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1.
The current study was designed to determine the Hepatitis C Virus (HCV) genotypes in a representative sample of HCV chronically infected patients in Saudi Arabia. All HCV isolates were genotyped by sequencing of the 5′UTR region and newly identified HCV isolates were identified. Specific universal primers targeting 5′UTR region were used for both amplification and sequencing of all isolates that resulted in 244 bp fragment which represent about 80% of 5′UTR region. Most of HCV isolates in this study were genotype 4 (76.4%) where only few isolates were recognized as genotype 1 (19.6%). All results were compared to HCV reference sequences from LOS ALAMOS HCV database, considering only the complete full genomes for the main phylogenetic analysis. Sequences that showed maximum identity (98% –100%) were selected. Most isolates were identical with HCV genotype 4 references. Some isolates were similar to different subtypes of HCV genotypes 4, 1 and 6. Phylogenetic analysis showed resemblance of most isolates to similar ones from the Far East, North America and Egypt. Using sequence Weblogo, Alignment analysis of isolated HCV genotypes 4 and 1 showed 92% and 95.5% nucleotide conservation, respectively. There was no predominant nucleotide in the varied sites, in both genotypes. All isolated sequences were submitted to GenBank database.  相似文献   

2.
The amino terminal region of the non structural gene 3 (NS3) of hepatitis C virus (HCV) is a chymotripsinlike serine-protease responsible for cleavage of the non structural proteins of Hepatitis C virus (HCV). In order to investigate the genetic variation of this region, we developed a nested PCR to obtain NS3 protease sequences from 54 patients chronically infected with HCV genotypes 1a, 1b and 3, respectively. Comparison of nucleotide and amino acids sequences of NS3 protease domain with consensus sequence obtained within the same genotype, showed 3.73% nucleotide divergence and 1.64% amino acid divergence in isolates of genotype 3a, whereas isolates 1a exhibited 4.45% nucleotide and 4% amino acid change, respectively. Finally, NS3 sequence from 1b isolates revealed 6.47% nucleotide and 3.5 % aa changes. Comparison of consensus amino acid sequences derived from isolates 1a, 1b and 3, with the HCV prototypes showed a low amino acid sequence diversity. However, the consensus sequence of HCV genotype 3 isolates showed an amino acid changed from the prototype, that was located within a region important for enzyme structure and activity. These results indicated that the NS3 protease gene is highly conserved within the same HCV genotype. The domains involved in enzyme function were highly conserved in 1a and 1b strains, whereas consensus sequence of isolates 3a showed that the majority of these strains were not perfectly conserved in one of such regions. These findings altogether suggested that the NS3 protease enzyme of HCV may constitute an important target for antiviral therapy, but the NS3 protease variability of isolates 3 within a region that is a potential target for antiviral therapy could pose a problem for structure based drug development.  相似文献   

3.
Hepatitis C virus (HCV) subtypes are pre-requisite to predict endemicity, epidemiology, clinical pathogenesis, diagnosis, and treatment of chronic hepatitis C infection. HCV genotypes 4 and 1 are the most prevalent in Saudi Arabia, however; less consensus data exist on circulating HCV subtypes in infected individuals. This study was aimed to demonstrate the virological surveillance, phylogenetic analysis, and evolutionary relationship of HCV genotypes 4 and 1 subtypes in the Saudi population with the rest of the world. Fifty-five clinical specimens from different parts of the country were analyzed based on 5′ untranslated region (5′ UTR) amplification, direct sequencing, and for molecular evolutionary genetic analysis. Pair-wise comparison and multiple sequence alignment were performed to determine the nucleotide conservation, nucleotide variation, and positional mutations within the sequenced isolates. The evolutionary relationship of sequenced HCV isolates with referenced HCV strains from the rest of the world was established by computing pairwise genetic distances and generating phylogenetic trees. Twelve new sequences were submitted to GenBank, NCBI database. The results revealed that HCV subtype 4a is more prevalent preceded by 1a in the Saudi population. Molecular phylogeny predicts the descendants’ relationship of subtype 4a isolates very close to Egyptian prototype HCV strains, while 1a isolates were homogeneous and clustering to the European and North American genetic lineages. The implications of this study highlight the importance of HCV subtyping as an indispensable tool to monitor the distribution of viral strains, to determine the risk factors of infection prevalence, and to investigate clinical differences of treatment outcomes among intergenotypic and intragenotypic isolates in the treated population.  相似文献   

