Comparison of Patient Satisfaction between Brachial Plexus Block (Axillary Approach) and General Anesthesia for Surgical Treatment of Distal Radius Fractures: A Historical Cohort Study

Background: Distal radius fracture surgery is performed under general (GA) or regional anesthesia with brachial plexus block (NB). Whether anesthesia type affects patient outcomes is unclear. This study retrospectively compared patient satisfaction between GA and NB after surgery. Methods: This was a historical cohort study of 80 (34 GA and 46 NB) patients who underwent volar plate fixation of distal radius fractures. Propensity score analysis was used to generate a set of matched cases (NB) and controls (GA), yielding 14 matched patient-pairs. The simplified patient satisfaction scale was compared for primary outcomes. Secondary outcomes were anesthesia and surgery duration, hospital stay length, adverse events, postoperative analgesic requirement, and wrist range of motion (ROM) 2 weeks and 3 months postoperatively. Results: After propensity score matching, patients in almost all cases in both groups were “Satisfied” (effect size: 0.1, p = 0.572), indicating little significant difference. Significant differences in adverse events and postoperative analgesic use observed before matching disappeared after matching. Anesthesia duration and hospital stay length were significantly shorter in the NB group (effect size: -1.27 and -0.77, p = 0.00074 and p = 0.0388, respectively), as was surgery duration (effect size: -0.84, p = 0.0122) after matching. Similar to before matching, wrist ROM significantly improved in the NB group (effect size: 1.11, p = 0.0279) in the early postoperative period, but the difference disappeared at 3 months postoperatively. Conclusions: Patient satisfaction between distal radius fracture surgery under GA and NB was similar. Nerve block could help shorten hospital stay length and surgery duration and improve postoperative functional recovery.

Incidence and characteristics of HBV reactivation in hematological malignant patients in south Egypt

AIM:To investigate characteristics of hepatitis B virus(HBV)implicated in HBV reactivation in patients with hematological malignancies receiving immunosuppressive therapy.METHODS:Serum samples were collected from 53 patients with hematological malignancies negative for hepatitis B surface antigen(HBsAg)before the start of and throughout the chemotherapy course.HBV reactivation was diagnosed when the HBsAg status changed from negative to positive after the initiation of chemotherapy and/or when HBV DNA was detected by realtime detection polymerase chain reaction(RTD-PCR).For detecting the serological markers of HBV infection,HBsAg as well as antibodies to the core antigen(antiHBc)and to the surface antigen were measured in the sera by CEIA.Nucleic acids were extracted from sera,and HBV DNA sequences spanning the S gene were amplified by RTD-PCR.The extracted DNA was further subjected to PCR to amplify the complete genome as well as the specific genomic sequences bearing the enhancerⅡ/core promoter/pre-core/core regions(nt1628-2364).Amplicons were sequenced directly.RESULTS:Thirty-five(66%)of the 53 HBsAg-negative patients were found to be negative serologically for antiHBc,and the remaining 18(34%)patients were positive for anti-HBc.Five of the 53(9.4%)patients with hematologic malignancies experienced HBV reactivation.Genotype D1 was detected in all five patients.Four types of mutant strains were detected in the S gene product of HBV strains and were isolated from 3 patients with HBV reactivation:T/S120,L143,and I126.HBV DNA was detected in the pretreatment HBsAg-negative samples in one of the five patients with HBV reactivation.In this patient,sequences encompassing the HBV full genome obtained from sera before the start of chemotherapy and at the time of de novo HBV hepatitis were detected and it showed 100%homology.Furthermore,in the phylogenetic tree,the sequences were clustered together,thereby indicating that this patient developed reactivation from an occult HBV infection.CONCLUSION:Past infection with HBV is a risk factor for HBV reactivation in Egypt.Mandatory anti-HBc screening prior to chemotherapy in patients with hematological malignancies is recommended.

