Objective To compare the effectiveness and safety of ultra-early (< 24 h)and delayed (≥ 24 h ) endovascular embolization of ruptured intracranial aneurysms with systematic review. Methods PubMed,Embase,the Cochrane Library,VIP,Wanfang Data,and China National Knowledge Internet (CNKI)were retrieved according to inclusion,exclusion criteria and retrieval strategies,and the clinical literature of ultra-early and delayed endovascular embolization for the treatment of ruptured intracranial aneurysms were obtained. The Review Manager 5. 3 software was used to conduct Meta-analysis for good prognosis rate,postoperative mortality,and postoperative rebleeding rate. Results A total of 10 articles were included,9 of them were retrospective control studies and 1 was prospective control study. A total of 2 021 patients were enrolled,including 970 patients treated with ultra-early treatment;1 051 patients treated with delayed treatment. There was significant difference in the good prognosis rate (OR,2. 67,95% CI 2. 07 -3. 44,P < 0. 01)and the postoperative rebleeding rate (OR,0. 23,95% CI 0. 11 -0. 47)between the ultra - early embolization group and the delayed embolization group (all P < 0. 01). There were no significant difference in the mortality between the two groups (OR,0. 76,95% CI 0. 51 -1. 13,P = 0. 17). The subgroup analysis showed that there were significant differences in the good prognosis rate in the ultra-early group compared with the early group (< 3 d,OR,1. 98,95% CI 1. 33 -2. 95)and the middle and late group (≥3 d,OR,4. 66,95% CI 2. 21 -9. 81,all P < 0. 01). Conclusion Compared with the delayed group, ultra-early embolization of ruptured intracranial aneurysms may improve the good prognosis rate,reduce the rebleeding rate,and not increase the mortality after procedure at the same time. However,more high quality and large sample randomized controlled trials are needed to confirm them.

Nuclear factor κB (NF-κB) is an important cellular transcription factor. The important role of NF-κB-mediated cell signal transduction pathway in apoptosis is a hot topic at home and abroad. In order to discover new regulators in NF-κB signaling pathway, a high-throughput cell-based screening model based on dual luciferase reporters system was established, a number of genes that can activate NF-κB signal pathway were obtained by screening of 439 novel function genes. Among them, TMEM9B can obviously activate NF-κB signaling pathway. Further experiments showed that TMEM9B activated NF-κB signaling pathway in a dose-dependent pattern. Western blotting and EMSA experiments confirmed that TMEM9B can promote the degradation of IκBα (a cytoplasm inhibitor of NF-κB), and cause NF-κB shift from the cytoplasm to nucleus. At the same time, flow cytometry result demonstrated TMEM9B can induce apoptosis in HEK293T and HeLa cells. In short, a stable and effective screening system for NF-κB has been established, through which TMEM9B was identified to be able to significantly activate NF-κB signal transduction pathway and thus cause cells apoptosis.

Objective To study the effect of sub-chronic exposure to dehamethrin(DM) on the behavior of mice in learning and memory.Methods 60 Female SPF Kunming mice were randomly divided into 4 groups and given DM by gavaging for 60 days.Morris water maze (MWM) was used to evaluate spatial memory in mice.Results After exposure to DM,the escape latency of the solvent control group and the treatment groups were (12.20±6.5)s,(14.99±5.4) s,(15.64±8.3)s,(22.71±6.2)s on the fifth day.The escape latency of the high-dose group was higher than those of the low-dose group (P=0.0041) and the solvent control group (P=0.019) in the navigation test.The number of crossing position of the platform in the high-dose group ((2.93± 1.53)times) and the middle-dose group ((3.40± 1.12) times) were lower than that in the solvent control group ((5.87 ± 1.55) times) and the low-dose group ((4.90± 1.41)times)(P＜0.05).Conclusion Sub-chronic exposure to DM can damage the spatial learning and memory of mice.

OBJECTIVETo determine whether the sonic hedgehog (Shh) signaling could regulate the expression of histone demethylases in the head and neck squamous cell carcinoma(SCC).

