A proposed mechanism by which Qishen Yiqi dropping pill improves cardiac energy metabolism in rats with heart failure based on metabolomics and network pharmacology / 药学学报

"Omics" and bioinformatics have brought new ideas to the study of traditional Chinese medicine. This study used metabonomics and network pharmacology to investigate the pharmacodynamic basis and regulation of Qishen Yiqi dropping pill (QDP) improving cardiac energy metabolism in rats with heart failure (HF). 1H NMR metabonomics analysis showed that eight metabolites, including carnitine, glutamine, creatine, proline, homocitrulline, lactic acid, taurine and alanine appeared significant callback after QDP treatment for HF. The results indicate that QDP regulates the metabolism of carbohydrate, lipid, ATP and protein. The animal experiment was conducted in accordance with the regulations of the Ethics Committee for Experimental Animal Management and Animal Welfare of Institute of Materia Medica, Chinese Academy of Medical Sciences. A "drug-component-target-disease" network was established using network pharmacology, and the "component-target" sub-network related to the above energy metabolism processes was extracted by combining metabonomics results. Results revealed 79 chemical compounds and 47 potential targets of QDP involved in the regulation of energy metabolism, and identified key chemical components including ursolic acid, notoginsenoside G, ginsenoside-Rh1, and core targets such as INS, PPARG, and AKT1. The results also demonstrated the complex multi-target and multi-component relationship between QDP and HF from the perspective of energy metabolism. The molecular docking technique verified a strong interaction between some targets and chemical compounds, with affinities less than -5 kcal·mol-1. The results of this study provide useful information for the clinical application, development, and utilization of QDP.

Diagnostic value of platelet parameters, fibrinogen and D-dimer in different Traditional Chinese Medicine syndromes of deep venous thrombosis / 国际中医中药杂志

Objective:To investigate the expression levels and diagnostic value of platelet parameters, fibrinogen and D-dimer in different Traditional Chinese Medicine (TCM) syndromes of deep venous thrombosis (DVT).Methods:From June 2015 to June 2019, a total of 500 DVT patients were enrolled and collected by two attending TCM doctors and classified according to syndromes differentiation. The differences of platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), platelet crit (PCT), platelet larger cell ratio (P-LCR), fibrinogen (FIB) and D-dimer were detected and compared.Results:According to TCM syndromes differentiation, 500 patients were divided into three groups, including 286 cases (57.2%) of downward flowing of damp-heat group, 132 cases (26.4%) of blood stasis and heavy damp group, and 82 cases (16.4%) of spleen-kidney-yang deficiency group. The levels of MPV, PDW, P-LCR, FIB and D-dimer among the groups were statistically significant difference ( P<0.05 or P<0.01). The MPV level was significantly higher and D-dimer level was significantly lower in blood stasis and heavy damp group than in the downward flowing of damp-heat group ( P<0.05). The levels of MPV, PDW and P-LCR in spleen-kidney-yang deficiency group were significantly higher than those in downward flowing of damp-heat group and blood stasis and heavy damp group ( P<0.05 or P<0.01). The levels of FIB and D-dimer were significantly lower than those in the downward flowing of damp-heat group and blood stasis and heavy damp group ( P<0.05 or P<0.01). The FIB (AUC=0.593) and D-Dimer (AUC=0.673) were statistically significant in the differential diagnosis of DVT between blood stasis and heavy damp group and spleen-kidney-yang deficiency group ( P<0.01). The MPV (AUC=0.601 5), PDW (AUC=0.615 4), P-LCR (AUC=0.606 1), FIB (AUC=0.616 4) and D-Dimer (AUC=0.721 8) were statistically significant in the differential diagnosis of DVT between downward flowing of damp-heat group and spleen-kidney-yang deficiency group ( P<0.01). Conclusion:The MPV, PDW, P-LCR, FIB and D-dimer have a certain correlation with DVT TCM syndrome types, and also have a certain reference value for its differential diagnosis, which can be used as an effective supplement to the objective indicators of Micro syndrome differentiation of traditional Chinese medicine.

