An-Luo-Hua-Xian Pill Improves the Regression of Liver Fibrosis in Chronic Hepatitis B Patients Treated with Entecavir.

Background and Aims: Chronic hepatitis B (CHB) can cause liver fibrosis and lead to cirrhosis and cancer. As the effectiveness of antiviral therapy to reverse liver fibrosis is limited, We aimed to evaluate the effect of An-Luo-Hua-Xian pill (ALHX) on fibrosis regression in CHB patients treated with entecavir (ETV). Methods: Treatment-naïve patients with CHB were randomly treated with ETV alone or combined with ALHX (ETV+ALHX) between October 1, 2013 and December 31, 2020. Demographic, laboratory, and liver histology data before and after 78 weeks of treatment were collected. The Ishak fibrosis score (F) was used and fibrosis regression required a decrease in F of ≥1 after treatment. Results: A total of 780 patients were enrolled, and 394 with a second liver biopsy after treatment were included in the per-protocol population, 132 in ETV group and 262 in ETV+ALHX group. After 78 weeks of treatment, the fibrosis regression rate in the ETV+ALHX group was significantly higher than that of the ETV group at baseline F≥3 patients: 124/211 (58.8%) vs. 45/98 (45.9%), p=0.035. The percentage of patients with a decreased liver stiffness measurement (LSM) was higher in the ETV+ALHX group: 156/211 (73.9%) vs. 62/98 (63.%), p=0.056. Logistic regression analysis showed that ETV combined with ALHX was associated with fibrosis regression [odds ratio (OR)=1.94, p=0.018], and a family history of hepatocellular carcinoma was on the contrary. (OR=0.41, p=0.031). Conclusions: ETV combined with ALHX increased liver fibrosis regression in CHB patients.

Clinical application of bronchial high-frequency ventilation in 2-port thoracoscopic segmentectomy.

To evaluate the safety and clinical application of a computer-aided surgery system (CAS) combined with high-frequency bronchial ventilation in 2-port thoracoscopic anatomical segmentectomy. A total of 301 patients who underwent 2-port thoracoscopic segmentectomy between January 1, 2019 and March 1, 2022 in the 960th Hospital of the People's Liberation Army and the Department of Thoracic Surgery of Zibo Municipal Hospital were retrospectively analyzed. The experimental and control groups were created according to the different methods of appearing the intersegmental plane of the lung. The experimental group comprised 152 patients who underwent CAS reconstruction combined with high-frequency ventilation, and the control group comprised 149 patients who underwent CAS reconstruction combined with expansion collapse. The characteristics of the patients, including age, sex, smoking history, forced expiratory volume in 1 second/forced vital capacity, Maximal ventilation, diameter of pulmonary nodules, intraoperative blood loss, postoperative drainage volume, drainage tube removal time, length of hospital stay after extubation, postoperative complication rate, operation time and appearance time of the intersegmental plane, were compared between the 2 groups. All patients completed the operation between high-frequency bronchial ventilation and expansion collapse group. There was no significant difference in Forced expiratory volume in 1 second/Forced vital capacity [(101.05 ±â€…11.86) vs (101.86 ±â€…11.61)], maximum expiratory volume [(86.36 ±â€…17.59 L) vs (85.28 ±â€…17.68 L)], the diameter of lung nodules [(13.61 ±â€…3.51 cm) vs (13.21 ±â€…3.41 cm)], intraoperative blood loss [(47.50 ±â€…45.90 mL) vs (48.49 ±â€…34.65 mL)], postoperative drainage volume [(425.16 ±â€…221.61 mL) vs (444.70 ±â€…243.72 mL)], drainage tube removal time [(3.88 ±â€…1.85 days) vs (3.43 ±â€…1.81 days)], or postoperative hospital stay [(6.07 ±â€…2.14 days) vs (5.82 ±â€…1.88 days) between the experimental group and the control group (P > .05)]. There were significant differences in operation time [(95.05 ±â€…26.85 min) vs (117.85 ±â€…31.70 min), P = .017] and intersegmental plane appearance time [(2.37 ±â€…1.03 min) vs (14.20 ±â€…3.23 min), P < .001]. High-frequency bronchial ventilation is safe and feasible when used in quickly and accurately identifying the intersegmental plane and is worthy of clinical application in 2-port thoracoscopic segmentectomy.