METHODSHuman recombinant SHH-N protein or over-expression of the mutant 2 smoothened (M2-SMO) was applied to activate the Shh signaling in tongue squamous cell carcinoma cell line-SCC-6 in this study. Cyclopamine was used to block the Shh signaling in SCC-6. The real-time reverse transcription (RT)-PCR was used to detect the expression of histone demethylases at the mRNA level.

RESULTSThe data showed that activation of the Shh signaling up-regulated the expression of histone demethylase, lysine-specific demethylase 8 (KDM-8) at the mRNA level by human recombinant SHH-N protein (1.841 ∼ 3.591 fold compare with untreated group; P < 0.01), over-expression of the M2-SMO also increased the expression of KDM-8 (1.358 ∼ 3.013 fold compared with empty vector group; P < 0.05), and after the Shh signaling was blocked by Cyclopamine, the expression of KDM-8 was down regulated (decreased 25.6% ∼ 66.6% compared with control cells, P < 0.05).

CONCLUSIONSHistone demethylase KDM-8 was downstream target gene of Shh signaling in head and neck squamous cell carcinoma cell line SCC-6, and its expression was positively regulated by the Shh signaling.

Carcinoma, Squamous Cell ; genetics ; metabolism ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Head and Neck Neoplasms ; genetics ; metabolism ; Hedgehog Proteins ; metabolism ; Histone Demethylases ; genetics ; metabolism ; Humans ; Mutant Proteins ; metabolism ; RNA, Messenger ; genetics ; Receptors, G-Protein-Coupled ; metabolism ; Recombinant Proteins ; metabolism ; Signal Transduction ; Smoothened Receptor ; Veratrum Alkaloids ; pharmacology

Worldwide sales of biologic drugs exceeded 100 billion USD in 2011. About 32% is from therapeutic monoclonal antibody (mAb). With many blockbuster biopharmaceutical patents expiring over the next decade, there is a great opportunity for biosimilar to enter the worldwide especially emerging market. Both European Medicines Agency (EMA) and Food and Drug Administration (FDA) have introduced regulatory frameworks for the potential approval of biosimilar mAb therapeutics. Rather than providing a highly abbreviated path, as in the case for small molecule chemical drug, approval for biosimilar mAb will require clinical trial and the details will be very much on a case-by-case basis. Since mAb is the dominant category of biologic drugs, mAb will be the focus of this review. First, the United States (US) and European Union (EU) approved mAb and those in phase 3 trials will be reviewed, then strategies on how to win biosimilar competition will be reviewed.
Animals ; Antibodies, Bispecific ; therapeutic use ; Antibodies, Monoclonal ; therapeutic use ; Antibodies, Monoclonal, Humanized ; therapeutic use ; Biosimilar Pharmaceuticals ; standards ; Clinical Trials, Phase III as Topic ; Drug Approval ; European Union ; Humans ; United States ; United States Food and Drug Administration

In 2013, the World Health Organization reported the first case of human infection with a new influenza A (H7N9) virus in China. This has caused damage and panic within certain areas in China. Therefore, analysis of this virus with bioinformatics technology is very necessary. Neuraminidase (NA) is one of the most important antigens of the influenza virus and an important target for anti-flu drugs. In this study, the nucleotide and protein sequences of NA gene of A/H7N9 influenza viruses were retrieved from the NCBI database, and MEGA 5.0 software was employed to construct a phylogenetic tree based on the nucleotide coding sequence; BioEdit software was used to align the nucleotide and protein sequences of NA and calculate the homologies of nucleotides and amino acids and then to analyze the important mutation sites of NA gene. The results demonstrated that the spread of influenza virus H7N9 showed certain geographical and temporal relations. The H7N9 virus isolated from China in 2013 belonged to Euroasiatic serotype, and its NA stalk region hadobvious variation, which may be one of the reasons that this virus infects human. These analyses may be very helpful for understanding the evolutionary relationship and mutation trend of A/H7N9 influenza viruses.
Databases, Genetic ; Evolution, Molecular ; Humans ; Influenza A Virus, H7N9 Subtype ; enzymology ; genetics ; Mutation ; Neuraminidase ; chemistry ; genetics ; Phylogeny ; Sequence Analysis

OBJECTIVEIsobaric tags for relative and absolute quantitation (iTRAQ) combined with mass spectrometry were used to screen differentially expressed plasma proteins in cold stress rats.

