Comparison of Serum Hepatitis B Virus RNA Levels and Quasispecies Evolution Patterns between Entecavir and Pegylated-Interferon Mono-treatment in Chronic Hepatitis B Patients.

Hepatitis B virus (HBV) RNA may independently predict virological and serological response. This study aimed to compare dynamic changes in serum HBV RNA levels and HBV quasispecies evolution patterns between entecavir and pegylated-interferon mono-treatment in chronic hepatitis B patients and to determine the clinical significance during treatment. TaqMan real-time PCR was used for quantitative analysis. HBV RNA levels were retrospectively determined in serial serum samples from 178 chronic hepatitis B patients who received either entecavir or pegylated-interferon treatment. Both serum HBV DNA and RNA quasispecies were analyzed via next-generation sequencing. Receiver operating characteristics (ROC) analysis was performed to evaluate the prediction value of individual biomarkers for hepatitis B e antigen (HBeAg) seroconversion. Patients who received pegylated-interferon treatment showed stronger declines in HBV RNA levels than did those who received entecavir treatment. Serum HBV RNA levels were lower in patients with subsequent HBeAg seroconversion. At baseline, the level of HBV RNA was better than other indicators in predicting HBeAg seroconversion. Moreover, the predictive value of serum HBV RNA levels was better in the entecavir group. Baseline HBV RNA exhibited a significantly higher genetic diversity than HBV DNA and had a significant decline after 4 weeks of entecavir treatment. Higher baseline genetic diversity may result in a better outcome in pegylated-interferon-treated patients. Serum HBV RNA levels showed different decline kinetics, and HBV RNA quasispecies showed different evolution patterns in entecavir and pegylated-interferon mono-treatment. Taken together, serum HBV RNA may serve as a promising biomarker of HBeAg seroconversion in patients during antiviral treatment.

Serum M2BPGi level is a novel predictive biomarker for the responses to pegylated interferon-α treatment in HBeAg-positive chronic hepatitis B patients.

Serum Mac-2-binding protein glycosylation isomer (M2BPGi) level was found to be a useful prognostic marker for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients treated with nucleoside/nucleotide analogs (NUCs) therapy, and the aim of our study is to evaluate the clinical implementation of M2BPGi level in the prediction of antiviral responses to pegylated-interferon-α (PEG-IFN-α) treatment in HBeAg-positive CHB patients. Ninety-six CHB patients who received PEG-IFN-α treatment for at least 48 weeks were recruited. The serum M2BPGi, alanine aminotransferase (ALT), hepatitis B surface antigen (HBsAg), HBeAg, and HBV DNA levels at baseline, weeks 4, 12, and 24 after PEG-IFN-α treatment were determined and their associations with antiviral responses were evaluated and the virological response (VR) rate and serological response (SR) rate after 48 weeks of treatment were 65.6% and 35.4%, respectively. Baseline serum M2BPGi level was significantly different between VR and non-VR (P = 0.002) or SR and non-SR groups (P = 0.012). Multivariate analyses suggested that baseline serum M2BPGi level was independently associated with VR and SR of PEG-IFN-α treatment at week 48. The area under the ROC curve (AUC) of baseline M2BPGi was 0.682 in predicting VR, which was superior to HBsAg (AUC = 0.566) or HBV DNA (AUC = 0.567). The AUC of baseline M2BPGi in predicting SR was 0.655, which was also higher than that of HBsAg (AUC = 0.548) or HBV DNA (AUC = 0.583). These results suggested that baseline serum M2BPGi level was a novel predictor of VR and SR for PEG-IFN-α treatment in HBeAg-positive CHB patients.

Serum WFA+ -M2BP levels for evaluation of early stages of liver fibrosis in patients with chronic hepatitis B virus infection.

