of OA,CRA and PCA in CRD patients suggest there is the correlation between the ocular blood supply and the pathological process of CRD,which remains to be observed further.
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<p><b>OBJECTIVE</b>To explore the value of the self-decompression bone block in interbody fusion.</p><p><b>METHODS</b>From April 2014 to May 2015, 42 patients with degenerative lumbar instability and spinal stenosis were treated by posterior vertebral lamina decompression and pedicle nail-rod fixation and unilateral modified transforaminal lumbar interbody fusion, including 18 males and 24 females. The treatment group had 24 cases with autologous pure decompression bone block as single interbody fusion material and the control group had 18 cases with cage and autologous bone as interbody fusion material. Clinical data, bone healing time, interbody fusion rate, intervertebral height and curative effect were analyzed in two groups.</p><p><b>RESULTS</b>All the patients were followed up for 12 to 24 months with an average of 16 months. There was no significant difference in age, sex ratio, degree of lumbar instability, or follow-up time between two groups(>0.05); and there was no significant difference in curative effect, intervertebral height loss, or interbody fusion rate between two groups(>0.05).</p><p><b>CONCLUSIONS</b>Using self-decompression bone block fusion can get high fusion rate, maintain good intervertebral height, obtain satisfactory curative effect. Its design was scientific and reasonable with less complication, which provide an effective, economic, and practical method for degenerative lumbar instability and spinal stenosis.</p>
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The paper investigates and analyzes the utilization of literature resources by readers in medical college libraries based on questionnaire survey to find out the problems and causes of literature resource construction work in medical college libraries,and puts forward a series of measures to improve and promote the utilization ratio of literature resources in medical college libraries and give full play to the functions of medical college libraries.
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Objective To establish a quantitative analysis method for determining 99mTc-HYNIC-PEG4-E[PEG4-c(RGDfK)]2 (99mTc-3PRGD2,a radioactive tumor agent)byγcounter, and to investigate the distribution of 99mTc-3PRGD2 in mice bearing with lung carcinoma xenograft. Methods The mice were divided into 4 normal groups and one blocking peptide group(control group). The 99mTc-3PRGD2(8μg/kg)was injected to mice bearing with lung carcinoma xenograft through the tail intravenous administration. Tissues of the normal mice were taken at 0.5,1,2 and 4 h. The control group were treated by 3PRGD2 and 99mTc-3PRGD2. The control mice were injected with the 3PRGD2 saline solution(2.5 mg/ml,0.2 ml)at 0.5 h earlier before the injection of 99mTc-3PRGD2. The tu?mor and organ tissues of the control mice were taken at 2 h. The radioactivity was detected by Gamma Counter. Results The radioac?tivity of 99mTc-3PRGD2 detected was high in the tumor and very low in brain. In addition,high radioactivity in kidneys and bladder sug?gested that the drug excreted by renal. Conclusion The results proved that the blocking peptide can competitively inhibit the combi?nation of 99mTc-3PRGD2 and integrinαvβ3 receptors.
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Objective To improve the synthesis process of chlorine f (1).Methods A "one-pot"method was applied to prepare Photosensitizer component (1),using pheophorbide a (3) as raw material by oxidating and cracking of the E-ring of (3) with bubbling oxygen in alcoholic solution of potassium hydroxide at 0 ℃ followed by refluxing in nitrogen atmosphere.In order to obtain the optimal synthetic procedure,the orthogonal experimental design of L9 (34 ) was adopted to investigate three different levels of four main factors i.e.ring opening reaction time,alcoholic variety,alkali concentration and refluxing reaction time.Results The target compound (1) was optimizedly synthesized through treatment of raw material (3) with bubbling oxy-gen in 25% ethanol solution of potassium hydroxide at 0℃ for 30 min,followed by refluxing in nitrogen atmosphere for 20 min in yield of 40.8%.Conclusion The procedure developed has some advantages of simple and safty operation,and high synthetic yield.
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Objective To optimize the synthesis of photosensitizer chlorine e6‐C15 monomethyl ester (1) .Methods Tar‐get compound 1 was synthesized through E ring cracking of pheophorbide a (3) in methanol solution of potassium hydroxide followed by adding H2 O for ester hydrolysis with“one‐pot” process .Four main factors that influencing the synthetic yield of target compound 1 are ring cleavage reaction time (A) ,reflux hydrolysis reaction time (B) ,alkali concentration (C) and weight ratio of material 3 to alkali (D) .Each of the four factors was chosen at three levels and evaluated by the orthogonal ex‐perimentaldesignofL9(34).Results Theoptimizationtermsofthesynthesisoftargetcompound1wereB1C2A2D1 .Theyield of compound 1 was raised from 43 .0% to 56 .5% .Conclusion The developed process has the advantages of simple operation , good safety and high reaction yield ,and is suitable for industrial production .