METHODSThirty health SPF Wistar rats were randomly divided into cold stress group A and control group B, then A and B were randomly divided into 3 groups (n = 5): A1, A2, A3 and B1, B2, B3. The temperature of room raising was (24.0 +/- 0.1) degrees C, and the cold stress temperature was (4.0 +/- 0.1) degrees C. The rats were treated with different temperatures until 12 h. The abdominal aortic blood was collected with heparin anticoagulation suction tube. Then, the plasma was separated for protein extraction, quantitative, enzymolysis, iTHAQ labeling, scx fractionation and mass spectrometry analysis.

RESULTSTotally, 1085 proteins were identified in the test, 39 differentially expressed proteins were screened, including 29 up-regulated proteins and 10 down-regulated proteins. Three important differentially expressed proteins related to cold stress were screened by bioinfonnatics analysis (Minor histocompatihility protein HA-1, Has-related protein Rap-1b, Integrin beta-1).

CONCLUSIONIn the experiment, the differentially expressed plasma proteins were successfully screened in cold stress rats. iTRAQ technology provided a good platform to screen protein diaguostic markers on cold stress rats, and laid a good foundation for further. study on animal cold stress mechanism.

Animals ; Blood Proteins ; chemistry ; Cold Temperature ; Mass Spectrometry ; Rats ; Rats, Wistar ; Stress, Physiological

OBJECTIVETo observe the effect of Qingfei Peiyuan Micro-pill (QPM) on HIV/AIDS patients with pulmonary infection of phlegm heat obstructing lung syndrome (PHOLS).

METHODSTotally 141 HIV/AIDS patients with pulmonary infection of PHOLS were randomly assigned to the treatment group (94 cases) and the control group (47cases). On the basis of Western medicine, patients in the treatment group took QPM. The therapeutic course for all was 28 days. The improvement of symptoms and signs was observed. The body temperature (BT), chest X ray, and white blood cells (WBCs) were detected.

RESULTSThe Chinese medical syndrome score was lower in the treatment group than in the control group at the 7th, 21st, and 28th day of treatment, showing statistical difference (P < 0.05). The efficacy was better in the treatment group than in the control group at the 7th, 21st, and 28th day of treatment, showing statistical difference (P < 0.05). The BT was lower in the treatment group than in the control group on the 7th day. There was no statistical difference in the patient number with normal WBCs on the 7th day (P > 0.05). But there was statistical difference in the patient number with normal WBCs on the 14th, 21st, and 28th day of treatment (P < 0.05). There was no statistical difference in the patient number with normal chest X ray on the 7th and 28th day of treatment (P > 0.05). But there was statistical difference in the patient number with normal chest X ray on the 14th and 21 st day of treatment (P < 0.05).

CONCLUSIONQPM had certain complementary effect on HIV/AIDS patients with pulmonary infection of PHOLS.

Acquired Immunodeficiency Syndrome ; complications ; Adult ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Respiratory Tract Infections ; complications ; drug therapy ; Treatment Outcome

Itraconazole has been used to treat superficial candidal infections in China for 12 years with promising efficacy and safety. This article retrospectively reviewed literatures published in the mainstream journals in China with an attempt to find a reasonable therapy for Chinese populations.
Antifungal Agents ; therapeutic use ; Candidiasis ; drug therapy ; Dermatomycoses ; drug therapy ; Female ; Humans ; Itraconazole ; therapeutic use ; Male ; Retrospective Studies ; Stomatitis ; drug therapy ; microbiology ; Vaginitis ; drug therapy ; microbiology