BACKGROUND & AIMS: Accurate evaluation of liver fibrosis is crucial for predicting progression of chronic hepatitis B virus (HBV) infection. We assessed the utility of a novel fibrosis glycobiomarker Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+ -M2BP) for evaluating liver fibrosis and disease progression in patients with chronic HBV infection. METHODS: We enrolled 774 patients with chronic HBV infection, with or without fibrosis, diagnosed by liver biopsy/FibroScan. Patients who underwent liver biopsy (n = 297) were divided into training (n = 221) and validation (n = 76) groups. Serum WFA+ -M2BP values were measured and compared with FIB-4 index, aspartate aminotransferase (AST)-to-platelet ratio (APRI) and AST-to-alanine aminotransferase ratio (AAR) using receiver-operating characteristic (ROC) analysis. RESULTS: Serum WFA+ -M2BP levels increased significantly with fibrosis progression (P < 0.0001). Area under the ROC curve of WFA+ -M2BP for diagnosing significant fibrosis was higher than that of FIB-4 (P = 0.198), APRI (P = 0.017) and AAR (P < 0.001), with sensitivity and specificity in the training set of 60.5% and 79.8% and validation set of 59.5% and 82.1%, respectively. Serum WFA+ -M2BP levels were significantly correlated with FibroScan values (P < 0.0001) and improved the accuracy of FibroScan in assessing significant fibrosis. Changes in WFA+ -M2BP levels were parallel with those in FibroScan values during nucleot(s)ide analogues therapy in patients with chronic HBV infection. CONCLUSIONS: WFA+ -M2BP is an accurate serum indicator for assessing early stages of liver fibrosis and may monitor regression of fibrosis during the treatment of chronic HBV infection. WFA+ -M2BP provides a simple and reliable alternative or complementary method to liver biopsy and FibroScan.

Kinetic resolution of α-methylene-ß-hydroxy esters catalyzed by acyl transfer catalyst An-PIQ.

A highly efficient nonenzymatic kinetic resolution of a series of structurally diverse racemic α-methylene-ß-hydroxy esters utilizing the acyl transfer catalyst An-PIQ and propionic anhydride is reported. This procedure provides recovered alcohols with extremely high ee's (up to >99%) in reasonable conversions and excellent selectivity factors (S up to 108). Several synthetically important substrates were resolved in gram-scale reactions, and highly optically pure α-methylene-ß-hydroxy esters were obtained with excellent S values and good yields.

Impact of heart failure on outcomes in patients with sepsis: A systematic review and meta-analysis.

BACKGROUND: Heart failure (HF) often affects the progress of sepsis patients, although its impact on outcomes is inconsistent and inconclusive. AIM: To conduct a systematic review and meta-analysis of the impact of HF on mortality in patients with sepsis. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library databases were searched to compare the outcomes of sepsis patients with HF. A random effect model was used to summarize the mortality data, and the odds ratio (OR) and 95% confidence interval (CI) were calculated as effect indicators. RESULTS: Among 18001 records retrieved in the literature search, 35712 patients from 10 separate studies were included. The results showed that sepsis patients with HF were associated with increased total mortality (OR = 1.80, 95%CI: 1.34-2.43; I2 = 92.1%), with high heterogeneity between studies. Significant subgroup differences according to age, geographical location, and HF patient sample were observed. HF did not increase the 1-year mortality of patients (OR = 1.11, 95%CI: 0.75-1.62; I2 = 93.2%), and the mortality of patients with isolated right ventricular dysfunction (OR=2.32, 95%CI: 1.29-4.14; I2 = 91.5%) increased significantly. CONCLUSION: In patients with sepsis, HF is often associated with adverse outcomes and mortality. Our results call for more high-quality research and strategies to improve outcomes for sepsis patients with HF.

Development and validation of a risk prediction model for breast cancer-related lymphedema in postoperative patients with breast cancer.

OBJECTIVE: Breast cancer-related lymphedema (BCRL) is a common post-operative complication in patients with breast cancer. Here, we sought to develop and validate a predictive model of BCRL in Chinese patients with breast cancer. METHODS: Clinical and demographic data on patients with breast cancer were collected between 2016 and 2021 at a Cancer Hospital in China. A nomogram for predicting the risk of lymphedema in postoperative patients with breast cancer was constructed and verified using R 3.5.2 software. Model performance was evaluated using area under the ROC curve (AUC) and goodness-of-fit statistics, and the model was internally validated. RESULTS: A total of 1732 postoperative patients with breast cancer, comprising 1212 and 520 patients in the development and validation groups, respectively, were included. Of these 438 (25.39%) developed lymphedema. Significant predictors identified in the predictive model were time since breast cancer surgery, level of lymph node dissection, number of lymph nodes dissected, radiotherapy, and postoperative body mass index. At the 31.9% optimal cut-off the model had AUC values of 0.728 and 0.710 in the development and validation groups, respectively. Calibration plots showed a good match between predicted and observed rates. In decision curve analysis, the net benefit of the model was better between threshold probabilities of 10%-80%. CONCLUSION: The model has good discrimination and accuracy for lymphedema risk assessment, which can provide a reference for individualized clinical prediction of the risk of BCRL. Multicenter prospective trials are required to verify the predictive value of the model.

