OBJECTIVE To explore the effect and underlying mechanism of leucine(Leu)on meta-bolic dysfunction-associated fatty liver disease induced by high fat diet(HFD)in mice.METHODS C57BL/6J male mice were randomly divided into chow diet(normal),chow diet+Leu(normal+Leu),HFD and HFD+Leu groups,with 10 mice in each group.The mice in the normal and normal+Leu groups received chow diet while those in the HFD and HFD+Leu groups received HFD.Drinking water for mice in the normal+Leu and HFD+Leu groups was supplemented with 1.5%Leu.The experiment lasted 24 weeks,total food and water intake of mice were recorded weekly to calculate energy and Leu intake respectively.Energy metabolism of mice was detected at week 20 by the Oxymas/CLAMS Animal Metabolic System heat production,CO2 exhalation,O2 consumption and respiratory exchange rate(RER).At the end of week 24,the mice were sacrificed and the livers were harvested,followed by the oil red O staining to reveal the fat content.Western blotting was performed to analyze the changes in the activity of the liver branched-chain α-keto acid dehydrogenase E1α(BCKDE1A),the activation of AMP-activated protein kinase alpha subunit(AMPKα),and the protein expressions of downstream effector molecules including silent information regulator 1(SIRT1)and peroxisome proliferator-activated receptor coactivator-1α(PGC-1α),fatty acid synthetase(FAS)and fatty acid binding protein 4(FABP4)in the liver of mice.RESULTS Total Leu intake of mice was significantly reduced in the HFD+Leu group,compared with the normal+Leu group.The mice fed with HFD significantly increased the energy intake body mass gain and liver mass,accompanied by fat accumulation in the liver,compared to the mice in the normal group.Simultaneously,the mice in the HFD group showed a decrease in CO2 exha-lation both by day and by night,and in the respiratory exchange ratio by day compared to the normal group.Compared with the HFD group,the body mass gain and liver mass obviously decreased in mice of the HFD+Leu group,and the liver fat accumulation was reduced.The mice in the HFD+Leu group exhib-ited higher heat production and O2 consumption,along with an increase in CO2 exhalation by day and by night.In addition,heat production,CO2 exhalation,and O2 consumption were significantly higher by night than by day(P<0.01).As for the respiratory exchange ratio,a night increase was seen in the mice from the normal group,normal+Leu group,and HFD group,but not in the HFD+Leu group.The results of Western blotting showed that compared with the normal group,the BCKDE1A phosphorylation inacti-vation was enhanced,AMPKα phosphorylation activation alleviated,the protein expressions of SIRT1 and PGC-1α downregulated(P<0.05),and the protein expressions of FAS and FABP4 increased in the livers of mice in the HFD group.Compared with the HFD group,the BCKDE1A phosphorylation inacti-vation was alleviated,AMPKα phosphorylation activation enhanced,the protein expressions of SIRT1 and PGC-1α increased,and the protein expressions of FAS and FABP4 downregulated in the livers of mice in the HFD+Leu group.CONCLUSION Leu can alleviate HFD-induced metabolic dysfunction-associated fatty liver disease in mice,which may be closely related to the promotion of energy metabo-lism and inhibition of fat synthesis.