4.
5.
A survey was conducted among the hemodialysis units of the city of Campo Grande, located in the state of Mato Grosso do Sul in the Mid-west region of Brazil, with the aim of investigating the prevalence, risk factors, and genotypes of hepatitis C virus (HCV) infection. A total of 163 patients were interviewed in five dialysis units. Serum samples were screened for anti-HCV. Positive samples were tested for HCV RNA and genotyped. The prevalence of anti-HCV was 11% (95% CI: 6.8-17.1). A history of transfusion with blood that was not screened for anti-HCV and length of time on hemodialysis were associated with HCV infection. HCV RNA was detected in 12 samples: ten were of genotype 1, subtypes 1a (75%) and 1b (8.3%), and two were of genotype 3, subtype 3a (16.7%).  相似文献   

6.
It has been reported that monoclonal antibodies (MAbs) to the E1E2 glycoproteins may have the potential to prevent hepatitis C virus (HCV) infection. The protective epitopes targeted by these MAbs have been mapped to the regionsencompassing amino acids 313–327 and 432–443. In this study, we synthesized these two peptides and tested the reactivity of serum samples from 336 patients, 210 of whichwere from Chronic Hepatitis C (CHC) patients infected with diverse HCV genotypes.The remaining 126 samples were isolated from patients who had spontaneously clearedHCV infection.In the chronic HCV-infected group (CHC group), the prevalence of human serum antibodies reactive to epitopes 313–327 and 432–443was 24.29%(51 of 210) and4.76%(10 of 210),respectively. In thespontaneousclearance group (SC group),the prevalence was 0.79%(1 of 126) and 12.70%(16 of 126), respectively.The positive serum samples that contained antibodies reactive to epitope 313–327 neutralizedHCV pseudoparticles (HCVpp) bearing the envelope glycoproteins of genotypes 1a or 1b and/or 4, but genotypes 2a, 3a, 5 and 6 were not neutralized. The neutralizing activity of these serum samples could not be inhibited by peptide 313–327. Six samples (SC17, SC38, SC86, SC92, CHC75 and CHC198) containing antibodies reactive to epitope 432–443 had cross-genotype neutralizing activities. Theneutralizing activityof SC38, SC86, SC92 and CHC75waspartiallyinhibited by peptide 432–443. However,the neutralizing activity of sample SC17 for genotype 4HCVpp and sample CHC198 for genotype 1b HCVppwere notinhibited by the peptide.This study identifies the neutralizing ability of endogenous anti-HCV antibodies and warrants the exploration of antibodies reactive to epitope432–443as sources for future antibody therapies.  相似文献   

7.
The aim of this study is to explore the prevalence of hepatitis C virus (HCV) infection among injection drug users (IDUs) with and without human immunodeficiency virus (HIV) infection in southern Taiwan. For 562 IDUs (265 anti-HIV negative, 297 anti-HIV positive), we analyzed liver function, anti-HIV antibody, anti-HCV antibody, HCV viral loads, and hepatitis B surface antigen (HBsAg). HIV RNA viral loads and CD4 cell count for anti-HIV-seropositive IDUs and the HCV genotype for HCV RNA-seropositive IDUs were measured. The seroprevalence rates of anti-HIV, anti-HCV, and HBsAg were 52.8%, 91.3%, and 15.3%, respectively. All the anti-HIV-seropositive IDUs were positive for HIV RNA. Anti-HCV seropositivity was the most important factor associated with HIV infection (odds ratio [OR], 25.06; 95% confidence intervals [CI], 8.97–74.9), followed by male gender (OR, 6.12; 95% CI, 4.05–9.39) and HBsAg seropositivity (OR, 1.90; 95% CI, 1.11–3.34). Among IDUs positive for anti-HCV, 80.7% had detectable HCV RNA. HCV viremia after HCV exposure was strongly related to HIV infection (OR, 6.262; 95% CI, 1.515–18.28), but negatively correlated to HBsAg seropositivity (OR, 0.161; 95% CI, 0.082–0.317). HCV genotype 6 was the most prevalent genotype among all IDUs (41.0%), followed by genotypes 1 (32.3%), 3 (12.8%), and 2 (5.6%). In conclusion, about half IDUs were infected with HIV and >90% with HCV infection. Male and seropositivity for HBsAg and anti-HCV were factors related to HIV infection among our IDUs. HIV was positively correlated, whereas hepatitis B co-infection was negatively correlated with HCV viremia among IDUs with HCV exposure. Different HCV molecular epidemiology was noted among IDUs.  相似文献   

8.