A blood-based 22-gene expression signature for hepatocellular carcinoma identification.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common and lethal malignancies. Early detection of HCC could largely reduce mortalities. Ultrasonography (US) and serum Alpha Fetoprotein (AFP) test are the screening methods that are most frequently applied to high-risk populations. Due to the poor performance of AFP testing, and the highly operator-dependent nature of US, a biomarker for HCC early diagnosis is highly sought after. We developed a method for HCC screening using a 22-gene expression signature. METHODS: Peripheral whole blood of 98 patients were processed through microarrays for the first round of feature selection via two strategies, Minimal Redundancy Maximal Relevance and Least Absolute Shrinkage and Selection Operator combined with Support Vector Machine (SVM). Candidate genes were combined for further validation through qPCR in an enlarged population with 316 samples with 104 chronic hepatitis, 112 liver cirrhosis (LC), and 100 HCC. RESULTS: A 22-gene signature was established in classifying HCC and non-cancer samples with good performance. The area under curve reached 0.94 in all of the samples and 0.93 in the AFP -negative samples. CONCLUSIONS: We have established a blood mRNA signature with high performance for HCC screening. Our results show transcriptome of peripheral blood could be valuable source for biomarkers.

Ulcerative colitis complicated with colonic necrosis, septic shock and venous thromboembolism: A case report.

BACKGROUND: Severe total colonic necrosis, septic shock and venous thromboembolism secondary to ulcerative colitis (UC) are rare and life-threatening. No such severe complications have been reported in the literature. CASE SUMMARY: We report a 36-year-old woman who developed total colonic necrosis and septic shock secondary to UC. The patient was treated with emergency surgery because computed tomography showed suspicious perforations. Persistent massive ascites occurred after operation and computed tomography angiography demonstrated portal vein, mesenteric vein and splenic vein thrombosis. The patient was discharged from hospital after active treatment. CONCLUSION: Clinicians should pay attention to venous thrombosis, colonic necrosis and septic shock in UC patients. Close observation of surgical indications and timely surgical intervention are the key to reduce mortality and complications in UC.

[Application of percutaneous vertebroplasty with the second injection for poor dispersion bone cement of Kümmel disease].

OBJECTIVE: To investigate clinical effect of percutaneous vertebroplasty with second injection for poor dispersion bone cement of Kümmel disease. METHODS: Eighty-eight patients with Kümmel disease were treated with vertebroplasty from February 2014 to December 2017, and 16 patients were found cement dispersion unsatisfactory during initial cement injection and were undertaken second cement injection during operation. Among patients, there were 1 male and 15 females aged from 63 to 82 years old with an average age of 72.7 years old. Distribution of fractured vertebrae were followed: 1 patient was on T10, 1 patient was on T11, 3 patients were on T12, 8 patients were on L1, 1 patient was on L2, and 2 patients were on L3. VAS and ODI score were compared before operation, 2 days after operation and the latest following-up, anterior vertebral height and local kyphosis angle of fractured vertebrae with intravertebral cleft were also observed. Postoperative complication was recorded. RESULTS: All patients were followed up from 5 to 22 months with average of 14.1 months. ODI score before operation, 2 days after operation and the latest following-up were 72.3±12.1, 56.8±5.0 and 12.1±5.3 respectively; VAS score before operation, 2 days after operation and the latest following-up were 7.8±0.6, 3.0±0.4 and 2.4±0.7, respectively; ODI score at 2 days was improved compared with before operation, while ODI and VAS score at the latest following-up was improved than that of 2 days after operation. Vertebral anterior compression rate and Cobb angle of the fractured vertebrae with intravertebral cleft were respectively corrected from (37.8±5.4)% and (15.1±2.0)°preoperative, to (4.7±1.4)% and (4.4±2.2)° at 2 days after operation, (4.9±1.5)% and (4.8±2.4)° at the latest following-up, there was significant difference between before operation and 2 days after operation, while there was no difference between 2 days after operation and the latest following-up. Three patients occurred cement leakage without pulmonary embolism and neurological impairment. Four patients occurred adjacent vertebrae fracture. There was no incidence of recollapsed vertebrae during follow-up period. CONCLUSIONS: Percutaneous vertebroplasty for Kümmel disease could receive satisfactory clinical results when cement dispersion was inadequate during initial cement injection by the second injection, and effectively prevent occurrence of vertebral re-collapse.