OBJECTIVE To explore the effect and underlying mechanism of leucine(Leu)on meta-bolic dysfunction-associated fatty liver disease induced by high fat diet(HFD)in mice.METHODS C57BL/6J male mice were randomly divided into chow diet(normal),chow diet+Leu(normal+Leu),HFD and HFD+Leu groups,with 10 mice in each group.The mice in the normal and normal+Leu groups received chow diet while those in the HFD and HFD+Leu groups received HFD.Drinking water for mice in the normal+Leu and HFD+Leu groups was supplemented with 1.5%Leu.The experiment lasted 24 weeks,total food and water intake of mice were recorded weekly to calculate energy and Leu intake respectively.Energy metabolism of mice was detected at week 20 by the Oxymas/CLAMS Animal Metabolic System heat production,CO2 exhalation,O2 consumption and respiratory exchange rate(RER).At the end of week 24,the mice were sacrificed and the livers were harvested,followed by the oil red O staining to reveal the fat content.Western blotting was performed to analyze the changes in the activity of the liver branched-chain α-keto acid dehydrogenase E1α(BCKDE1A),the activation of AMP-activated protein kinase alpha subunit(AMPKα),and the protein expressions of downstream effector molecules including silent information regulator 1(SIRT1)and peroxisome proliferator-activated receptor coactivator-1α(PGC-1α),fatty acid synthetase(FAS)and fatty acid binding protein 4(FABP4)in the liver of mice.RESULTS Total Leu intake of mice was significantly reduced in the HFD+Leu group,compared with the normal+Leu group.The mice fed with HFD significantly increased the energy intake body mass gain and liver mass,accompanied by fat accumulation in the liver,compared to the mice in the normal group.Simultaneously,the mice in the HFD group showed a decrease in CO2 exha-lation both by day and by night,and in the respiratory exchange ratio by day compared to the normal group.Compared with the HFD group,the body mass gain and liver mass obviously decreased in mice of the HFD+Leu group,and the liver fat accumulation was reduced.The mice in the HFD+Leu group exhib-ited higher heat production and O2 consumption,along with an increase in CO2 exhalation by day and by night.In addition,heat production,CO2 exhalation,and O2 consumption were significantly higher by night than by day(P<0.01).As for the respiratory exchange ratio,a night increase was seen in the mice from the normal group,normal+Leu group,and HFD group,but not in the HFD+Leu group.The results of Western blotting showed that compared with the normal group,the BCKDE1A phosphorylation inacti-vation was enhanced,AMPKα phosphorylation activation alleviated,the protein expressions of SIRT1 and PGC-1α downregulated(P<0.05),and the protein expressions of FAS and FABP4 increased in the livers of mice in the HFD group.Compared with the HFD group,the BCKDE1A phosphorylation inacti-vation was alleviated,AMPKα phosphorylation activation enhanced,the protein expressions of SIRT1 and PGC-1α increased,and the protein expressions of FAS and FABP4 downregulated in the livers of mice in the HFD+Leu group.CONCLUSION Leu can alleviate HFD-induced metabolic dysfunction-associated fatty liver disease in mice,which may be closely related to the promotion of energy metabo-lism and inhibition of fat synthesis.

Oleic acid(OA),a monounsaturated fatty acid(MUFA),has previously been shown to reverse saturated fatty acid palmitic acid(PA)-induced hepatic insulin resistance(IR).However,its underlying molecular mechanism is unclear.In addition,previous studies have shown that eicos-apentaenoic acid(EPA),a ω-3 polyunsaturated fatty acid(PUFA),reverses PA-induced muscle IR,but whether EPA plays the same role in hepatic IR and its possible mechanism involved need to be further clarified.Here,we confirmed that EPA reversed PA-induced IR in HepG2 cells and compared the proteomic changes in HepG2 cells after treatment with different free fatty acids(FFAs).A total of 234 proteins were determined to be differentially expressed after PA+OA treat-ment.Their functions were mainly related to responses to stress and endogenous stimuli,lipid meta-bolic process,and protein binding.For PA+EPA treatment,the PA-induced expression changes of 1326 proteins could be reversed by EPA,415 of which were mitochondrial proteins,with most of the functional proteins involved in oxidative phosphorylation(OXPHOS)and tricarboxylic acid(TCA)cycle.Mechanistic studies revealed that the protein encoded by JUN and reactive oxygen species(ROS)play a role in OA-and EPA-reversed PA-induced IR,respectively.EPA and OA alle-viated PA-induced abnormal adenosine triphosphate(ATP)production,ROS generation,and calcium(Ca2+)content.Importantly,H2O2-activated production of ROS increased the protein expression of JUN,further resulting in IR in HepG2 cells.Taken together,we demonstrate that ROS/JUN is a common response pathway employed by HepG2 cells toward FFA-regulated IR.

Lung cancer is one of the most common malignancies with the highest incidence rate and mortality rate worldwide, and non-small cell lung cancer (NSCLC) accounts for about 85%. Only 5% NSCLC patients are anaplastic lymphoma kinase (ALK) rearrangement positive NSCLC, but the prognosis of these patients is poor, and treatment is urgent. Ensartinib (X-396), a next-generation ALK tyrosine kinase inhibitor (ALK-TKI), has shown greater potency on inhibiting ALK activity and controlling brain metastases than crizotinib, which is indicated for the treatment of crizotinib-resistant, ALK-positive NSCLC patients. Several phase I to III clinical trials included both healthy volunteers and NSCLC patients have been conducted both in China and abroad. In this review, we briefly summarized the results of these trials, and preliminary efficacy, safety, pharmacology and pharmacokinetics/pharmacodynamics of ensartinib were discussed.

OBJECTIVETo investigate the clinicpathologic features and diagnosis of plasmablastic lymphoma (PBL).

METHODSEleven cases of PBL were collected and followed up, with review of the literature. HIV and EBV status and their relationships with the tumor were specially compared as well.

