Current status and perspectives of fibroblast growth factor 21 in nonalcoholic fatty liver disease / 临床肝胆病杂志

Fibroblast growth factor 21 (FGF21) is a peptide hormone predominantly secreted by the liver and plays a crucial role in maintaining whole-body energy metabolism and regulating insulin sensitivity. A large number of clinical studies have demonstrated that serum FGF21 levels are increased in obese patients with non-alcoholic fatty liver disease (NAFLD), and high circulating FGF21 is a sensitive biomarker for predicting the onset and progression of NAFLD. Injection of exogenous FGF21 can effectively alleviate pathological process in both animal models and NAFLD patients. This review aims to describe the molecular mechanism underlying the hepatoprotective effects of FGF21; to summarize the current data and challenges of the clinical trials on FGF21 analogs and receptor agonists in the treatment of NAFLD and nonalcoholic steatohepatitis (NASH); and to speculate the future directions of FGF21 as a diagnosis and treatment for NAFLD.

APPL2 Negatively Regulates Olfactory Functions by Switching Fate Commitments of Neural Stem Cells in Adult Olfactory Bulb via Interaction with Notch1 Signaling / 神经科学通报·英文版

Adult olfactory neurogenesis plays critical roles in maintaining olfactory functions. Newly-generated neurons in the subventricular zone migrate to the olfactory bulb (OB) and determine olfactory discrimination, but the mechanisms underlying the regulation of olfactory neurogenesis remain unclear. Our previous study indicated the potential of APPL2 (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 2) as a modulating factor for neurogenesis in the adult olfactory system. In the present study, we report how APPL2 affects neurogenesis in the OB and thereby mediates olfactory discrimination by using both in vitro neural stem cells (NSCs) and an in vivo animal model-APPL2 transgenic (Tg) mice. In the in vitro study, we found that APPL2 overexpression resulted in NSCs switching from neuronal differentiation to gliogenesis while APPL2 knockdown promoted neurogenesis. In the in vivo study, APPL2 Tg mice had a higher population of glial cells and dampened neuronal production in the olfactory system, including the corpus callosum, OB, and rostral migratory stream. Adult APPL2 Tg mice displayed impaired performance in olfactory discrimination tests compared with wild-type mice. Furthermore, we found that an interaction of APPL2 with Notch1 contributed to the roles of APPL2 in modulating the neurogenic lineage-switching and olfactory behaviors. In conclusion, APPL2 controls olfactory discrimination by switching the fate choice of NSCs via interaction with Notch1 signaling.

APPL2 Negatively Regulates Olfactory Functions by Switching Fate Commitments of Neural Stem Cells in Adult Olfactory Bulb via Interaction with Notch1 Signaling / 神经科学通报·英文版

Adult olfactory neurogenesis plays critical roles in maintaining olfactory functions. Newly-generated neurons in the subventricular zone migrate to the olfactory bulb (OB) and determine olfactory discrimination, but the mechanisms underlying the regulation of olfactory neurogenesis remain unclear. Our previous study indicated the potential of APPL2 (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 2) as a modulating factor for neurogenesis in the adult olfactory system. In the present study, we report how APPL2 affects neurogenesis in the OB and thereby mediates olfactory discrimination by using both in vitro neural stem cells (NSCs) and an in vivo animal model-APPL2 transgenic (Tg) mice. In the in vitro study, we found that APPL2 overexpression resulted in NSCs switching from neuronal differentiation to gliogenesis while APPL2 knockdown promoted neurogenesis. In the in vivo study, APPL2 Tg mice had a higher population of glial cells and dampened neuronal production in the olfactory system, including the corpus callosum, OB, and rostral migratory stream. Adult APPL2 Tg mice displayed impaired performance in olfactory discrimination tests compared with wild-type mice. Furthermore, we found that an interaction of APPL2 with Notch1 contributed to the roles of APPL2 in modulating the neurogenic lineage-switching and olfactory behaviors. In conclusion, APPL2 controls olfactory discrimination by switching the fate choice of NSCs via interaction with Notch1 signaling.

