Machine Learning Model for Predicting Axillary Lymph Node Metastasis in Clinically Node Positive Breast Cancer Based on Peritumoral Ultrasound Radiomics and SHAP Feature Analysis.

OBJECTIVE: This study seeks to construct a machine learning model that merges clinical characteristics with ultrasound radiomic analysis-encompassing both the intratumoral and peritumoral-to predict the status of axillary lymph nodes in patients with early-stage breast cancer. METHODS: The study employed retrospective methods, collecting clinical information, ultrasound data, and postoperative pathological results from 321 breast cancer patients (including 224 in the training group and 97 in the validation group). Through correlation analysis, univariate analysis, and Lasso regression analysis, independent risk factors related to axillary lymph node metastasis in breast cancer were identified from conventional ultrasound and immunohistochemical indicators, and a clinical feature model was constructed. Additionally, features were extracted from ultrasound images of the intratumoral and its 1-5 mm peritumoral to establish a radiomics feature formula. Furthermore, by combining clinical features and ultrasound radiomics features, six machine learning models (Logistic Regression, Decision Tree, Support Vector Machine, Extreme Gradient Boosting, Random Forest, and K-Nearest Neighbors) were compared for diagnostic efficacy, and constructing a joint prediction model based on the optimal ML algorithm. The use of Shapley Additive Explanations (SHAP) enhanced the visualization and interpretability of the model during the diagnostic process. RESULTS: Among the 321 breast cancer patients, 121 had axillary lymph node metastasis, and 200 did not. The clinical feature model had an AUC of 0.779 and 0.777 in the training and validation groups, respectively. Radiomics model analysis showed that the model including the Intratumor +3 mm peritumor area had the best diagnostic performance, with AUCs of 0.847 and 0.844 in the training and validation groups, respectively. The joint prediction model based on the XGBoost algorithm reached AUCs of 0.917 and 0.905 in the training and validation groups, respectively. SHAP analysis indicated that the Rad Score had the highest weight in the prediction model, playing a significant role in predicting axillary lymph node metastasis in breast cancer. CONCLUSION: The predictive model, which integrates clinical features and radiomic characteristics using the XGBoost algorithm, demonstrates significant diagnostic value for axillary lymph node metastasis in breast cancer. This model can provide significant references for preoperative surgical strategy selection and prognosis evaluation for breast cancer patients, helping to reduce postoperative complications and improve long-term survival rates. Additionally, the utilization of SHAP enhancing the global and local interpretability of the model.

Astrocyte-derived SerpinA3N promotes neuroinflammation and epileptic seizures by activating the NF-κB signaling pathway in mice with temporal lobe epilepsy.

Impaired activation and regulation of the extinction of inflammatory cells and molecules in injured neuronal tissues are key factors in the development of epilepsy. SerpinA3N is mainly associated with the acute phase response and inflammatory response. In our current study, transcriptomics analysis, proteomics analysis, and Western blotting showed that the expression level of Serpin clade A member 3N (SerpinA3N) is significantly increased in the hippocampus of mice with kainic acid (KA)-induced temporal lobe epilepsy, and this molecule is mainly expressed in astrocytes. Notably, in vivo studies using gain- and loss-of-function approaches revealed that SerpinA3N in astrocytes promoted the release of proinflammatory factors and aggravated seizures. Mechanistically, RNA sequencing and Western blotting showed that SerpinA3N promoted KA-induced neuroinflammation by activating the NF-κB signaling pathway. In addition, co-immunoprecipitation revealed that SerpinA3N interacts with ryanodine receptor type 2 (RYR2) and promotes RYR2 phosphorylation. Overall, our study reveals a novel SerpinA3N-mediated mechanism in seizure-induced neuroinflammation and provides a new target for developing neuroinflammation-based strategies to reduce seizure-induced brain injury.

GSH-Activatable Aggregation-Induced Emission Cationic Lipid for Efficient Gene Delivery.