RESULTSIn the current cohort, 10 patients were serologically HIV negative; the male to female ratio was 8 to 3, and the median age was 57 years. Ten cases showed extranodal involvement and one case was nodal based. At presentation, five patients had mid-facial involvement, including sinonasal area (3 cases) and oral cavity (2 cases). Histologically, six were PBL of oral mucosa type, and five were PBL with plasmacytic differentiation. In all cases, the neoplastic cells expressed CD138 and MUM-1, and were negative for CD20 and CD3ε; the median Ki-67 index was 80%. Five cases were EBER1/2 in situ hybridization positive. IgH or/and Igκ gene rearrangement was detected in all five cases examined.

CONCLUSIONSMost patients were no congenital or acquired immunodeficiency in the retrospective study. Of the died patients, EBER1/2 in situ hybridization were negative and their disease staging were Ⅳ, The neoplastic cells were immunoblastic or plasmablastic, sometimes the plasmacytoid cell can be seen and the neoplastic cell had mature plasma cell phenotype, the pathologic diagnosis of the lymphoma is still controversial now. Differentiate with plasma cell neoplasm is difficult, it is necessary to accumulate more cases for advanced study and observation in the future.

Female ; Gene Rearrangement ; Humans ; In Situ Hybridization ; Male ; Middle Aged ; Multiple Myeloma ; Plasma Cells ; Plasmablastic Lymphoma ; diagnosis ; pathology ; RNA, Viral ; metabolism ; Retrospective Studies

Objective To investigate the effect of a fast-track based clinical nursing pathway of hepatic carcinoma on patient satisfaction and job satisfaction of nurses. Methods A total of 91 primary hepatic carcinoma (PHC) patients undergoing elective hepatectomy were enrolled and were divided into two groups by admission time, namely the control group (48 cases) and the experimental group (43 cases). The patients in the control group received traditional perioperative nursing care of hepatectomy, while the cases in the experimental group participated in fast-track nursing pathway. Patient satisfaction and nurse job satisfaction were measured before and after implementation. Results Final analysis included 45 patients in the control group and 40 patients in the experimental group. In the experimental group, the total score of patient satisfaction and the scores of all dimensions (including services and techniques, concern and care, services and techniques and overall satisfaction) were (132.75 ± 13.71), (48.30 ± 6.53), (42.60 ± 4.62), (35.98 ± 3.85), (5.88 ± 0.94), while they were (122.89 ± 16.62), (44.53 ± 7.74), (39.49 ± 5.67), (33.53±4.40), (5.33±1.13) in the control group. And the scores of the experimental group were significantly higher than that of the control group (t=-2.961, t=-2.409, t=-2.753, t=-2.709, t=-2.389, P<0.05). Furthermore,after implementing the fast-track clinical nursing pathway,the total score of nurse job satisfaction and the scores of six factors were (143.23 ± 9.40), (28.45 ± 2.72), (24.82 ± 2.28), (23.05 ± 1.33), (13.91 ± 1.95), (15.05 ± 1.43), (16.64 ± 1.65) while they were (127.36 ± 13.14), (25.68 ± 4.16), (19.64 ± 2.75), (20.23 ± 2.35), (13.23 ± 2.22), (13.68 ± 2.01), (14.50 ± 1.95) before the implementation. The former was significantly better than the latter (t =-12.462,-7.743,-12.670,-6.560,-2.417,-1.483,-6.587,P<0.05). However, no differences were observed in the other two dimensions of wages and benefits andwork-family balance(t =-1.945,-1.312,P>0.05) since the scores after implementation were (13.86 ± 2.12), (7.45 ± 1.57), while that of (13.18 ± 2.30)、(7.23 ± 1.41) were obtained before performance. Conclusions Application of fast- track nursing pathway in perioperative patients with PHC can contribute to promoting the level of patient satisfaction and job satisfaction of nurses and improving nursing quality. It is suggested that this nursing pathway will have more potential value for PHC patients.

