Objective To investigate the regulatory mechanism of Notch signaling pathway by YAP in non-alcoholic steatohep-atitis(NASH)liver fibrosis,and assess the intervention effect of Cigu Xiaozhi prescription in detoxification and phlegm treatment.Methods C57BL/6J mice were randomly divided into different groups,including a normal group,NASH liver fibrosis model group,verteporfin(VP)intervention group,VP+Chinese medicine(Cigu Xiaozhi prescription)low-dose group,VP+Chinese medicine high-dose group,and dimethyl sulfoxide control group.The methionine/choline-deficient diet combined with low-dose CCl4 was used to construct the NASH liver fibrosis model.The degree of liver fibrosis was evaluated using hematoxylin and eosin(HE)and Masson staining.Four protein factors associated with liver fibrosis were detected using enzyme-linked immunosorbent assay,and hydroxyproline levels in the mouse liver was determined using the alkaline water method.The localization of α-SMA,ColⅠ,YAP,and Notch1 proteins in the liver was determined using immunohistochemistry.Additionally,the mRNA and protein expression levels of the Notch signaling pathway molecules,namely Notch1/2,J agged1,and DLL4,were assessed using real-time quantitative PCR and Western blotting analyses,respectively.Results The HE and Masson staining results revealed that the liver cells of NASH liver fibrosis mice were swollen and the cytoplasm was transparent.Additionally,evident fibrosis was observed in the hepatic lobule,portal area,and sinus;it was accompanied by heightened levels of inflam-matory cell infiltration,a large number of fat droplets,and instances of local hepatocyte necrosis,dissolution,and cirrhosis.The four factors associated with liver fibrosis showed a substantial increase(P<0.01).α-SMA,ColⅠ,YAP,and Notch1 were localized in the cytoplasm of hepatocytes.YAP,Notch1/2,and Jagged1 were highly expressed in the liver(P<0.01)but were downregulated after intervention with VP and VP+high and low doses of Cigu Xiaozhi prescription(P<0.05).Meanwhile,DLL4 factor was upregulated in the VP+high-dose of Cigu Xiaozhi prescription group(P<0.05).Conclusion YAP may inhibit activation of the Notch pathway by downregulating Notch1/2 and Jagged1 and upregulating DLL4,thereby interfering with the occurrence of liver fibrosis in NASH.Treatment with Cigu Xiaozhi pre-scription may inhibit Notch signaling pathway activation by downregulating YAP,Notch1/2,and Jagged1 and upregulating DLL4 through its multi-components and multi-targets properties,ultimately slow the progression of liver fibrosis in NASH.

Osteoporosis is a chronic skeletal disease characterized by low bone mass， destruction of bone tissue microarchitecture， and imbalance of bone homeostasis， leading to increased bone fragility and increased risk of fractures. Oxidative stress caused by the disruption of the balance between excess reactive oxygen species （ROS） and the anti-oxidative system is an important factor in the occurrence and progression of osteoporosis. Nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） is an important anti-oxidative stress pathway. Nrf2 is a primary factor in regulating cellular oxidative stress. Activating Nrf2 can stimulate the expression of HO-1. HO-1 is a key enzyme whose metabolites are bile green Oxygen， carbon monoxide， and free iron. The metabolites can scavenge ROS， thereby exerting an antioxidant effect in cells. At present， domestic and foreign scholars have reported that the Nrf2/HO-1 signaling pathway is closely related to the occurrence and development of osteoporosis and the mechanism of drugs. Chinese medicine can effectively solve the insufficiency of western medicine with multi-target， multi-channel， and multi-level advantages. Chinese medicine can resist oxidative stress， inflammatory response， and apoptosis by regulating the Nrf2/HO-1 signaling pathway， thus treating osteoporosis. This article reviewed the relationship between Nrf2/HO-1 signaling pathway and its key target protein factors and osteoporosis， to clarify the important role of the Nrf2/HO-1 signaling pathway in osteoporosis. At the same time， a systematic summary of Chinese medicines targeting and regulating the Nrf2/HO-1 signaling pathway for the treatment of osteoporosis was conducted， to provide a theoretical basis for further precise treatment of osteoporosis.