The key to gene therapy is the design of biocompatible and efficient delivery systems. In this work, a glutathione (GSH)-activated aggregation-induced-emission (AIE) cationic amphiphilic lipid, termed QM-SS-KK, was prepared for nonviral gene delivery. QM-SS-KK was composed of a hydrophilic biocompatible lysine tripeptide headgroup, a GSH-triggered disulfide linkage, and a hydrophobic AIE fluorophore QM-OH (QM: quinoline-malononitrile) tail. The peptide moiety could not only efficiently compact DNA but also well modulate the dispersion properties of QM-SS-KK, leading to the fluorescence-off state before GSH treatment. The cleavage of disulfide in QM-SS-KK by GSH generated AIE signals in situ with a tracking ability. The liposomes consisted of QM-SS-KK, and 1,2-dioleoylphosphatidylethanolamine (DOPE) (QM-SS-KK/DOPE) delivered plasmid DNAs (pDNAs) into cells with high efficiency. In particular, QM-SS-KK/DOPE had an enhanced transfection efficiency (TE) in the presence of 10% serum, which was two times higher than that of the commercial transfection agent PEI25K. These results highlighted the great potential of peptide and QM-based fluorescence AIE lipids for gene delivery applications.

Benzobis(imidazole) derivatives as STAT3 signal inhibitors with antitumor activity.

Polycyclic aromatic systems have been considered good biological probes, but some may also be good scaffolds for drug development. In this study, a series of benzobis(imidazole) derivatives were identified as STAT3 signal inhibitors, among which compound 24 showed significant inhibition of IL-6 induced JAK/STAT3 signalling pathway activation. Moreover, 24 inhibited cancer cell growth and migration, and induced cell apoptosis as well as cycle arrest in human hepatocellular carcinoma cells (HepG2) and oesophageal carcinoma cells (EC109). Compound 24 also displayed obvious antitumor activity in a mouse HepG2 cell xenograft tumor model without affecting the body weight. These results confirmed that 24 was a potential STAT3 signal inhibitor with certain antitumor activity.

(+)-Isocryptotanshinone derivatives and its simplified analogs as STAT3 signaling pathway inhibitors.

Isocryptotanshinone (ICTS), a natural product with potential signal transducer and activator of transcription-3 (STAT3) signaling pathway inhibitory activity, shows significant inhibitory activity against several tumors. In this study, a series of ICTS derivatives and simplified analogs containing a 1, 4-naphthoquinone core was designed, synthesized, and evaluated. The results demonstrated that most target compounds were potent STAT3 signaling pathway inhibitors based on their mechanism of inhibition of STAT3 phosphorylation. Moreover, based on the obtained data, the structure-activity relationship (SAR) was rationally deduced. Simultaneously, molecular docking of the compound 16r suggested its possible interaction mode with STAT3. To further verify anticancer activity, all target compounds were tested using HCT116, HepG2, MCF-7, A549, and U251 cell lines. Interestingly, compared with different tumor cell lines, the HCT-116 cell line was determined to be the most sensitive. Furthermore, compounds 21e, 16r, 28a, and 16e showed a dose-dependent inhibition of the growth of HCT116 cells. Thus, the SAR of ICTS derivatives and its simplified analogs was determined, and some of them were discovered to be potential anticancer candidates owing to their ability to inhibit the STAT3 signaling pathway.

SIP/CacyBP promotes autophagy by regulating levels of BRUCE/Apollon, which stimulates LC3-I degradation.

BRUCE/Apollon is a membrane-associated inhibitor of apoptosis protein that is essential for viability and has ubiquitin-conjugating activity. On initiation of apoptosis, the ubiquitin ligase Nrdp1/RNF41 promotes proteasomal degradation of BRUCE. Here we demonstrate that BRUCE together with the proteasome activator PA28γ causes proteasomal degradation of LC3-I and thus inhibits autophagy. LC3-I on the phagophore membrane is conjugated to phosphatidylethanolamine to form LC3-II, which is required for the formation of autophagosomes and selective recruitment of substrates. SIP/CacyBP is a ubiquitination-related protein that is highly expressed in neurons and various tumors. Under normal conditions, SIP inhibits the ubiquitination and degradation of BRUCE, probably by blocking the binding of Nrdp1 to BRUCE. On DNA damage by topoisomerase inhibitors, Nrdp1 causes monoubiquitination of SIP and thus promotes apoptosis. However, on starvation, SIP together with Rab8 enhances the translocation of BRUCE into the recycling endosome, formation of autophagosomes, and degradation of BRUCE by optineurin-mediated autophagy. Accordingly, deletion of SIP in cultured cells reduces the autophagic degradation of damaged mitochondria and cytosolic protein aggregates. Thus, by stimulating proteasomal degradation of LC3-I, BRUCE also inhibits autophagy. Conversely, SIP promotes autophagy by blocking BRUCE-dependent degradation of LC3-I and by enhancing autophagosome formation and autophagic destruction of BRUCE. These actions of BRUCE and SIP represent mechanisms that link the regulation of autophagy and apoptosis under different conditions.

