BACKGROUND: Psoriasis is a chronic inflammatory skin disease, affecting about 0.6% of the Chinese population. Many patients are not well controlled by conventional treatments, thus there is need for new treatment regimens. In this study, we assessed the efficacy and safety of secukinumab in Chinese patients with moderate to severe plaque psoriasis. METHODS: This study was a 52-week, multicentre, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 trial. A sub-population of study participants (≥18 years) of Chinese ethnicity were randomized to receive subcutaneous injections of 300 or 150 mg secukinumab, or placebo. The co-primary endpoints were psoriasis area severity index (PASI) 75 and Investigator's Global Assessment (IGA) 0/1 at Week 12. RESULTS: A total of 441 Chinese patients were enrolled in this study. Co-primary outcomes were achieved; 300 and 150 mg secukinumab were superior to placebo as shown in the proportion of patients that achieved PASI 75 (97.7% and 87.2% vs. 3.7%, respectively; P < 0.001), and IGA 0/1 (82.3% and 69.7% vs. 2.7%; P < 0.001) at Week 12. Treatment efficacy was maintained until Week 52. There was no increase in overall adverse events with secukinumab relative to placebo throughout the 52-week period. CONCLUSION: Secukinumab is highly effective and well tolerated in Chinese patients with moderate to severe plaque psoriasis. TRIAL REGISTRATION ClinicalTrials.gov, NCT03066609; https://clinicaltrials.gov/ct2/show/record/NCT03066609.
Antibodies, Monoclonal/therapeutic use* ; Antibodies, Monoclonal, Humanized ; China ; Double-Blind Method ; Humans ; Psoriasis/drug therapy* ; Severity of Illness Index ; Treatment Outcome

OBJECTIVETo detect whether the murine T-cell lymphoma cell line EL4 could be infected by murine cytomegalovirus (MCMV), and to observe the morphological changes and apoptosis of El4 cells before and after infection.

METHODSEL4 cells were infected with MCMV smith strain with 1, 10 and 100 multiplicity of infection (MOI) respectively. The morphology of the cells was observed by light microscopy and Wright's-Giemsa staining. The survival rate was calculated by trypan blue staining. RT-PCR-based assay was used to detect the copy number of MCMV-DNA in the infected ELA cells. Flow cytometry was used to detect apoptosis. RT-qPCR was used to detect the mRNA expression levels of P53, P21, cFlip and Caspase 8. The protein expression levels of Caspase8, P53, BAX, BCL-2 and Cleaved Caspase3 proteins were detected by Western blot.

RESULTSAfter Wright-Giemsa staining, it was found that the infected EL4 cells displayed larger volume, irregular nuclei and the folded twist under light microscopy. Compared with the normal control group, the survival rate of EL4 cells decreased, and the apoptosis rate statistically significantly (P<0.05) increased with the increasing MOI and the infected time in each group. While, the level of apoptosis protein P53, BAX/BCL-2, Cleaved-caspase3 and Caspase8 were up-regulated. And the survival rate, apoptosis rate and the apoptosis protein level of infected EL4 cells with MOI=10 were the most obvious at the 5day. Compared with MCMV infection group (MOI=60), the content of MCMV DNA in EL4 cells was decreased in MCMV+GGV group ［MOI=60, GCV 25 (g/ml)］, and the cell apoptosis rate and apoptosis protein expression of P53, Caspase8, BAX/BCL-2 were decreased (P<0.05).

CONCLUSIONMurine T-cell lymphoma cell line EL4 can be infected by MCMV and displayes an obvious apoptosis phenomenon. MCMV may up-regulate the expression levels of apoptosis protein P53, BAX-BCL-2, Cleaved-caspase3 and Caspase8 in EL4 cells. The drug ganciclovir reduces the copy mumber of MCMV DNA in infected EL4 cells and inhibited the killing effect of MCMV on EL4 cells.

Animals ; Apoptosis ; Caspase 8 ; Ganciclovir ; Lymphoma, T-Cell ; Mice ; Muromegalovirus

Periplaneta americana is an important medicinal insect. A series of new drugs developed from it have remarkable clinical effects and are in great demand in the market. Because of unclear biology, the quality and yield of P. americana are affected. Understanding the developmental threshold temperature and effective accumulated temperature of P. americana can provide theoretical basis for standardized culture of P.americana. Under climate chamber, the threshold temperature and effective accumulated temperature for egg development of P. americana to were determined through effective accumulated temperature law. The threshold temperature was （15.8±0.71）°C, the effective accumulated temperature was 415.8±38.05 degree days. A model of the relationship between temperature and developmental rates was established.
Animals ; Ovum ; physiology ; Periplaneta ; physiology ; Temperature