[Correlation between gut microbiota and liver biochemical indicators in patients with chronic hepatitis B].

Chronic hepatitis B (CHB) is a global epidemic disease caused by hepatitis B virus that can lead to hepatic failure, even liver cirrhosis and hepatocellular carcinoma. The occurrence and development of CHB are closely related to the changes in the gut microbiota communities. To explore the relationship between the structure of gut microbiota and liver biochemical indicators, 14 CHB patients (the CHB group) and 11 healthy people (the CN group) were randomly enrolled in this study. Our results demonstrate that CHB caused changes in the gut microbiota communities and biochemical indicators, such as alanine transaminase, total bilirubin and gamma glutamyl transferase. Furthermore, CHB induced imbalance of the gut microbiota. Prevotella, Blautia, Ruminococcus, Eubacterium eligens group, Bacteroides uniformis and Ruminococcus sp. 5_1_39BFAA were associated with the critical biochemical indicators and liver injury, suggesting a new approach to CHB treatment.

Nrp-1 Mediated Plasmatic Ago2 Binding miR-21a-3p Internalization: A Novel Mechanism for miR-21a-3p Accumulation in Renal Tubular Epithelial Cells during Sepsis.

The mechanism underlying sepsis-associated acute kidney injury (SAKI), which is an independent risk factor for sepsis-associated death, is unclear. A previous study indicates that during sepsis miR-21a-3p accumulates in renal tubular epithelial cells (TECs) as the mediator of inflammation and mediates TEC malfunction by manipulating its metabolism. However, the specific mechanism responsible for the accumulation of miR-21a-3p in TECs during sepsis is unrevealed. In this study, a cecal ligation and puncture- (CLP-) induced sepsis rat model and rat TEC line were used to elucidate the mechanism. Firstly, miR-21a-3p and Ago2 levels were found out to increase in both plasma and TECs during sepsis, and the increase of intracellular Ago2 and miR-21a-3p could be mitigated when Ago2 was either inactivated or downregulated in septic plasma. Moreover, membrane Nrp-1 expression of TECs was increased significantly during sepsis and Nrp-1 knockdown also mitigated the rise of both the intracellular Ago2 and miR-21a-3p levels in TECs incubated with septic plasma. Furthermore, it was revealed that Ago2 can be internalized by TECs mediated with Nrp-1 and this process had no effect on the intracellular content of miR-21a-3p. Both Ago2 and miR-21a-3p could bind to TECs derived Nrp-1 directly. Finally, it was determined that miR-21a-3p was internalized by TECs via Nrp-1 and Ago2 facilitated this process. Taken together, it can be concluded from our results that Ago2 binding miR-21a-3p from septic plasma can be actively internalized by TECs via Nrp-1 mediated cell internalization, and this mechanism is crucial for the rise of intracellular miR-21a-3p content of TECs during sepsis. These findings will improve our understanding of the mechanisms underlying SAKI and aid in developing novel therapeutic strategies.

Total superior vena cava reconstruction guided by preoperative three-dimensional (3D)-computed tomography bronchography and angiography.

