Finite element study on the micromechanics of cement-augmented proximal femoral nail anti-rotation (PFNA) for intertrochanteric fracture treatment.

Blade cut-out is a common complication when using proximal femoral nail anti-rotation (PFNA) for the treatment of intertrochanteric fractures. Although cement augmentation has been introduced to overcome the cut-out effect, the micromechanics of this approach remain to be clarified. While previous studies have developed finite element (FE) models based on lab-prepared or cadaveric samples to study the cement-trabeculae interface, their demanding nature and inherent disadvantages limit their application. The aim of this study was to develop a novel 'one-step forming' method for creating a cement-trabeculae interface FE model to investigate its micromechanics in relation to PFNA with cement augmentation. A human femoral head was scanned using micro-computed tomography, and four volume of interest (VOI) trabeculae were segmented. The VOI trabeculae were enclosed within a box to represent the encapsulated region of bone cement using ANSYS software. Tetrahedral meshing was performed with Hypermesh software based on Boolean operation. Finally, four cement-trabeculae interface FE models comprising four interdigitated depths and five FE models comprising different volume fraction were established after element removal. The effects of friction contact, frictionless contact, and bond contact properties between the bone and cement were identified. The maximum micromotion and stress in the interdigitated and loading bones were quantified and compared between the pre- and post-augmentation situations. The differences in micromotion and stress with the three contact methods were minimal. Micromotion and stress decreased as the interdigitation depth increased. Stress in the proximal interdigitated bone showed a correlation with the bone volume fraction (R2 = 0.70); both micromotion (R2 = 0.61) and stress (R2 = 0.93) at the most proximal loading region exhibited a similar correlation tendency. When comparing the post- and pre-augmentation situations, micromotion reduction in the interdigitated bone was more effective than stress reduction, particularly near the cement border. The cementation resulted in a significant reduction in micromotion within the loading bone, while the decrease in stress was minimal. Noticeable gradients of displacement and stress reduction can be observed in models with lower bone volume fraction (BV/TV). In summary, cement augmentation is more effective at reducing micromotion rather than stress. Furthermore, the reinforcing impact of bone cement is particularly prominent in cases with a low BV/TV. The utilization of bone cement may contribute to the stabilization of trabecular bone and PFNA primarily by constraining micromotion and partially shielding stress.

Mitochondria protective and anti-apoptotic effects of peripheral benzodiazepine receptor and its ligands on the treatment of asthma in vitro and vivo.

BACKGROUND: Asthma is a prevalent respiratory inflammatory disease. Abnormal apoptosis of bronchial epithelial cells is one of the major factors in the progression of asthma. Peripheral benzodiazepine receptors are highly expressed in bronchial epithelial cells, which act as a component of the mitochondrial permeability transition pore to regulate its opening and closing and apoptosis of bronchial epithelial cells. We aimed to investigate the mechanisms by which peripheral benzodiazepine receptor and its ligands, agonist 4'-Chlorodiazepam (Ro5-4864) and antagonist 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide (PK 11,195), modulate the mitochondrial function and cell apoptosis in the treatment of asthma. METHODS: In vitro study, Ro5-4864 and PK 11,195 were utilized to pretreat cells prior to the inflammatory injury induced by Lipopolysaccharide. The reactive oxygen species, the apoptosis of cell, the mitochondrial membrane potentials, the ultrastructures of the mitochondria and the expression levels of peripheral benzodiazepine receptors and apoptosis-related proteins and genes were detected. In vivo study, mice were administrated intraperitoneally with Ro5-4864 and PK 11,195 before sensitized and challenged by ovalbumin. Serum IgE and bronchoalveolar lavage fluid cytokines were detected, and lung tissues were underwent the histopathological examination. RESULTS: The ligands of peripheral benzodiazepine receptor counteracted the effects of the increase of reactive oxygen species, the elevated extent of apoptosis, the decrease of mitochondrial membrane potentials and the disruption of mitochondrial ultrastructures induced by Lipopolysaccharide. The ligands also promoted the expression of anti-apoptosis-related proteins and genes and inhibited the expression of pro-apoptosis-related proteins and genes. Besides, the ligands reduced the levels of serum IgE and bronchoalveolar lavage fluid cytokines in asthmatic mice and attenuated the histopathological damage of lungs. CONCLUSION: Peripheral benzodiazepine receptor serves as a potential therapeutic target for the treatment of asthma, with its ligands exerting mitochondrial protective and anti-apoptotic effects on bronchial epithelial cells.

Prediction of intravenous immunoglobulin retreatment in children with Kawasaki disease using models combining lymphocyte subset and cytokine profile in an East Asian cohort.