Objective

Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection has been proved to be a growing public health concern. The prevalence and genotypic pattern vary with geographic locations. Limited information is available to date with regard to HCV genotype and its clinical implications among those former commercial blood donor communities. The aims of this study were to genetically define the HCV genotype and associated clinical characteristics of HIV/HCV co-infected patients from a region with commercial blood donation history in central China.

Methods

A cross sectional study, including 164 HIV infected subjects, was conducted in Shanxi province central China. Serum samples were collected and HCV antibody testing, AST and ALT testing were performed. Seropositive samples were further subjected to RT-PCR followed by direct sequence coupled with phylogenetic analysis of Core-E1 and NS5B regions performed in comparison with known reference genotypes.

Findings

A total of 139 subjects were HCV antibody positive. Genotype could be determined for 88 isolates. Phylogenetic analysis revealed that the predominant circulating subtype was HCV 1b (65.9%), followed by HCV 2a (34.1%). The HCV viral load in the subjects infected with HIV1b was significantly higher than those infected with HCV 2a (P = 0.006). No significant difference for HCV RNA level was detected between ART status, CD4+ cell count level and HIV RNA level. Serum AST and ALT level were likely to increase with HCV RNA level, although no significance was observed. Those who had conducted commercial donation later than 1991 (OR 3.43, 95% CI: 1.12–10.48) and had a short duration of donation (OR 0.35, 95% CI: 0.13–0.96) were more likely to be infected with HCV 1b.

Conclusion

These results suggest that HCV subtype 1b predominates in this population, and the impact of HIV status and ART on HCV disease progression is not significantly correlated.  相似文献   

9.
In order to investigate the hepatitis C virus (HCV) infection prevalence and risk factors in hemophiliacs in Central Brazil, 90 patients were interviewed and serum samples tested for HCV RNA and anti-HCV antibodies. An overall prevalence of 63.3% (CI 95%: 53.0-72.7) was found. Multivariate analysis of risk factors showed that number of blood transfusions was significantly associated with this infection. Most hemophiliacs received locally produced cryoprecipitate. All infected patients were transfused before the screening of blood units for anti-HCV. However, hemophiliacs who received exclusively screened cryoprecipitate were HCV negative. It confirms the expected decline in transfusion-acquired hepatitis C.  相似文献   

10.
J S Li  S P Tong  L Vitvitski  D Lepot  C Trépo 《Gene》1991,105(2):167-172
A hepatitis C virus (HCV) cDNA covering part of the nonstructural region, NS3, was amplified from the serum of 50 out of 76 French non-A, non-B hepatitis patients by the nested polymerase chain reaction (PCR). Determination of a 407-bp sequence from four such cases revealed the presence of two different virus genotypes, F1 and F2, which exhibited 19-20% sequence divergence. F1 was represented by three of the four isolates and showed a sequence homology of about 97.5% to the prototype American HCV isolate, but of only 79% to a reported Japanese isolate. In contrast, F2 had 91.6% homology to the Japanese isolate, but only 81% homology to the prototype American HCV. PCR products from the 50 samples were hybridized with labeled F1 and F2 fragments under stringent conditions; results indicated the F1-related strain(s) as the major HCV genotype. Furthermore, a total of 1477 bp of sequence has been determined for one of the isolates belonging to the F1 category. These results will have implications for the PCR detection of HCV infection and production of HCV vaccines, especially for European countries.  相似文献   