BACKGROUND: The treatment of superior vena cava syndrome caused by invasive thymoma is challenging. This paper aims to explore the application of preoperative three-dimensional computed tomography bronchography and angiography (3D-CTBA) for total superior vena cava reconstruction. METHODS: Total superior vena cava reconstruction guided by preoperative 3D-CTBA in the treatment of superior vena cava syndrome offers more accurate surgical evaluation and more effective procedure of multidisciplinary team (MDT), assists radical dissection and vascular reconstruction as planed in the way of "Step by Step". It also makes the follow-up procedure more effective. RESULTS: High-quality thoracic computed tomography (CT) image is essential. A medical team ensures procedural success with 3D-CTBA. Using this approach, five patients have been treated successfully. The average operative length was 324 minutes and the average blood loss was 190 mL. There was no surgical mortality. Five patients are alive. CONCLUSIONS: Total superior vena cava reconstruction guided by preoperative 3D-CTBA is an effective technology for radical resection of mediastinal lesions combined with artificial vascular replacement. Meanwhile, 3D-CTBA improves the efficiency of MDT and surgical planning. It contributes to alleviate symptoms of SVCS and improve the quality of postoperative life.

Unsatisfying antiviral therapeutic effect in patients with mother-to-child transmissed chronic hepatitis B virus infection: a prospective multi-center clinical study.

BACKGROUND: Few data are available regarding the progression of liver disease and therapeutic efficacy in chronic hepatitis B virus (HBV) carriers infected by mother-to-child transmission (MTCT). This study aimed to investigate these two aspects by comparing the adult chronic HBV carriers in MTCT group with those in horizontal transmission group. METHODS: The 683 adult chronic HBV patients qualified for liver biopsy including 191 with MTCT and 492 with horizontal transmission entered the multi-center prospective study from October 2013 to May 2016. Biopsy results from 217 patients at baseline and 78 weeks post antiviral therapy were collected. RESULTS: Patients infected by MTCT were more likely to have e antigen positive (68.6% vs. 58.2%, χ = -2.491, P = 0.012) than those with horizontal transmission. However, in patients with MTCT, levels of alkaline phosphatase (ALP) (P = 0.031), Fibroscan (P = 0.013), N-terminal propeptide of Type III procollagen (PIIINP) (P = 0.014), and Laminin (LN) (P = 0.006) were high, in contrast to the patients with horizontal transmission for whom the levels of albumin (ALB) (P = 0.041), matrix metalloproteinase-3 (MMP-3) (P = 0.001) were high. The 47.2% of patients with MTCT and 36.8% of those with horizontal transmission had significant liver fibrosis (P = 0.013). Following antiviral therapy for 78 weeks, 21.2% and 38.0% patients with MTCT and horizontal transmission acquired hepatitis B e antigen (HBeAg) clearance, respectively (P = 0.043), and the virological response rates were 54.7% and 74.1% in the MTCT and horizontal groups, respectively (P = 0.005). MTCT was a risk factor for HBeAg clearance and virological response. CONCLUSION: Adult patients with MTCT were more prone to severe liver diseases, and the therapeutic efficacy was relatively poor, which underlined the importance of earlier, long-term treatment and interrupting perinatal transmission. TRIAL REGISTRATION: NCT01962155; https://clinicaltrials.gov.

A nomogram prediction model for recurrent laryngeal nerve lymph node metastasis in thoracic oesophageal squamous cell carcinoma.

BACKGROUND: The metastasis rate to the recurrent laryngeal nerve lymph node (RLN LN) is high, but resection of it is challenging and increases complications. This study explored the risk factors for the RLN LN metastasis in thoracic oesophageal squamous cell carcinoma and developed a novel scoring system to predict it. METHODS: We retrospectively analysed the clinicopathological data of 265 patients between 2015 and 2018. Univariate and multivariate analyses were performed to screen for risk factors and establish a logistic regression model to predict the risk of RLN LN metastasis. A nomogram was constructed accordingly. Further analyses were conducted regarding right and left RLN LN metastasis alone. RESULTS: (I) The metastatic rates of the left and right RLN LN were 15.1% and 20.4%, respectively. (II) Multivariate logistic regression analysis showed that the short axis diameter of the left RLN LN, short axis diameter of the right RLN LN, maximum diameter of the tumor, tumor location, subcarinal lymph node status and paraoesophageal lymph node status were all independent risk factors for RLN LN metastasis. (III) Multivariate logistic regression analysis showed that the short axis diameter of right RLN LN, tumor location and subcarinal lymph node status were independent risk factors for right RLN LN metastasis. (IV) Multivariate logistic regression analysis showed that short axis diameter of left RLN LN was an independent risk factor for left RLN LN metastasis. CONCLUSIONS: The metastatic rates of the left and right RLN LNs were high and can be predicted according to these nomograms.