Objectives: For children with Kawasaki disease (KD) at high risk of developing coronary artery lesions and requiring retreatment with intravenous immunoglobulin (IVIG), the availability of accurate prediction models remains limited because of inconsistent variables and unsatisfactory prediction results. We aimed to construct models to predict patient's probability of IVIG retreatment combining children's individual inflammatory characteristics. Methods: Clinical manifestations and laboratory examinations of 266 children with KD were retrospectively analysed to build a development cohort data set (DC) and a validation cohort data set (VC). In the DC, binary logistic regression analyses were performed using R language. Nomograms and receiver operating curves were plotted. The concordance index (C index), net reclassification index, integrated discrimination improvement index and confusion matrix were applied to evaluate and validate the models. Results: Models_5V and _9V were established. Both contained variables including the percentages of CD8+ T cells, CD4+ T cells, CD3+ T cells, levels of interleukin (IL)-2R and CRP. Model_9V additionally included variables for IL-6, TNF-α, NT-proBNP and sex, with a C index of 0.86 (95% CI 0.79-0.92). When model_9V was compared with model_5V, the NRI and IDI were 0.15 (95% CI 0.01-0.30, P < 0.01) and 0.07 (95% CI 0.02-0.12, P < 0.01). In the VC, the sensitivity, specificity and precision of model_9V were 1, 0.875 and 0.667, while those of model_5V were 0.833, 0.875 and 0.625. Conclusion: Model_9V combined cytokine profiles and lymphocyte subsets with clinical characteristics and was superior to model_5V achieving satisfactory predictive power and providing a novel strategy early to identify patients who needed IVIG retreatment.

Diagnostic value of liver stiffness measurement combined with risk scores for esophagogastric variceal bleeding in patients with hepatitis B cirrhosis.

PURPOSE: To assess the predictive value of liver stiffness measurement (LSM) and three bleeding risk scoring systems for esophagogastric varices bleeding (EGVB) in patients with hepatitis B cirrhosis during hospitalization. METHODS: In this study, 210 patients who had hepatitis B cirrhosis were selected as the subjects. They were categorized into two groups based on whether EGVB occurred during hospitalization: a bleeding group (70 cases) and a non-bleeding group (140 cases). Logistic regression was used to analyze the factors related to the occurrence of EGVB, and the diagnostic performance was evaluated using a receiver operating characteristic (ROC) curve. RESULTS: Significant differences were observed between the two groups in systolic blood pressure, platelet count, albumin, urea nitrogen, LSM, pre-endoscopic Rockall score (PRS), Glasgow-Blatchford score (GBS), and AIMS65 score (P < 0.05). The correlation analysis showed that LSM had significant positive relationship with PRS, GBS and AIMS65 score. Logistic regression analysis revealed that LSM and GBS score were independent risk factors for EGVB occurrence during hospitalization. ROC curve analysis showed that the combined prediction model of LSM and GBS score had the best prediction performance for EGVB occurrence, with an ROC curve area of 0.811, which was significantly better than the three risk scoring systems (P < 0.05), but similar to the predicted value of LSM (P = 0.335). CONCLUSIONS: The combination of LSM and GBS score can significantly improve the predictive efficacy of EGVB occurrence in patients with hepatitis B cirrhosis during hospitalization, which has important clinical significance for patients' prognosis.

Determining optimal ALT cut-off values for predicting significant hepatic histological changes in patients with normal ALT in the grey zone of chronic hepatitis B virus infection.

BACKGROUND AND AIMS: We aimed to define gender-specific, optimal alanine aminotransferase (ALT) cut-off values for the prediction of significant liver histological changes (SLHC) in Chinese patients with grey zone (GZ) chronic hepatitis B (CHB) and normal ALT. METHODS: In a retrospective study, we included 1101 consecutive patients with GZ CHB and normal ALT assigned to training or internal validation cohorts. We included an independent cohort of 842 patients for external validation. We performed receiver operating characteristic (ROC) curve, smoothed curve fitting, and threshold effect analyses to determine optimal ALT cut-off values. Area under the curve (AUC) values were calculated to assess their predictive performance. RESULTS: A proportion of 79.3% of patients with GZ CHB and normal ALT (≤40 U/L) had SLHC. ROC curve analysis initially identified optimal ALT cut-off values of 29 U/L (male) and 22 U/L (female). After smoothed curve fitting and threshold effect analyses, new optimal cut-off values were 27 U/L for males and 24 U/L for females. AUCs for these values were 0.836 (male) and 0.833 (female) in the internal validation cohort, and 0.849 (male) and 0.844 (female) in the external validation cohort. The accuracy and discriminative ability of the newly defined ALT cut-off values were greater than those of the current recommendations. CONCLUSION: This study established novel optimal ALT cut-off values for more precise prediction of SLHC among Chinese patients with GZ CHB and normal ALT levels. This may help identify individuals who will benefit from timely antiviral therapy.

