Analysis of therapeutic effect of cervical radiofrequency ablation on persistent HR-HPV infection

Background:To investigate the therapeutic effect of cervical radiofrequency ablation on high risk-HPV persistent infection.Methods:One hundred patients with persistent high risk-HPV infection diagnosed in our hospital from April 2019 to February 2020 were selected.Those in the same period were randomly selected by SPSS19.0 software machine according to the ratio of 1:1,and divided into the treatment group(BBT-RF-A radiofrequency group)and the observation group(recombinant human interferon suppository group)with 50 cases in each group.The negative conversion rate of high risk-HPV between the 2 groups was compared at the 6th and 12th months after treatment,and the types of persistent HR-HPV infection in Changle were studied.Results:The negative conversion rates of HR-HPV in the treatment group were 60%(35/50)and 82%(41/50)at 6 and 12 months after treatment,respectively,while the negative conversion rates of high risk-HPV in the observation group were 30%(15/50)and 44%(22/50)at 6 and 12 months after treatment,respectively.The negative conversion rates in the treatment group were significantly higher than those in the observation group(P<0.05).Studying the main types of high risk-HPV persistent infection has guiding value for HPV vaccine injection in Changle.Conclusion:Self-clotting cutter radiofrequency ablation has a good effect on the negative conversion rate of high risk-HPV persistent infection.These results suggest that the main types of single persistent cervical HR-HPV infection are 16,52 and 58,not including the 18 types.

The role of bacterial biofilm in persistent infections and control strategies

Bacterial biofilms can be viewed as a specific type of persistent bacterial infection. After initial invasion, microbes can attach to living and non-living surfaces, such as prosthetics and indwelling medical devices, and form a biofilm composed of extracellular polysaccharides, proteins, and other components. In hosts, bioffim formation may trigger drug resistance and inflammation, resulting in persistent infections. The clinical aspects of biofilm formation and leading strategies for hiofilm inhihitors will be discussed in this mini-review.

Strategies used by helicobacter pylori to establish persistent infection

Helicobacter pylori(H. pylori) is a Gram-negative and motile bacterium that colonizes the hostile microniche of the human stomach, then persists for the host's entire life, if not effectively treated. Clinically, H. pylori plays a causative role in the development of a wide spectrum of diseases including chronic active gastritis, peptic ulceration, gastric adenocarcinoma, and gastric mucosaassociated lymphoid tissue lymphoma. Due to the global distribution of H. pylori, it is no exaggeration to conclude that smart strategies are contributing to adaptation of the bacterium to its permanent host. Thirty-four years after the discovery of this bacterium, there are still many unanswered questions. For example, which strategies help the bacterium to survive in this inhospitable microniche? This question is slightly easier to answer if we presume the same clinical concept for both persistent infection and disease. Understanding the mechanisms governing H. pylori persistence will improve identification of the increased risk of diseases such as gastric cancer in patients infected with this bacterium. A well-defined and longterm equilibrium between the human host and H. pylori allows bacterial persistence in the gastric microniche; although this coexistence leads to a high risk of severe diseases such as gastric cancer. To escape the bactericidal activity of stomach acid, H. pylori secretes large amounts of surface-associated and cytosolic urease. The potential to avoid acidic conditions and immune evasion are discussed in order to explain the persistence of H. pylori colonization in the gastric mucosa, and data on bacterial genetic diversity are included. Information on the mechanisms related to H. pylori persistence can also provide the direction for future research concerning effective therapy and management of gastroduodenal disorders. The topics presented in the current review are important for elucidating the strategies used by H. pylori to help the bacterium persist in relation to the immune system and the many unfavorable features of living in the gastric microniche.