11.
目的:探讨502例丙型肝炎患者病毒基因分型的情况,分析其与性别和年龄的关系,为丙型肝炎的防治提供参考。方法:收集贵州地区502例丙型肝炎患者的血液标本,采用PCR-荧光探针法检测丙型肝炎病毒基因型,并对检测数据进行统计学分析。结果:共检出4种基因型及5种基因亚型,主要以1b型、3b型为主,其次是6a、3a型,2a型较少。不同性别丙型肝炎病毒(HCV)基因型分布比较,差异有统计学意义(x2=11.029,P=0.026),男、女性患者均以1b型、3b型为主要基因型,但男性感染者明显多于女性。各个年龄组HCV基因型分布比较,差异有统计学意义(x2=102.946,P=0.000),40-59岁组感染者最多,以1b型为主,其次是20-39岁组,以3b型为主,≥60岁组感染人数较少,以1b型为主。结论:贵州地区HCV呈现多基因型分布,1b、3b型为主要流行基因型,6a、3a型次之,其余基因型较少,不同性别、年龄的HCV基因型分布存在差异性。  相似文献   

12.
A molecular study was conducted to investigate the prevalence of Hepatitis C virus genotypes in HCV infected population of Balochistan. Forty HCV seropositive samples belonging to seven different locations of Balochistan were collected from different health care centres. Qualitative analysis of these samples using PCR resulted in 28 positive samples. The PCR positive samples were subjected to genotyping using the method described by Ohno et al (J Clin Microbiol 35:201–202, 1997) with minor modifications. Genotyping of 28 samples revealed three different genotypes including 3a, 3b and 1a. The most prevalent genotype was 3a with rate of 50% followed by genotype 3b and 1a, respectively. Nine samples remained untyped, suggesting the need of further investigation of genotypes in this region. It has been proposed that sequencing of these samples may be helpful to unreveal these genotypes and further epidemiology of HCV genotypes. Further more, extensive and large scale studies are needed to understand the epidemiology of HCV genotypes, as no such study has been carried in this province.  相似文献   

13.
Certain host single nucleotide polymorphisms (SNPs) affect the likelihood of a sustained virological response (SVR) to treatment in subjects infected with hepatitis C virus (HCV). SNPs in the promoters of interleukin (IL)-10 (-1082 A/G, rs1800896), myxovirus resistance protein 1 (-123 C/A, rs17000900 and -88 G/T, rs2071430) and tumour necrosis factor (TNF) (-308 G/A, rs1800629 and -238 G/A, rs361525) genes and the outcome of PEGylated α-interferon plus ribavirin therapy were investigated. This analysis was performed in 114 Brazilian, HCV genotype 1-infected patients who had a SVR and in 85 non-responders and 64 relapsers. A significantly increased risk of having a null virological response was observed in patients carrying at least one A allele at positions -308 [odds ratios (OR) = 2.58, 95% confidence intervals (CI) = 1.44-4.63, p = 0.001] or -238 (OR = 7.33, 95% CI = 3.59-14.93, p < 0.001) in the TNF promoter. The risk of relapsing was also elevated (-308: OR = 2.87, 95% CI = 1.51-5.44, p = 0.001; -238: OR = 4.20, 95% CI = 1.93-9.10, p < 0.001). Multiple logistic regression of TNF diplotypes showed that patients with at least two copies of the A allele had an even higher risk of having a null virological response (OR = 16.43, 95% CI = 5.70-47.34, p < 0.001) or relapsing (OR = 6.71, 95% CI = 2.18-20.66, p = 0.001). No statistically significant association was found between the other SNPs under study and anti-HCV therapy response.  相似文献   

14.
The majority of hepatitis C virus (HCV) infection results in chronic infection, which can lead to liver cirrhosis and hepatocellular carcinoma. Global burden of hepatitis C virus (HCV) is estimated at 150 million individuals, or 3% of the world’s population. The distribution of the seven major genotypes of HCV varies with geographical regions. Since Asia has a high incidence of HCV, we assessed the distribution of HCV genotypes in Thailand and Southeast Asia. From 588 HCV-positive samples obtained throughout Thailand, we characterized the HCV 5’ untranslated region, Core, and NS5B regions by nested PCR. Nucleotide sequences obtained from both the Core and NS5B of these isolates were subjected to phylogenetic analysis, and genotypes were assigned using published reference genotypes. Results were compared to the epidemiological data of HCV genotypes identified within Southeast Asian. Among the HCV subtypes characterized in the Thai samples, subtype 3a was the most predominant (36.4%), followed by 1a (19.9%), 1b (12.6%), 3b (9.7%) and 2a (0.5%). While genotype 1 was prevalent throughout Thailand (27–36%), genotype 3 was more common in the south. Genotype 6 (20.9%) constituted subtype 6f (7.8%), 6n (7.7%), 6i (3.4%), 6j and 6m (0.7% each), 6c (0.3%), 6v and 6xa (0.2% each) and its prevalence was significantly lower in southern Thailand compared to the north and northeast (p = 0.027 and p = 0.030, respectively). Within Southeast Asia, high prevalence of genotype 6 occurred in northern countries such as Myanmar, Laos, and Vietnam, while genotype 3 was prevalent in Thailand and Malaysia. Island nations of Singapore, Indonesia and Philippines demonstrated prevalence of genotype 1. This study further provides regional HCV genotype information that may be useful in fostering sound public health policy and tracking future patterns of HCV spread.  相似文献   