Serotype distribution and drug resistance of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis isolated from nasopharynx of Uygur children / 中华儿科杂志

Objective@#To investigate the serotype distribution and antimicrobial susceptibility pattern of Streptococcus pneumoniae (S. pneumoniae), Haemophilus influenzae (H. influenzae) and Moraxella catarrhalis (M. catarrhalis) isolates collected from nasopharyngeal swabs from Uygur children in Kashi.@*Methods@#Nasopharyngeal swabs were collected from inpatient Uygur children aged from 1 month to 5 years with respiratory infections from the pediatric department, the First People's Hospital of Kashi, Xinjiang Uygur Autonomous Region. Antimicrobial susceptibilities of the isolates were determined with E-test and KB disk diffusion methods. The production of β-lactamase was detected for H. influenzae and M. catarrhalisisolates using nitrocefin disc method. Quellung test and latex agglutination test were adopted to identify serotypes of S. pneumoniae and H. influenzae isolates.@*Results@#Forty-seven S. pneumoniae, 13 H. influenzae and 16 M. catarrhalis isolates were detected. All of the 47 S. pneumoniae isolates were sensitive to parenteral penicillin, amoxicillin-clavulanic acid, vancomycin and levofloxacin; the susceptibility rates to cefotaxime, imipenem and chloramphenicol were 94% (44/47), 89% (42/47), and 98% (46/47). The resistance rate to erythromycin was 74% (35/47). The most common serotype of S. pneumoniae was serotype 19A (10 strains, 21%). The coverage rate of 13-valent conjugate vaccine (PCV13) was 70% (33/47). None of the 13 H. influenzae isolates could be typed. They were highly susceptible to tested β-lactams antibiotics, except ampicillin. Only one H. influenzae isolate could produce β-lactamase, and two isolates were identified as β-lactamase-negative-ampicillin-resistant ones. The sixteen M. catarrhalis isolates were all positive in β-lactamase detection, but sensitive to amoxicillin-clavulanic acid, cephalosporins and meropenem.@*Conclusions@#In Kashi, Xinjiang Uygur Autonmous Region, S. pneumoniae isolates from Uygur children were highly sensitive to parenteral penicillin and other β-lactams antibiotics. H. influenzae isolates from Uygur children were highly susceptible to amoxicillin-clavulanic acid, cephalosporins and ciprofloxacin. All M. catarrhalis isolates from Uygur children could produce β-lactamase, but were sensitive to the enzyme inhibitors and cephalosporins.

Study on the Expression of Secretory Phospholipase A2-Ⅱ A in Lesions of Psoriasis Vulgaris / 现代检验医学杂志

Objective To discuss the relationship between the expression of secretory Phospholipase A2-Ⅱ A(sPLA2-ⅡA) and the pathogenesis psoriasis vulgaris patients lesions.Methods Using Psoriasis Area Severity Index(PASI),50 psoriasis vulgaris were divided into three groups:mild (n =16),moderate (n =18) and severe group (n =16),and compared to the non-psoriasis control group (n=52).The serum level of sPLA2-ⅡA in psoriasis vulgaris patients and the normal control group were detected using ELISA methods.Using RT-PCR,mRNA expression levels of sPLA2-ⅡA and subtypes were detected.Using western blot,the expression levels of Akt and p-Akt were detected.Results The serum level of sPLA2-ⅡA in the psoriasis lesion's group was significantly higher than that in the healthy control (t=13.62,P＜0.01).The mRNA expression of sPLA2-ⅡA in the lesion of psoriasis was significantly higher than that in health control (t=113.41,P＜0.01).In the other subtypes,the mRNA expression of sPLA2 had no distinctive.Among the three groups (mild group,moderate group and severe group),the difference in serum level and mRNA expression of sPLA2-ⅡA were statistically significant (F =28.12,69.62,P＜0.01).There was statistical significance among three groups (t=3.14,5.14,6.38,all P＜0.01;t=4.77,10.42,10.58,all P＜0.01).The expression of Akt/p-Akt in the psoriasis lesion's group were higher than that in health control (t=17.79,19.04,P＜0.01).Conclusion The expression of sPLA2-ⅡA would be associated with order of severity in lesions of psoriasis vulgaris.The pathway was relate to expression of Akt and p-Akt.