Objective Toevaluatetheclinicalvalueofmagneticresonanceenterography (MRE)indiagnosingCrohn’sdisease (CD).Methods ThearticlesconcerningthediagnosisofCD byusing MRE weresystematicallysearchedindatabasesincluding PubMed,EMbase,CochraneLibrary,WebofScience,CNKI,CBM,WanFangandVIPdata.Tworeviewersindependentlyscreenedliterature, extracteddata,andassessedbiasriskofincludedstudiesbyusingtheQUADAS-2.Then,thisMeta-analysiswasperformedbyusing Stata12.0software.Thepooledweightedsensitivity,specificity,positivelikelihoodratio(PLR),negativelikelihoodratio (NLR)and diagnosticoddsratio(DOR)werecalculated,thesummaryreceiveroperatingcharacteristiccurve(sROC)wasdrawnandtheAUC wascalculated.Results Atotalof16studieswereincluded,involving1276patientsand919bowelsegments.TheresultsofMeta-analysisshowed that,thepooledsensitivity,specificity,PLR,NLR,DORandAUCofMREdiagnosingCDwere0.87(95%CI:0.79,0.92),0.92(95%CI:0.89, 0.94),10.6(95%CI:7.4,15.2),0.15(95%CI:0.09,0.24),72.69(95%CI:32.7,161.51),0.95(95%CI:0.93,0.97),respectively.Theresultsof subgroupanalysissuggestedthat,thestudytype,MRT-field,pathogenicsiteanddiagnosticcriteriaplayedlittleeffectonthevalueof MREdiagnosingCD (P>0.05).Conclusion MREhadhigheraccuracyfordiagnosingCDand mayservedasanefficientimaging methodfordiagnosingCD.

Objective To investigate the protective effect of high-density lipoprotein (HDL) on the mice cardiac myocytes induced by oxygen and glucose deprivation (OGD).Methods Cardiac cells of primary scavenger receptor-B1 knockout mice (SR-B1-/-) and normal C57 mice (SR-B1+/+) were obtained by protease digestion and differential adhesion method. ① The two kinds of cells were divided into normal control group (Con group), OGD group, OGD+HDL group. Propidium iodide (PI) staining were used to determine the necrosis of cardiac myocytes. ② SR-B1+/+cardiac cells were divided into Con group, OGD group, OGD+HDL group, and phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) inhibitor LY294002 group. PI staining were used to determine the necrosis of cardiac myocytes. TUNEL staining was used to determine the cell apoptosis. The kit was used to determine the contents of MB isoenzyme of creatine kinase (CK-MB) and lactate dehydrogenase (LDH) in the culture medium supernatant. The expressions of SR-B1 and Akt protein were determined by Western Blot.Results ① In SR-B1+/+ cardiomyocytes, HDL could inhibit cell necrosis induced by OGD. There was no protective effect of HDL on OGD in the SR-B1-/- cardiomyocytes.② The study of SR-B1+/+ cells was showed that compared with Con group, necrotic cells were significantly increased and cell activity were significantly decreased, the cell viability were significantly decreased, the contents of LDH and CK-MB in supernatant were significantly increased, the expressions of phosphorylated Akt (p-Akt) and SR-B1 were significantly decreased in OGD group. Compared with OGD group, the number of necrotic cells in the OGD+HDL group was significantly decreased [PI positive cells rate: (26.71±5.94)％ vs. (64.24±18.34)％], the cell activity was significantly increased [(63.84±6.95)％ vs. (26.71±5.13)％], the contents of LDH and CK-MB in supernatant were significantly decreased [LDH (U/L): 896.3±161.5 vs. 1568.3±243.5, CK-MB (U/L): 304.3±72.9 vs. 583.6±81.6], the expressions of p-Akt and SR-B1 were significantly increased (p-Akt/t-Akt: 0.84±0.13 vs. 0.18±0.06, SR-B1/β-actin: 1.23±0.19 vs. 0.09±0.02), with statistically significant differences (allP < 0.05). Compared with OGD+HDL group, necrotic cells in LY294002 group were increased, cell activity was decreased, LDH and CK-MB contents in supernatant were increased, p-Akt and SR-B1 expressions were decreased; there was no statistical difference between LY294002 group and OGD group. There was no significant difference in cell apoptosis among the 4 groups.Conclusions HDL has protective effect on the mice myocardial cells. The mechanism may be related with the up regulation of the expression of SR-B1 protein by the activation of PI3K/Akt pathway.