The effect of metformin on lipid disorders as measured by nuclear magnetic metabolomics and metabolic flux analysis / 药学学报

Studies have found that metformin is not only the preferred drug for lowering blood sugar, but also shows lipid-lowering and weight-loss effects. The purpose of this study was to use a hyperlipidemia hamster model to investigate the lipid-lowering effect of metformin and its effect on important metabolic pathways in lipid metabolism disorders. Fifty golden hamsters were divided into a control group, a model group, metformin high- and low-dose groups, and a simvastatin group. A high-fat diet was fed for 1 week to create the model, and then drug was administered for 11 weeks with the high-fat diet. Serum was taken for measurement of blood lipid and blood glucose at 2, 6, and 9 weeks after administration, and at weeks 3, 5, and 9 feces and urine were collected for 1H NMR metabolomics tests. After 11 weeks of intravenous injection of [U-13C6] glucose, serum was collected for a 13C NMR metabolic flux test. The results showed that the administration of metformin can significantly reduce blood lipids and glucose levels and can significantly affect metabolic pathways such as sugar metabolism, lipid metabolism, ketone metabolism, amino acid metabolism, and intestinal flora metabolism. The results of the metabolic flux analysis showed that the high-fat diet reduced the metabolism of tricarboxylic acids by 37.48%. After administration of low and high doses of metformin the metabolism of tricarboxylic acid increased by 98.14% and 143.10%, respectively. After administration of simvastatin tricarboxylic acid metabolism increased by 33.18%. The results indicate that metformin has a significant effect on promoting energy metabolism. This study used a combination of metabolomics and metabolic flow to explore the effect of metformin on lipid metabolism disorders and quantifies changes in the key pathway of energy metabolism-the tricarboxylic acid cycle. This study provides useful information for the study of the efficacy and mechanism of metformin, as well as a practical technical method for the screening of lipid-lowering drugs based on a hamster model.

Application of polymeric porcelain color-masking cast posts in the aesthetic repair of anterior teeth: a case report / 华西口腔医学杂志

Many patients with large-area tooth defect need cast post-core crown restoration. However, the color defect of the cast post-core will affect the final restorative result, especially that of the anterior teeth. A new technology of color masking by applying CERAMAGE polymeric porcelain to the cast metal post-core surface improves the color of a full-ceramic restoration of anterior teeth and may provide a new alternative for the aesthetic repair of anterior teeth with a large area of defective tooth.

Alterations in the transmural gradient of ventricular repolarization with different pacing sites in normal and heart failure canines / 生理学报

Alterations of the transmural gradient of repolarization may contribute to the increase of transmural dispersion of repolarization and ventricular arrhythmias. The transmural gradient of repolarization may play an important role in sudden death associated with left ventricular epicardial pacing. To investigate the changes of transmural gradient dispersion of ventricular repolarization with different pacing sites in heart failure (HF) canines, 8 mongrel dogs were randomized into healthy group and HF group (n = 4). We mapped the monophasic action potential duration (MAPD) in the subendocardial, subepicardial and mid-myocardial layers of the left ventricle (LV) in canines of healthy and HF groups during right atrium (RA) pacing, right ventricular apical endocardial (RV) pacing, left ventricular lateral epicardial (LV) pacing and biventricular (Biv) pacing respectively. The results showed that in the healthy group, the MAPDs were significantly different among the three layers during RA pacing (all P 0.05). In the HF group, the MAPDs in all three layers were prolonged compared with those in the same locations in the healthy group (all P 0.05). By MAP recording with our new mapping electrode, we found a transmural MAPD gradient among the three layers of the LV during RA pacing and the gradient between the subendocardial and subepicardial layers vanished during RV, LV or Biv pacing in healthy dogs. In contrast, there was no transmural MAPD gradient during RA, RV, LV or Biv pacing in HF dogs. These results are helpful to understand the mechanism of ventricular arrhythmias in patients with HF.