Necroptosis and Apoptosis Contribute to Cisplatin and Aminoglycoside Ototoxicity.

Ototoxic side effects of cisplatin and aminoglycosides have been extensively studied, but no therapy is available to date. Sensory hair cells, upon exposure to cisplatin or aminoglycosides, undergo apoptotic and necrotic cell death. Blocking these cell death pathways has therapeutic potential in theory, but incomplete protection and lack of therapeutic targets in the case of necrosis, has hampered the development of clinically applicable drugs. Over the past decade, a novel form of necrosis, termed necroptosis, was established as an alternative cell death pathway. Necroptosis is distinguished from passive necrotic cell death, in that it follows a cellular program, involving the receptor-interacting protein kinase (RIPK) 1 and RIPK3. In this study, we used pharmacological and genetic interventions in the mouse to test the relative contributions of necroptosis and caspase-8-mediated apoptosis toward cisplatin and aminoglycoside ototoxicity. We find that ex vivo, only apoptosis contributes to cisplatin and aminoglycoside ototoxicity, while in vivo, necroptosis as well as apoptosis are involved in both sexes. Inhibition of necroptosis and apoptosis using pharmacological compounds is thus a viable strategy to ameliorate aminoglycoside and cisplatin ototoxicity.SIGNIFICANCE STATEMENT The clinical application of cisplatin and aminoglycosides is limited due to ototoxic side effects. Here, using pharmaceutical and genetic intervention, we present evidence that two types of programmed cell death, apoptosis and necroptosis, contribute to aminoglycoside and cisplatin ototoxicity. Key molecular factors mediating necroptosis are well characterized and druggable, presenting new avenues for pharmaceutical intervention.

Risk Factors and Nomogram for Pancreatic Stone Formation in Chronic Pancreatitis over a Long-Term Course: A Cohort of 2,153 Patients.

BACKGROUND: Pancreatic stones are pathognomonic of chronic pancreatitis (CP). This study aimed to determine the incidence, identify risk factors, and develop a nomogram for pancreatic stones in CP patients. METHODS: Patients with CP admitted to our center from January 2000 to December 2013 were enrolled. Cumulative rates of pancreatic stones after the onset of CP and after the diagnosis of CP were calculated. Patients were randomly assigned, in a 2:1 ratio, to the training and validation cohort. Based on the training cohort, risk factors were identified through Cox proportional hazards regression model, and nomogram was developed. Internal and external validations were performed based on the training and validation cohort, respectively. RESULTS: With a total of 2,153 CP patients, pancreatic stones were detected in 1,626 (75.5%) patients, with a median follow-up of 7.8 years. Age at the onset of CP, body mass index, smoking, diabetes mellitus, pancreatic pseudocyst, biliary stricture, severe acute pancreatitis, and type of pain were identified risk factors for pancreatic stones development. The nomogram with these 8 factors achieved good accuracy. CONCLUSIONS: The nomogram achieved an individualized prediction of pancreatic stones development in CP. It may help the management of pancreatic stones.

Simultaneous determination of thirteen substances related to NAFLD in mouse brain tissue using 3-aminobutyric acid as internal standard by HPLC-FLD.

Disorders of certain branched-chain amino acids may be associated with the occurrence and development of non-alcoholic fatty liver disease. Measurement of related branched-chain amino acid levels could provide a reference for the clinical and scientific research of the non-alcoholic fatty liver disease. An established HPLC-FLD method was used to quantify aspartic acid, glutamate, glutamine, glycine, taurine, tyrosine, 4-amino butanoic acid, tryptophan, methionine, valine, phenylalanine, isoleucine and leucine in mouse brain tissue. Brain tissue samples mixed with internal standard (3-aminobutyric acid) were processed, then derivatized with 2-O-phthaldialdehyde, and finally separated on an ODS2 column through gradient elution at a flow rate of 1.0 ml·min-1 . The excitation and emission wavelengths were set at 340 and 455 nm, respectively. The mobile phase A was 100% methanol and the mobile phase B consisted of 30 mmol·L-1 sodium acetate (pH 6.8). The injection volume was 20 µl and the single run time was 45 min. Several parameters, accuracy, precision, and stability, were verified and the results showed the established method had good sensitivity and resolution for all of the 13 compounds and internal standard in mouse brain.