[Unilateral Wiltse intermuscular approach and contralateral decompression for the treatment of thoracolumbar burst fracture].

OBJECTIVE: To compare the clinical effects and multifidus muscle injury of different approaches, including unilateral Wiltse intermuscular approach and intramuscular approach combined with contralateral decompression, in treating thoracolumbar burst fracture. METHODS: Forty-three patients with thoracolumbar burst fracture were enrolled in the study from January 2010 to December 2014, including 29 males and 14 females with an average age of 42.3 years old(ranged from 21 to 64 years old). The patients were treated with posterior pedicle screw fixation and unilateral decompression and were divided into Wiltse intermuscular approach group (group A) and intramuscular approach group (group B) according to surgical approach. Operation time and intraoperative bleeding were recorded for all patients; visual analogue scale(VAS) was compared 1 d preoperatively, 1 week, 12 months postoperatively between two groups; preoperation and 12 months postoperatively, the fractured vertebral canal and two-sides multifidus muscle of the same section were observed and compared by CT measure between two groups. RESULTS: All the patients were follow-up for 14 to 21 months with an average of 16.3 months. Partial wound non-healing occurred in 3 patients and the wound ultimately healing after debridgement suture and change dressings. No screw breakage was found. There was significant difference in operation and intraoperative bleeding operation between two groups (P<0.05), while there was no significant difference in VAS score of 1 d preoperatively, 1 week, 12 months postoperatively between two groups(P>0.05). As for CT measurement results, postoperative vertebral canal narrow ratio was significant decreased in all patients(P<0.05), while perioperative changes of the two-sides multifidus muscle cross section area and density were significant in group A (P<0.05), but there was no significant difference in group B (P>0.05). Neurologic status of all patients got recovery at final follow-up. CONCLUSIONS: The method of unilateral Wiltse intermuscular approach combined with contralateral decompression for the treatment of thoracolumbar burst fracture has good clinical effects, also it is less invasive and less damage to multifidus muscle compared with intramuscular approach.

[Outcomes and related factors of C5 nerve root palsy after cervical posterior single open-door laminoplasty].

OBJECTIVE: To analyze the clinical outcomes and related factors of C5 palsy following cervical laminectomy in treating multi-segments cervical spondylotic myelopathy. METHODS: From January 2010 to June 2014, 80 patients with spondylotic myelopathy underwent C3-C6 open-door laminoplasty(group A) and 80 patients C4-C6 open-door laminoplasty (group B). The mean age was (68.4±9.2) years (44 males and 36 females) in group A and the mean age was (66.8±8.9) years (48 males and 32 females) in group B. Japanese Orthopaedic Association(JOA) score, Visual Analogue Score, incidence of C5 palsy, time of onset, grade of muscle weakness, other accompanying cervical nerve root palsies, recovery time were used to evaluate clinical effects before operation and at last follow-up. Radiographically, changes of Cobb angle of sagittal plane from C2-C7, cervical range of motion, minimal spinal cord diameter on MRI were analyzed before operation and at last follow-up. RESULTS: All the patients were followed up from 6 to 15 months with an average of (12.4±3.2) months. No obvious differences were observed between change of VAS of cervical and upper limb, JOA, Cobb angle, cervical range of motion, minimal spinal cord diameter on MRI. C5 nerve root palsy occurred in 7 cases (8.75%) in group A, including 4 cases of upper limb pain, 3 cases of upper limb pain, and 2 cases of residual upper limb pain and sensory loss at the last follow-up. C5 nerve root palsy occurred in 5 cases (7.5%) in group B, 3 cases of upper limb pain, 2 cases of upper limb sensory loss, and all patients recovered normal radiation pain and sensory loss at the last follow-up. There was no significant difference in the incidence of C5 nerve root palsy between the two groups. C5 nerve root palsy, deltoid muscle, accompanied by neurological symptoms, recovery time were(2.3±1.0) N, 30 cases (37.5%), (11.4±1.0) weeks in group A, (2.8±0.8) N, 23 cases (28.8%), (8.2±0.8) weeks in group B, there was no significant difference on deltoid muscle decreased between the two groups, accompanied by neurological symptoms and the recovery time in group A was worse than the group B. CONCLUSIONS: Comparison of the two kinds of operation, the probability of postoperative C5 nerve root palsy was equal, but the C5 nerve root palsy in patients with C4-C6 open-door laminoplasty showed lighter symptom and faster recovery.