Hypoxia Potentiated Lung Cancer Cell Migration and Invasion by up-regulating HIF1α/JAK2/STAT3 Axis and Activating MMP13 Transcription.

Excessive aggressive migration and invasion are important factors that increase the mortality of cancer patients. Matrix metalloproteinase 13 (MMP13) expression is positively correlated with lung cancer malignancy. However, the mechanism underlying an elevated MMP13 expression is not clearly defined. In this study, we demonstrated that hypoxia induced by CoCl2 enhanced the expression of HIF1α, JAK2, STAT3 and MMP13 in A549 cells. A positive correlation between HIF1α and MMP13 expression was observed in lung adenocarcinoma patients. Mechanically, hypoxia upregulated HIF1α/JAK2/STAT3 signal axis, promoted transcription factor STAT3 to bind to MMP13 promoter region, and activated MMP13 transcription, finally promoted cell invasion and migration. However, stattic (STAT3 inhibitor) could reverse this effect caused by STAT3 in A549 cells. Together our data indicated that hypoxia might promote lung cancer cell migration and invasion through the HIF1α/JAK2/STAT3 axis by activating MMP13 transcription. MMP13 could be a promising therapeutic target for lung adenocarcinoma metastasis.

Liver Stiffness Measurement can Predict Liver Inflammation in Chronic Hepatitis B Patients with Normal Alanine Transaminase.

Background and Aims: To determine whether liver stiffness measurement (LSM) indicates liver inflammation in chronic hepatitis B (CHB) with different upper limits of normal (ULNs) for alanine aminotransferase (ALT). Methods: We grouped 439 CHB patients using different ULNs for ALT: cohort I, ≤40 U/L (439 subjects); cohort II, ≤35/25 U/L (males/females; 330 subjects); and cohort III, ≤30/19 U/L (males/females; 231 subjects). Furthermore, 84 and 96 CHB patients with normal ALT (≤40 U/L) formed the external and prospective validation groups, respectively. We evaluated the correlation between LSM and biopsy-confirmed liver inflammation, and determined diagnostic accuracy using area under the curve (AUC). A noninvasive LSM-based model was developed using multivariate logistic regression. Results: Fibrosis-adjusted LSM values significantly increased with increasing inflammation. The AUCs of LSM in cohorts I, II, and III were 0.799, 0.796, and 0.814, respectively, for significant inflammation (A≥2) and 0.779, 0.767, and 0.770, respectively, for severe inflammation (A=3). Cutoff LSM values in all cohorts for A≥2 and A=3 were 6.3 and 7.5 kPa, respectively. Internal, external, and prospective validations showed high diagnostic accuracy of LSM for A≥2 and A=3, and no significant differences in AUCs among the four groups. LSM and globulin independently predicted A≥2. The AUC of an LSM-globulin model for A≥2 exceeded those of globulin, ALT, and AST, but was similar to that of LSM. Conclusions: LSM predicted liver inflammation and guided the indication of antiviral therapy for CHB in patients with normal ALT.

Development a novel nomogram model for predicting significant hepatic histological changes in chronic hepatitis B virus carriers.

A proportion of chronic hepatitis B virus (HBV) carriers with normal alanine transaminase (ALT) present with significant liver histological changes (SLHC). To construct a noninvasive nomogram model to identify SLHC in chronic HBV carriers with different upper limits of normal (ULNs) for ALT. The training cohort consisted of 732 chronic HBV carriers who were stratified into four sets according to different ULNs for ALT: chronic HBV carriers I, II, III, and IV. The external validation cohort comprised 277 chronic HBV carriers. Logistic regression and least absolute shrinkage and selection operator analyses were applied to develop a nomogram model to predict SLHC. A nomogram model-HBGP (based on hepatitis B surface antigen, gamma-glutamyl transpeptidase, and platelet count) demonstrated good performance in diagnosing SLHC with area under the curve (AUCs) of 0.866 (95% confidence interval [CI]: 0.839-0.892) and 0.885 (95% CI: 0.845-0.925) in the training and validation cohorts, respectively. Furthermore, HBGP displayed high diagnostic values for SLHC with AUCs of 0.866 (95% CI: 0.839-0.892), 0.868 (95% CI: 0.838-0.898), 0.865 (95% CI: 0.828-0.901), and 0.853 (95% CI: 0.798-0.908) in chronic HBV carriers I, II, III, and IV, respectively. Additionally, HBGP showed greater ability in predicting SLHC compared with the existing predictors. HBGP has shown high predictive performance for SLHC, and thus may lead to an informed decision on the initiation of antiviral treatment.