Uprighting a mesially tilted mandibular second molar by using a dental implant as anchorage: a case report / 华西口腔医学杂志

After tooth has been removed for a long time, adjacent teeth may tilt to occupy the edentulous space, leading to a break in the occlusal 3D equilibrium and a lack of restorative space. This case report presents a mandibular second molar uprighting with anchorage from a dental implant.

Semiquantitative parameters of 18F-FDG PET/CT, gene mutation states of epidermal growth factor receptor and anaplastic lymphoma kinase in prognosis evaluation of patients with lung adenocarcinoma / 北京大学学报(医学版)

OBJECTIVE@#To explore the valuable predictors for evaluating progression-free survival (PFS) in patients with lung adenocarcinoma, we analyzed the potential roles of standardized uptake value (SUV)-derived parameters from 18F-FDG PET/CT, combining with the gene mutation states of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), and other clinical characteristics.@*METHODS@#Data of 84 lung adenocarcinoma patients pre-treated, who underwent 18F-FDG PET/CT scans, EGFR gene mutations test, ALK rearrangement assay and other relative tests, were retrospectively collected. Then a series of clinical parameters including EGFR/ALK mutation status and SUV-derived features [maximum standardized uptake value (SUVmax), average of standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)] were evaluated. Best possible cutoff points for all measuring parameters were calculated using receiver operating characteristic curve (ROC) analysis. Survival analysis was performed using Cox proportional hazards model to determine the prognostic markers for progression-free survival (PFS). Survival curves were obtained through Log-rank test and Kaplan-Meier curve.@*RESULTS@#The median follow-up period was 31 months (24 to 58 months). It was found that SUVmax (≥3.01), SUVmean (≥2.25), MTV (≥25.41 cm3), and TLG (≥55.02) of the primary tumors were significantly associated with PFS in univariate Cox proportional hazards regression. Then regardless of age, gender, co-morbidity, EGFR/ALK mutation status, and treatment program, TLG (≥ 55.02, HR=4.965, 95%CI: 1.360-18.133), TNM stage (Ⅲ/Ⅳ, HR=7.811, 95%CI: 2.977-20.489), pro-gastrin releasing peptide (proGRP) (≥45.65 ng/L, HR=4.070, 95%CI: 1.442-11.487), tissue polypeptide antigen (TPA) (≥68.20 U/L, HR=6.996, 95%CI: 1.458-33.574), alkaline phosphatase (ALP) (≥82.50 IU/L, HR=4.160, 95%CI: 1.416-12.219) and ratio of activated partial thromboplastin time (aPTTR) (≥1.16: HR=4.58, 95%CI: 1.913-10.946) showed the independently relevant to PFS through multivariate Cox proportional hazards analysis. The EGFR mutant (P=0.343) and ALK rearrangement (P=0.608) were not significant either in survival analysis.@*CONCLUSION@#High SUV-derived parameters (SUVmax, SUVmean, MTV and TLG) might provide prognostic value to some extent. Especially, TLG, and other clinical features [TNM stage, proGRP, TPA, ALP, and aPTTR] could be independently and significantly associated with PFS of lung adenocarcinoma patients. However, EGFR/ALK gene status could not be effectively relevant to PFS in lung adenocarcinoma patients.

The omics perspective on heart failure research / 药学学报

Heart failure is the end stage of many cardiovascular diseases. It seriously affects the safety and quality of life of nearly 40 million people worldwide. At present, the clinical and pathophysiological characteristics of some types of heart failure are unknown, and there is no effective diagnosis and treatment. In recent years, genomics, transcriptomics, epigenomics, proteomics, metabolomics and other omics technologies have been widely used in disease research, providing new opportunities for the prevention, diagnosis and treatment of diseases. These strategies have also brought hope for the reduction in heart failure mortality. Based on the current status of clinical treatment of heart failure, this article reviews the roles and potential applications of these various omics technologies and their opportunities in the study of the pathogenesis of heart failure, clinical diagnosis and treatment, and related drug pharmacodynamics and mechanism of action.