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Background Peanut (Arachis hypogaea L.) is an important economic and oilseed crop. Long-term rainless conditions and seasonal droughts can limit peanut yields and were conducive to preharvest aflatoxin contamination. To elucidate the molecular mechanisms by which peanut responds and adapts to water limited conditions, we isolated and characterized several drought-induced genes from peanut roots using a suppression subtractive hybridization (SSH) technique. Results RNA was extracted from peanut roots subjected to a water stress treatment (45% field capacity) and from control plants (75% field capacity), and used to generate an SSH cDNA library. A total of 111 non-redundant sequences were obtained, with 80 unique transcripts showing homology to known genes and 31 clones with no similarity to either hypothetical or known proteins. GO and KEGG analyses of these differentially expressed ESTs indicated that drought-related responses in peanut could mainly be attributed to genes involved in cellular structure and metabolism. In addition, we examined the expression patterns of seven differentially expressed candidate genes using real-time reverse transcription-PCR (qRT-PCR) and confirmed that all were up-regulated in roots in response to drought stress, but to differing extents. Conclusions We successfully constructed an SSH cDNA library in peanut roots and identified several drought-related genes. Our results serve as a foundation for future studies into the elucidation of the drought stress response mechanisms of peanut.
Subject(s)
Arachis/genetics , Stress, Physiological/genetics , Droughts , RNA/isolation & purification , Gene Library , Sequence Analysis , DNA, Complementary/isolation & purification , Plant Roots , Gene Expression Regulation, Plant , Reverse Transcriptase Polymerase Chain Reaction , Dehydration , Nucleic Acid Hybridization/methodsABSTRACT
<p><b>OBJECTIVE</b>To determine the changes in the levels of endogenous metabolites in rats with chronic immobilization stress (CIS) taking Xiaoyao Powder (XYP) and its modified prescription version, which lacks the volatile oils extracted from Herba Menthae.</p><p><b>METHODS</b>Twenty-four experimental male SD rats were randomly divided into 4 groups of 6 rats each: control, model, XYP-1 (containing volatile oils from Herba Menthae), and XYP-2 (lacking volatile oils). All rats except control group rats were subjected to CIS 3 h per day for 21 consecutive days. Groups XYP-1 and XYP-2 were given the extracted XYS with or without volatile oils (3.854 g/kg; suspended in distilled water) via gavage 1 h before CIS each day for 21 days. Rats were anesthetized using intraperitoneal injection of pentobarbital sodium (40 mg/kg) on the 22nd day. Observations were made using a Varian INOVA 600 MHz NMR spectrometer at 27 °C. Carr-Purcell-Meiboom-Gill (CPMG) and longitudinal eddy-delay (LED) were applied, resulting in spectra showing only the signals from micro- and macro-metabolites.</p><p><b>RESULTS</b>Compared to controls, rats subjected to CIS showed increased levels of plasma metabolites, such as acetic acid, choline, N-glycoprotein (NAC), saturated fatty acid, and blood sugars. Levels of low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and unsaturated fatty acids were decreased. The biochemical effects of XYS were characterized by elevated levels of VLDL, LDL, threonine, methionine, and glutamic acid in plasma.</p><p><b>CONCLUSION</b>Some common and characteristic metabolites on the anti-CIS of XYP and its modified prescription were obtained. The metabolomics technology is a valuable tool and may be used to identify the specific metabolites and potential biomarkers of therapeutic effect of Chinese medicinal prescriptions.</p>
Subject(s)