Clinical Relevance of HLA Gene Variants in HBV Infection.

Host gene variants may influence the natural history of hepatitis B virus (HBV) infection. The human leukocyte antigen (HLA) system, the major histocompatibility complex (MHC) in humans, is one of the most important host factors that are correlated with the clinical course of HBV infection. Genome-wide association studies (GWASs) have shown that single nucleotide polymorphisms (SNPs) near certain HLA gene loci are strongly associated with not only persistent HBV infection but also spontaneous HBV clearance and seroconversion, disease progression, and the development of liver cirrhosis and HBV-related hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB). These variations also influence the efficacy of interferon (IFN) and nucleot(s)ide analogue (NA) treatment and response to HBV vaccines. Meanwhile, discrepant conclusions were reached with different patient cohorts. It is therefore essential to identify the associations of specific HLA allele variants with disease progression and viral clearance in chronic HBV infection among different ethnic populations. A better understanding of HLA polymorphism relevance in HBV infection outcome would enable us to elucidate the roles of HLA SNPs in the pathogenesis and clearance of HBV in different areas and ethnic groups, to improve strategies for the prevention and treatment of chronic HBV infection.

Role of serum hepatitis B virus marker quantitation to differentiate natural history phases of HBV infection.

PURPOSE: The purpose of this study was to characterize roles of serum hepatitis B virus marker quantitation in differentiation of natural phases of HBV infection. METHODS: A total of 184 chronic hepatitis B (CHB) patients were analyzed retrospectively. Patients were classified into four categories: immune tolerant phase (IT, n = 36), immune clearance phase (IC, n = 81), low-replicative phase (LR, n = 31), and HBeAg-negative hepatitis phase (ENH, n = 36), based on clinical, biochemical, serological, HBV DNA level and histological data. RESULTS: Hepatitis B surface antigen (HBsAg) quantitation in four phases were 4.7 ± 0.2, 3.8 ± 0.5, 2.5 ± 1.2 and 3.4 ± 0.4 log10 IU/mL, respectively. There were significant differences between IT and IC (p < 0.001) and between LR and ENH phases (p < 0.001). Quantitation of hepatitis B e antigen (HBeAg) in IT and IC phases are 1317.9 ± 332.9 and 673.4 ± 562.1 S/CO, respectively (p < 0.001). Hepatitis B core antibody (HBcAb) quantitation in the four groups were 9.48 ± 3.3, 11.7 ± 2.8, 11.2 ± 2.6 and 13.2 ± 2.9 S/CO, respectively. Area under receiver operating characteristic curve (AUCs) of HBsAg and HBeAg at cutoff values of 4.41 log10 IU/mL and 1118.96 S/CO for differentiation of IT and IC phases are 0.984 and 0.828, with sensitivity 94.4 and 85.2 %, specificity 98.7 and 75 %, respectively. AUCs of HBsAg and HBcAb at cutoff values of 3.4 log10 IU/mL and 10.5 S/CO for differentiation of LR and ENT phases are 0.796 and 0.705, with sensitivity 58.1 and 85.7 %, and specificity 94.4 and 46.2 %, respectively. CONCLUSIONS: HBsAg quantitation has high predictive value and HBeAg quantitation has moderate predictive value for discriminating IT and IC phase. HBsAg and HBcAb quantitations have moderate predictive values for differentiation of LR and ENH phase.