A novel phenotype with splicing mutation identified in a Chinese family with desminopathy / 中华医学杂志(英文版)

BACKGROUND@#Desminopathy, a hereditary myofibrillar myopathy, mainly results from the desmin gene (DES) mutations. Desminopathy involves various phenotypes, mainly including different cardiomyopathies, skeletal myopathy, and arrhythmia. Combined with genotype, it helps us precisely diagnose and treat for desminopathy.@*METHODS@#Sanger sequencing was used to characterize DES variation, and then a minigene assay was used to verify the effect of splice-site mutation on pre-mRNA splicing. Phenotypes were analyzed based on clinical characteristics associated with desminopathy.@*RESULTS@#A splicing mutation (c.735+1G>T) in DES was detected in the proband. A minigene assay revealed skipping of the whole exon 3 and transcription of abnormal pre-mRNA lacking 32 codons. Another affected family member who carried the identical mutation, was identified with a novel phenotype of desminopathy, non-compaction of ventricular myocardium. There were 2 different phenotypes varied in cardiomyopathy and skeletal myopathy among the 2 patients, but no significant correlation between genotype and phenotype was identified.@*CONCLUSIONS@#We reported a novel phenotype with a splicing mutation in DES, enlarging the spectrum of phenotype in desminopathy. Molecular studies of desminopathy should promote our understanding of its pathogenesis and provide a precise molecular diagnosis of this disorder, facilitating clinical prevention and treatment at an early stage.

Expert consensus on biomechanical research of dental implant / 华西口腔医学杂志

Current biomechanical research of dental implants focuses on the mechanical damage and enhancement mechanism of the implant-abutment interface as well as how to obtain better mechanical strength and longer fatigue life of dental implants. The mechanical properties of implants can be comprehensively evaluated by strain gauge analysis, photo elastic stress analysis, digital image correlation, finite element analysis, implant bone bonding strength test, and measurement of mechanical properties. Finite element analysis is the most common method for evaluating stress distribution in dental implants, and static pressure and fatigue tests are commonly used in mechanical strength test. This article reviews biomechanical research methods and evaluation indices of dental implants. Results provide methodology guidelines in the field of biomechanics by introducing principles, ranges of application, advantages, and limitations, thereby benefitting researchers in selecting suitable methods. The influencing factors of the experimental results are presented and discussed to provide implant design ideas for researchers.

Spinal Interleukin-10/β-Endorphin Pathway Suppresses Neuropathic Pain in Infant Rats / 中山大学学报(医学科学版)

@#【Objective】To unmask the mechanisms underlying the suppression of infant neuropathic pain after peripheral nerve injury.【Methods】Rats were subjected to spared nerve injury(SNI)at postnatal 10 d or 33 d. Mechanical paw withdrawal thresholds as well as spinal interleukin-10(IL-10)and the β-endorphin precursor gene proopiomelanocortin(POMC)mRNA expression were detected 7 d after surgery. The IL-10 or β-endorphin neutralizing antibody was intrathecally injected for 3 d(the 7 th-9 th day after surgery)and mechanical paw withdrawal thresholds were tested 1 h after each injection. Spinal IL-10 mRNA and POMC mRNA were detected by RT-qPCR.【Results】In contrast to adult rats,infant rats subjected to SNI displayed no mechanical allodynia but an increase in spinal cord IL-10 and POMC mRNA expression. Intrathecal administration of the IL-10 antibody and β-endorphin antibody evoked neuropathic painlike behaviors in infant rats. SNI-induced POMC mRNA increase was blocked by the pretreatment with intrathecal the IL-10 antibody,while the increased IL-10 mRNA expression was not affected by the β-endorphin antibody pretreatment.【Conclusions】The suppression of neuropathic pain in infant rats may be mediated by activation of spinal IL-10/β-endorphin pathway.

