BACKGROUND: A left-to-right shunting animal model is needed to study chronic pulmonary vascular remodeling of congenital heart attachment disease in adult.OBJECTIVE: To observe the characteristics of chronic pulmonary arterial hypertension in rat models subjected to left-to-right shunting.DESIGN, TIME AND SETTING: Randomized controlled animal modeling observation was performed in Experimental Animal Center, Xinqiao Hospital, the Third Military Medical University of Chinese PLA from April 2008 to April 2009.MATERIALS: A total of 80 male inbred line healthy SD rats of specified-pathogens free class, 4 weeks old, weighing 95-110 g, were randomly assigned into control group (n=40) and shunt operation group (n=40). A shrinking polyethylene blood vessel connector (proximal part inner diameter was 0.6 mm and outer diameter was 0.8 mm, while distal part's was 0.8 mm and 1.0 mm, respectively, 1.6 mm long), was applied.METHODS: Shunt operation group underwent left-to-right shunting through right common carotid artery and external jugular vein connected by shrinking polyethylene blood vessel connector. Control group underwent sham operation. At 4, 8, 12 and 16 weeks postoperation, ten models were determined with a series in procedures: hemodynamics detection, pathological sample preparation, hematoxylin-eosin staining, imaging analysis and so on.MAIN OUTCOME MEASURES: Changes in right ventricular systolic pressure, right ventricular hypertrophy index of right ventricle to left ventricle plus interventricular septum, and relative medial wall thickness in moderate sized pulmonary arteries in rats of shunt group and control group.RESULTS: All animal were survived. The pulmonary blood flow in shunt group was significantly higher than control groups (P<0.01). Compared with control group, right ventricular systolic pressure elevated obviously and right ventricular hypertrophy index were significantly higher in shunt group at 12 and 16 weeks (P<0.01). Compared with control group, the relative medial wall thickness in pulmonary arteries also elevated obviously in shunt group at 12 and 16 weeks (P<0.01).CONCLUSION: Left-to-right continuous low-flow shunt in rats can induced right ventricle accommodated with the change of right ventricular systolic pressure and promote chronic pulmonary arterial remodeling continuously. The procedure of establishing left-to-right shunting models with common carotid artery and external jugular vein connection, is a stable tool for studying chronic pulmonary arterial hypertension induced by low flow.

Objective To investigate the roles of the expressions of B cell lymphoma-2 (bcl-2) and Bcl-assosiated X (bax) in the pulmonary vascular remodeling (PVR) of pulmonary arterial hypertension (PAH) secondary to left-right shunt congenital heart disease (CHD).Methods A total of 80 SPF SD rats were randomly divided into 8 groups,shunt groups (SⅠ,SⅡ,SⅢ and SⅣ) and control groups (CⅠ,CⅡ,CⅢ and CⅣ).PAH rat model was established in the shunt groups by left-to-right shutting,and the control groups received sham operation.The rats from Ⅰ,Ⅱ,Ⅲ and Ⅳ groups were sacrificed in 4,8,12 and 16 weeks after operation.Mean pulmonary arterial pressure (mPAP) was recorded.Pathologic observations were made to assess pulmonary vascular remodeling.Their lung tissues were detected by in situ hybridization histochemistry (ISHH) technique and Western blotting for bcl-2 and bax.And apoptosis of pulmonary artery smooth muscle cells (PSMCs) and endothelial cells (ECs) were also detected by TUNEL.Results After 12 weeks or 16 weeks shunt,following indexes of the shunt groups were significantly higher than the control groups (P