Risk Factors and Nomogram for Common Bile Duct Stricture in Chronic Pancreatitis: A Cohort of 2153 Patients.

GOALS: To identify the risk factors and develop nomograms for common bile duct (CBD) stricture in chronic pancreatitis (CP) patients. BACKGROUND: CBD stricture is a common complication in CP and has a variable clinical presentation ranging from asymptomatic to overt jaundice and cholangitis. STUDY: Patients with CP admitted to Changhai Hospital (Shanghai, China) from January 2000 to December 2013 were enrolled. Cumulative rates of CBD stricture after onset and diagnosis of CP were calculated. Patients were randomly assigned, in a 2:1 ratio, to the training and validation cohort. On the basis of the training cohort, risk factors for CBD stricture and symptomatic CBD stricture were identified through Cox proportional hazards regression model, and nomograms was developed, respectively. Internal and external validations were performed based on the training and validation cohort, respectively. RESULTS: With a total of 2153 patients, the median duration of follow-up was 7.0 years. CBD strictures were detected in 340 (15.8%) patients, whereas 159 of them were symptomatic. Male gender, age at onset of CP, smoking, body mass index, and morphology of main pancreatic duct were identified risk factors for CBD stricture development. Age at onset of CP, body mass index, and type of pain were identified risk factors for symptomatic CBD stricture development. Both nomograms achieved good concordance indexes with well-fitted calibration curves. CONCLUSIONS: The nomogram achieved an individualized prediction of symptomatic CBD stricture development in CP patients. It may help the early diagnosis and intervention of symptomatic CBD stricture and reduce the rates of severe adverse events.

Autoantibody detection is not recommended for chronic pancreatitis: a cross-sectional Study of 557 patients.

BACKGROUND: Autoimmune factor was regarded as one of the risk factors in the pathogenesis of chronic pancreatitis (CP), especially for autoimmune pancreatitis (AIP). However, whether autoimmune factor plays a role in non-AIP CP or not was unknown. METHODS: Hospitalized patients with non-AIP CP from January 2010 to October 2016 were detected for 22 autoantibodies at the time of hospital admission. Autoantibodies with frequency > 0.5% were enrolled to calculate the frequency in historial healthy controls through literature search in PubMed. Differentially expressed autoantibodies were determined between patients and historial healthy controls, and related factors were identified by multivariate logistic regression analysis. RESULTS: In a total of 557 patients, 113 cases were detected with 19 kinds of positive autoantibodies, among them anti-ß2-glycoprotein I (ß2-GPI) antibody was most frequent (9.16%). Compared with historial healthy controls, the frequencies of serum ß2-GPI and anti SS-B antibody in patients were significantly higher, while frequencies of anti-smooth muscle antibody and anticardiolipin antibody were significantly lower (all P < 0.05). Multivariate logistic regression analysis result showed that diabetes mellitus (OR = 2.515) and common bile duct stricture (OR = 2.844) were the risk factors of positive ß2-GPI antibody in patients while diabetes mellitus in first-/second-/third-degree relatives (OR = 0.266) was the protective factor. There were no related factors for other three differentially expressed autoantibodies. CONCLUSIONS: Four autoantibodies were expressed differentially between patients with non-AIP CP and historial healthy controls. Due to limited significance for diagnosis and treatment of chronic pancreatitis, autoantibodies detection is not recommended conventionally unless suspected of AIP.

The Accuracy and Feasibility of Robotic Assisted Lead Implantation in Nonhuman Primates.

OBJECTIVES: Deep brain stimulation (DBS) and stereo-electroencephalography (SEEG) electrode implantation are the most important and frequent manipulations in nonhuman primates (NHP) neuromodulation research. However, traditional methods tend to be arduous and inaccurate. MATERIALS AND METHODS: Twelve adult male rhesus monkeys were selected for the study, with six subthalamic nucleus (STN) DBS, six anterior nucleus of the thalamus (ANT) DBS and six hippocampus-SEEG (Hippo-SEEG) electrodes implantation. Mean Euclidean errors of entrance and the target were calculated by postoperative image fusion, and the correlation between entrance and target error, as well as the differences among the various manipulations, were analyzed. The accuracy of target was further confirmed by gross anatomy examination. Moreover, the time consumption was recorded. RESULTS: The mean (±SD) Euclidean errors of the target point and entry point of the three manipulations were STN-DBS: 1.05 ± 0.54 mm and 0.52 ± 0.17 mm; ANT-DBS: 1.12 ± 0.74 mm and 0.58 ± 0.24 mm; and Hippo-SEEG: 2.68 ± 1.03 mm and 1.47 ± 0.63 mm. Significant differences were observed in both target and entry point errors between the DBS and Hippo-SEEG groups, with superior accuracy in the DBS group. The entrance errors had a significantly positive correlation with the target errors in the STN-DBS and Hippo-SEEG groups. Moreover, the time consumption in robotic surgery was much shorter than that in the traditional method, without any severe complications. CONCLUSION: The application of robot-assisted lead implantation in NHP neuromodulation research is feasible, accurate, safe, and efficient, and can prospectively be beneficial to neurological studies.