Association of learning and living style with dyslexia in school-aged children / 中国学校卫生

Objective@#To investigate the association between the learning and living style with developmental dyslexia in school-aged children.@*Methods@#Using stratified cluster sampling, a total of 11 668 schoolaged children (grade 2 to 6) in the cities of Wuhan, Hangzhou and Jining were selected to participate in this programme from April 2017 to April 2018. The investigation tools combined the questionnaire on associated factors for reading ability, Dyslexia Checklist for Chinese Children and Pupil Rating Scale Revised Screening for Learning.@*Results@#Pupils with more than 20 minutes of exercise each day (OR=0.43-0.64) and at least 1-2 times per week (OR=0.34-0.48) had a lower risk of dyslexia. The association was observed between going to the library more than 1-2 times per semester (OR=0.41-0.62) and the decrease risk of dyslexia. Lacking active learning (OR=7.76, 95%CI=4.71-12.78), scheduled reading time (OR=2.55, 95%CI=2.01-3.23) and extracurricular training classes (OR=1.62, 95%CI=1.27-2.07) were positively associated with dyslexia. There was no significant difference in screen time duration between dyslexic and non-dyslexic children. Using electronic devices for learning was associated with decreased risk of dyslexia (OR=0.47, 95%CI=0.33-0.67), while playing video games was correlated with increased risk of dyslexia (OR=1.67, 95%CI=1.16-2.41).@*Conclusion@#Physical exercise, good study habits and using the electronic products in a proper way could reduce the risk of dyslexia to a certain extent. Parents and teachers should guide the school-aged children to develop a good learning and living style.

Quality of life and determinants among children with dyslexia in China / 中国学校卫生

Objective@#To examine the Quality of life among school-aged children with dyslexia in target city and to provide scientific evidence for improving the quality of life of children with dyslexia.@*Methods@#By using cluster sampling,students from grade 3 to grade 6 from 6 primary schools in a middle-sized were selected and administered with questionnaire survey. According to the criteria of dyslexia, dyslexic children and non-dyslexic children were identified and the difference of the Quality of Life was compared.@*Results@#Totally 3 673 children were collected, and 119 of them were identified as dyslexia(3.24%).The prevalence of dyslexia differed by gender,grades,educational level of parents(χ2=24.77,11.75,18.50,9.79,P<0.05). The Quality of Life which below the average proportion accounted for 30.3% of dyslexic children and 16.7% of normal children. Quality of life scored signiticantly different between dyslexic children and non-dyslexia children, including psychosocial functioning domain(134.54±30.88)(143.49±32.53), physical and mental health domain(2.71±0.84)(2.92±0.81) vs (2.83±0.90)(3.06±0.87), the living satisfaction domain(2.95±0.87)(3.14±0.87)(t=-6.09，-5.48，-5.44，-4.50，P<0.01),with dyslexic group significantly lower than that of non-dyslexic group.@*Conclusion@#The Quality of Life of Dyslexic children was in a poor condition.

Focus on children dyslexia, starting with public health policy / 中国学校卫生

Abstract@#As a common neurodevelopmental disorder, dyslexia causes a series of adverse outcomes throughout the lifespan, while the public is less aware to it. This review aims to provide experiences for completing domestic policies, as well as to improve the understanding of dyslexia of the public in China by introducing some public health policies, interventions, and special service organizations and the associations related to dyslexia domestic and overseas. The information discussed in this article may serve as a useful model developing or revising policies or guidelines for meeting the needs of children with dyslexia.