OBJECTIVE Toinvestigatetheantidepressantandantianxietyeffectofproanthocyani-dins(OPC)inchronicallystressedratsanditsunderlyingmechanism.METHODS Onemethodwas selected from 8 different stress methods each day,and the rats were treated with OPC (25,50 and 1 00 mg·kg -1 )1 h before the stress method.The chronically stressed model was established.After 21 d stress experi ment,the i mmobility ti me in force swi mming test,sucrose consu mption and the nu mber of marbles buried in the marble burying test were observed respectively each day.OPC (25,50 and 1 00 mg·kg -1 )was given 1 h before each test.In addition,Western blotting was used to analyze the expression of brain derived neurotrophic factor (BDNF) and phosphorylated cyclic AMP response element-bindingprotein(p-CREB)inthehippocampusandfrontalcortex.RESULTS Comparedwith the control group,the chronically stressed group showed obvious depressive-like and anxiety-like behav-ior,while the immobility time decreased from (90.57 ±4.27)s in chronically stressed group to (78.25 ± 2.53)s (P<0.05),(72.12 ±3.21 )s(P<0.05)and (60.77 ±3.41 )s (P<0.05)when ig given OPC 25,50 and 100 mg·kg -1 respectively,the ratio of sucrose preference increased from (42.80 ±4.92)%to (67.54 ±4.32)%(P<0.05)and (72.21 ±7.99)%(P<0.05)when ig given OPC 50 and 1 00 mg· kg -1 respectively,the number of buried marbles decreased from 1 .57 ±0.21 in chronically stressed group to 0.63 ±0.26 (P<0.05)and 0.44 ±0.1 8 (P<0.05)when ig given OPC 50 and 1 00 mg·kg -1 respectively.The expression of p-CREB in the hippocampus and frontal cortex distinctively increased in OPC group (25,50 and 100 mg·kg -1 )(P<0.05),so did the expression of BDNF in the hippocampus andfrontalcortexinOPCgroup(50and100mg·kg-1)(P<0.05).CONCLUSION OPCcanreverse the depressive-like and anxiety-like behavior in chronically stressed rats,which may be related to the cAMP-CREB-BDNF signal transduction cascades.

Objective To examine the effects of acute hypobaric hypoxia on abilities of learning and memory,the water content in brain,the level of nitric oxide(NO) and endothelin-1 (ET-1) in hippocampus of mice.Methods The acute hypobaric hypoxia environment were made by putting the mice in a hypobaric chamber simulated at altitude of 6 000 meters for 8 hours.The capabilities of learning and memory of mice were detected by Morris water maze test.The content of water in hippocampus were examined by measuring the ratio of dry/wet weight,and the level of NO and ET-1 in brain was detected by colorimetric method.Results Morris water maze test showed that the mean escape latency of mice in the hypobaric hypoxia group were longer than that in the normobaric normoxia group((44.60±7.80) s vs (26.39±8.44)s,P＜0.01),and the target quadrant residence time were decreased((19.78±2.74) s vs (22.98±6.14)s,P＜ 0.05).Compared with the normobaric normoxia group (NO:(2.37 ± 1.07) μmol/gProt,ET-1:(38.87 ± 6.17) ng/L),the water content in brain of mice in the hypobaric hypoxia group was increased (P＜ 0.05),meanwhile,both the level of NO ((4.48 ± 1.45) μmol/gProt) and ET-1 ((52.09±6.75)ng/L) in brain were increased too(P＜0.01).Conclusion Hypobaric hypoxia can decrease the abilities of learning and memory of mice,and these changes might be related with the increased water content and the increased level of NO and ET-1 in hippocampus of mice.