Persistent occult hepatitis B virus infection:Experimental findings and clinical implications

Hepatitis B virus (HBV) is a highly pathogenic virus that causes chronic liver diseases in millions of people globally. In addition to a symptomatic, serologically evident infection, occult persistent HBV carriage has been identified since nucleic acid amplification assays of enhanced sensitivity became introduced for detection of hepadnaviral genomes and their replicative intermediates. Current evidence indicates that occult HBV infection is a common and long-term consequence of resolution of acute hepatitis B. This form of residual infection is termed as secondary occult infection (SOI). The data from the woodchuck model of HBV infection indicate that exposure to small amounts of hepadnavirus can also cause primary occult infection (POI) where virus genome, but no serological makers of exposure to virus, are detectable, and the liver may not be involved. However, virus replicates at low levels in the lymphatic system in both these forms. We briefly summarize the current understanding of the nature and characteristics of occult hepadnaviral persistence as well as of its documented and expected pathological consequences.

Experimental Intramammary Infection with a Strain of <i>Escherichia coli</i>Isolated from a Cow with Persistent <i>E. coli</i>Mastitis

Transient E. coli intramammary infections (IMI) are usually associated with rapid onset of clinical signs including mammary gland swelling and abnormal milk with rapid clearance of bacteria from milk. Conversely, reports have described strains of E. coli showing very different clinical trends. Persistent E. coli IMI are associated with mild clinical symptoms that disappear shortly after the onset of infection, possibly flaring-up intermittently during lactation. In the present study, we evaluated a strain of E. coli isolated from a cow with persistent mastitis to determine if the experimental infection model mimics naturally occurring persistent E. coli IMI. Uninfected mammary quarters of 7 Holstein heifers were infused within 10 days of calving with 50 colony-forming units of a persistent E. coli strain. Six of 7 heifers developed mild clinical mastitis with elevated rectal temperatures within 9 to 36 h after infusion. The challenge strain was isolated intermittently in milk from all infected mammary quarters during the first two weeks after infusion and 3 animals continued to shed E. coli periodically during the sampling period. One animal shed E. coli intermittently in milk for 172 d after challenge and developed clinical mastitis four times during this period. The isolated strain had an identical pulsed-field gel electrophoresis profile as the E. coli strain used to infuse mammary glands. The experimental IMI model described here mimics very closely naturally occurring persistent E. coli IMI, thus providing an excellent in vivo model to better understand pathogenesis and to facilitate development of control strategies for this important mastitis pathogen.

In situ hybridization detection of persistent infection and viral RNA distribution in laboratory rats with hemorrhagic fever with renal syndrome virus

Digoxigenin-labelled Hantaan specific cDNA probes were used in the present study for in situ hybridization detection of hemorrhagic fever with renal syndrome virus(HFRSV) persistent infection and viral RNA distribution in naturally infected laboratory rat

The Identification of Three Sizes of Core Proteins during the Establishment of Persistent Hepatitis C Virus Infection in vitro

Similar to Hepatitis C virus (HCV) infection in humans, HCVcc infection can also result in persistent and chronic infection. The core protein is a variable protein and exists in several sizes. Some sizes of core proteins have been reported to be related to chronic HCV infection. To study the possible role of the core protein in persistent HCV infection, a persistent HCVcc infection was established, and the expression of the core protein was analysed over the course of the infection. The results show that there are three sizes of core proteins (p24, p21 and p19) expressed during the establishment of persistent HCVcc infection. Of these, the p21 core protein is the mature form of the HCV core protein. The p24 core protein is the phosphorylated form of p21. The p19 core protein appears to be a functional by-product generated during the course of infection. These three core proteins are all localized in the cytoplasm and can be encapsidated into the HCV virion. The appearance of the p19 and p24 core proteins might be related to acute HCVcc infection and chronic infection respectively and may play an important role in the pathology of a HCV infection.

STUDY OF PERSISTENT VIRAL INFECTION IN AN ANIMAL MODEL OF VIRAL MYOCARDITIS BY PCR

Objective To study the role of persistent viral infection in the mechanism of viral myocarditis. Methods A mice model of CVB3m viral myocarditis wes made and the viral RNA in mice myocardium and whole bind sample wes tested by using polymerase chain reaction (PCR ) technique. The pathological changes in mice myocardium were determined. Results De day 3, the viral gene in whole bind and myocardium wes found, which portly became negative on day 8, but the change of myocardial anthology borne obvious. Although the bind specimens wers tested negatively on day 12, the viral gene in mice myocardium remained positive within 120d. Conclusion This study indicates that persistent viral infection plays a role in the pathogenesis of viral myocarditis.