Utility of tricalcium phosphate and osteogenic matrix cell sheet constructs for bone defect reconstruction

AIM: To determine the effects of transplanting osteogenic matrix cell sheets and beta-tricalcium phosphate(TCP) constructs on bone formation in bone defects.METHODS: Osteogenic matrix cell sheets were prepared from bone marrow stromal cells(BMSCs), and a porous TCP ceramic was used as a scaffold. Three experimental groups were prepared, comprised of TCP scaffolds(1) seeded with BMSCs;(2) wrapped with osteogenic matrix cell sheets; or(3) both. Constructs were implanted into a femoral defect model in rats and bone growth was evaluated by radiography, histology, biochemistry, and mechanical testing after 8 wk. RESULTS: In bone defects, constructs implanted with cell sheets showed callus formation with segmentalor continuous bone formation at 8 wk, in contrast to TCP seeded with BMSCs, which resulted in bone nonunion. Wrapping TCP constructs with osteogenic matrix cell sheets increased their osteogenic potential and resulting bone formation, compared with conventional bone tissue engineering TCP scaffolds seeded with BMSCs. The compressive stiffness(mean ± SD) values were 225.0 ± 95.7, 30.0 ± 11.5, and 26.3 ± 10.6 MPa for BMSC/TCP/Sheet constructs with continuous bone formation, BMSC/TCP/Sheet constructs with segmental bone formation, and BMSC/TCP constructs, respectively. The compressive stiffness of BMSC/TCP/Sheet constructs with continuous bone formation was significantly higher than those with segmental bone formation and BMSC/TCP constructs.CONCLUSION: This technique is an improvement over current methods, such as TCP substitution, and is useful for hard tissue reconstruction and inducing earlier bone union in defects.

Classifying genotype F of hepatitis B virus into F1 and F2 subtypes

AIM： To explore the propriety of providing hepatitis B virus （HBV） genotypes F and H with two distinct genotypes. METHODS： Eleven HBV isolates of genotype F （HBV/F） were recovered from patients living in San Francisco, Japan, Panama, and Venezuela, and their full-length sequences were determined. Phylogenetic analysis was carded out among them along with HBV isolates previously reported. RESULTS： Seven of them clustered with reported HBV/F Isolates in the phylogenetic tree constructed on the entire genomic sequence. The remaining four flocked on another branch along with three HBV isolates formerly reported as genotype H. These seven HBV isolates, including the four in this study and the three reported, had a sequence divergence of 7.3-9.5% from the other HBV/F isolates, and differed by 〉13.7% from HBV isolates of the other six genotypes （A-E and G）. Based on a marked genomic divergence, falling just short of 〉8% separating the seven genotypes, these seven HBV/F isolates were classified into F2 subtype and the former seven into F1 subtype provisionally. In a pairwise comparison of the S-gene sequences among the 7 HBV/F2 isolates and against 47 HBV/F1 isolates as well as 136 representing the other six genotypes （A-E and G）, two clusters separated by distinct genetic distances emerged.CONCLUSION： Based on these analyses, dassifying HBV/ F isolates into two subtypes （F1 and F2） would be more appropriate than providing them with two distinct genotypes （F and H）.

New combination test for hepatitis C virus genotype and viral load determination using Amplicor GT HCV MONITOR test v2.0

AIM: To develop a new sensitive and inexpensive hepatitis C virus (HCV) combination test (HCV Guideline test) that enables the determination of HCV genotypes 1, 2 and 3, and simultaneous determination of HCV viral load using commercial Amplicor GT HOV MONITOR test v2.0 (microwell version). METHODS: The HCV Guideline test used the PCR product generated in commercial Amplicor GT HCV Monitor test v2.0 for viral load measurement using microwell plate version of Amplicor HCV Monitor and also captured on separate plates containing capture probes and competitive oligonucleotide probes specific for HCV genotypes 1, 2 and 3, The HCV genotype was subsequently determined using the biotin-labeled PCR product and five biotin-labeled HCV-specific probes. RESULTS: The sensitivity of the HCV Guideline test was 0.5 KIU/mL. Specificity of the HCV Guideline test was confirmed by direct sequencing of HCV core region and molecular evolutionary analyses based on a panel of 31 samples. The comparison of the HCV Guideline test and an in-house HCV core genotyping assay using 252 samples from chronic hepatitis C patients indicated concordant results for 97.2% of samples (59.5% genotype 1, 33.7% genotype 2, 6.0% genotype 3, and 0.8% mixed genotypes). Similarly, the HCV Guideline test showed concordance with a serological test, and the serological test failed to assign any serotype in 12.7% of the samples, indicating a better sensitivity of the HCV Guideline test. CONCLUSION: Clinically, both viral load and genotypes (1, 2 and 3) have been found to be major predictors of antiviral therapy outcome regarding chronic hepatitis C based on guidelines and they are, in normal circumstances, performed as separate stand-alone assays. The HCV Guideline test is a useful method for screening large cohorts in a routine clinical setting for determining the treatment regimen and for predicting the outcome of antiviral therapy of chronic hepatitis C.