The effects of anesthesia methods and anesthetics on postoperative delirium in the elderly patients: A systematic review and network meta-analysis.

Study objective: Postoperative delirium (POD) is one of the serious postoperative complications in elderly patients, which is always related to long-term mortality. Anesthesia is often considered a risk factor for POD. This systematic review and network meta-analysis (NMA) aimed to assess the impact of different anesthesia methods and anesthetics on POD. Measurements: We searched for studies published in PubMed, Embase, Web of Science, Scopus, and Cochrane Library (CENTRAL) from inception to 18 March 2022. RevMan 5.3 and CINeMA 2.0.0 were used to assess the risk of bias and confidence. Data analysis using STATA 17.0 and R 4.1.2. STATA 17.0 was used to calculate the surface under the cumulative ranking curve (SUCRA) and provide network plots with CINeMA 2.0.0. NMA was performed with R 4.1.2 software gemtc packages in RStudio. Main results: This NMA included 19 RCTs with 5,406 patients. In the pairwise meta-analysis results, only regional anesthesia (RA) with general anesthesia (GA) vs. GA (Log OR: -1.08; 95% CI: -1.54, -0.63) were statistically different in POD incidence. In the NMA results, there was no statistical difference between anesthesia methods, and psoas compartment block (PCB) with bupivacaine was superior to the desflurane, propofol, sevoflurane, and spinal anesthesia with bupivacaine of POD occurrence. Conclusion: Our study indicated that RA and GA had no significant effect on POD, and there was no difference between anesthesia methods. Pairwise meta-analysis showed that, except for RA with GA vs. GA, the rest of the results were not statistically different. Besides, PCB with bupivacaine may benefit to reduce POD incidence. Systematic review registration: https://www.crd.york.ac.uk/prospero/dis play_record.php?ID=CRD42022319499, identifier PROSPERO 2022 CRD42022319499.

Ultrasound measurements for evaluation of changes in upper airway during anaesthesia induction and prediction difficult laryngoscopy: a prospective observational study.

Upper airway collapsibility after anaesthesia induction may be associated with unpredictable difficult airway. However, most works on airway anatomy are tended to morphological description before anaesthesia. This study aimed to evaluate the changes of upper airway after anaesthesia induction and using pre-anesthetic ultrasound measurements to predict Difficult Laryngoscopy (DL). We included 104 eligible subjects with complete data, who were performed tracheal intubations under general anaesthesia in the study. The upper airway changes before and after anaesthesia induction were determined by seven neck ultrasound measurements, included as follow: (1) Distance from skin to under surface of Tongue (DT), (2) Thickness of the thickest part of Tongue body (TT), (3) Hyoid Mental Distance (HMD), (4) Depth of Hyoid (DH), (5) Width of Hyoid (WH), (6) Distance from Skin to Epiglottis (DSE), (7) Depth of the anterior combination of the Vocal Cords (DVC). DL was evaluated with Cormack-Lehane (CL). Data regarding HMD [from 45.3 (42.4-48.5) to 41.1 (38.5-44.9) mm], DH [from 8.7 (6.6-10.9) to 7.0 (5.3-9.1) mm], DSE [from 20.1 (16.6-22.5) to 19.5 (16.5-21.6) mm] and the DVC [from 7.1 (5.7-8.3) to 6.8 (5.7-7.9) mm] were decreased (P < 0.05), while the DT [from 15.9 (13.1-18.4) to 17.4 (14.5-19.8) mm] was increased (P > 0.05) after anaesthesia induction. Additionally, when cut-off value of DSE was 21.25 mm before anaesthesia, it may be better predicted to DL [sensitivity 80.0% (95% CI: 60.7-91.6%) and specificity 83.8% (95% CI: 73.0-91.0%)]. The upper airway after induction showed the propensity of collapsibility by ultrasound measurements. Compared with other indicators, the DSE assessed by ultrasound might be considered to a valuable predictor of DL.Trial registration: The study was registered in ClinicalTrials.gov on 23th Jan 2019, ChiCTR1900021123.

Gut microbiota of hepatitis B virus-infected patients in the immune-tolerant and immune-active phases and their implications in metabolite changes.