Analytical research on HPV infection among women in Xingjiang Kashgar area / 国际检验医学杂志

Objective To investigate the exfoliative cell HPV infection situation,genotype distibution and charactristics among female population in Kashgar area.Methods The cervical exfoliated cells specimens were collected from 1548 women,and 23 genotypes of HPV were detected by using the PCR reverse dot blot hybridization method.The HPV infection situation and its genotypes were analyzed.Results The HPV infection positive rate was 33.33% (485/1 548),in which the HPV-16 infection rate was 10.3%;HPV52 infection rate was 9.9%;HPV58 infection rate was 7.6%,HPV53 infection rate was 7.2%;the single subtype infection rate was was 66.8%,the multiple infection rate was 33.2%;the HPV infection rate was highest(43.3%) in female population aged 41-50 years old,which was extremely higher than that in other age groups(P<0.05).Conclusion The HPV infection among female population of Kashgar area is dominated by HPV16,the HPV infection rate is highest in female population aged aged 41-50 years old,which provides a theoretical basis for the HPV prevention and control work of related departments in Kashgar area.

Predictive value of serum lactate combined with PIRO score in prognosis of septic patients / 中华急诊医学杂志

Objective To investigate the predictive value of serum lactate combined with PIRO (Predisposition,Infection,Response and Organ dysfunction) score in the development of multiple organs dysfunction syndrome (MODS) in septic patients and to study procalcitonin (PCT),in order to provide guidelines for clinical care.Methods From April 2015 to July 2016,a total of 752 sepsis patients were enrolled and divided into MODS group (n =488) and non-MODS group (n =264) according to the criteria of MODS.At 28 d after admission,these patients were divided into survival group (n =477) and death group (n =275).PCT and lactate levels in serum were measured,and PIRO score of these patients was calculated.Then the differences in levels of PCT and lactate in serum were compared among patients at different PIRO score categories.ROC was constructed to observe the clinical values of the biomarkers,PIRO score and lactate combined with PIRO score in predicting prognosis.Result PCT,lactate levels in serum and PIRO score were significantly higher in MODS group and death group,showing significant positive correlation.The areas under ROC curves (AUCs) of serum lactate combined with PIRO score for predicting MODS were 0.906,which was significantly higher than that of serum PCT (0.716),serum lactate (0.851) and PIRO score (0.840) alone (all P ＜ 0.05).Serum PCT,serum lactate and PIRO score were the independent predictors of MODS.Conclusions Serum lactate in combination with PIRO score was a valuable indicator in predicting development of MODS in septic patients.

Fibroblast Growth Factor 21 Protects against Atherosclerosis via Fine-Tuning the Multiorgan Crosstalk

Fibroblast growth factor 21 (FGF21) is a metabolic hormone with pleiotropic effects on energy metabolism and insulin sensitivity. Besides its antiobese and antidiabetic activity, FGF21 also possesses the protective effects against atherosclerosis. Circulating levels of FGF21 are elevated in patients with atherosclerosis, macrovascular and microvascular complications of diabetes, possibly due to a compensatory upregulation. In apolipoprotein E-deficient mice, formation of atherosclerotic plaques is exacerbated by genetic depletion of FGF21, but is attenuated upon replenishment with recombinant FGF21. However, the blood vessel is not the direct target of FGF21, and the antiatherosclerotic activity of FGF21 is attributed to its actions in adipose tissues and liver. In adipocytes, FGF21 promotes secretion of adiponectin, which in turn acts directly on blood vessels to reduce endothelial dysfunction, inhibit proliferation of smooth muscle cells and block conversion of macrophages to foam cells. Furthermore, FGF21 suppresses cholesterol biosynthesis and attenuates hypercholesterolemia by inhibiting the transcription factor sterol regulatory element-binding protein-2 in hepatocytes. The effects of FGF21 on elevation of adiponectin and reduction of hypercholesterolemia are also observed in a phase-1b clinical trial in patients with obesity and diabetes. Therefore, FGF21 exerts its protection against atherosclerosis by fine-tuning the interorgan crosstalk between liver, brain, adipose tissue, and blood vessels.