E Sequence Analysis of Persistently Infected Mutant Japanese Encephalitis Virus Strains

Summary： A persistent infection model was established after human hepatoma cells infected by Japanese encephalitis viruses were subcultured for several times. Viral titers of mutant viruses in persistently infected cells were examined by plaque methods using BHK cells. Nucleotides of the E coding region of two wild and two mutant viruses were amplified by RT-PCR. PCR products were sequenced by ABI-PRSM^TM310 sequencing system. Compared to JaGAr-01 wild strains, four amino acids were replaced （E61Tyr→Asp, E219His→Tyr, E384Val→Glu, E418Pro→Ala） in the E sequence of JaGAr-01 persistently-infected mutant strains. Eleven amino acid replacement （E51Arg →Ser, E61Tyr→Asp, E83Lys→Glu, E123Ser→Arg, E209Arg→Lys, E227Pro→Ser, E276Asp→er, E290Arg→Lys, E387Lys→Arg, E418Leu→Pro, E454Arg→Gly） was also noted when we compared the E sequence between persistently infected Nakayama and its wild strains. A lot of similarities of amino acid sequence between mutant strains JaGAr-01 and Nakayama were also noted. It was concluded that geno-variation existed in E region of mutant viruses and the mutant protein encoded by E region, especially the mutation of E61 （Tyr→Asp） may contribute to the maintenance of the persistent infection of Japanese encephalitis virus.

HLA class Ⅱ associated with outcomes of hepatitis B and C infections

Several factors influence the clinical course of hepatitis B virus(HBV)and hepatitis C virus(HCV)infection.The human leukocyte antigen(HLA)system,the major histocompatibility complex(MHC)in humans,has been considered one of the most important host factors with respect to outcomes.To date,conventional genotyping studies have shown that HLA classⅡloci are mainly associated with spontaneous clearance of HBV and HCV.However,the specific HLA locus associated with the outcomes of hepatitis virus infection remains unclear.A recent genome-wide association study(GWAS)using a comprehensive approach for human genotyping demonstrated single nucleotide polymorphisms(SNPs)associated with the outcomes of hepatitis virus infection.Examination of large numbers of cohorts revealed that several SNPs in both HLA-DPA1 and HLADPB1 loci are associated with persistent HBV infection in Asian populations.To date,however,few studies have focused on HLA-DP because polymorphisms of HLA-DP haplotype do not vary greatly as compared with other loci of HLA.There are not enough studies to reveal the function of HLA-DP.GWAS additionally detected candidate SNPs within HLA loci associated with chronic HBV or HCV hepatitis,hepatic fibrosis,and the development of hepatocellular carcinoma.The results of one cohort were not always consistent with those of other cohorts.To solve several controversial issues,it is necessary to validate reported SNPs on HLA loci in global populations and to elucidate the HLA-allele-regulated molecular response to hepatitis virus infection.

Pathogenesis of occult chronic hepatitis B virus infection

Occult hepatitis B infection(OBI) is characterized by hepatitis B virus(HBV) DNA in serum in the absence of hepatitis B surface antigen(HBsAg) presenting HBsAg-negative and anti-HBc positive serological patterns.Occult HBV status is associated in some cases with mutant viruses undetectable by HBsAg assays;but more frequently it is due to a strong suppression of viral replication and gene expression.OBI is an entity with world-wide diffusion.The failure to detect HBsAg,despite the persistence of the viral DNA,is due in most cases to the strong suppression of viral replication and gene expression that characterizes this"occult"HBV infection;although the mechanisms responsible for suppression of HBV are not well understood.The majority of OBI cases are secondary to overt HBV infection and represent a residual low viremia level suppressed by a strong immune response together with histological derangements which occurred during acute or chronic HBV infection.Much evidence suggests that it can favour the progression of liver fibrosis and the development of hepatocellular carcinoma.