BACKGROUND: The microbes and metabolomics of microbiota dysbiosis in the gut in the different phases of hepatitis B virus (HBV) infection are not fully understood. AIM: To investigate the specific gut microbiota and metabolites of the immune-tolerant (IT) and immune-active (IA) phases of chronic hepatitis B (CHB). METHODS: Clinical fecal samples from healthy individuals and patients in the IT and IA phases of HBV infection were collected. Next, non-target metabolomics, bioinformatics, and 16S rDNA sequencing analyses were performed. RESULTS: A total of 293 different metabolites in 14 phyla, 22 classes, 29 orders, 51 families, and 190 genera were identified. The four phyla of Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria were the most abundant, accounting for 99.72%, 99.79%, and 99.55% in the healthy controls, IT-phase patients, and IA-phase patients, respectively. We further identified 16 genera with different richness in the IT phase and IA phase of HBV infection. Of the 134 named metabolites, 57 were upregulated and 77 were downregulated. A total of 101 different metabolic functions were predicted in this study, with 6 metabolic pathways having the highest enrichments, namely carbohydrate metabolism (14.85%), amino acid metabolism (12.87%), lipid metabolism (11.88%), metabolism of cofactors and vitamins (11.88%), xenobiotic biodegradation (9.9%), and metabolism of terpenoids and polyketides (7.92%). CONCLUSION: These findings provide observational evidence of compositional alterations of the gut microbiome and some related metabolites in patients with IT-phase or IA-phase HBV infection. Further studies should investigate whether microbiota modulation can facilitate the progression of CHB and the cause-effect relationship between the gut microbiota and CHB.

Advantages of a Novel Model for Predicting Hepatic Fibrosis in Chronic Hepatitis B Virus Carriers Compared with APRI and FIB-4 Scores.

Background and Aims: Aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) are widely used to assess liver fibrosis in chronic hepatitis B virus (HBV) infection. Currently, the definition of normal alanine aminotransferase (ALT) is controversial. We aimed to examine the diagnostic value of APRI and FIB-4 in chronic HBV carriers with different upper limits of normal (ULNs) for ALT. Methods: 581 chronic HBV carriers were divided into the following four groups based on different ULNs for ALT: chronic HBV carriers I, II, III, and IV. Furthermore, 106 chronic HBV carriers formed an external validation group. Predictive values of APRI and FIB-4 were elucidated using the area under the curve (AUC). A liver fibrosis-predictive model-GPSA (named for its measure of gamma glutamyl transpeptidase, platelet count, HBsAg and albumin) was developed using multivariate logistic regression analysis. Results: In chronic HBV carriers I, the AUCs of APRI and FIB-4 were 0.680 and 0.609 for significant fibrosis and 0.678 and 0.661 for cirrhosis, respectively. The AUCs of GPSA for significant fibrosis in the training group, internal group, and external validation group were 0.877, 0.837, and 0.871, respectively. The diagnostic value of GPSA differed among chronic HBV carriers I, II, III, and IV, with AUCs for significant fibrosis being 0.857, 0.853, 0.868, and 0.905 and AUCs for cirrhosis being 0.901, 0.905, 0.886, and 0.913, respectively. GPSA showed a higher diagnostic value than APRI and FIB-4 for predicting significant fibrosis in the four groups. Conclusions: The GPSA model allows for accurate diagnosis of liver fibrosis in chronic HBV carriers with different ULN for ALT.

Early Family Intervention in Children with Language Delay: The Effect of Language Level and Communication Ability.

Language development delay refers to the children's oral expression ability or language understanding ability obviously lagging behind the normal development level of children of the same age. The efficacy of early family intervention in children with language delays is promising. The observational study was conducted involving 120 children aged 0∼3 years treated in the pediatric health department of the Third Affiliated Hospital of Zunyi Medical University for language delay. They were assessed for eligibility and recruited. The eligible children were grouped by 1 year, 2 years, and 3 years and were assessed on the Gesell Developmental Schedules and Normal Development of Social Skills from Infant to Junior High School Children (S-M) at the time of initial diagnosis and after the family language intervention. The family language intervention was performed by the parents and lasted for 6 months. All eligible children had a development quotient (DQ) > 86 in motor ability before and after the intervention. All eligible children had a DQ < 86 before the family language intervention in adaptive ability, social ability, and language ability and a DQ > 86 after the intervention. Family language intervention was associated with significant improvement in social life skills in all children, with higher independent living, exercise, operation, interaction, and participation in group activities and self-management after the intervention. Early family intervention yields significant efficacy in children with language delays in Zunyi City by improving the language ability and communication ability of young children, which provides a reference for clinical treatment.