Risk factor for steatorrhea in pediatric chronic pancreatitis patients.

BACKGROUND: Pediatric patients always suffer from chronic pancreatitis (CP), especially those with steatorrhea. This study aimed to identify the incidence of and risk factors for steatorrhea in pediatric CP. To our best knowledge, there is no pediatric study to document the natural history of steatorrhea in CP. METHODS: CP patients admitted to our center from January 2000 to December 2013 were enrolled. Patients were assigned to the pediatric (< 18 years old) and adult group according to their age at onset of CP. Cumulative rates of steatorrhea in both groups were calculated. Risk factors for both groups were identified, respectively. RESULTS: The median follow-up duration for the whole cohort was 7.6 years. In a total of 2153 patients, 13.5% of them were pediatrics. The mean age at the onset and the diagnosis of CP in pediatrics were 11.622 and 19.727, respectively. Steatorrhea was detected in 46 patients (46/291, 15.8%) in the pediatric group and in 447 patients (447/1862, 24.0%) in the adult group. Age at the onset of CP (hazard ratio [HR], 1.121), diabetes mellitus (DM, HR, 51.140), and severe acute pancreatitis (SAP, HR, 13.946) was identified risk factor for steatorrhea in the pediatric group. CONCLUSIONS: Age at the onset of CP, DM and SAP were identified risk factors for the development of steatorrhea in pediatric CP patients. The high-risk populations were suggested to be followed up closely. They may benefit from a full adequate pancreatic exocrine replacement therapy.

Simultaneous determination of nine analytes related to the pathogenesis of diabetic encephalopathy in diabetic rat cortex and hippocampus by HPLC-FLD.

The determination of amino acids and monoamine with actions like neurotransmitters or modulators has become increasingly important for studying the relationship between the dysfunction of neurotransmitters and the pathogenesis of diabetic encephalopathy. Here, a high-performance liquid chromatography with fluorescence detection method was developed to simultaneously determine nine monoamines and amino acids including three excitatory neurotransmitters (aspartate, glutamate, and serotonin), four inhibitory neurotransmitters (glycine, γ-aminobutyric acid, taurine, dopamine), a precursor of 5-HT (tryptophan) and methionine using homoserine as the internal standard. The separation was performed on a BDS column with methanol-buffer solution of 35 mmol/L sodium acetate and 5 mmol/L citric acid (pH 6.0) using a simple gradient elution. Several parameters including specificity, precision, and recovery were validated after optimization of the analytical conditions. The developed method was successfully applied to determine the cortex and the hippocampus samples from Sprague-Dawley rats. Our results showed that various neurotransmitters involved in diabetes mellitus may tend to be differentially modulated and present a different alteration tendency at different time course, which might be associated with the duration of diabetes mellitus.

[Effect of different initial processing methods on quality of gardenia].

To investigate the effect of different initial processing methods on the quality of Gardenia and determine the best cooking time in gardenia processing through the determination of index components content. The contents of geniposide, crocetin Ⅰ and total iridoid glycosides in Gardenia were determined before storage, six months after storage and one year after storage. During storage, the contents of geniposide, crocetin Ⅰ and total iridoid glycosides in directly dried Gardenia were 1.68%, 0.45% and 6.45% respectively. The contents of geniposide, crocetin Ⅰ and total iridoid glycosides in Gardenia with different steaming time were 1.34%-0.5%, 0.28%-0.06% and 6.09%-1.59% respectively. The contents of geniposide, crocetin Ⅰ and total iridoid glycosides in Gardenia with different boiling time (adding alum)were 1.42%-0.41%, 0.35%-0.07% and 6.40%-1.65% respectively. The direct drying of Gardenia samples could not achieve the function of killing enzyme and protecting glycosides. The enzymes from degradation of the index components were basically destroyed after steaming time of 13 min or boiling (adding alum) time of 8 min, achieving the function of killing enzyme and protecting glycosides.