Distribution of HBV genotypes among HBV carriers in Benin:phylogenetic analysis and virological characteristics of HBV genotype E

AIM: To determine the distribution of Hepatitis B virus (HBV) genotypes in Benin, and to clarify the virological characteristics of the dominant genotype.METHODS: Among 500 blood donors in Benin, 21 HBsAg-positive donors were enrolled in the study. HBV genotypes were determined by enzyme immunoassay and restriction fragment length polymorphism. Complete genome sequences were determined by PCR and direct sequencing.RESULTS: HBV genotype E (HBV/E) was detected in 20/21 (95.2%), and HBV/A in 1/21 (4.8%). From the age-specific prevalence of HBeAg to anti-HBe seroconversion (SC) in 19 HBV/E subjects, SC was estimated to occur frequently in late teens in HBV/E.The comparison of four complete HBV/E genomes from HBeAg-positive subjects in this study and five HBV/E sequences recruited from the database revealed that HBV/E was distributed throughout West Africa with very low genetic divers ity (nucleotide homology 96.7-99.2%).Based on the sequences in the basic core promoter (BCP)to precore region of the nine HBV/E isolates compared to those of the other genotypes, a nucleotide substitution in the BCP, G1757A, was observed in HBV/E.CONCLUSION: HBV/E is predominant in the Republic of Benin, and SC is estimated to occur in late teens in HBV/E. The specific nucleotide substitution G1757A in BCP, which might influence the virological characteristics,is observed in HBV/E.

Characteristics of escape mutations from occult hepatitis B virus infected patients with hematological malignancies in South Egypt

AIM To investigate the prevalence and virological characteristics of occult hepatitis B virus(HBV) infections in patients with hematological malignancies in South Egypt.METHODS Serum samples were collected from 165 patients with hematological malignancies to monitor titers of HBV DNA, hepatitis B surface antigen(HBs Ag), and antibodies to HBV core(anti-HBc) and surface antigens. Serum samples negative for HBs Ag and positive for anti-HBc were subjected to nucleic acid extraction and HBV DNA detection by real-time polymerase chain reaction. DNA sequences spanning the S region were analyzed in cases with occult HBV infection. In vitro comparative study of constructed 1.24-fold wild type and S protein mutant HBV genotype D clones was further performed. RESULTS HBV DNA was detected in 23(42.6%) of 54 patients with hematological malignancies who were HBsA g negative, but anti-HBc positive, suggesting the presence of occult HBV infection. The complete HBV genome was retrieved from 6 occult HBV patients, and P120 T and S143 L were detected in 3 and 2 cases, respectively. Site directed mutagenesis was done to produce 1.24-fold genotype D clones with amino acid mutations T120 and L143. The in vitro analyses revealed that a lower level of extracellular HBsA g was detected by chemiluminescence enzyme immunoassay(CLEIA) with the clone containing T120 mutation, compared with the wild type or the clone with S143 L mutation despite the similar levels of extracellular and intracellular HBs Ag detected by Western blot. Southern blot experiments showed that the levels of intracellular HBV DNA were not different between these clones. CONCLUSION Occult HBV infection is common in patients with hematological malignancies and associated with P120 T and S143 L mutations. 120 T mutation impairs the detection of HBsA g by CLEIA.