BACKGROUND: Adipose-derived mesenchymal stem cells (ADMSCs) have been reported to improve wound healing. However, type I collagen secreted by ADMSCs will contribute to scar formation. Therefore, inhibiting type I collagen secretion from ADMSCs will strengthen its clinical application. OBJECTIVE: To investigate the effect of 1,25(OH)2D3on secretion of type I collagen by ADMSCs and its mechanism. METHODS: Human ADMSCs were isolated by collagenase digestion, and identified by flow cytometry. ADMSCs at passage 4 were cultured in DMEM/F12 medium containing different concentrations of 1,25(OH)2D3(10-7, 10-8, 10-9, 10-10and 0 mol/L) respectively for 4 days. Then, the concentration of type I collagen in cell supernatant was measured by ELISA. Real-time PCR and western blot were used to detect the expression of Smad3 at mRNA and protein levels and phosphorylated protein Smad3 level in ADMSCs cultured with and without 1,25(OH)2D3. To analyze the contribution of Smad3 to the effect of 1,25(OH)2D3, Smad3 inhibitor was added to culture medium 30 minutes before adding 1,25(OH)2D3, and type I collagen in cell supernatant was detected by ELISA at 4 days after addition of SMAD3 inhibitor. RESULTS AND CONCLUSION: 1,25(OH)2D3inhibited the secretion of type I collagen by ADMSCs in a dose-dependent manner. The results of real-time PCR and western blot showed that the expression of Smad3 was upregulated by 1,25(OH)2D3, and the results of western blot showed that the phosphorylated Smad3 protein level in ADMSCs was significantly increased by 1,25(OH)2D3. Moreover, the inhibition of type I collagen secretion by 1,25(OH)2D3could be blocked by Smad3 inhibitor. These results indicate that 1,25(OH)2D3can inhibit the secretion of type I collagen from ADMSCs by up-regulating the expression of Smad3.

OBJECTIVETo review the recent progress of multilayer stents in treating arterial aneurysms and to draw an initial conclusion about its paradigm.

DATA SOURCESPubMed database and ELSEVIER database were searched with the keywords "cardiatis" or "multilayer stent" for relevant articles from January 2008 to September 2012. Relevant websites (provided by Cardiatis) were also involved in the review process.

STUDY SELECTIONWell-controlled, relatively large-scale, retrospective studies as well as meaningful individual cases were all selected as materials.

RESULTSA total of 23 articles were involved in this review. The newly introduced Cardiatis multilayer stent aims at creating an active flow-modulating barrier between normal blood flow and aneurismal sac, which can induce thrombosis within aneurismal sac and preserve collateral circulation at the same time. Currently, it has been applied for complicated aneurysms located in different segments of the arterial system.

CONCLUSIONThis new concept of multilayer uncovered stent offers a promising alterative in the treatment of arterial aneurysms. However, a further large-scale clinical and hemodynamic study is required to evaluate the long-term effects.

Aneurysm ; physiopathology ; therapy ; Databases, Factual ; Hemodynamics ; physiology ; Humans ; Retrospective Studies ; Stents

BACKGROUNDMost of endovascular stent-graft modifications to preserve side branch must be customized according to extensive pre-operative assessment, which may not be possible in many hospitals and emergency settings. The study was to develop a novel stent-grafts system that would allow in situ "fenestration", with less reliance on preoperative imaging.

METHODSThe magnitude of pressure difference (PD) between left subclavian artery (LSA) and aortic arch were measured in 12 experimental pigs. Changes of PD before and after LSA was covered were analyzed respectively. The novel stent graft was made by multi-dimensional and multiple textiles forming technology. According to the PD measurement in pigs, we evaluated the feasibility of the stent-graft in a mock circulation system.

RESULTSIn pigs, the blood pressure of aortic arch was significantly higher than that of LSA after it was covered (P < 0.001) and PD was (42.78 ± 5.17) mmHg. After target vessel was covered and when PD between the LSA and aorta reached the magnitude measured in pigs, contrast media oozed from the cranny of graft to the LSA, which was generated by sliding and deformation of yarns of novel stent-graft.

CONCLUSIONSThe study proposes the design of pressure difference-induced perforation aortic stent-grafts system and verifies that the PD between LSA and aortic arch is high enough to allow in situ "fenestration" by stent graft made by multi-dimensional and multiple textiles forming technology.

Animals ; Aorta, Thoracic ; surgery ; Blood Pressure ; physiology ; Blood Vessel Prosthesis ; Blood Vessel Prosthesis Implantation ; Prosthesis Design ; Subclavian Artery ; Swine

OBJECTIVETo investigate thoracic aortic longitudinal elastic strength in β-aminopropionitrile (BAPN) treated rat model of aortic dissection (AD).