Animals , Male , Rats , Blood Proteins , Metabolism , Chronic Disease , Drug Evaluation, Preclinical , Drugs, Chinese Herbal , Chemistry , Pharmacology , Therapeutic Uses , Metabolome , Powders , Rats, Sprague-Dawley , Restraint, Physical , Stress, Psychological , Blood , Drug Therapy , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To describe the clinical features, treatments and prognosis of very low birth weight infants (VLBWIs) requring mechanical ventilation, to assess the risk factors associated with the mortality of VLBWIs, and to evaluate the significance of the scoring system based on clinical risk index for babies (CRIB) and the score for neonatal acute physiology-perinatal extension II (SNAPPE-II) for predicting mortality risk for premature infants in China.</p><p><b>METHODS</b>Perinatal data were collected from 127 VLBWIs requring mechanical ventilation who were admitted to the neonatal intensive care unit (NICU) from January 2010 to October 2011.</p><p><b>RESULTS</b>The enrolled infants had a mean gestational age of 31±2 weeks, a mean birth weight of 1290±170 g, a male/female ratio of 1.23∶1, and extremely low birth weight infant accounting for 6.3%. Of the 127 cases, 48.0% were administered with pulmonary surfactant (PS), and 49.6% received endotracheal intubation ventilation. The overall in-hospital mortality was 41.7%. Multivariate logistic regression revealed the following independent risk factors for mortality: low birth weight, multiple birth, cesarean section, and low PaO2/FiO2 ratio (OR = 1.611, 7.572, 4.062, and 0.133 respectively; P<0.05). SNAPPE-II and CRIB showed good performance in predicting prognosis, with areas under the ROC curve of 0.806 and 0.777 respectively.</p><p><b>CONCLUSIONS</b>The overall mortality rate of VLBWIs is still relatively high. The high-risk factors for VLBWI mortality include low birth weight, multiple birth, cesarean section, and low PaO2/FiO2 ratio. The neonatal illness severity scoring system (using SNAPPE-II and CRIB) can be used to quantify illness severity in premature infants.</p>
Subject(s)
Adult , Female , Humans , Infant, Newborn , Male , Hospital Mortality , Infant, Very Low Birth Weight , Logistic Models , Prospective Studies , ROC Curve , Respiration, Artificial , Risk FactorsABSTRACT
<p><b>OBJECTIVE</b>The aim of this paper was to investigate the factors associated with viral response and HBeAg seroconversion and the relationship between them at different stages of interferon treatment in HBeAg-positive chronic hepatitis B patients.</p><p><b>METHODS</b>PEG-IFN alfa-2a was injected subcutaneously in doses of 180 microg once a week for 48 weeks to HBeAg-positive chronic hepatitis B patients, and the patients were followed for another 24 weeks after the treatment. The serum HBV DNA load was measured by real-time quantitative PCR assay. Microparticle enzyme immunoassay analysis (MEIA) was then carried out by an automatic enzyme immunoassay analysis instrument to measure HBeAg and anti-HBe. Virological response and HBeAg seroconversion rates, and the factors associated with them were analyzed.</p><p><b>RESULTS</b>The differences in ALT baselines between viral responding and non-responding groups were significant at treatment time and at the end of the follow-up period. These differences were also significant in patients with HBeAg seroconversion at 12 weeks and at the end of the follow-up period compared with the non-conversion group. No significant difference of HBV DNA baseline was observed between the HBeAg seroconversion and non-conversion group. At 12, 24 and 48 weeks, in patients with viral response during the treatment, their HBeAg seroconversion rates were 43.8%, 21.4% and 18.9% respectively; their respective HBeAg seroconversion rates remaining at 72 weeks were 42.9%, 33.3% and 27.6%. HBeAg seroconversion was related to HBV DNA negativity at 48 weeks treatment in the multivariate analysis (OR=2.15, 95.0% CI=1.744-2.664, P less than 0.01).</p><p><b>CONCLUSIONS</b>Viral response and early and sustained HBeAg seroconversion were associated with pretreatment ALT levels. HBeAg seroconversion was related to viral response during IFN treatment, but not to the baseline HBV DNA load.</p>
Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Antiviral Agents , Therapeutic Uses , Hepatitis B e Antigens , Blood , Hepatitis B virus , Hepatitis B, Chronic , Blood , Drug Therapy , Virology , Interferon-alpha , Therapeutic Uses , Polyethylene Glycols , Therapeutic Uses , Recombinant ProteinsABSTRACT
The aim of the study was to look for the chemical constituents of the herb of Lysimachia foenum-graecum. The herb of Lysimachia foenum-graecum was extracted with 70% EtOH. The isolation and purification was performed with a combination of multi-column chromatography and the structure was determined by spectral analysis. The flavonoid compound was obtained and elucidated as kaempferol-7-O(4"-(E)-p-coumaroyl-)-alpha-L-rhmanopyranosyl)-3-O-beta-D-glucopyranosyl (1-->4)-alpha-L-rhmanopyranosyl (1-->2)-beta-D-glucopyranoside. It is a new flavonoid compound.