Bone regeneration with osteogenic matrix cell sheet and tricalcium phosphate:An experimental study in sheep

AIM To determine the effects of a cell sheet created from sheep bone marrow and tricalcium phosphate(TCP) on osteogenesis.METHODS Bone marrow cells were harvested from a sheep and cultured in a minimal essential medium(MEM) containing ascorbic acid phosphate(AscP) and dexamethasone(Dex). After 2 wk, the formed osteogenic matrix cell sheet was lifted from the culture dish using a scraper. Additionally, harvested bone marrow cells were cultured in MEM only as a negative control group, and in MEM with AscP, Dex, and β-glycerophosphate as a positive control group. For in vitro evaluation, we measured the alkaline phosphatase(ALP) activity and osteocalcin(OC) content in the media of the cultured cells from each group. For in vivo analysis, a porous TCP ceramic was used as a scaffold. We prepared an experimental group comprising TCP scaffolds wrapped with the osteogenic matrix cell sheets and a control group consisting of the TCP scaffold only. The constructs wereimplanted subcutaneously into athymic rats and the cell donor sheep, and bone formation was confirmed by histology after 4 wk.RESULTS In the in vitro part, the mean ALP activity was 0.39 ± 0.03 mg/well in the negative control group, 0.67 ± 0.04 mg/well in the sheet group, and 0.65 ± 0.07 mg/well in the positive control group. The mean OC levels were 1.46 ± 0.33 ng/well in the negative control group, 3.92 ± 0.16 ng/well in the sheet group, and 4.4 ± 0.47 ng/well in the positive control group, respectively. The ALP activity and OC levels were significantly higher in the cell sheet and positive control groups than in the negative control group(P < 0.05). There was no significant difference in ALP activity or OC levels between the cell sheet group and the positive control group(P > 0.05). TCP constructs wrapped with cell sheets prior to implantation showed bone formation, in contrast to TCP scaffolds alone, which exhibited poor bone formation when implanted, in the subcutaneous layer both in athymic rats and in the sheep. CONCLUSION This technique for preparing highly osteoinductive TCP may promote regeneration in large bone defects.

Increased osteogenesis with hydroxyapatite constructs combined with serially-passaged bone marrow-derived mesenchymal stem cells

We have previously reported on both the osteogenic potential of hydroxyapatite (HA) combined with bone marrow-derived mesenchymal stem cells (BMSCs) and a method involving osteogenic matrix cell sheet transplantation of BMSCs. In the present study, we assessed the osteogenic potential of serially-passaged BMSCs, both in vitro and in vivo. We also assessed whether an additional cell-loading technique can regain the osteogenic potential of the constructs combined with serially-passaged BMSCs. The present study revealed that passage (P) 1 cells cultured in osteogenic-induced medium showed strong positive staining for alkaline phosphatase (ALP) and Alizarin Red S, whereas P3 cells showed faint staining for ALP, with no Alizarin Red S staining. Staining of P1, P2 and P3 cells were progressively weaker, indicating that the osteogenic potential of the serially-passaged rat BMSCs is lost after P3 in vitro. The in vivo study showed that little bone formation was observed in the HA constructs seeded with P3 cells, 4 weeks after subcutaneous implantation. However, P3 cell/HA constructs which had increased cell-loading showed abundant bone formation within the pores of the HA construct. ALP and osteocalcin mRNA expression in these constructs was significantly higher than that of constructs with regular cell-seeding. The present study indicates that the osteogenic potential of the constructs with serially-passaged BMSCs is increased by additional cell-loading. This method can be applied to cases requiring hard tissue reconstruction, where BMSCs require serial expansion of cells.

Modifying oxygen tension affects bone marrow stromal cell osteogenesis for regenerative medicine

AIM To establish a hypoxic environment for promoting osteogenesis in rat marrow stromal cells(MSCs) using osteogenic matrix cell sheets(OMCSs).METHODS Rat MSCs were cultured in osteogenic media under one of four varying oxygen conditions: Normoxia(21% O_2) for 14 d(NN), normoxia for 7 d followed by hypoxia(5% O_2) for 7 d(NH), hypoxia for 7 d followed by normoxia for 7 d(HN), or hypoxia for 14 d(HH). Osteogenesis was evaluated by observing changes in cell morphology and calcium deposition, and by measuring osteocalcin secretion(ELISA) and calcium content. In vivo syngeneic transplantation using OMCSs and β-tricalcium phosphate discs, preconditioned under NN or HN conditions, was also evaluated by histology, calcium content measurements,and real-time quantitative PCR.RESULTS In the NN and HN groups, differentiated, cuboidal-shaped cells were readily observed, along with calcium deposits. In the HN group, the levels of secreted osteocalcin increased rapidly from day 10 as compared with the other groups, and plateaued at day 12(P < 0.05). At day 14, the HN group showed the highest amount of calcium deposition. In vivo, the HN group showed histologically prominent new bone formation, increased calcium deposition, and higher collagen type Ⅰ?messenger RNA expression as compared with the NN group.CONCLUSION The results of this study indicate that modifying oxygen tension is an effective method to enhance the osteogenic ability of MSCs used for OMCSs.