METHODSTwenty-nine young rats (Sprague-Dawley) were divided into tow groups, control group (n = 12) and BAPN group (n = 17). Seventeen rats were treated with 0.25% BAPN mixed in feed for 6 weeks. All the rats were sacrificed in the end of experiment and aorta was harvested for biomechanical and pathological study. Longitudinal elastic strength and stress were detected and analyzed by material testing machine. Elasticity modulus as well as maximum stretching length, draw ratio, maximum load, maximum strength, and maximum extensibility was calculated according to the analysis with thickness and area of aortic media.

RESULTSNine BAPN-treated rats died of aortic dissecting aneurysm rupture during the experiment. The diameter of the aneurysms was (6.33 ± 1.17) mm and the length was (9 ± 5) mm. The maximum diameter significantly increased in BAPN-induced rats with AD (group B2) compared with without AD (group B1) and control group ((6.49 ± 1.20) mm vs. (1.45 ± 0.11), (1.25 ± 0.26); F = 165.257, P = 0.001 and 0.000, respectively), but there was no significance between group B1 and control group (P = 0.108). Thickness and area of aortic media in BAPN-induced rats significantly increased compared with control group (F = 27.277 and 27.153, P = 0.000 and 0.000, respectively), but there was no significance of area between group B1 and B2 (P = 0.540). Maximum stretching length, draw ratio, maximum load, maximum strength maximum extensibility and elasticity modulus were significantly decreased from group B2, group B1 to control group (P < 0.01, respectively).

CONCLUSIONSThis study built a successful model of AD. Biomechanical analysis and the decrease of maximum stretching length, draw ratio, maximum load, maximum strength maximum extensibility and elasticity modulus may explain the formation of AD partly.

Aminopropionitrile ; pharmacology ; Aneurysm, Dissecting ; chemically induced ; Animals ; Aorta ; pathology ; physiopathology ; Biomechanical Phenomena ; Disease Models, Animal ; Elastic Modulus ; Male ; Rats ; Rats, Sprague-Dawley

ObjectiveTo investigate the effect of drinking brick tea with low-fluoride level on prevention of tea type fluorosis.MethodsHandahangacha,Hadayinggegacha,Dalainuoyi town,in Keshiketengqi Inner Mongolia endemic fluorosis area were selected as test points,and brick tea with fluoride [(204.5 ± 10.2),(308.2 ±15.4)mg/kg] was given for 12 months.Dental fluorosis,clinical skeletal fluorosis,and X-ray diagnosis of skeletalfluorosis [according to “Endemic Skeletal Fluorosis Diagnostic Criteria” (WS 192-2008)] of adults 20 to 70 years of age were examined and level of fluoride before and after the prevention trial,in brick tea,drinking water,milk tea and urine were tested (fluoride ion selective electrode method),and fluoride intake through tea was calculated.ResultsDetection rate of adult dental fluorosis in Handahangacha was 68.89％ (62/90),clinical detection of skeletal fluorosis was 55.32％ (52/94),and X-ray detection of skeletal fluorosis was 65.17％ (58/89); adult dental fluorosis detection rate in Hadayinggegacha was 54.84％(51/93),clinical detection of skeletal fluorosis was 65.69％(67/102),and X-ray detection rate of skeletal fluorosis was 61.36％ (54/88).Brick tea fluoride was (831.4 ±138.9),(864.3 ± 134.6)mg/kg before the prevention trial in Handahangacha and Hadayinggegacha,respectively,drinking water fluoride content was (0.27 ± 0.05),(0.54 ± 0.24)mg/L,fluoride content of milk tea was (216 ± 1.12),(2.82 ± 1.38)mg/L,adult urine fluoride content was (2.78 ± 1.57),(2.96 ± 1.80)mg/L,and fluoride intake through milk tea was (8.12 ± 5.84),(6.42 ± 5.04)mg/d,respectively; after the prevention trial the fluoride content of brick tea was (204.5 ± 10.2),(308.2 ± 15.4)mg/kg,fluoride content of drinking water (0.34 ± 0.11),(0.62 ± 0.30)mg/L,fluoride content of milk tea(0.97 ± 0.33),(1.83 ± 0.66)mg/L,fluoride content in urine(1.29 ± 0.55),( 1.47 ±0.62)mg/L,fluoride intake through milk tea (3.45 ± 2.05),(3.71 ± 2.07)mg/d,respectively; in Handahan and Hadayinggegacha after the prevention trial the fluoride in brick tea,milk tea,urine fluoride,and fluoride intake through milk tea was significantly lower than that before the trial (t =14.30,12.97 ;6.46,3.95;6.69,5.72;6.27,3.57,all P ＜ 0.01 ).Fluoride intake in Handahangacha through milk tea was within the state heath standard limits( ＜ 3.5mg/d).ConclusionDrinking low-fluoride brick tea can prevent drinking brick tea type fluorosis,the preventive effect is especially more reliable with low fluoride brick tea (204.5 ± 10.2)mg/kg.