Objective To explore the effects and molecular mechanisms of suberoylanilide hydroxamic acid (SAHA) on ovarian carcinoma. Methods (1)Two groups of ovarian carcinoma cell lines (SKOV3 and SKOV3/DDP, HO8910 and HO8910-PM) were exposed to SAHA (1, 3, 5 and 7μmol/L SAHA,group 1-group 4). CCK-8 method was employed to eval-uate the inhibitory effects of SAHA.(2)Ovarian cancer cell lines treated with SAHA (2 or 5μmol/L SAHA) were used as 1 and 2 groups. Flow cytometry was performed following staining with Annexin V-FITC and PI for cell cycle and apoptosis.(3) Reverse transcription polymerase chain reaction (RT-PCR) and Western blot assay were used to assess the mRNA and pro-tein expression levels of phenotypic correlation factor. Results (1)After 48 h of SAHA treatment,the OD value of SKOV3, SKOV3/DDP,and HO8910 showed a trend of gradually reduce (P<0.05).(2)The apoptotic rates were significantly higher in SAHA 1 and SAHA 2 groups than those of control group (P<0.05). Compared with control group, after 48 h of SAHA treat-ment,S phase and G2/M phase of SKOV3 and SKOV3/DDP cells increased;G0/G1 phase of HO8910 and HO8910-PM cells increased in SAHA 1 and 2 groups (P<0.05).(3)The expression levels of CyclinB1 and Cdc2 (p34) mRNA were significant-ly lower in SAHA 1 and 2 groups than those of control group,while the expression levels of Caspase-3,p21 and p53 mRNA expression were significantly higher in SAHA 1 and 2 groups than those of control group. Furthermore,the expression of Ac-Histone H3,Ac-Histone H4,p53 protein were markedly improved,and CyclinB1,Cdc2(p34) protein decreased in SAHA 1-4 groups. Conclusion SAHA may suppress cell growth, induce apoptosis and cause cycle arrest in ovarian carcinoma cells by promoting histone acetylation or modulating their phenotype-related proteins of Caspase-3, p53, CyclinB1 and Cdc2(p34).

BACKGROUND:When the intervertebral disc is under stress, the hydraulic pressure generated inside the nucleus pulposus makes the annulus fibrosus extend outward and expand, and the annulus colagen fibers are stretched so that the extracelular matrix of annulus fibrosus cels is also under the pressure. In the intervertebral disc, aggrecan is the main component of proteoglycans, matrix metaloproteinase-2 is a major enzyme for extracelular matrix degradation, and tissue inhibitor of metaloproteinase is a multifunctional specific inhibition factor for matrix metaloproteinase activity. There is a mutual regulation between the latter two to keep the homeostasis between them.
OBJECTIVE: To investigate the mechanism of cyclic tensile strain in the metabolism of intervertebral disc annulus matrix.
METHODS:Rat anulus fibrosus cels were subjected to 2% or 10% cyclic tensile strain at 1.0 Hz for 2 and 12 hours using Flexcel4000 tension system. Then cels were colected and cultured in conditioned medium for gene and protein detection. Real-time quantitative PCR was used to detect mRNA expression of aggrecan, matrix metaloproteinases-2 and tissue inhibitor of metaloproteinase-2. Gelatin zymography was used to detect matrix metaloproteinases-2 activity.
RESULTS AND CONCLUSION:The use of 2% cyclic tensile strain had no obvious effect on the stress fiber of actin cytoskeleton, whereas actin cytoskeleton was depolymerized in response to 10% cyclic tensile strain. The 2% cyclic tensile strain raised the expression of Aggrecan at 12 hours; whereas raised the matrix metaloproteinases-2 and tissue inhibitor of metaloproteinase-2 at 2 hours, both of which were in homeostasis; matrix metaloproteinases-2 activity had no significant changes. 10% cyclic tensile strain had no effect on the mRNA expression of Aggrecan. No matter stretching 2 or 12 hours, the matrix metaloproteinases-2 was up-regulated, and the tissue inhibitor of metaloproteinase-2 was down-regulated, both of which were not in balance. Moreover, the matrix metaloproteinases-2 activity was not significantly changed. These findings indicate that the mRNA expressions of Aggrecan, matrix metaloproteinases-2 and tissue inhibitor of metaloproteinase-2 alter in response to cyclic tensile strain in rat anulus fibrosus cels, and the tensile strain induces different mechano-responses in the actin cytoskeleton.