15.
An investigation was conducted involving 255 renal transplant recipients in the state of Goiás, Central Brazil, to determine the prevalence of hepatitis C virus (HCV), its risk factors, the genotypes involved, and the level of alanine aminotransferase (ALT) present in the patients. All serum samples were tested for anti-HCV antibodies and HCV RNA. Forty-one patients were anti-HCV and/or HCV RNA positive, resulting in an overall HCV infection prevalence of 16.1% (95% CI: 11.9-21.3). A multivariate analysis of risk factors showed that a history of blood transfusions without anti-HCV screening, the length of time spent on hemodialysis, and renal transplantation before 1994 are all associated with HCV positivity. In HCV-positive patients, only 12.2% had ALT levels above normal. Twenty-eight samples were genotyped as genotype 1, subtypes 1a (62.5%) and 1b (31.3%), and two samples (6.2%) were genotype 3, subtype 3a. These data show a high prevalence of HCV infection and low ALT levels in the studied population. The risk factor analysis findings emphasize the importance of public health strategies such as anti-HCV screening of candidate blood and organ donors, in addition to the stricter adoption of hemodialysis-specific infection control measures. The present study also demonstrates that HCV genotype 1 (subtype 1a) is predominant in this population.  相似文献   

16.
A single-nucleotide polymorphism (SNP) upstream of interleukin (IL)28B was recently identified as an important predictor of the outcome of chronic hepatitis C patients treated with pegylated interferon plus ribavirin (PEG-IFN/RBV). The aim of this study was to investigate the association between the IL28B gene polymorphism (rs12979860) and virological response in chronic hepatitis C patients. Brazilian patients (n = 263) who were infected with hepatitis C virus (HCV) genotype 1 and were receiving PEG-IFN/RBV were genotyped. Early virological response (EVR) (12 weeks), end-of-treatment response (EOTR) (48 weeks), sustained virological response (SVR) (72 weeks) and relapse were evaluated using conventional and quantitative polymerase chain reaction (PCR) assays. The frequency of the C allele in the population was 39%. Overall, 43% of patients experienced SVR. The IL28B CC genotype was significantly associated with higher treatment response rates and a lower relapse rate compared to the other genotypes [84% vs. 58% EVR, 92% vs. 63% EOTR, 76% vs. 38% SVR and 17% vs. 40% relapse rate in CC vs. other genotypes (CT and TT), respectively]. Thus, the IL28B genotype appears to be a strong predictor of SVR following PEG-IFN/RBV therapy in treatment-naïve Brazilian patients infected with HCV genotype 1. This study, together with similar research examining other SNPs, should help to define adequate protocols for the treatment of patients infected with HCV genotype 1, especially those with a poor prognosis.  相似文献   

17.
HCV infection is a leading cause of chronic liver disease, including cirrhosis of the liver. There are at least six major genotypes and more than 50 subtypes of HCV. The prevalence and distribution of HCV genotypes depend on geographical location. The aim of this study was to identify and compare the HCV genotypes in HCV infected blood donors and patients. In this cross-sectional study, 167 serum samples from 103 blood donors and 64 patients with hepatitis C were investigated for HCV genotypes. HCV genotyping was carried out using type-specific primers from the core region of the viral genome. The highest frequency was for genotype 1a, with 53 and 34 (51.5% versus 53.1%) of subjects in blood donors and patients respectively. Genotype 3a and 1b were the other frequent genotypes with 4 and 16 (3.9% versus 25%) and 39 and 10 (37.9% versus 15.6%) subjects, respectively. There was not any statistical significant association between the place of infection of the patients and genotype. The results of this study indicate that the distribution of genotypes in the two populations was similar. The dominant HCV genotypes between blood donors and patients were 1a, 3a and 1b respectively.  相似文献   