Extracorporeal shock wave lithotripsy is safe and effective for pediatric patients with chronic pancreatitis.

Background and aims Pancreatic extracorporeal shock wave lithotripsy (P-ESWL) is recommended as the first-line treatment for pancreatic stones. However, how well P-ESWL performs in pediatric patients remains unclear. We aimed to evaluate the safety and efficacy of P-ESWL for pediatric patients with chronic pancreatitis. Methods This prospective observational study was conducted in patients with painful chronic pancreatitis who underwent P-ESWL. Patients aged under 18 years were included in the pediatric group; patients aged over 18 years who underwent P-ESWL in the same period were assigned to the control group. For investigation of long-term follow-up, the pediatric group were matched with patients from the control group in a 1:1 ratio. The primary outcomes were P-ESWL complications and pain relief. The secondary outcomes included: stone clearance, physical and mental health, quality of life score, and growth and developmental state. Results From March 2011 to March 2015, P-ESWL was performed in 1135 patients (72 in the pediatric group, 1063 in the control group). No significant differences were observed in the occurrence of P-ESWL complications between the two groups (11.1 % vs. 12.8 %; P = 0.68). Among the 67 pediatric patients (93.1 %) who underwent follow-up for 3.0 years (range 1.3 - 5.2), complete pain relief was achieved in 52 patients (52 /67; 77.6 %); this value was not significantly different from that of the matched controls (55 /69; 79.7 %; P = 0.94). Conclusions P-ESWL is safe and effective for pediatric patients with chronic pancreatitis. It can promote significant pain relief and stone clearance, and can benefit growth and development.

Risk factors and nomogram for pancreatic pseudocysts in chronic pancreatitis: A cohort of 1998 patients.

BACKGROUND AND AIM: Pancreatic pseudocyst is a common complication of chronic pancreatitis. The identification of risk factors and development of a nomogram for pancreatic pseudocysts in chronic pancreatitis patients may contribute to the early diagnosis and intervention of pancreatic pseudocysts. METHODS: Patients with chronic pancreatitis admitted to our center from January 2000 to December 2013 were enrolled. Cumulative rates of pancreatic pseudocysts after the onset of chronic pancreatitis and after the diagnosis of chronic pancreatitis were calculated. Patients were randomly assigned, in a 2:1 ratio, to the training and validation cohort. Based on the training cohort, risk factors were identified through Cox proportional hazards regression model, and nomogram was developed. Internal and external validations were performed based on the training and validation cohort, respectively. RESULTS: With a total of 1998 patients, pancreatic pseudocysts were detected in 228 (11.41%) patients. Age at the onset of chronic pancreatitis, smoking, and severe acute pancreatitis were identified risk factors for pancreatic pseudocysts development while steatorrhea and pancreatic stones were protective factors. Incorporating these five factors, the nomogram achieved good concordance indexes of 0.735 and 0.628 in the training and validation cohorts, respectively, with well-fitted calibration curves. CONCLUSION: The nomogram achieved an individualized prediction of pancreatic pseudocysts development in chronic pancreatitis. It may help the early diagnosis and management of pancreatic pseudocysts.

Acoustic Radiation Force Impulse (ARFI) Elastography and Serological Markers in Assessment of Liver Fibrosis and Free Portal Pressure in Patients with Hepatitis B.