BACKGROUND:There is a high morbidity after spinal cord injury, and the therapeutic strategy is limited to early surgical intervention, medication and post-treatment exercise that only can improve the motor function slightly. However, there is no effective cure method. OBJECTIVE:To study the effect of partition-type spinal cord catheter combined with bone marrow stromal stem cels on T8 spinal cord transection damage in rats. METHODS:Fifty rats were randomized into five groups (n=10 per group): group I, T8 spinal cord transection (5 mm) was made in rats with no treatment; group II, the partition-type tube was inserted into the injured site after modeling; group III, partition-type tube combined with bone marrow stromal stem cels was implanted into the injured site after modeling; group IV, partition-type tube combined with polyglycolic acid fibers was implanted into the injured site after modeling; group V, partition-type tube combined with bone marrow stromal stem cels and polyglycolic acid fibers was implanted into the injured site after modeling. RESULTS AND CONCLUSION:At 2 and 12 weeks postoperatively, Basso, Beattie and Bresnahan scores were significantly higher in the groups III and IV than the groups I, II, IV (P < 0.05). At 12 weeks postoperatively, the latency of motor evoked potential below the injury plane was significantly decreased in group V compared with groups I, II, III, IV (P < 0.05). Immunohistochemical results displayed that in the groups III and V, regenerated nerve fibers grew positively and arranged orderly among the tubes, and there was no obvious winding phenomenon. Under transmission electron microscopy, a certain number of myelinated nerve fibers were found as bridges among groups. These findings indicate that the partition-type chitosan tube combined with bone marrow stromal stem cels has a good connection with the injured spinal cord a good connection to restore part of electrophysiological properties, accelerate the axon regeneration, recover the motor function, thereby providing a new direction for the treatment of spinal cord injury. Cite this article:Zhao XW, Liu X, Yu DP, Rong H, Yu XS, Yang CS, Liu T, Zhao TB. Partition-type spinal cord catheter combined with bone marrow stromal stem cels in the repair of spinal cord transection injury in rats. Zhongguo Zuzhi Gongcheng Yanjiu. 2016;20(1):42-48.

Objective To investigate the safety and short-term clinical outcomes of percutaneous targeted positioning bone cement augmentation treatment for osteoporotic compression fracture nonunion. Methods A total of 32 cases of osteoporotic vertebral compression fracture nonunion, with clinical course of more than 6 months between September 2009 and September 2012 were selected. Under local anesthesia and radiological monitoring, targeted positioning puncture was carried out to inject bone cement to strengthen the lesions of nonunion. Visual analogue scale (VAS), activities of daily living (ADL) and radiographic results were compared among preoperative 1 day and postoperative 1 day, 3 months, 6 months, and 12 months. Results The operation was successfully completed in 34 vertebrae of the 32 cases. Postoperative radiographic observation found no cement leakage. As compared to preoperative level, the VAS scores significantly deceased at postoperative 1 day, 3 months, 6 months, and 12 months (P<0. 05), with significant decrease from postoperative 3 months to 12 months (P<0. 05). At postoperative 3 months, 6 months, and 12 months, the ADL scores significantly increased as compared to preoperation (P <0. 05). No significant differences were seen in vertebral anterior and middle height between the preoperation and postoperation (P>0. 05). Conclusion Percutaneous targeted positioning bone cement augmentation treatment for osteoporotic compression fracture nonunion is safe and effective.