Subject(s)
Flavonoids , Chemistry , Glucosides , Chemistry , Molecular Conformation , Molecular Structure , Plant Components, Aerial , Chemistry , Plants, Medicinal , Chemistry , Primulaceae , ChemistryABSTRACT
<p><b>OBJECTIVE</b>To investigate the efficacy and safety of adefovir dipivoxil (ADV, DAIDING) for Chinese chronic hepatitis B patients with lamivudine (LAM) resistance.</p><p><b>METHODS</b>This study was a multicenter, double-blind clinical trial. 209 chronic hepatitis B patients with LAM resistance were randomly put in an ADV, DAIDING or a LAM group. After 24 and 48-weeks of treatment, serum HBV DNA levels were measured by quantitative PCR and liver function tests; HBV serology and safety assessments were also conducted.</p><p><b>RESULTS</b>The mean reduction of HBV DNA from baseline at 24 and 48 weeks was significantly greater in the ADV group compared with that in the LAM group (2.40 log10 vs 0.94 log10, P < 0.01; 2.71 log10 vs 1.07 log10, P < 0.01). In the ADV group, the virological response and ALT normalization at 24 and 48 weeks were significantly higher than those in the LAM group. There was no significant difference between the two groups in the portion of HBeAg reduction, HBeAg seroconversion and incidence of adverse events. There was no severe adverse event related to the investigational product, DAIDING, in this trial.</p><p><b>CONCLUSION</b>DAIDING (ADV) is effective and safe for the treatment of chronic hepatitis B patients with LAM resistance.</p>
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Adenine , Therapeutic Uses , Antiviral Agents , Therapeutic Uses , Double-Blind Method , Drug Resistance, Viral , Hepatitis B, Chronic , Drug Therapy , Lamivudine , Pharmacology , Organophosphonates , Therapeutic UsesABSTRACT
<p><b>OBJECTIVE</b>To investigate the anatomic variation of nonrecurrent laryngeal nerve (NRLN) and its surgical identification and prevention during thyroidectomy.</p><p><b>METHODS</b>The database of 5 NRLN cases was analyzed to investigate the difference of operative maneuvers and procedures.</p><p><b>RESULTS</b>All 5 NRLN were located in the right side. Two cases were found have vocal cord paralysis and 1 case recovered in 3 cases who have NRLN injures.</p><p><b>CONCLUSIONS</b>Any transverse bond should not be cut between vascular and laryngeal except middle thyroid vein. Recurrent laryngeal nerve (RLN) should be dissected during thyroid excision. Cervical pneumogastric nerve should be systematic dissected to detect whether RNLN is exist, if RLN is not exist in the same side.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Intraoperative Complications , Recurrent Laryngeal Nerve , Recurrent Laryngeal Nerve Injuries , Thyroid Diseases , General Surgery , Thyroidectomy , Methods , Vocal Cord ParalysisABSTRACT
<p><b>OBJECTIVE</b>To evaluate the efficacy and investigate the influencing factors of the interferon (IFN) retreatment for patients with chronic hepatitis C relapsed after a previous IFN treatment.</p><p><b>METHODS</b>A retrospective study was designed to analyze the retreatment with IFN of 60 relapsed chronic hepatitis C patients. All patients were from a randomized, opened and multi-center clinical trial about the efficacy and security of PEG-IFNalpha-2a compared to CIFNalpha-2a in the treatment of chronic hepatitis C in China. There were 35 patients treated with PEG-IFNalpha-2a and 25 with CIFNalpha-2a. The main parameter to evaluate the efficacy was sustained viral response (SVR) rate. The influence of viral concentration in serum, genotype and drug categories on the responses to IFN were analyzed.</p><p><b>RESULTS</b>For all the patients, the end of treatment virus response (ETVR) and SVR rates were 55.00% and 35.00% respectively. ETVR rate of PEG-IFNalpha-2a was significantly higher than that of CIFNalpha-2a (74.29% and 28.00% respectively, P < 0.01). SVR rate of PEG-IFNalpha-2a was also markedly higher than that of CIFNalpha-2a (45.71% and 20.00% respectively, P < 0.05). However, there was no significant difference between the high and low viral load groups. Among the patients with genotype 1, ETVR and SVR rates of PEG-IFNalpha-2a (75.00%, 45.83%) were significantly higher than those of CIFNalpha-2a (22.22%, 11.11%), (P < 0.01, P < 0.05 respectively), but in patients with genotype non-1, there were no such differences between the two groups.</p><p><b>CONCLUSION</b>Some relapsed patients were not responsive to the IFN retreatment. The efficacy of PEG-IFNalpha-2a was superior to CIFNalpha-2a. The conventional IFN was not suggested to be used in the relapsed cases with genotype 1. The viral load was not associated with the efficacy of IFN retreatment.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Antiviral Agents , Therapeutic Uses , Hepatitis C, Chronic , Therapeutics , Interferon-alpha , Therapeutic Uses , Interferon-beta , Interferons , Therapeutic Uses , Polyethylene Glycols , Therapeutic Uses , Recombinant Proteins , Recurrence , Retrospective StudiesABSTRACT