Heterogeneity of white adipose tissue: molecular basis and clinical implications

Adipose tissue is a highly heterogeneous endocrine organ. The heterogeneity among different anatomical depots stems from their intrinsic differences in cellular and physiological properties, including developmental origin, adipogenic and proliferative capacity, glucose and lipid metabolism, insulin sensitivity, hormonal control, thermogenic ability and vascularization. Additional factors that influence adipose tissue heterogeneity are genetic predisposition, environment, gender and age. Under obese condition, these depot-specific differences translate into specific fat distribution patterns, which are closely associated with differential cardiometabolic risks. For instance, individuals with central obesity are more susceptible to developing diabetes and cardiovascular complications, whereas those with peripheral obesity are more metabolically healthy. This review summarizes the clinical and mechanistic evidence for the depot-specific differences that give rise to different metabolic consequences, and provides therapeutic insights for targeted treatment of obesity.

Clinical application and advances in research on microspheres in TACE for hepatocellular carcinoma / 中华肝胆外科杂志

Hepatocellular carcinoma (HCC) accounts for more than 90％ of primary liver cancer.Surgical resection is the standard modality of treatment.However,resection can only be performed in a minority of patients at the time of diagnosis.Data from several recently published studies are encouraging and suggest that TACE (transcatheter hepatic arterial chemoembolization) is superior to conservative treatment in patients with hepatocellular carcinoma who are not eligible for surgery.The traditional embolic agents such as iodized oil and gelatin sponge significantly prolonged survival in patients with HCC.However,the effects of these embolic agents are temporary.A new embolic agent,microspheres has attracted a lot of attention in our country and abroad.These microspheres can be divided into two categories:pure microspheres and carrier microspheres.In this paper,we review these two types of microspheres.

Clinical implications of plasma adipocyte fatty acid binding protein levels in patients with obesity and type 2 diabetes / 中国医师杂志

ObjectiveTo explore the relationship between plasma A-FABP and obesity type and degree,glucose and lipid metabolism parameters and insulin sensitivity.MethodsPlasma adipocyte fatty acid binding protein (A-FABP) was detected by double antibody sandwich ELISA in fasting status in subjects with normal glucose regulation and normal weight (NW-NGR,n =44),overweight or obese subjects with normal glucose regulation (OB-NGR,n =36),newly-diagnosed type 2 diabetes mellitus (T2DM) and its subgroups of T2DM with normal weight ( NW-T2DM,n =89 ) and T2D)M with overweight or obesity (OB-T2DM,n =44).And glucose,lipids,insulin levels as well as anthropometrical parameters such as body mass index ( BMI ),fat content ( Fat％ ),waist circumference (WC) and waist hip ratio (WHR) were measured.Meanwhile insulin sensitivity was assessed by HOMA-IR.ResultsAfter age and sex adjustment,plasma A-FABP levels in OB-NGR,NW-T2DM,and OB-T2DM were significantly higher than that of NW-NGR [11.32(6.54 - 15.43)μg/L,14.60(10.35 -20.10) μg/L,18.25(12.85 -26.65) μg/L vs 9.32(3.72 - 14.00) μg/L,all P ＜0.05].There was no difference in plasma A-FABP levels between OB-NGR and NW-T2DM [ 11.32 (6.54 - 15.43 ) vs 14.60 ( 10.35 -20.10) μg/L,P ＞ 0.05 ],but the plasma A-FABP levels in OB-NGR and NW-T2DM were significantly lower than that of OB-T2DM [ 11.32(6.54 - 15.43) μg/L,14.60( 10.35 -20.10) μg/L vs 18.25( 12.85 -26.65 ) μg/L,P ＜0.01 ].In a multiple stepwise regression analysis,HOMA-IR,sex,WC and age were the most significant independent determinants for plasma A-FABP concentration (all P ＜ 0.05 ).Conclusions Plasma A-FABP is strongly associated with the abdominal obesity and insulin resistance,measurement of plasma A-FABP concentrations might be useful for diagnosis of abdominal obesity and type 2 diabetics.