Selected Cytokines Serve as Potential Biomarkers for Predicting Liver Inflammation and Fibrosis in Chronic Hepatitis B Patients With Normal to Mildly Elevated Aminotransferases.

Previous studies of small cohorts have implicated several circulating cytokines with progression of chronic hepatitis B (CHB). However, to date there have been no reliable biomarkers for assessing histological liver damage in CHB patients with normal or mildly elevated alanine aminotransferase (ALT). The aim of the present study was to investigate the association between circulating cytokines and histological liver damage in a large cohort. Also, this study was designed to assess the utility of circulating cytokines in diagnosing liver inflammation and fibrosis in CHB patients with ALT less than 2 times the upper limit of normal range (ULN). A total of 227 CHB patients were prospectively enrolled. All patients underwent liver biopsy and staging by Ishak system. Patients with at least moderate inflammation showed significantly higher levels of CXCL-11, CXCL-10, and interleukin (IL)-2 receptor (R) than patients with less than moderate inflammation (P < 0.001). Patients with significant fibrosis had higher levels of IL-8 (P = 0.027), transforming growth factor alpha (TGF-α) (P = 0.011), IL-2R (P = 0.002), and CXCL-11 (P = 0.032) than the group without significant fibrosis. In addition, 31.8% and 29.1% of 151 patients with ALT < 2 × ULN had at least moderate inflammation and significant fibrosis, respectively. Multivariate analysis demonstrated that CXCL-11 was independently associated with at least moderate inflammation, and TGF-α and IL-2R independently correlated with significant fibrosis in patients with ALT < 2 × ULN. Based on certain cytokines and clinical parameters, an inflammation-index and fib-index were developed, which showed areas under the receiver operating characteristics curve (AUROC) of 0.75 (95% CI 0.66-0.84) for at least moderate inflammation and 0.82 (95% CI 0.75-0.90) for significant fibrosis, correspondingly. Compared to existing scores, fib-index was significantly superior to aspartate aminotransferase (AST) to platelet ratio index (APRI) and FIB-4 score for significant fibrosis. In conclusion, CXCL-11 was independently associated with at least moderate inflammation, whereas IL-2R and TGF-α were independent indicators of significant fibrosis in both, total CHB patients and patients with normal or mildly elevated ALT. An IL-2R and TGF-α based score (fib-index) was superior to APRI and FIB-4 for the diagnosis of significant fibrosis in patients with normal or mildly elevated ALT.

Inhibition of lung adenocarcinoma cells by insulin-like growth factor-I receptor and Kirsten rat sarcoma mutations: A mutation analysis with antisense oligodeoxynucleotide.

BACKGROUND: Kirsten rat sarcoma (KRAS) mutations are widespread in lung adenocarcinoma patients. The combined utilization of KRAS antisense oligodeoxynucleotide (ASODN) and insulin-like growth factor-I receptor (IGF-IR) may inhibit the proliferation of A549 cell lines of lung adenocarcinoma. METHODS: Point mutations of the KRAS gene in A549 cells were detected by polymerase chain reaction with special sequence primers (PCR-SSP) and gene sequence analysis; ASODN was designed and synthesized according to the mutation specialty of KRAS; and the correlation of gene mutations and clinicopathological features were analyzed. Inhibition on the proliferation and morphostructure change were measured by methyl thiazolyl tetrazolium and colony-forming unit assays. Flow cytometry was used to evaluate the expression of KRAS and IGF-IR proteins and cell apoptosis and reverse transcriptase-polymerase chain reaction were used to detect the expression of KRAS and IGF-IR messenger ribonucleic acid (mRNA). Male nude mice were used to form the mice-human lung cancer model and show the inhibition of KRAS ASODN on A549 cells. RESULTS: PCR-SSP and gene sequence analysis results showed that the codon 12 of KRAS had changed from GGT to GTT. KRAS ASODN or IGF-IR ASODN could inhibit cell proliferation and promote apoptosis of A549 cells. However, the combined utilization of KRAS ASODN and IGF-IR ASODN could inhibit cell proliferation and promote apoptosis more powerfully than exclusive use of KRAS ASODN or IGF-IR ASODN. CONCLUSION: The two ASODNs can inhibit the proliferation of lung adenocarcinoma cells through decreasing the expression of KRAS and IGF-IR mRNA and protein.