Clinical impact of gastrointestinal endoscopy on the early detection of pharyngeal squamous cell carcinoma: A retrospective cohort study

BACKGROUND In recent years,with the growing availability of image-enhanced gastrointestinal endoscopy,gastroenterologists have contributed to the early detection of pharyngeal squamous cell carcinomas(SCC).AIM To clarify the clinical characteristics of pharyngeal SCCs detected by gastrointestinal endoscopy.METHODS This is a retrospective cohort study conducted in a single-center,a university hospital in Japan.We retrospectively assessed the clinical records of 522 consecutive patients with oropharyngeal or hypopharyngeal SCC who were examined in our hospital between 2011 and 2018.The lesions were classified into two groups:Group GE(detected by gastrointestinal endoscopy)and Group non-GE(detected by means other than gastrointestinal endoscopy).The clinical characteristics were compared between the two groups.Continuous data were compared using the Mann–Whitney U test.Pearson’sχ2 test or Fisher's exact test was used to analyze the categorical data and compare proportions.The Kaplan–Meier method was used to estimate the cumulative patient survival rates.RESULTS In our study group,the median age was 65 years and 474 patients(90.8%)were male.One hundred and ninety-six cases(37.5%)involved the oropharynx and 326 cases(62.5%)involved the hypopharynx.Three hundred and ninety-five cases(75.7%)had some symptoms at the time of diagnosis.One hundred and forty-five(27.8%)cases had concurrent ESCC or a history of ESCC.One hundred and sixtyfour(31.4%)cases were detected by gastrointestinal endoscopy and classified as Group GE.The proportions of asymptomatic cases,cTis-1 cases and cases with no lymph node metastasis were significantly higher in Group GE than Group non-GE(61.6%vs 7.3%,P<0.001,32.9%vs 12.0%,P<0.001 and 69.5%vs 19.0%,P<0.001).Endoscopic laryngo-pharyngeal surgery or endoscopic submucosal dissection were performed in only 0.6%of the lesions in Group non-GE but in 21.3%of the lesions in Group GE(P<0.001).Overall survival was significantly longer in Group GE than in Group non-GE(P=0.018).The 2-year and 4-year survival rates were 82.5%and 70.7%in Group GE,and 71.5%and 59.0%in Group non-GE,respectively.CONCLUSION Gastrointestinal endoscopy plays an important role in the early detection and improving the prognosis of pharyngeal SCCs.

Liver Stiffness Measurement Is Useful to Predict Early Recurrence of Hepatocellular Carcinoma after Sustained Virological Responses by Direct Antiviral Agents in Patients with Hepatitis C

Background: Recently, increases in the risk of Hepatocellular carcinoma (HCC) recurrence in patients with hepatitis C virus (HCV) due to the administration of direct antivirals agents (DAA) have been reported. Methods: One hundred and nineteen patients who were treated with DAA and achieved sustained viral response (SVR) were prospectively followed-up for over two years by transient elastography with liver stiffness measurements (LSM). Fourteen out of 119 patients (12%) had a history of being treated for HCC by radiofrequency ablation or resection and achieved complete responses after previous HCC treatments before the initiation of DAA. HCC was diagnosed by contrast-enhanced computed tomography (CT) or enhanced magnetic resonance imaging (MR). CT or MR was performed before the DAA treatment and every 6 months after during the follow-up. LSM was performed at the initiation of DAA (LSM0), at 24 weeks after the start of DAA (LSM24), at 48 weeks after that (LSM48) and at 2 years after that (LSM2y). Results: LSM0, LSM24, LSM48 and LSM2y of 105 patients without HCC were 7.5 (3.027.0), 6.0 (2.5 - 31.6), 4.6 (2.6?- 25.2) and 4.4 (3.1 - 29.9) kPa, respectively, showing significant improvements. Three out of 105 patients (2.9%) subsequently developed HCC and their LSM showed improvements. Eight out of fourteen patients (57%) with a history of HCC treatments subsequently developed HCC recurrence. LSM0 in the eight patients with recurrence increasing from 12.1 to 27.0 kPa, LSM24 from 9.9 to 26.6 kPa and LSM48 from 9.6 to 18.0 kPa. On the other hand, the six other patients without recurrence had LSM values that were less than 12.0 kPa at last. Based on the ROC analysis, LSM0 15.4, LSM24 12.8 and LSM48 9.6 kPa were identified as cut-off values. Conclusion: HCV patients previously treated for HCC with high LSM values before and after DAA have an elevated risk of HCC recurrence, particularly LSM24 >12.8 kPa and LSM48 >9.6 kPa.