Objective To analyze the immunophenotypic characteristics of the patients with minimal residual disease (MRD) positive acute B lymphocytic leukemia (B-ALL). Methods The leukemia-associated immunophenotype (LAIP) of 106 cases with MRD positive B-ALL from Department of Hematology, Tianjin KingMed Diagnois Center between June 2014 and January 2016 were retrospectively analyzed. CD10, CD13/CD33, CD19, CD38, CD58, CD45 and other antibodies were used to analyze the MRD of B-ALL. Results All the patients were positive for CD19. CD34 was negatively or weakly positive expressed in 27 cases (25.4％). CD10 was negatively or weakly positive expressed in 23 cases (21.7％). CD10 was strongly positive in 24 cases (22.6％). Totally, CD10 was weakly or strongly expressed in 47 cases (44.3％). CD58 was strongly positive in 98 cases (92.5％). CD13/CD33 was positively or weakly positive expressed in 64 cases (60.4％). CD38 was negative or weakly expressed in 33 cases (31.1％). CD45 was negative in 21 cases (19.8％). 15 cases (14.1％) were positive for 6 types of LAIP; 30 (28.3％) cases were positive for 5 types of LAIP; 42 (39.6％) cases were positive for 4 types of LAIP; 13 (12.3％) cases were positive for 3 types of LAIP;5 cases (4.7％) were positive for 2 types of LAIP; only one case (0.9％) was positive for 1 type of LAIP. Conclusion The combination of CD58, CD13/CD33, CD10, CD38 and CD34 antibodies can distinguish the neoplastic blast/immature B lymphocytes from progenitor B cells. This strategy has a high accuracy for the judgement of MRD in B-ALL.

With the gradual aggravation of aging in China， the prevalence of osteoporosis is increasing year by year. Osteoporosis has become a major public health problem threatening the health of middle-aged and elderly people， especially middle-aged and elderly women. There are many predisposing factors and complex pathogenesis of osteoporosis. The interpretation of osteoporosis has been the focus of clinical research in recent years. How to prevent and treat osteoporosis more effectively has also become a major problem faced by researchers. In recent years， the balance and homeostasis of calcium and phosphorus regulated by intestinal absorption， renal excretion and bone have become one of the hot topics， and the balance and homeostasis of calcium and phosphorus in vivo are the key to normal bone homeostasis. At the same time， as a complex microbial community living in the gastrointestinal tract， intestinal flora can produce a variety of regulators affecting metabolism. It has been widely confirmed that it acts on the body indirectly or directly， in multiple ways and targets to prevent and treat osteoporosis. Therefore， further exploring the role and mechanism of intestine kidney bone axis in osteoporosis plays a far-reaching significance for the prevention and treatment of osteoporosis. In recent years， scholars have made a lot of exploration on the prevention and treatment of osteoporosis with traditional Chinese medicine （TCM）， and found that TCM can intervene the expression of intestinal flora and play the effect of prevention and treatment of osteoporosis. Based on the "intestine kidney bone axis"， this paper briefly discusses the integrated traditional Chinese and western medicine of kidney and osteoporosis， intestine and osteoporosis， intestine kidney axis， the treatment of kidney from intestine， intestine and osteoporosis， and the application of TCM in regulating intestinal flora in osteoporosis， in order to provide new ideas for the prevention and treatment of osteoporosis.

With the improved understanding of driver mutations in non-small cell lung cancer (NSCLC), expanding the targeted therapeutic options improved the survival and safety. However, responses to these agents are commonly temporary and incomplete. Moreover, even patients with the same oncogenic driver gene can respond diversely to the same agent. Furthermore, the therapeutic role of immune-checkpoint inhibitors (ICIs) in oncogene-driven NSCLC remains unclear. Therefore, this review aimed to classify the management of NSCLC with driver mutations based on the gene subtype, concomitant mutation, and dynamic alternation. Then, we provide an overview of the resistant mechanism of target therapy occurring in targeted alternations ("target-dependent resistance") and in the parallel and downstream pathways ("target-independent resistance"). Thirdly, we discuss the effectiveness of ICIs for NSCLC with driver mutations and the combined therapeutic approaches that might reverse the immunosuppressive tumor immune microenvironment. Finally, we listed the emerging treatment strategies for the new oncogenic alternations, and proposed the perspective of NSCLC with driver mutations. This review will guide clinicians to design tailored treatments for NSCLC with driver mutations.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Tumor Microenvironment/genetics*