BACKGROUNDLiver injury is one of the most important adverse effects of antiretroviral therapy, leading to therapy changing or discontinuation. Data on liver injury in human immunodeficiency virus-1-infected patients receiving antiretroviral therapy are limited in China. The purpose of this study was to investigate the features of liver injury in human immunodeficiency virus type 1-infected patients receiving non-nucleosides reverse transcriptase inhibitors-based antiretroviral therapy in China.

METHODSSeventy-five patients on antiretroviral therapy containing non-nucleosides reverse transcriptase inhibitors were retrospectively studied. The patients were divided into 2 groups: group 1 (with liver injury, n = 45) and group 2 (without liver injury, n = 30). The features of liver injury were analyzed. The sex, age, baseline CD4 counts, hepatitis B virus (HBV) and/or hepatitis C virus (HCV) co-infection, hepatotoxic drug use and nevirapine or efavirenz use were compared between two groups.

RESULTSForty-five patients (60.0%), 31 (68.9%) males and 14 (31.1%) females, aged 12 to 52 years (averaged (39 ± 9) years), experienced at least one episode of liver injury. Forty (53.3%) patients were co-infected with HBV and/or HCV, 42 (56%) patients had concomitant use of antituberculosis drugs or cotrimoxazole, 46 (61.3%) and 29 (38.7%) patients received regimen containing nevirapine and efavirenz, respectively. Grade 1 liver injuries were observed in 26 (57.8%) patients, grade 2 in 16 (35.6%), grade 3 in 2 (4.0%) and grade 4 in 1 (2.2%). Three (6.7%) patients discontinued highly active antiretroviral therapy (HAART) due to liver injury. In group 1, there were 29 (64.4%) patients co-infected with HBV and/or HCV, 32 (71.1%) patients received regimen containing nevirapine, and 30 (66.7%) patients had concomitant use of anti-tuberculosis drugs or cotrimoxazole, respectively, significantly higher than those in group 2 (11 (36.7%), 14 (46.7%) and 12 (40%), respectively; P = 0.018, 0.033, 0.023, respectively). The sex, age, baseline CD4 counts and disease stage were not factors associated with liver injury.

CONCLUSIONSLiver injury associated with HAART containing non-nucleosides reverse transcriptase inhibitors was mild to moderate and those who were co-infected with HBV and/or HCV, had concomitant use of antituberculosis drugs or cotrimoxazole and received a regimen containing nevirapine were prone to liver injury while receiving HAART.

Acquired Immunodeficiency Syndrome ; drug therapy ; Adolescent ; Adult ; Antiretroviral Therapy, Highly Active ; adverse effects ; Chemical and Drug Induced Liver Injury ; etiology ; Child ; Female ; HIV-1 ; Humans ; Male ; Middle Aged ; Nevirapine ; adverse effects ; Retrospective Studies ; Reverse Transcriptase Inhibitors ; adverse effects

BACKGROUNDPDK1 is an essential protein kinase that plays a critical role in mammalian development. Mouse lacking PDK1 leads to multiple abnormalities and embryonic lethality at E9.5. To elucidate the role of PDK1 in the heart, we investigated the cardiac phenotype of mice that lack PDK1 in the heart in different growth periods and the alteration of PDK1 signaling in human failing heart.

METHODSWe employed Cre/loxP system to generate PDK1(flox/flox): α-MHC-Cre mice, which specifically deleted PDK1 in cardiac muscle at birth, and tamoxifen-inducible heart-specific PDK1 knockout mice (PDK1(flox/flox):MerCreMer mice), in which PDK1 was deleted in myocardium in response to the treatment with tamoxifen. Transmural myocardial tissues from human failing hearts and normal hearts were sampled from the left ventricular apex to analyze the activity of PDK1/Akt signaling pathways by Western blotting.

RESULTSPDK1(flox/flox): α-MHC-Cre mice died of heart failure at 5 and 10 weeks old. PDK1(flox/flox) -MerCreMer mice died of heart failure from 5 to 21 weeks after the initiation of tamoxifen treatment at 8 weeks old. We found that expression levels of PDK1 in human failing heart tissues were significantly decreased compared with control hearts.

CONCLUSIONOur results suggest that PDK1 signaling network takes part in regulating cardiac viability and function in mice, and may be also involved in human heart failure disease.

3-Phosphoinositide-Dependent Protein Kinases ; Adult ; Animals ; Female ; Glycogen Synthase Kinase 3 ; physiology ; Heart ; physiology ; Heart Failure ; enzymology ; etiology ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Middle Aged ; Myosin Heavy Chains ; physiology ; Protein-Serine-Threonine Kinases ; metabolism ; Proto-Oncogene Proteins c-akt ; physiology ; Signal Transduction ; Tamoxifen ; pharmacology