Spectrometric analyses of larotaxel and larotaxel liposomes quantification by high performance liquid chromatography / 北京大学学报(医学版)

OBJECTIVE@#Larotaxel is a new chemical structure drug, which has not been marketed worldwide. Accordingly, the standard identification and quantification methods for larotaxel remain unclear. The spectrometric analyses were performed for verifying weight molecular formula, molecular weight and chemical structure of larotaxel. Besides, a quantification method was developed for measuring larotaxel in the liposomes.@*METHODS@#The molecular formula, molecular weight and chemical structure of larotaxel were studied by using mass spectrometry (MS), infra-red (IR), nuclear magnetic resonance (NMR) and ultraviolet-visible (UV-vis) spectrometric techniques. The absorption wavelength of larotaxel was investigated by UV-vis spectrophotometry full-wavelength scanning. Besides, a quantification method was developed by high performance liquid chromatography (HPLC), and then validated by measuring the encapsulation efficacy of larotaxel liposomes.@*RESULTS@#The four spectral characteristics of larotaxel were revealed and the corresponding standard spectra were defined. It was confirmed that larotaxel had the structure of tricyclic diterpenoids, with the molecular formula of C45H53NO14, the molecular weight of 831.900 1, and the maximum absorption wavelength of 230 nm. The quantitative method of larotaxel was established by using HPLC with a reversed phase C18 column (5 μm, 250 mm×4.6 mm), a mobile phase of acetonitrile-water (75:25, volume/volume), and a detection wavelength of 230 nm. The validation study exhibited that the established HPLC method was stable, and had a high recovery and precision in the quantitative measurement of larotaxel in liposomes. In addition, a new kind of larotaxel liposomes was also successfully prepared. The particle size of the liposomes was about 105 nm, with an even size distribution. And the encapsulation efficiency of larotaxel in the liposomes was above 80%.@*CONCLUSION@#The present study offers reference standard spectra of larotaxel, including MS, IR, NMR, and UV-vis, and confirms the molecular formula, molecular weight and chemical structure of larotaxel. Besides, the study develops a rapid HPLC method for quality control of larotaxel liposomes.

Research progress on alkaloid monomer analgesic preparations / 中国中药杂志

Pain is one of the problems that seriously affect people's quality of life for thousands of years. The causes of pain are complex and varied,and long-term pain can also lead to depression. It has become a research hotspot to develop analgesic preparations with significant drug effects and small side effects. Recent studies have shown that certain alkaloid monomers have analgesic targets such as γ-aminobutyric acid,cannabinoids,and capsaicin. If their preparation is applied to the analgesic field,they can make up for the defects such as strong addiction and side effects of traditional opioid and non-steroidal analgesic drugs,but there is no relevant literature to summarize the research results in this field. This article first introduces the mechanism of pain production and the target of analgesia. Based on this,the application status of alkaloid monomer analgesic preparations approved by China Food and Drug Administration( CFDA)( number varieties,type of dosage form,drug description,analgesic mechanism and advantages) was analyzed,and the research dynamics of alkaloid monomer analgesic preparations( new formulation and new technology) were reviewed. Finally,some problems in this field were pointed out,such as imperfect medication information,inadequate transformation of research results,and too few kinds of analgesic components in developed alkaloids. The development direction was also pointed out for the above problems,with a view to provide reference for further development and in-depth research.

Changes of transport sugar content in different organs of Rehmannia glutinosa / 中国中药杂志