A novel HBsAg-based model for predicting significant liver fibrosis among Chinese patients with immune-tolerant phase chronic hepatitis B: a multicenter retrospective study.

BACKGROUND: Hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) in the immune-tolerant (IT) phase is significantly associated with high risk for hepatocellular carcinoma, suggesting requirement for antiviral therapy, particularly for those with histological liver injury. This study aimed to establish a non-invasive panel to assess significant liver fibrosis in IT chronic hepatitis B. PATIENTS AND METHODS: One hundred and thirteen IT-phase CHB patients were retrospectively recruited and divided into two histopathological groups according to their histological profiles: necroinflammatory score <4 (N <4)/fibrosis score ⩽1 (F0-1), and necroinflammatory score ⩾4 (N ⩾4)/fibrosis score ⩾2 (F2-4). Multivariate analysis was conducted to assess the predictive value of the non-invasive model for significant liver fibrosis. RESULTS: IT-phase CHB patients with N <4/F0-1 had significantly higher HBsAg levels than those with N ⩾4/F2-4. The optimal HBsAg level of log 4.44 IU/mL for significant liver fibrosis (F ⩾2) gave an area under the curve (AUC) of 0.83, sensitivity of 81.1%, specificity of 81.6%, positive predictive value (PPV) of 68.2%, and negative predictive value (NPV) of 89.9%. An IT model with HBsAg and gamma glutamyl transpeptidase (GGT) in combination was established, and it had an AUC of 0.86, sensitivity of 86.5%, specificity of 81.6%, PPV of 69.6, NPV of 92.5, and accuracy of 83.2% to predict F ⩾2 in the IT-phase CHB patients. Notably, the IT model exhibited higher predictive value than the existing aspartate aminotransferase-to-platelet ratio index, Fibrosis-4 score, and GGT to platelet ratio. CONCLUSION: The established IT model combining HBsAg and GGT has good performance in predicting significant liver fibrosis in IT-phase CHB patients.

Effect of liver inflammation on accuracy of FibroScan device in assessing liver fibrosis stage in patients with chronic hepatitis B virus infection.

BACKGROUND: Transient elastography (FibroScan) is a new and non-invasive test, which has been widely recommended by the guidelines of chronic hepatitis B virus (HBV) management for assessing hepatic fibrosis staging. However, some confounders may affect the diagnostic accuracy of the FibroScan device in fibrosis staging. AIM: To evaluate the diagnostic value of the FibroScan device and the effect of hepatic inflammation on the accuracy of FibroScan in assessing the stage of liver fibrosis in patients with HBV infection. METHODS: The data of 416 patients with chronic HBV infection who accepted FibroScan, liver biopsy, clinical, and biological examination were collected from two hospitals retrospectively. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic performance of FibroScan for assessing the stage of liver fibrosis. Any discordance in fibrosis staging by FibroScan and pathological scores was statistically analyzed. Logistic regression and ROC analyses were used to analyze the accuracy of FibroScan in assessing the stage of fibrosis in patients with different degrees of liver inflammation. A non-invasive model was constructed to predict the risk of misdiagnosis of fibrosis stage using FibroScan. RESULTS: In the overall cohort, the optimal diagnostic values of liver stiffness measurement (LSM) using FibroScan for significant fibrosis (≥ F2), severe fibrosis (≥ F3), and cirrhosis (F4) were 7.3 kPa [area under the curve (AUC) = 0.863], 9.7 kPa (AUC = 0.911), and 11.3 kPa (AUC = 0.918), respectively. The rate of misdiagnosis of fibrosis stage using FibroScan was 34.1% (142/416 patients). The group of patients who showed discordance between fibrosis staging using FibroScan and pathological scores had significantly higher alanine aminotransferase and aspartate aminotransferase levels, and a higher proportion of moderate to severe hepatic inflammation, compared with the group of patients who showed concordance in fibrosis staging between the two methods. Liver inflammation activity over 2 (OR = 3.53) was an independent risk factor for misdiagnosis of fibrosis stage using FibroScan. Patients with liver inflammation activity ≥ 2 showed higher LSM values using FibroScan and higher rates of misdiagnosis of fibrosis stage, whereas the diagnostic performance of FibroScan for different fibrosis stages was significantly lower than that in patients with inflammation activity < 2 (all P < 0.05). A non-invasive prediction model was established to assess the risk of misdiagnosis of fibrosis stage using FibroScan, and the AUC was 0.701. CONCLUSION: Liver inflammation was an independent risk factor affecting the diagnostic accuracy of FibroScan for fibrosis stage. A combination of other related non-invasive factors can predict the risk of misdiagnosis of fibrosis staging using FibroScan.