A novel real-time RT-PCR with TaqM an-MGB probes and its application in detecting BVDV infections in dairy farms

A real-time RT-PCR assay using Taq Man-MGB probes was developed to detect and type the bovine viral diarrhea virus（BVDV） in cattle.Universal primers and Taq Man-MGB probes were designed from the 5′-untranslated region of known pestiviral sequences.Prior to optimizing the assay, c RNAs were transcribed in vitro from the BVDV 1 and BVDV 2 RTPCR products to make standard curves.The detection limit of the assay was 1.72×102 copies for BVDV 1 and 2.14×102copies for BVDV 2.The specificity of the assay evaluated on several BVDV strains including bovine herpesvirus 1（BHV 1）, foot and mouth disease virus（FMDV） and several classical swine fever virus（CSFV） strains showed specific detection of the positive virus over 40 cycles.The assay was highly reproducible with the coefficient of variance ranging from 1.04 to 1.33% for BVDV 1 and from 0.83 to 1.48% for BVDV 2, respectively.Using this method, we tested a total of 2 327 cattle from three dairy farms for the presence of BVDV persistently infected（PI） animals.In this assay, each RT-PCR template contained a mixture of ten samples from different animals.The occurrence rate of PI cattle in three farms ranging from 0.9 to 2.54% could represent partly the PI rates in cattle farm in China.In conclusion, using our real-time PCR assay, we could effectively detect and type BVDV and identify PI cattle in a rapid and cost-effective manner.

Occult hepatitis B virus infection:A complex entity with relevant clinical implications

Occult hepatitis B virus(HBV) infection is a world-wide entity,following the geographical distribution of detectable hepatitis B.This entity is defined as the persistence of viral genomes in the liver tissue and in some instances also in the serum,associated to negative HBV surface antigen serology.The molecular basis of the occult infection is related to the life cycle of HBV,which produces a covalently closed circular DNA that persists in the cell nuclei as an episome,and serves as a template for gene transcription.The mechanism responsible for the HBsAg negative status in occult HBV carriers is a strong suppression of viral replication,probably due to the host’s immune response,co-infection with other infectious agents and epigenetic factors.There is emerging evidence of the potential clinical relevance of occult HBV infection,since this could be involved in occult HBV transmission through orthotopic liver transplant and blood transfusion,reactivation of HBV infection during immunosuppression,impairing chronic liver disease outcome and acting as a risk factor for hepatocellular carcinoma.Therefore it is important to bear in mind this entity in cryptogenetic liver diseases,hepatitis C virus/ HIV infected patients and immunosupressed individuals.It is also necessary to increase our knowledge in this fascinating field to define better strategies to diagnose and treat this infection.

Regulation of microRNA by hepatitis B virus infection and their possible association with control of innate immunity

Hepatitis B virus(HBV)chronically infects more than350 million people worldwide.HBV causes acute and chronic hepatitis,and is one of the major causes of cirrhosis and hepatocellular carcinoma.There exist complex interactions between HBV and the immune system including adaptive and innate immunity.Tolllike receptors(TLRs)and TLR-signaling pathways are important parts of the innate immune response in HBV infections.It is well known that TLR-ligands could suppress HBV replication and that TLRs play important roles in anti-viral defense.Previous immunological studies demonstrated that HBV e antigen(HBeAg)is more efficient at eliciting T-cell tolerance,including production of specific cytokines IL-2 and interferon gamma,than HBV core antigen.HBeAg downregulates cytokine production in hepatocytes by the inhibition of MAPK or NF-κB activation through the interaction with receptor-interacting serine/threonine protein kinase.MicroRNAs(miRNAs)are also able to regulate various biological processes such as the innate immune response.When the expressions of approximately 1000 miRNAs were compared between human hepatoma cells HepG2 and HepG2.2.15,which could produce HBV virion that infects chimpanzees,using real-time RT-PCR,we observed several different expression levels in miRNAs related to TLRs.Although we and others have shown that HBV modulates the host immune response,several of the miRNAs seem to be involved in the TLR signaling pathways.The possibility that alteration of these miRNAs during HBV infection might play a critical role in innate immunity against HBV infection should be considered.This article is intended to comprehensively review the association between HBV and innate immunity,and to discuss the role of miRNAs in the innate immune response to HBV infection.