Expression of TS, RRM1, ERCC1, TUBB3 and STMN1 Genes in Tissues of Non-small Cell Lung Cancer and its Significance in Guiding Postoperative Adjuvant Chemotherapy.

BACKGROUND: To explore the expression of TS, RRM, ERCC1, TUBB3 and STMN1 genes in the tissues of patients with non-small cell lung cancer (NSCLC) and its significance in guiding the postoperative adjuvant chemotherapy. MATERIALS AND METHODS: Real time polymerase chain reaction (PCR) was applied to detect the expression of TS, RRM, ERCC1, TUBB3 and STMN1 genes in the tissues of NSCLC patients so as to analyze the relationship between the expression of each gene and the clinical characteristics and to guide the postoperative individualized chemotherapy according to the detection results of NSCLC patients. RESULTS: Expression of TS gene was evidently higher in patients with adenocarcinoma than those with non-adenocarcinoma (P=0.013) and so was the expression of ERCC1 (P=0.003). The expression of TUBB3 gene was obviously higher in NSCLC patients in phases I/II and IV than those in phase III (P1=0.021; P2=0.004), and it was also markedly higher in patients without lymph node metastasis than those with (P=0.008). The expression of STMN1 gene was apparently higher in patients in phase I/II than those in phase IV (P=0.002). There was no significant difference between the rest gene expression and the clinical characteristics of NSCLC patients (P>0.05). Additionally, the disease- free survival (DFS) was significantly longer in patients receiving gene detections than those without (P=0.021). CONCLUSIONS: The selection of chemotherapeutic protocols based singly on patients' clinical characteristics has certain blindness. However, the detection of tumor-susceptible genes can guide the postoperative adjuvant chemotherapy and prolong the DFS of NSCLC patients.

pH-Sensitive gold nanoclusters: preparation and analytical applications for urea, urease, and urease inhibitor detection.

Herein, we reported for the first time a facile synthetic process of gold nanoclusters (AuNCs) by using N-acetyl-L-cysteine both as a reducing agent and as a protection ligand. Based on the pH stimuli-responsive properties of the as-prepared AuNCs, we constructed a pH-sensing platform for the detection of urea, urease, and urease inhibitors.

Expression of programmed cell death 5 protein inhibits progression of lung carcinoma in vitro and in vivo via the mitochondrial apoptotic pathway.

Lung cancer is one of the most common and serious types of cancer, and is characterized by uncontrolled cell growth and metastasis from lung tissues to other body parts. The programmed cell death 5 (Pdcd5) protein is known to accelerate apoptosis in different cell types of tumor. The aim of the present study was to explore the role of Pdcd5 in lung carcinoma and to identify the mechanisms underlying the antitumorigenic properties of Pdcd5 in lung cancer. First, we detected and compared the expression of Pdcd5 in healthy and highly differentiated adenocarcinoma lung tissues. The results of histochemical staining and western blot analysis demonstrated that Pdcd5 expression is markedly decreased in highly differentiated lung adenocarcinoma. Next, we used the lung adenocarcinoma cell line A549 to study the effects of Pdc5 expression on proliferation and colony formation. The results revealed that the expression of Pdcd5 significantly inhibits cell proliferation and colony formation in A549 cells. Importantly, Pdcd5 expression induced tumor cell apoptosis, and the apoptotic proteins caspase-3 and -9 were activated. The expression of B-cell lymphoma 2 (Bcl-2) was reduced and that of Bcl2­associated X protein (Bax) was increased, overall suggesting that the intrinsic apoptotic pathway is activated. Furthermore, using a mice xenograft model and vectors for stable expression or silencing of Pdcd5, we showed that stable expression of the protein significantly increases the survival rate of mice in vivo (P<0.01 compared to control). In conclusion, both in vitro and in vivo experiments demonstrated that Pdcd5 expression inhibits proliferation and induces apoptosis in the A549 cell line, indicating that the Pdcd5 protein may play an important role in the progression of lung cancer. Therefore, Pdcd5 may be a promising target for the therapy of lung carcinoma.