Use of Cryopreserved Osteogenic Matrix Cell Sheets for Bone Reconstruction

Skeletal diseases, such as nonunion and osteonecrosis, are now treatable with tissue engineering techniques. Single cell sheets called osteogenic matrix cell sheets (OMCSs) grown from cultured bone marrow-derived mesenchymal stem cells show high osteogenic potential;however, long preparation times currently limit their clinical application. Here, we report a cryopreservation OMCS transplantation method that shortens OMCS preparation time. Cryopreserved rat OMCSs were prepared using slow- and rapid-freezing methods, thawed, and subsequently injected scaffold-free into subcutaneous sites. Rapid- and slow-frozen OMCSs were also transplanted directly to the femur bone at sites of injury. Slow-freezing resulted in higher cell viability than rapid freezing, yet all two cryopreservation methods yielded OMCSs that survived and formed bone tissue. In the rapid- and slow-freezing groups, cortical gaps were repaired and bone continuity was observed within 6 weeks of OMCS transplantation. Moreover, while no significant difference was found in osteocalcin expression between the three experimental groups, the biomechanical strength of femurs treated with slow-frozen OMCSs was significantly greater than those of non-transplant at 6 weeks post-injury. Collectively, these data suggest that slow-frozen OMCSs have superior osteogenic potential and are better suited to produce a mineralized matrix and repair sites of bone injury.

Real-world Effectiveness and Tolerability of Interferonfree Direct-acting Antiviral for 15,849 Patients with Chronic Hepatitis C:A Multinational Cohort Study

Background and Aims:As practice patterns and hepatitis C virus(HCV)genotypes(GT)vary geographically,a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal.This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs,focusing on GT3 and GT6.Methods:We analyzed the sustained virological response(SVR12)of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific,North America,and Europe between 07/01/2014–07/01/2021.Results:The mean age was 62±13 years,with 49.6%male.The demographic breakdown was 91.1%Asian(52.9%Japanese,25.7%Chinese/Taiwan residents,5.4%Korean,3.3%Malaysian,and 2.9%Vietnamese),6.4%White,1.3%Hispanic/Latino,and 1%Black/African-American.Additionally,34.8%had cirrhosis,8.6%had hepatocellular carcinoma(HCC),and 24.9%were treatment-experienced(20.7%with interferon,4.3%with direct-acting antivirals).The largest group was GT1(10,246[64.6%]),followed by GT2(3,686[23.2%]),GT3(1,151[7.2%]),GT6(457[2.8%]),GT4(47[0.3%]),GT5(1[0.006%]),and untyped GTs(261[1.6%]).The overall SVR12 was 96.9%,with rates over 95%for GT1/2/3/6 but 91.5%for GT4.SVR12 for GT3 was 95.1%overall,98.2%for GT3a,and 94.0%for GT3b.SVR12 was 98.3%overall for GT6,lower for patients with cirrhosis and treatment-experienced(TE)(93.8%)but≥97.5%for tretment-naive patients regardless of cirrhosis status.On multivariable analysis,advanced age,prior treatment failure,cirrhosis,active HCC,and GT3/4 were independent predictors of lower SVR12,while being Asian was a significant predictor of achieving SVR12.Conclusions:In this diverse multinational realworld cohort of patients with various GTs,the overall cure rate was 96.9%,despite large numbers of patients with cirrhosis,HCC,TE,and GT3/6.SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent(>91%).