Endotipsitis: A case report with a literature review on an emerging prosthetic related infection

AIM: To investigate the etiology and management of a poorly understood complication of transjugular intrahepatic portosystemic shunt; "endotipsitis".METHODS: A MEDLINE database search was carriedout, reviewing all papers with specific words in the title or abstract, and excluding appropriately. Of 283 papers that were reviewed, 22 papers reporting 53 cases in total were included in the analyses. RESULTS: No predominant etiology for endotipsitis was identified, but gram-positive organisms were more common among early-onset infections(P < 0.01). A higher mortality rate was associated with Staphylococcus aureus and Candida spp infections(P < 0.01). There was no trend in choice of antibiotic based on the microorganisms isolated and treatment varied from the guidelines of other vegetative prosthetic infections. In endotipsitis "high risk" organisms have been identified, emphasizing the importance of ensuring optimal antimicrobial therapy and adjunctive management strategies.CONCLUSION: Higher mortality rate was associated with Staphylococcus aureus and Candida spp infections. A prospective multicenter trial is needed before specific treatment can be recommended.

Risk factors for ribavirin treatment failure in Asian organ transplant recipients with chronic hepatitis E infection

BACKGROUND Hepatitis E virus(HEV)infection is a cause of chronic hepatitis in immunosuppressed patients.Sustained virologic response rates to a 12-wk course of ribavirin therapy were reported to be>70%in the West.This study describes the outcome of HEV treatment in a transplant center in Singapore.AIM To study the outcome of ribavirin treatment in a series of chronic HEV patients,and the cause of treatment failure.METHODS We studied all of the transplant recipients who were diagnosed with HEV infection between 2012 to 2015.The outcome of therapy and virologic relapse are monitored for three years after the end of therapy.RESULTS Ten transplant recipients(4 liver,5 kidney,and 1 bone marrow transplantation)with positive HEV RNA were studied.Nine patients received at least 12 wk of ribavirin therapy,and the remaining patient resolved after reducing immunosuppression therapy.Two subjects had prolonged viremia that lasted more than one year,despite continuous ribavirin therapy.Four ribavirin-treated patients(44.4%)had HEV RNA relapse after achieving a virologic response by the end of treatment.The overall failure rate is 66.7%.Being a kidney transplant recipient is the strongest risk factor for not achieving an initial sustained virologic response(0/5 treated,Chi-Square test,P<0.05).The most common side effect of ribavirin is anemia(100%)(haemoglobin reduction of 3-6.2 g/dL).Seven patients required either a blood transfusion or erythropoietin therapy.CONCLUSION The sustained virologic response rate of 12-wk ribavirin therapy for HEV infection in this Asian series was lower than expected.Kidney transplant recipients had a higher rate of treatment failure due to higher immunosuppression requirements and adverse effects.

宫颈HR-HPV持续性感染者中医体质及流行病学相关因素调查分析

目的探讨持续性宫颈高危型人乳头瘤病毒(HR-HPV)感染患者中医体质的特点及流行病学相关的危险因素。方法收集2021年11月至2022年10月于广州中医药大学深圳医院(福田)妇科进行宫颈癌筛查、符合纳排标准的72例持续性HR-HPV感染患者作为阳性组,另收集同一时段检查的HPV阴性且无其他基础疾病的105例健康女性作为阴性组,对其中医体质、流行病学相关因素进行问卷调查并进行统计学分析。结果平和质与持续性HR-HPV感染呈负相关,是保护性体质;职业为自由职业或家庭主妇、机关或专业技术人员及每日进食蔬菜水果与持续性HR-HPV感染呈负相关,较职业为体力劳动者或服务业、饮食上营养不均衡人群感染持续性HR-HPV的风险低;既往性伴侣个数、衣原体感染次数与持续性HR-HPV感染呈正相关,是持续性HR-HPV感染的危险因素。结论持续性HR-HPV感染与中医体质及流行病学相关因素具有相关性。

Stochastic HIV Infection Model with CTLs Immune Response Driven by Lévy Jumps

This paper mainly investigates the effect of the lévy jumps on the stochastic HIV infection model with cytotoxic T lymphocytes (CTLs) immune response. First, we prove that there is a unique global positive solution in any population dynamics, then we find sufficient conditions for the extinction of the disease. For proofing the persistence in mean, a special Lyapunov function be established, we obtain that if the infected CD4+ T-cells and virus particles will persistence in mean. Finally, numerical simulations are carried out to illustrate the theoretical results.