Background and objective Cetuximab is a monoclonal antibody directed against epidermal growth fac-tor receptor. Emerging evidence showed improved effcacy with the addition of cetuximab to chemotherapy in advanced non-small cell lung cancer (NSCLC), but the data in oriental population are limited. hTe aim of this study is to investigate the eff-cacy of cetuximab in combination with chemotherapy in Chinese patients with advanced NSCLC.Methods NSCLC patients receiving cetuximab in combination with chemotherapy in Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College were enrolled and retrospectively analyzed. Clinical characteristic, effcacy, outcome and toxicity data were analyzed.Results A total of 40 patients were enrolled into this study in which 29 were male, 36 with adenocarcinoma. In the 23 patients who had received palliative chemotherapy previously (with a median of 2 prior chemotherapy regimens), the median progression-free survival (PFS) atfer the last prior chemotherapy regimen was 2.3 months. For the overall population, 13 (32.5%) patients achieved partial response atfer cetuximab in combination with chemotherapy. Response rate were 52.9% (9/17) and 17.4% (4/23) in chemotherapy-naive patients and chemotherapy-treated patients, respectively (P=0.018). hTe median PFS was 4.8 months for the overall population. In chemotherapy-naive patients and chemotherapy-treated patients, the median PFS was 8.4 months and 4.1 months, respectively (P=0.062). hTe estimated median overall survival was 17.1 months. Toxicities were generally manageable and no treatment-related deaths occurred.Conclusion Cetuximab in addition to che-motherapy appears to be associated with promising effcacy and acceptable toxicity proifle in Chinese patients with advanced NSCLC. Further validation is needed.

Objective To survey the current situation of hypertension among "three minority ethnic groups" in Inner Mongolia Autonomous Region.Methods Hypertension epidemiological survey among Three Minority Ethnic Groups and Han nationality aged ≥ 18 years was performed from June to December 2010.Results The prevalence rate of hypertension among the surveyed population was 29.4％ (630/2 146) (standardized prevalence was 34.6％).The prevalence rate of hypertension in male was 33.8％ (359/1 062) (standardized prevalence was 39.9％),and the prevalence rate in female was 25.0％ (271/1 084) (standardized prevalence was 26.6％),and the prevalence rate in male was higher than in female (P ＜ 0.01).The prevalence rate of hypertension for the Oroqen nationality,Ewenki nationality and Daur nationality was 33.8％ (92/272),32.4％ (170/524),and 30.2％ (174/576) respectively (standardized prevalence was 33.7％,33.1％,and 3 1.3％),and which was significantly higher than in the Han nationality (25.1％ (194/774),P ＜ 0.01) (standardized prevalence was 25.8％).The awareness,treatment and control rate of hypertension in the Oroqen nationality residents was 64.1％ (59/92),56.5％ (52/92),27.2％ (25/92) (standardized rate was 63.5％,56.8％ and 27.4％),and 60.0％ (102/170),53.5％ (91/170),24.1％ (41/170) (standardized rate was 62.9％,56.7％,26.6％) in the Ewenki nationality residents,and 59.2％ (103/174),54.0％ (94/174),20.7％ (36/174) (standardized rate was 60.3％,54.7％,21.4％) in the Daur nationality residents,and 65.0％ (126/194),57.7％ (112/194),27.3％ (53/194) (standardized rate was 63.3％,56.5％,27.1％) in the Han nationality residents.Awareness rate,treatment rate and control rate were similar among different nationalities (all P ＞ 0.05).Conclusion The prevalence rate of hypertension among " three minority ethnic groups" residents in Inner Mongolia Autonomous Region is high and comprehensive prevention and therapy strategies are warranted to reduce the hypertension burden in these residents.