Serum ceruloplasmin can predict liver fibrosis in hepatitis B virus-infected patients.

BACKGROUND: The presence of significant liver fibrosis in hepatitis B virus (HBV)-infected individuals with persistently normal serum alanine aminotransferase (PNALT) levels is a strong indicator for initiating antiviral therapy. Serum ceruloplasmin (CP) is negatively correlated with liver fibrosis in HBV-infected individuals. AIM: To examine the potential value of serum CP and develop a noninvasive index including CP to assess significant fibrosis among HBV-infected individuals with PNALT. METHODS: Two hundred and seventy-five HBV-infected individuals with PNALT were retrospectively evaluated. The association between CP and fibrotic stages was statistically analyzed. A predictive index including CP [Ceruloplasmin hepatitis B virus (CPHBV)] was constructed to predict significant fibrosis and compared to previously reported models. RESULTS: Serum CP had an inverse correlation with liver fibrosis (r = -0.600). Using CP, the areas under the curves (AUCs) to predict significant fibrosis, advanced fibrosis, and cirrhosis were 0.774, 0.812, and 0.853, respectively. The CPHBV model was developed using CP, platelets (PLT), and HBsAg levels to predict significant fibrosis. The AUCs of this model to predict significant fibrosis, advanced fibrosis, and cirrhosis were 0.842, 0.920, and 0.904, respectively. CPHBV was superior to previous models like the aspartate aminotransferase (AST)-to-PLT ratio index, Fibrosis-4 score, gamma-glutamyl transpeptidase-to-PLT ratio, Forn's score, and S-index in predicting significant fibrosis in HBV-infected individuals with PNALT. CONCLUSION: CPHBV could accurately predict liver fibrosis in HBV-infected individuals with PNALT. Therefore, CPHBV can be a valuable tool for antiviral treatment decisions.

Novel predictive models using serum ceruloplasmin levels for hepatic steatosis in patients with chronic hepatitis B infection.

AIMS: To evaluate the significance of serum ceruloplasmin (CP) to diagnosis hepatic steatosis (HS) in Chronic hepatitis B (CHB) patients. METHODS: A total of 360 CHB patients with HS (n = 136) or without HS (n = 224) were included. Relationships between CP and HS degrees were analyzed by Spearman rank correlation. HS-predictive models including CP were constructed using multivariate logistic regression analysis and compared to other HS predicting indexes. RESULTS: Serum CP were significantly higher in CHB patients with HS than in patients without HS (P < 0.001) and were positively correlated with HS degree (r = 0.487, P < 0.001). The area under the receiver-operating characteristic curves (AUCs) of using CP to predict HS (S ≥ 1), moderate and severe steatosis (S ≥ 2) and severe steatosis (S = 3) were 0.758, 0.794 and 0.883, respectively. Multivariate analysis showed that CP, age, high density lipoprotein (HDL) and hemoglobin were independent predictors of HS, and CP, body mass index and HDL were independent predictors of moderate and severe HS. Two novel indexes for predicting HS of CHB patients were generated. The AUC of HSCHB-1 (for S ≥ 1) and HSCHB-2 (for S ≥ 2) were 0.881 and 0.916 in the training group, and 0.865 and 0.841 in the validation group, respectively. HSCHB-1 was superior to HS index (P < 0.001), fatty liver disease index (P = 0.0043) and steatosis index of patients with hepatitis B virus infection (P = 0.0029) in predicting HS in CHB patients. CONCLUSIONS: HS of CHB patients was positively associated with serum CP. HSCHB-1 and HSCHB-2 with inclusion of CP are two novel models for predicting HS in CHB patients.

A hepatic stem cell vaccine is superior to an embryonic stem cell vaccine in the prophylaxis and treatment of murine hepatocarcinoma.

Stem cells and cancer cells express a common subset of antigens called oncofetal antigens. Theoretically, vaccination with stem cells is effective at boosting the preexisting anticancer immune response. Herein we describe the efficacy of two stem cell-based vaccines in the prophylaxis and treatment of subcutaneous hepatic tumors transplanted into mice. C57BL/6j mice were vaccinated weekly with either hepatic stem cells (HSCs) or embryonic stem cells (ESCs) for three weeks, followed by a subcutaneous challenge with Hepa 1-6 cells at one week (group 1) or four weeks (group 2) after vaccination. No tumor formation was observed in HSC-vaccinated mice when challenged within one week after vaccination (group 1), but tumors formed in 10% of mice in the ESC-vaccinated group and in 60% of mice in the unvaccinated group. When the long-term memory response was examined (group 2), only 10% of HSC-vaccinated mice and 20% of ESC-vaccinated mice developed macroscopic hepatocarcinomas compared to 60% of the unvaccinated mice. Besides their function as prophylactic vaccines, administration of either HSC or ESC could be a potential treatment for cancer. In mice with subcutaneous hepatocarcinomas, complete clearance of tumor burden was observed in 80% of mice receiving HSC vaccination, but 40% of ESC-vaccinated mice presented with tumors that did not increase in size over time. These data support that HSC is a superior vaccine candidate for durable antitumor protection in this hepatocarcinoma model.