消疣汤对宫颈HR-HPV持续感染患者疗效及对宫颈癌Hela细胞上皮间充质转化的影响

目的探究消疣汤对宫颈HR-HPV持续感染患者的疗效及对宫颈癌Hela细胞上皮间充质转化(EMT)影响。方法收集高危型人乳头瘤病毒(HR-HPV)持续感染且病理分级为CINⅠ级的患者114例随机均分为干扰素组和消疣汤组,干扰素组应用重组人干扰素α-2b凝胶、消疣汤组在干扰素组的基础上给予消疣汤治疗,与治疗3个月时评价两组患者中医症候积分和临床疗效;将宫颈癌Hela细胞随机分为空白对照组(Control组),消疣汤低剂量组(XYD-L组,1 g/L)、中剂量组(XYD-M组,2 g/L)及高剂量组(XYD-H组,4 g/L),于24、48及72 h时,采用CCK-8法Hela细胞增殖能力、Transwell法检测侵袭能力、蛋白质印迹法检测细胞中E-Cadherin、N-Cadherin、Vimentin表达。结果与Control组相比,XYD-L组、XYD-M组和XYD-H组Hela细胞增殖能力、侵袭数目及细胞中N-Cadherin、Vimentin蛋白表达明显降低,细胞中E-Cadherin蛋白表达均明显增加(P<0.05);XYD-H组宫颈癌细胞增殖能力、侵袭数目及细胞中N-Cadherin、Vimentin蛋白表达明显低于XYD-L组、XYD-M组,细胞中E-Cadherin蛋白表达明显高于XYD-L组、XYD-M组(P<0.05);干扰素组HR-HPV持续感染患者治疗3个月时的临床疗效总有效率为78.95%、消疣汤组临床疗效总有效率(94.74%),P<0.05;和治疗前相比,治疗后两组患者中医症候积分明显降低(P<0.05);与治疗后干扰素组相比,消疣汤组患者中医症候积分明显降低(P<0.05)。结论消疣汤可明显改善宫颈HR-HPV持续感染患者临床症状,其机制可能与消疣汤影响宫颈癌细胞EMT及细胞的增殖和侵袭有关。

门诊宫颈防癌筛查女性HPV感染情况及HR-HPV持续性感染的Logistic回归分析

目的探讨门诊宫颈防癌筛查女性人乳头瘤病毒(HPV)感染情况及高危型人乳头瘤病毒(HR-HPV)持续性感染的危险因素。方法选取2021年1月至2022年12月在浙江省东阳市妇幼保健院接受宫颈防癌筛查的340例女性作为研究对象,根据是否发生HPV感染分为HPV感染组(n=72)和HPV未感染组(n=268)。分析HPV感染情况及HR-HPV持续性感染的危险因素。结果HPV感染72例(21.18%),单一HPV亚型感染55例(76.38%),多重感染17例(23.61%)。72例HPV感染患者中持续性感染17例(23.61%),其中HR-HPV持续性感染11例(64.71%)。年龄≥35岁、妊娠次数>2次、初次性交年龄<25岁、性生活频率>5次/月、有宫颈阴道炎症、性伴侣人数>2名、避孕方式为口服避孕药、同房后无卫生习惯的女性HR-HPV持续性感染率更高(P<0.05)。年龄≥35岁、妊娠次数>2次、有宫颈阴道炎症、避孕方式为口服避孕药是宫颈防癌筛查女性HR-HPV持续性感染的危险因素(P<0.05)。结论在女性宫颈防癌筛查者中HPV感染占比较高,年龄越大、妊娠次数越多、有宫颈阴道炎症且避孕方式为口服避孕药的女性HR-HPV持续性感染风险越高。