Raffinose series oligosaccharides are the transport and storage sugars of many plants, Rehmannia glutinosa is one of the commonly used Chinese herbal medicines, medicinal parts ist he roots. Root and tuber of R. glutinosa contains stachyose, raffinose and other oligosaccharides, but the study about the process of growth and development of other organs in the non-structural changes in sugar content is rare.In this study, leaves, stems and roots of R. glutinosa were used as materials to analyze the diurnal variation and the changes of sugar content of sucrose, raffinose and stachyose in different organs of R. glutinosa. The results showed that the content of sucrose in R. glutinosa leaves gradually increased from seedling stage.However, the content of stachyose did not change much at the early stage of growth, and the stachyose rapidly increased at the later stage of growth. The raffinose content gradually decreased throughout the growing season, young leaves of R. glutinosa have higher ability to sucrose synthesis than mature leaves, while mature leaf has higher raffinose and stachyose synthesis ability than young leaves. Sucrose and stachyose content in stem gradually increased, while there was little change in raffinose content. The content of raffinose and stachyose in root increased rapidly from the beginning of fast growing period, while the content of sucrose did not change much. The content of sucrose in leaves of R. glutinosa did not change much at day and night, while the daily changes of raffinose and stachyose contents were very obvious. The contents of raffinose and stachyose in daytime were higher than those at night. The content of raffinose in root and stem was not changed much, but the change of stachyose in root, stem and leaf was very obvious, especially in stem and leaf. In summary, the leaf is the main synthetic organ of raffinose, leaves, stems and roots are stachyose synthesis organ. Sucrose, raffinose and stachyose are the major transport forms of carbohydrates in R. glutinosa.

Instructional mode of biomedical electronics based on constructivism / 医疗卫生装备

Objective To demonstrate the feasibility and necessity of constructivist pedagogy for teaching biomedical electronics so as to create a new instructional mode. Methods The new mode for teaching biomedical electronics was discussed from two aspects of teaching thought and practice with considerations on constructivist pedagogy connotation as well as the actualities of teaching resources and object. Results Instructional thoughts which boosted students' thinking ability,learning habits and confidence were developed.The instructional practice,which included integrated teaching units, problem-based discussion,task-driven experiment content,was also been achieved.Conclusion The reform of instructional mode gains high practical effect, and provides pedagogical implications to other specialized courses of biomedical engineering.

Role of ceramide in development and progression of nonalcoholic fatty liver disease / 临床肝胆病杂志

Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome caused by liver damage factors except alcohol and has the major feature of diffuse macrovesicular hepatocyte steatosis.Thetwo-hit hypothesis can partly explain the pathogenesis of NAFLD.Recent studies have found that ceramide is a key molecular messenger involved in the development and progression of NAFLD,and as a sphingolipid,it is closely associated with the two-hit hypothesis.This article reviews the role of ceramide in NAFLD.

Signal Transducer and Activator of Transcription 3 for the Differentiation of Hepatocellular Carcinoma from Cirrhosis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Overexpression and constitutive activation of signal transducer and activator of transcription (STAT) 3 have been suggested in the tumorigenesis of many human cancers, including multiple carcinomas, melanoma, and lymphoma. The diagnosis of hepatocellular carcinoma (HCC) in lobectomy specimens is usually straightforward, but distinguishing cirrhosis from well-differentiated HCC can be challenging in core biopsies. Our aims were to investigate the expression level of STAT3 and phosphorylated STAT3 (pSTAT3) in HCC and cirrhosis, and the application of STAT3 in the differential diagnosis of HCC and cirrhosis.</p><p><b>METHODS</b>Sixty cases were divided into three groups: patients with HCC only (Group 1), HCC and cirrhosis (Group 2), and cirrhosis only (Group 3). Formalin-fixed and paraffin-embedded tissue sections were stained immunohistochemically for STAT3, pSTAT3, and CD163. The values obtained from the tissue sections of each group were compared in statistical analysis.</p><p><b>RESULTS</b>STAT3 showed a high level in HCC and was a significant marker for differentiating HCC from cirrhosis (P < 0.0001). The odds ratio between HCC and cirrhosis increased 34.4 times when the intensity of STAT3 increased by 1 level. Spearman's correlation and Chi-square tests also demonstrated that expression level of STAT3 did not correlate with age, gender, or the presence of a cirrhotic background.</p><p><b>CONCLUSIONS</b>STAT3 staining differs significantly in HCC and cirrhosis. The findings reinforce the role of STAT3 in the tumorigenesis of HCC and provide a useful marker to differentiate HCC from cirrhosis in challenging liver biopsies.</p>