<p><b>OBJECTIVE</b>To investigate the relationship between hepatitis C virus (HCV) genotype, serum viral load and ALT levels, and the factors associated with the viral relapse after IFN treatment in patients with chronic hepatitis C.</p><p><b>METHODS</b>The HCV RNA levels were determined with Cobas Amplicor Monitor Test, version 2.0, and HCV genotypes were examined by means of PCR products of 5' NTR digested with restriction endonucleases. The patients with chronic hepatitis C were treated with PEG-IFN alpha -2a and Roferon-A for 24 weeks. Those with a viral response after 24 week treatment were followed for an additional 24 weeks. The association of clinical characteristics, such as sex, age, the way of the HCV infection, IFN treatment history and platelet counts, and the HCV genotype, virus load and medicine used for the viral relapse after IFN treatment were analyzed.</p><p><b>RESULTS</b>Of the 208 chronic hepatitis C patients, the ALT levels were not related to HCV RNA levels (r = 0.093, P > 0.05). No difference of ALT levels between HCV genotypes was found, and the HCV RNA load was also of no difference between HCV genotype 1 patients and non 1 patients. Of the 119 patients with viral response after 24 week treatment, 58 cases (48.7%) relapsed after another 24 week's follow-up. Relapse was not significantly related to the clinical characteristics, such as sex, age, mode of the infection, treatment history of IFN, AST/ALT ratio, platelet counts and the baseline viral load. Among patients with genotype 1 virus, the relapse rate was significantly higher than those patients with non-genotype 1 virus (54.5% vs 32.1%, P=0.039). The relapse rate after PEG-IFN alpha -2a treatment was lower than that of Roferon-A treatment (47.0% vs. 52.8%), but not significantly.</p><p><b>CONCLUSION</b>The viral relapse of chronic hepatitis C patients after IFN treatment was significantly associated with the genotypes of the HCV.</p>
Subject(s)
Female , Humans , Male , Middle Aged , Antiviral Agents , Therapeutic Uses , Genotype , Hepacivirus , Genetics , Hepatitis C, Chronic , Drug Therapy , Virology , Interferon-alpha , Therapeutic Uses , RNA, Viral , Blood , Recombinant Proteins , Recurrence , Treatment Outcome , Viral LoadABSTRACT
<p><b>OBJECTIVES</b>To establish an animal model of HCV transgenic mice to elucidate the pathogenesis of hepatitis C virus infection and function of the viral structural proteins.</p><p><b>METHODS</b>Structural gene of HCV were amplified and recombined into eukaryotic expression vectors, pcDNA4HisMax and pMT/BiP/V5-His A, after their expressive activity was confirmed to detect the structural protein in the transfected COS7 and S2 cells by Western blot. The fertilized expression element, which contained CMV or pMT promoter, structural gene of HCV and polyadenylation signal sequence, was microinjected into 1736 C57BL/6 mouse fertilized ova. The ova were then replanted into the oviducts of 69 pseudopregnant recipient mice.</p><p><b>RESULTS</b>Twenty-five recipient mice were impregnated and later produced 105 newborns; 49 of them died from unknown causes and 57 survived. After the specific HCV structural genes were identified by PCR and Southern blot hybridization, 26 founders were obtained; among them 10 were stable expression mice and 16 were the inducible ones. The rate of founders developed from implanted embryos was only 1.50%. Through hybridization with normal mice, 58 hybrid mice have been obtained at present.</p><p><b>CONCLUSION</b>Two kinds of different transgenic mice of HCV were developed; one is of stable expression, and the other is inducible. This transgenic mice model may create an opportunity for studying the function of the structural gene of HCV and elucidate its pathogenicity.</p>