Objective To assess the prospect of integrated biphasic silk fibroin scaffold made by annulus fibrosus-nu?cleus pulposus tissue engineering in application as integrated intervertebral disc(IVD). Methods An integrated annulus fi brosus-nucleus pulposus(AF-NP)biphasic scaffold was made by silk fi broin using two different uncomplicated methods which were paraffin spheres-leaching method(outer AF phase)and phase separation method(inner NP phase). The scaf?fold was investigated by general observation, stereomicroscope and scanning electron microscopy(SEM). Its pore size, poros?ity, and compressive elastic modulus were determined. AF and NP cells were isolated from rabbit IVD and seeded into the corresponding phase of the scaffold respectively. The cell-scaffold complex was cultured for 48 hours. The biocompatibility of the scaffold was evaluated by SEM, live/dead staining while CCK-8 assay was used to assess cell proliferation. Results Stereomicroscope and SEM showed that AF phase and NP phase integrated perfectly without cross-linking. Both phases pos?sessed highly interconnected porous structure [pore size of AF and NP phase were(220.0±23.1)μm and(90.0±17.8)μm, re?spectively] and highly porosity(AF and NP phase were respectively 91%and 93%). In addition, this silk biphasic scaffold had impressive mechanical properties(150.7 ± 6.8)kPa. SEM revealed that disc cells attached to regions of pore walls, dis?tributed uniformly and secreted extracellular matrix. Live/Dead staining and cell count kit-8(CCK-8)analysis showed that the silk composite scaffold was non-cytotoxic to disc cells. Conclusion This silk biphasic AF-NP scaffold has satisfied pore size, porosity, biomechanical properties and biocompatibility, so it is ideal candidate for IVD tissue engineering.

Objective To investigate the application of PKH26 fluorescent labeling on nucleus pulposus cells isolat-ed from bovine coccyx disc, and to provide nucleus pulposus tissue engineering with traceable nucleus pulposus cells by PKH26 fluorescence labelling. Methods Nucleus pulposus primary cells were isolated from the nucleus pulposus tissue de-tached from bovine coccyx disc by enzymatic digestion, and observed under the inverted microscope. Safranin O, toluidine blue and type Ⅱ collagen immunocytochemistry methods used to stain for passage one generation cells. Nucleus pulposus cells were labeled with PKH26 fluorescence in accordance with the instructions. The cell activity, fluorescence intensity at d0, d14 and d28 of culture, characteristics of proliferation and the expression of gene in labeled cells were assessed. Re-sults Isolated nucleus pulposus cells amounted to (1.56 ± 0.35) × 106/g. Under the inverted microscope, primary cells ad-hered at the 4 th day of culture, grew in groups, and covered the bottom of culture flask at the 13 th day. Both primary cells and the P1 generation cells were chondrocyte-like morphology. The staining of safranin O, toluidine blue and typeⅡcolla-gen immunocytochemistry for P1 generation of nucleus pulposus cells showed positive results. The cell activity before and af-ter PKH26 labeling showed more than 95%, and the fluorescence intensity at d0, d14 and d28 performed a decreasing trend, but still showed detect strong fluorescence at d28. There were no significant differences in proliferation and the expression of gene (collagen typeⅠandⅡ, aggrecan) before and after cell labeling (P>0.05). Conclusion As the seed cells of tissue en-gineering, nucleus pulposus cells isolated from bovine coccyx can reach a satisfactory number and maintain cartilage-like phenotype, and no changes shown in the biological characteristics after labeling. PKH26 labeled nucleus pulposus cells are suitable for the traceable cells in vivo study.

Objective To understand the current status of infections of intestinal parasites of population in Taixing City,Ji-angsu Province. Methods The infection rates and densities of human intestinal parasites were investigated according to the methods of the National Investigation Scheme on Human Principal Parasites,and the data of society,economy and disease con-trol were collected and analyzed. Results Among 2 556 people investigated in five villages,16 persons were found with intesti-nal parasites, with an infection rate of 0.63%. The infection rate was higher in residents with a low education level than in others and it was higher in the age group over 50 years than in the group under 50 years. The infection density was mild and the most was the single parasite infection. Conclusions The current status of intestinal parasite infections of population in Taixing City has reached the county-level control standard of Jiangsu Province. Therefore,the preventive strategy and measures should be ad-justed and the monitoring work should be strengthened.

OBJECTIVE To investigate ESBLs-producing Escherichia coli and Klebsiella pneumoniae and their antibiotic resistance changing at the same area in different period.METHODS Using Bio-Merieux ATB susceptibility test panels microdilution broth method to detect the antibiotic resistance of E.coli and K.pneumoniae,in addition to the use of phenotypic confirmatory test to detect the ESBLs.RESULTS The ESBLs-producing rate of E.coli and K.pneumoniae during 1999-2001 compared with 2003-2005,was elevated more than double.To imipenem,cefoxitin,piperacillin/tazobactam,and amikacin,the resistant rate was relatively lower,but to other ?-lactams,aminoglycosides,quinolones and sulfonamides,the resistant rate increased significantly in both periods compared,the differences were significant(P