CCNB1 is a prognostic biomarker for ER+ breast cancer.

Identification of effective prognostic biomarkers and targets are of crucial importance to the management of breast cancer. CCNB1 (also known as CyclinB1) belongs to the highly conserved cyclin family and is significantly overexpressed in various cancer types. In this study, we demonstrated that CCNB1 had significant predictive power in distant metastasis free survival, disease free survival, recurrence free survival and overall survival of ER+ breast cancer patients. We also found that CCNB1 was closely associated with hormone therapy resistance. In addition, gene set enrichment analysis (GSEA) revealed that its expression was positively associated with genes overexpressed in endocrine therapy resistant samples. Finally, using CCNB1-Drug interaction network, we demonstrated the interactions between CCNB1 and several available cancer drugs. Overall, we suggest that CCNB1 is a biomarker for the prognosis of ER+ breast cancer and monitoring of hormone therapy efficacy. It is also a promising target for developing new strategies to prevent or even reverse hormone therapy resistance. Moreover, CCNB1 expression may help to monitor hormone therapy and to direct personalized therapies. Nevertheless, in vivo and in vitro experiments and multi-center randomized controlled clinical trials are still needed before its application in clinical settings.

[Correlation of hepatocyte expression of hepatitis B viral core antigen and the clinicopathological characters in chronic hepatitis B patients].

OBJECTIVE: To investigate the relationship between the expression of hepatitis B virus (HBV) core antigen and viral replication and liver tissue inflammation damage in chronic hepatitis B (CHB) patients, and to analyze the relationship of core antigen expression differences with clinical and pathological features in e antigen-negative and e antigen-positive CHB patients. METHODS: Sixty-three treatment-naive patients diagnosed with CHB who underwent liver biopsy were included in this retrospective analysis. Liver pathology was assessed, and the karyotype, pulp type, and pulp karyotype were determined. Core and e antigen expression was quantitatively determined by automated immunoassay. Blood samples were used to determine the amount of peripheral lymphocytes or monocytes and HBV DNA load. Results The median titer of HBV DNA was significantly higher in the CHB patients with e antigen positivity (n = 48) than those with e antigen negativity (n = 15) (5.4 * 106 copies/ml vs. 5.4 * 104 copies/ml, P = 0.003). The core antigen positive expression rate was significantly higher in the e antigen-positive CHB patients than in the e antigen-negative CHB patients (80.33% vs. 53.33%, P = 0.042). For the e antigen-positive CHB patients, the HBV DNA titer in karyotype core antigen cases was higher than that in the pulp karyotype mixed-type cases (P = 0.008) and in the negative cases (P = 0.013); in addition, the karyotype patients showed higher titer than the plasma patients (P = 0.019). Also for the e antigen-positive CHB patients, the HBV DNA titer was positively correlated with the rank level of pulp karyotype in core antigen expression (r = 0.589, P = 0.003) but negatively correlated with lobular inflammation, interface inflammation, and fibrosis level (r = -0.552, P = 0.000; r = -0.381, P = 0.008; r = -0.555, P = 0.000); in addition, the level of peripheral blood lymphocytes was negatively correlated with lobular inflammation and fibrosis level (r = -0.361, P = 0.012; r = -0.356, P = 0.013). For the e antigen-negative CHB patients, the level of peripheral blood lymphocytes was negatively correlated with lobular inflammation and interface inflammation (r = -0.702, P = 0.004; r = -0.578, P = 0.024), while the level of peripheral blood mononuclear cells was negatively correlated with lobular inflammation, interface inflammation, and fibrosis level (r = -0.682, P = 0.005; r = -0.620, P = 0.014; r = -0.527, P = 0.044); in addition, age positively correlated with interface inflammation (r = 0.690, P = 0.004). CONCLUSION: The pulp karyotype mixed-type of core antigen expression may reflect the level of HBV replication. Negative expression of core antigen may be associated with variation in pre-C or C zone. The monocyte-macrophage system may be involved in the pathogenesis of e antigen-negative CHB, while the mechanism of immune escape may play an important role in increasing HBV DNA titer in an e-antigen-negative CHB condition.