Characteristics of CpG Islands and their quasispecies of full-length hepatitis B virus genomes from patients at different phases of infection.

BACKGROUND: CpG islands in hepatitis B virus (HBV) genome are potential targets for methylation mediated gene silencing, and may be involved in the pathogenesis of HBV infection. To date, their characteristics in HBV quasispecies (QS) remain largely unknown. The purpose of this study was to investigate the characteristics of CpG islands in HBV QS. METHODS: Forty patients diagnosed as acute hepatitis B (AHB, n = 10), immune-tolerant HBV carriers (IT, n = 9), chronic hepatitis B (CHB, n = 11), or acute on chronic liver failure (ACLF, n = 10), were enrolled in this case-control study. A total of 599 clones were isolated, and full-length HBV genomes were sequenced. RESULTS: CpG island II (CGII) in AHB group was shorter in length and its QS heterogeneity was lower than that in the chronic infection group. Among the chronic infection subgroups, CGII and CpG island III (CGIII) in IT group were longer and their heterogeneity was lower compared to CHB and ACLF groups. Length of CGII correlated with HBV DNA levels positively while the complexity and diversity of CGII correlated with HBV DNA levels negatively. Moreover, CGII and CGIII were shorter in genotype B than those in genotype C, while QS complexity and diversity of either CGII or CGIII had no significant difference between genotype B and C. CONCLUSIONS: Overall, our results suggest that the distribution, length and QS heterogeneity of CpG islands in full-length HBV genome differ across clinical phases of infection, of which the mechanism warrants further study.

Quantitative hepatitis B surface antigen combined with hepatitis B e antigen as sustained virological response predictors during extended therapy with Peginterferon alfa-2a for hepatitis B e antigen-positive chronic hepatitis B.

BACKGROUND: The best strategy for chronic hepatitis B patients with poor response to 48 weeks of Peginterferon-based therapy has been controversial and the predictive value of hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA levels for determining the sustained virological response (SVR) of these patients is uncertain. OBJECTIVES: To optimize management of these patients and evaluate the use of these serobiomarkers to predict SVR. STUDY DESIGN: Eighty-one patients with an unsatisfactory response after 48 weeks of Peginterferon-based therapy were treated with extended Peginterferon therapy with or without nucleo(s) tide analogues (NAs), for a total of 96 weeks of Peginterferon treatment. HBsAg, HBeAg and HBV DNA levels were measured serially during the treatment and follow-up. RESULTS AND CONCLUSIONS: Twenty-six of 81 patients (32.1%) attained SVR during the 72-week follow-up. The SVR rate was not statistically different between groups receiving 1-year prolongation of Peginterferon with or without NAs. The serum HBsAg cut-off of 1800IU/mL at week 48 had area under curve (AUC) of 0.727, and the serum HBsAg cut-off of 1500IU/mL, combined with HBeAg loss at week 72, had AUC of 0.753 to predict SVR during the follow-up. In conclusion, extended treatment with Peginterferon with or without NAs for patients with unsatisfactory response after 48 weeks of Peginterferon-based therapy is a promising strategy to achieve SVR, and quantitative serum HBsAg at week 48 and HBsAg level combined with HBeAg loss at week 72 of therapy can predict SVR to prolongation therapy with Peginterferon.