Angiopoietin-like protein 3 and adiponectin levels in patients with metabolic syndrome / 中南大学学报(医学版)

Objective To investigate the changes of serum angiopoietin-like protein 3 (Angptl3) and adiponectin levels in patients with metabolic syndrome (MS) in order to understand their association with the MS. Methods Serum Angptl3 and adiponectin levels were measured by sandwich ELISA in a group of 111 patients with MS and 152 normal controls. Results Serum adiponectin was lower in the MS patients than in the control subjects [4.22(1.01-23.29) μg/mL vs. 5.41(0.97-22.27) μg/mL, P＜0.05]. With regard to serum Angptl3, there was no significant difference between the 2 groups(P＞0.05). Serum adiponectin was correlated to Angptl3 and high density lipoprotein-cholesterol (HDL-C)(P＜0.001) and negatively correlated to body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR), triglyceride (TG), fasting plasma glucose (FBG), fasting insulin (FINS) and homeostatic model assessment method-insulin resistance (HOMA-IR) (P＜0.001). Serum Angptl3 was positively correlated with adiponectin (P＜0.001). Serum adiponectin was found to be independently positive determinant for Angptl3 concentrations (b′=0.256, P＜0.001). Adiponectin was inversely correlated with TG and HOMA-IR (b′=-0.234, -0.145, P＜0.001). Conclusion Adiponectin is decreased in MS patients and may be correlated to Angptl3.

Solitary necrotic nodule of the liver:MRI findings / 中华放射学杂志

Objective To determine the characteristic features of solitary necrotic nodule(SNN)of the liver on precontrast and dynamic contrast enhanced magnetic resonance(MR)imaging.Methods We retrospectively reviewed 15 patients with histopathologically proved SNN.All of the images were evaluated for lesion features including the number,shape,size,location,border,signal intensity and pattern of enhancement.Results Sixteen lesions were found in 15 patients.Nonenhaneed T1-and T2 weighted images depicted 15 lesions in 14 patients and 14 lesions in 13 patients respectively.Maximum diameter of 14 lesions was less than 3 cm.On unenhanced T1-weighted images,5 lesions were hypointense,9 lesions were slishtly hypointense,and 1 was isointense with hypointense capsule and central punctate hypointense foci.Among14 lesions demonstrated on T2-weighted images,5 were hyperintense,4 were slightly hyperintense,3 were slightly hypointense,and 2 were hypointense.Punctate or linear high signal intensities were found in2 lesions.All lesions were not enhanced after contrast injection.On portal venous and delayed phase.all lesions appeared significantly hypointense with well-defined border.The shape was irregular in 12 lesions and was round or oval in 4 lesions.No enhancement was found in the lesion except thin delayed enhancement in capsules of 3 lesions after contrast agent administration.Conclusion Characteristic MRI features of SNN are helpful for distinguishing SNN from other hepatic lesions.

Transarterial embolization for hemorrhage due to spontaneous rupture in hepatocellular carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of transarterial embolization (TAE) for intraperitoneal hemorrhage due to spontaneous rupture in hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>Fourty-two patients with ruptured HCC were divided into 4 groups according to the type of their previous treatment: Group A-TAE followed by elective hepatectomy 15, Group B- TAE alone 11, Group C-emergency operation 6 and group D-medical conservative management 10.</p><p><b>RESULTS</b>Celiac arteriography done before the present treatment showed extravasation of contrast material in 7 (26.9%) of the 26 patients in group A and B, and hypervascular tumor was observed in the rest. The hemostasis success rate of group A, B and C were 100%, which were much higher than that of group D (40%) (P < 0.05). The in-hospital mortality rates of group A, B and C were 0, 3.8% and 16.7% (P > 0.05), which were much lower than that of group D (80%) (P < 0.01). The 1-year survival rate of group A (76.3%) was higher than those in groups B (47.5%) and C (43.7%) (P < 0.05). There was no 1-year survivor in group D.</p><p><b>CONCLUSION</b>Transarterial embolization is safe and effective for hemorrhage due to spontaneous rupture in hepatocellular carcinoma. For resectable lesions, TAE is a preferential treatment to be given first, then followed by elective hepatectomy.</p>

THE INFLUENCES OF TRACE ELEMENT SELENIUMAND VITAMIN E ON SERUM LIPID PEROXIDE AND SERUM GPT IN RAT / 营养学报

The level of serum lipid peroxide in rat is increased as the age of rat increased gradually. When the animals were injected with sodium selenite (0.1mg/kg) and vitamin E (4mg/kg) for five weeks the serum lipid peroxide level was decreased, the combined use of sodium selenite and vitamin E could decrease the level of SGPT apparently.