Serum programmed cell death protein 5 (PDCD5) levels is upregulated in liver diseases.

Intracellular protein molecules are detected in the blood following release from damaged cells. PDCD5 is widely expressed in most types of normal human tissue and is unregulated in cells undergoing apoptosis. It is therefore hypothesized that release of PDCD5 into the circulation might be a specific marker of apoptosis. In this study, a sandwich ELISA was developed for quantification of soluble PDCD5 protein and used to investigate serum PDCD5 levels in liver diseases. The highest levels of PDCD5 were detected in acute icteric hepatitis (AIH) patients compared with normal subjects and other detected liver diseases, such as chronic active hepatitis B (CAHB), chronic persistent hepatitis B (CPHB) and and liver cirrhosis (LC). Increased PDCD5 levels correlated well with ALT and AST in AIH and CAHB patients. In patients with CPHB, increased PDCD5 levels correlated well with AST, TBI, DBIL, and IBIL. In LC patients, PDCD5 levels correlated well with AST/ALT and DBIL. More importantly, increased PDCD5 levels were also observed in patients with normal ALT or AST levels. These data demonstrate a correlation between increased levels of PDCD5 in serum and liver disease progression and indicate the potential utility of serum PDCD5 as a biomarker for monitoring liver injury.

Methylation of the glutathione-S-transferase M3 gene promoter is associated with oxidative stress in acute-on-chronic hepatitis B liver failure.

Chronic hepatitis B (CHB) is a major cause for liver disease worldwide, ranking as the first cause for liver cirrhosis and hepatocellular carcinoma. Acute-on-chronic hepatitis B liver failure (ACHBLF) is most commonly caused by acute severe exacerbation during CHB virus infection. The pathophysiology of ACHBLF is still poorly understood. Glutathione-S-transferase (GST) M3 belongs to GSTs superfamily and it has been demonstrated to contribute to oxidative stress-mediated liver damage. The present study was aimed to determine the potential association between GSTM3 promoter methylation and oxidative stress in ACHBLF patients. Thirty ACHBLF patients, 30 CHB patients and 10 healthy controls were included in this study. Methylation of GSTM3 promoter was determined using methylation-specific PCR (MSP) method. Plasma biomarkers for oxidative stress including malondialdehyde (MDA) and GST were detected by enzyme-linked immunosorbent assay (ELISA). Model for end-stage liver disease (MELD) scoring system was used for predicting the severity and prognosis of liver failure. ACHBLF patients had significant higher GSTM3 promoter methylation rate than CHB patients (30% versus 6.7%, χ(2) = 5.455, P = 0.020). Plasma MDA and GST levels were significantly increased in ACHBLF patients compared with CHB patients. Meanwhile, MDA, MELD scores and mortality rate were significantly higher in methylated group than those in unmethylated group of ACHBLF patients. Furthermore, plasma MDA levels were positively correlated with MELD scores of ACHBLF (r = 0.588, P = 0.001). In conclusion, the methylation of GSTM3 promoter may contribute to oxidative stress-associated liver damage and correlate with the disease severity in ACHBLF.