BACKGROUND The aim of this study was to investigate the feasibility of using acoustic radiation force impulse (ARFI) elastography, AST-to-platelet ratio index (APRI), and FIB-4 in assessing liver fibrosis and free portal pressure in patients with hepatitis B. MATERIAL AND METHODS We enrolled 126 patients with hepatitis B who underwent liver surgery at the General Surgery Department of the First Affiliated Hospital of Shihezi University Medical School from February 2013 to August 2015. Preoperatively, shear wave velocity (SWV) of the liver was measured with the Siemens S2000 ultrasound system to reflect liver stiffness. Serological markers were collected and fibrosis indices APRI and FIB-4 were calculated. Intraoperatively, liver tissues were harvested and free portal pressure (FPP) was measured. Postoperatively, fibrosis of liver tissues was pathologically staged. RESULTS The results of SWV, APRI, FIB-4, and FPP were all correlated with the degree of liver fibrosis (Spearman correlation coefficients: r=0.777, P<0.001; r=0.526, P<0.001; r=0.471, P<0.001; p<0.000; r=0.675, p<0.000). Receiver operating characteristic curve (ROC) analysis showed that the areas under the curve (AUC) of ARFI, APRI, and FIB-4 in diagnosing liver fibrosis were 0.830, 0.768, and 0.717, respectively, for stage F≥1; 0.861, 0.773, and 0.754, respectively, for stage F≥2; 0.941, 0.793, and 0.779, respectively, for stage F≥3; and 0.945, 0.783, and 0.754, respectively, for stage F=4. SWV, APRI, and FIB-4 were all correlated with FPP (Pearson correlation coefficients: 0.387, P<0.001; 0.446, P<0.001; 0.419, P<0.001). CONCLUSIONS ARFI, APRI, and FIB-4 can assess liver fibrosis in patients with hepatitis B when assessing the portal venous pressure. The difference in diagnostic efficacy between the 3 was not significant.

Usefulness of Contrast-Enhanced Ultrasonography for Predicting Esophageal Varices in Patients with Hepatitis B Virus (HBV)-Related Cirrhosis.

BACKGROUND The aim of this study was to investigate the usefulness of contrast-enhanced ultrasonography (CEUS) in predicting of esophageal varices (EV) and assessing high-risk EV in patients with hepatitis B virus (HBV)-related cirrhosis. MATERIAL AND METHODS Patients with HBV-related cirrhosis who had undergone endoscopy were prospectively recruited. Hepatic dynamic CEUS was performed. Regions of interest (ROI) were drawn on the hepatic artery, hepatic vein, portal vein, and liver parenchyma to measure the corresponding features, such as arrival times. Spearman's correlation analysis was used to determine the relations between several dynamic CEUS features and the degree of EV. Receiver operating characteristics (ROC) curves were constructed to investigate the diagnostic performance of CEUS in assessing the presence of EV and high-risk EV. RESULTS Fifty-eight patients (44 men; mean age 51.3 years) were included in this study. Of these, 18 (31.0%), 12 (20.7%), 11 (19.0%), and 17 (29.3%) of patients had grade 0, 1, 2, and 3 EV, respectively. Grade 2 and grade 3 EV were considered high-risk EV. Among the CEUS features, the area under the ROC curves of intrahepatic transit time (HV-HA, i.e., the difference between hepatic vein arrival time and hepatic artery arrival time) both for assessment of the presence of EV and high-risk EV (0.883 and 0.915, respectively) were larger than the other indices. HV-HA was negatively correlated with the grade of EV. An HV-HA of under 8.2 s indicated the presence of EV and under 7 s indicated high-risk EV. CONCLUSIONS Dynamic CEUS imaging is useful in assessing the presence of EV and high-risk EV in patients with HBV-related cirrhosis.

miR-142-3p acts as an essential modulator of neutrophil development in zebrafish.

Neutrophils play critical roles in vertebrate innate immune responses. As an emerging regulator in normal myelopoiesis, the precise roles of microRNA in the development of neutrophils have yet to be clarified. Using zinc-finger nucleases, we have successfully generated heritable mutations in miR-142a and miR-142b and showed that hematopoietic-specific miR-142-3p is completely deleted in miR-142 double mutant zebrafish. The lack of miR-142-3p resulted in aberrant reduction and hypermaturation of neutrophils in definitive myelopoiesis, as well as impaired inflammatory migration of neutrophils in the fetal stage. Furthermore, the adult myelopoiesis in the miR-142-3p-deficient zebrafish was also affected, producing irregular hypermature neutrophils with increased cell size and a decreased nucleocytoplasmic ratio. Additionally, miR-142-3p-deficient zebrafish are expected to develop a chronic failure of myelopoiesis with age. Transcriptome analysis showed an aberrant activation of the interferon γ (IFN-γ) signaling pathway in myelomonocytes after miR-142-3p deletion. We found that the reduced number and hypermaturation of neutrophils caused by loss of miR-142-3p was mainly mediated by the abnormally activated IFN-γ signaling, especially the upregulation of stat1a and irf1b. Taken together, we uncovered a novel role of miR-142-3p in maintaining normal neutrophil development and maturation.