18.
Hepatitis C is a liver disease caused by the hepatitis C virus (HCV). The treatment of HCV infection has become more complicated due to various genotypes and subtypes of HCV. The treatment of HCV has made significant advances with direct-acting antivirals. However, for the choice of medicine or the combination of drugs for hepatitis C, it is imperative to detect and discriminate the crucial HCV genotypes. The main objective of this study was to determine the pattern of circulating HCV genotypes in southern Iran, from 2016 until 2019. The other aim of the study was to determine possible associations of patients’ risk factors with HCV genotypes. A total of 803 serum samples were collected in 4 years (2016–2019) from patients with HCV antibody positive results. A total of 728 serum samples were HCV-RNA positive. The prevalence of HCV genotypes was detected using the genotype-specific RT-PCR test for serum samples obtained from 615 patients. The HCV genotype 1 (G1) was the most prevalent (48.8%) genotype in the area, with G1a, G1b, and mixed G1a/b representing 38.4%, 10.1%, and 0.3%, respectively. Genotype 3a was the next most prevalent (47.2%). Mixed genotypes 1a/3a were detected in 22 (3.6%) and finally G4 was found in 3 (0.5%) patients. The other HCV genotypes were not detected in any patient. Genotype 1 (1a and 1b alone, 1a/1b and 1a/3a coinfections) is the most prevalent HCV genotype in southern Iran. HCV G1 shows a significantly higher rate in people under 40 years old.  相似文献   

19.
The clonal variability of the hepatitis C virus (HCV) protease gene in 24 individuals with HCV genotypes 1a, 1b, 2b, and 3a who were coinfected with the human immunodeficiency virus was evaluated. Within-genotype variability at the nucleotide and amino acid levels ranged from 6.5 to 8.6% and 2.2 to 3.8%, respectively. After adjustments were made for correlation of intrapatient clonal variation, mixed-model analysis indicated that nucleotide and amino acid variability among patients with different genotypes did not differ significantly. However, within individual patients, clonal variability differed by up to 5.3% and 5.8% at the nucleotide and amino acid levels, respectively, and genotype 1a had significantly greater nucleotide variability than other genotypes (P = 0.01). Significant variability exists within HCV protease gene variants at the patient level and could affect the effectiveness of HCV protease inhibitors.  相似文献   

20.
Concurrent infection with hepatitis C virus (HCV) and hepatitis B virus (HBV) was not uncommon in China. To date, information on predictors of response to treatment of dually-infected HCV/HBV is limited. The aim of this study was to evaluated whether determination of the interleukin 28B (IL-28B) polymorphism statuses sufficient to predict treatment response of interferon (IFN)-based therapy in patients chronically infected with both hepatitis B and C viruses. We investigated the role of IL28B variations (rs8099917 and rs12979860) in response to IFN-based treatment and evaluated its association with the risk of the null virological response (NVR) in HCV /HBV dually-infected patients. We found that the overall distributions of the genotypes among the sustained virological response (SVR), NVR groups were significantly different (P<0.001): patients with the rs8099917 TG genotype had an increased risk of NVR (odds ratio [OR] =2.37 95% confidence interval [CI] =1.16–4.83, P =0.017), and those with the GG genotype had a further increased risk of NVR (OR=4.23, 95% CI =1.17-15.3, P=0.027). The rs12979860 allele was also highly associated with treatment failure (CT/TT vs. CC; OR =2.04, 95%CI =1.05-3.97, P =0.037). Moreover, we found that IL28B rs8099917 G variants (TG+GG) interact with HCV genotype 1(G1) to result in higher risk of NVR (P=0.009), and that they are also associated with HBV DNA reactivation (TG+GG vs. TT, P=0.005). Furthermore, multivariate regression analysis show that the rs8099917 G allele was the most important factor significantly associated with a NVR in HCV G1 patients. This study suggest that IL28B genotyping may be a valid pretreatment predictor of which patients are likely to respond to treatment in this group of difficult-to-treat HCV/HBV dually-infected patients.  相似文献   

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