ObjectiveTo investigate the regulatory effects of traditional Chinese medicine (TCM) Shufengxuanfeijiedu formula on Janus kinase signal transducer and activators of transcription (JAK-STAT) of lung tissues in mice with influenza viral pneumonia.Methods According to random number table, 60 mice were randomly divided into six groups with 10 mice in each group: normal group (N), model group (M), Tamiflu control group (C) and low (SL), medium (SM), high dose (SH) Shufengxuanfeijiedu formula groups. The mouse model of influenza virus pneumonia was reproduced by dropping of 0.05 mL 4LD50 inflluenza virus FM1 strain which can be adapted to lung tissue into the nose; while the N received nose instillation of 0.05 mL normal saline. After successful modeling for 2 hours, distilled water was given orally (by lavage) to N and M; Duffy (oseltamivir) 2.5 g·mL-1·d-1 was administrated to C; the TCM SL, SM, SH were intragastrically administered with different doses of shufengxuanfeijiedu decoction into the corresponding groups respectively (the ingredients of prescription: chrysanthemum, mulberry leaf, almond, platycodon root, forsythia, bupleurum etc. forming granules), according to the suitable dose of granules used for human body surface, the dose used for mouse surface area was calculated, the high dose means the dose used in the medium dose group doubled, the low dose means 1/2 dose used in medium group, once a day, once 0.2 mL for consecutive 4 days. Afterwards, the lung tissues were collected, the mouse differential gene expressions related to JAK-STAT pathway were detected by gene chip technology, the standards for screening of differential gene expression were as follows: up-regulated gene was P < 0.05, and the log2ratio > 1; down-regulation gene wasP < 0.05, and log2ratio < -1. The levels in lung tissue kinase (JAK) andγinterferon (IFN-γ) mRNA expressions were determined by real-time fluorescence quantitative reverse transcription polymerase chain reaction (RT-qPCR).Results Compared with those in N, the differential expression gene transcription activator, STAT5 [log2 (N/M) = 2.32], interleukin 4 receptor alpha subunit [IL4RA, log2 (N/M) = 4.77], interleukin 12 receptor [IL12R, log2 (N/M) = 1.58], JAK [log2 (N/M) = 2.41] were all obviously up-regulated, and IFN was significantly down-regulated [log2 (N/M) = -1.45] in M. Compared with those in M, C group IFN [log2 (C/M) = 1.51], various TCM dose groups [log2 (SL/M) = 1.46, log2 (SM/M) = 1.72, log2 (SH/M) = 1.40] differential expression gene IFN was significantly up-regulated, STAT5 [log2 (C/M) = -2.06, log2 (SL/M) = -1.41, log2 (SM/M) = -2.10, log2 (SH/M) = -1.89], IL4RA [log2 (C/M) = -2.52, log2 (SL/M) = -1.85, log2 (SM/M) = -2.74, log2 (SH/M) = -1.39), IL12R [log2 (C/M) = -1.48, log2 (SL/M) = -0.10, log2 (SM/M) = -1.58, log2 (SH/M) = -0.53], JAK [log2 (C/M) = -1.44, log2 (SL/M) = -0.88, log2 (SM/M) = -1.74, log2 (SH/M) = -0.53] were significantly down-regulated. In M, the JAK mRNA expression was obviously elevated (2-ΔΔCt: 3.17±0.94 vs. 1.01±0.13,P < 0.05), while the IFN-γ mRNA expression was decreased (2-ΔΔCt: 0.15±0.48 vs. 1.01±0.12,P < 0.05); compared with M, the JAK mRNA expressions in C, SM and SH groups were all obviously decreased (2-ΔΔCt: 2.02±0.63, 1.19±0.30, 1.59±0.67 vs. 3.17±0.94, allP < 0.05); while the IFN-γmRNA expressions in C, SL, SM and SH groups were elevated (2-ΔΔCt: 0.61±0.12, 0.41±0.13, 0.85±0.14, 0.78±0.20 vs. 0.15±0.48, allP < 0.05).Conclusions Shufengxuanfeijiedu formula can ameliorate the mice immune pathological injury of lung tissues induced by influenza virus by regulating JAK-STAT signal pathway and balancing Th1/2 via up-regulating the expression of IFN-γ.