乙型肝炎病毒基因型C亚型和核心启动子、前C/核心区基因变异的关系

目的研究慢性乙型肝炎病毒(HBV)感染者中HBV基因型C亚型(HBV/C)的核心启动子、前C/核心区基因变异情况,分析HBV/C亚型的病毒学特征。方法用酶联免疫法(ELISA)筛选出79例HBV/C,再用聚合酶链反应-限制性酶长度多态性分析方法(PCR-RFLP)进行HBV/C亚型分析;同时针对HBV核心启动子、preC/核心区基因进行半巢式PCR及PCR产物直接测序。结果①79例HBV/C中,33例(41·8%)为HBV/C1亚型,46例(58·2%)为HBV/C2亚型。②HBV/C1亚型仅见于来自中国南方的患者(P<0·0001)。③A1898位点变异仅见于HBV/C1亚型(P=0·056),V1753位点变异在HBV/C1亚型中多见(P<0·05);HBV/C2以T1858(90%)、A1896(40%)位点变异多见(P<0·008)。T1762/A1764位点变异在HBV/C两种亚型中均常见。④肝细胞癌(HCC)患者中,V1753和T1762/A1764变异最常见(P<0·05)。结论HBV/C1和HBV/C2在中国有明显的地区差异;V1753合并T1762/A1764双变异与发展为HCC相关,尤其在HBV/C1患者。

MicroRNA and liver cancer

Hepatocellular carcinoma(HCC)is a major cause of cancer-related deaths worldwide.HCC is characterized by a poor prognosis and an ever increasing number of scientific studies aim to find new diagnostic,prognostic,and therapeutic targets.MicroRNAs(miRNAs),small non-coding RNAs that regulate the gene expression in many processes,have been shown to play a crucial role in regulating hepatocellular carcinoma.miRNAs may act as oncogenic miRNAs and tumor suppressor miRNAs and regulate cancer cell proliferation,invasion,and metastasis by being differently upregulated or downregulated and targeting the genes related with carcinogenesis.miRNAs secreted from cancer cells are found circulating in the blood,presenting an opportunity for their use as diseaserelated biomarkers.Moreover,extracellular vesicle-derived miRNAs are known to reflect the cell of origin and function and may provide effective biomarkers for predicting diagnosis and prognosis and new therapeutic target in HCC.In this article,we describe the most recent findings regarding the molecular mechanisms and gene regulation of microRNA in HCC,as well as their application in diagnosis/prognosis and treatment.

Quantitative hepatitis B surface antigen in predicting recurrence of hepatitis B-related hepatocellular carcinoma after liver transplantation

Aim:Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) for chronic hepatitis B (CHB) can be associated with reappearance of hepatitis B surface antigen (HBsAg). The current study determined the significance of HBsAg qualitatively and quantitatively using a highly sensitive assay in recurrent HCC after transplantation. Methods:Consecutive patients with HBV-related HCC with LT were included. Oral nucleos(t)ide analogues without hepatitis B immune globulin were used as hepatitis B virus (HBV) prophylaxis. Quantitative HBsAg levels were performed at time of transplant, at 1 month, 3 and 6 months post transplant using a highly sensitive (hs)-HBsAg assay. Results:One hundred and fourteen patients were included, with a median follow-up of 80 months, with 24 cases of HCC recurrence, and a cumulative rate of 20.7% at 5 years. There was significant correlation between time of tumor recurrence and time of HBsAg reappearance (r = 0.551,P = 0.027). Early HCC recurrence was associated with higher median level of hs-HBsAg at the time of transplant (72.85vs. 69.70 IU/mL,P = 0.018). Using a hs-HBsAg cut-off level of 0.0005 IU/mL, patients with levels above this threshold at 3 and 6 months were associated with higher rate of early HCC recurrence (28.6%vs. 3.0% and 26.9%vs. 2.9% respectively, bothP =0.0006). There was no significant difference in HCC recurrence between positive and negative HBsAg using the conventional qualitative HBsAg assay. Conclusion:Serum hs-HBsAg levels of≥ 0.0005 IU/mL at 3 to 6 months after LT is associated with higher rates of early HCC recurrence, and may be useful as an early tumor marker.