Pain degree of three different incisions and relationship between incisions local infiltration and nausea-vomiting in patients receiving LC / 中国内镜杂志

Objective To discuss the pain degree of the three different incisions (subxiphoid, navel, right abdomen) and the relationship between incisions local infiltration and nausea-vomiting after Laparoscopic Cholecystectomy (LC). Methods 100 patients (ASA I) scheduled for elective surgery were randomly divided into 5 groups (n = 20): Subxiphoid Group (Group A), Navel Group (Group B), Right Abdomen Group (Group C), All Incisions Group (Group D) and Control Group (Group E). Before the incisions were sutured, patients in Group A, Group B and Group C received incisions local infiltration of Ropivacaine (0.5％, 3 ml) in subxiphoid, navel and right abdomen. Patients in Group D received incisions local infiltration of Ropivacaine (0.5％, 3 ml) in all the three incisions. Patients in Group E received saline with the same volume (3 ml) in all the three incisions. The Visual Analogue Scale (VAS) pain scores were recorded when the patients left the operating room, 2 hours, 4 hours, 8 hours, 16 hours and 24 hours after the operation. The circumstances of nausea-vomiting were also recorded. Results Demographic parameters were similar among groups. The VAS pain scores declined with time gone by. The VAS pain scores:Group A< Group D < Group C < Group B < Group E (F = 7.16, P = 0.000). Comparison between groups: The VAS pain scores in Group A and Group D were significantly less than these in Group C and Group B. The VAS pain scores in Group C and Group B were significantly less than these in Group E. There is a difference among all the groups about the percentages of nausea-vomiting. The percentages of Group B were significantly less than these in the other 4 Groups (χ2 = 10.39, P = 0.034). Conclusions The pain of the subxiphoid incision was the most severe pain in the patients receiving LC. Compared with the other two incisions local infiltration, subxiphoid incision local infiltration proved to be the most effective treatment in reducing the VAS pain scores in patient receiving LC. Navel incision local infiltration proved to be the most effective treatment in reducing the percentages of nausea-vomiting after LC.

Ceruloplasmin, a reliable marker of fibrosis in chronic hepatitis B virus patients with normal or minimally raised alanine aminotransferase.

AIM: To develop a non-invasive model to evaluate significant fibrosis and cirrhosis by investigating the association between serum ceruloplasmin (CP) levels and liver fibrosis in chronic hepatitis B (CHB) patients with normal or minimally raised alanine aminotransferase (ALT). METHODS: Serum samples and liver biopsy were obtained from 193 CHB patients with minimally raised or normal ALT who were randomly divided into a training group (n = 97) and a validation group (n = 96). Liver histology was evaluated by the METAVIR scoring system. Receiver operator characteristic curves were applied to the diagnostic value of CP for measuring liver fibrosis in CHB patients. Spearman rank correlation analyzed the relationship between CP and liver fibrosis. A non-invasive model was set up through multivariate logistic regression analysis. RESULTS: Serum CP levels individualized various fibrosis stages via area under the curve (AUC) values. Multivariate analysis revealed that CP levels were significantly related to liver cirrhosis. Combining CP with serum GGT levels, a CG model was set up to predict significant fibrosis and liver cirrhosis in CHB patients with normal or minimally raised ALT. The AUC, sensitivity, specificity, positive predictive value, and negative predictive value were 0.84, 83.1%, 78.6%, 39.6%, and 96.5% to predict liver cirrhosis, and 0.789, 80.26%, 68.38%, 62.25%, and 84.21% to predict significant fibrosis. This model expressed a higher AUC than FIB-4 (age, ALT, aspartate aminotransferase, platelets) and GP (globulin, platelets) models to predict significant fibrosis (P = 0.019 and 0.022 respectively) and revealed a dramatically greater AUC than FIB-4 (P = 0.033) to predict liver cirrhosis. CONCLUSION: The present study showed that CP was independently and negatively associated with liver fibrosis. Furthermore, we developed a novel promising model (CG), based on routine serum markers, for predicting liver fibrosis in CHB patients with normal or minimally raised ALT.