Objective To understand the global economic burden of diseases due to needle stick injuries(NSIs), obtain relevant evidence,and prompt the relevant departments to pay attention to the precaution of NSIs.Methods Literatures about NSIs published from 1990 to May 2016 were searched from PubMed,ScienceDirect,EBSCO-host,Cochrane,CNKI,and Wanfang database.According to world bank inflation rate and currency rate in 2015, cost of needle stick injury in each study was adjusted to US dollars in December 2015,merge comparison analysis was performed.Results A total of 7 literatures were included,3 American studies and 4 studies from Sweden,Ko-rea,Belgium,and Taiwan Region of China respectively.Studies in mainland China only focused on the incidence of NSIs,studies about cost were not found.Two studies did not identify studied population,the remaining 5 studies were about all staff in the medical institutions.Cost analysis method:Of 7 literatures,3 were first-hand data analy-sis,4 were derived from the model.Scope of cost research:4 studies estimated the direct cost,2 calculated direct and indirect cost respectively,only 1 study estimated the summation of direct and indirect cost.The total cost per inj ury (direct cost + indirect cost)was $747-$2173,direct and indirect cost were $167-$617 and $322-$455 respectively.Conclusion Global economic burden of NSIs is heavy and still undervalued;NSIs occur frequently in China,but attention is inadequate,research on economic burden is lacking,relevant departments should pay atten-tion to the prevention and follow-up treatment process of NSIs.

Objective To study the protective effect of chlorogenic acid(CGA)on the apoptosis of PC12 cells induced byβ-amyloid protein23-35(Aβ25-35)and its mechanism. Methods The cells model of death was estab-lished by Aβ25-35 (20 μmol/L)-induced PC12 cells. The cells were interfered with 5 different concentrations of CGA. CCK-8 assay was used to detect cells viability to determine the 3 concentrations of CGA in future experi-ments. The cells were divided randomly into control group ,model group and interference groups with 3 different concentrations of CGA. Cells apoptosis rates were detected by flow cytometry;colorimetry method was used to detect MDA,SOD and GSH-Px. The mitochondrial membrane potential(MMP)was detected by fluorescent staining and the expression of caspase-3 by western blot. Results Compared with model group,the cells viability of CGA groups were increased but the apoptosis rates were reduced;the activity of SOD and GSH-Px were increased but the level of MDA,MMP and caspase-3 were decreased(P<0.05). Conclusions CGA has a protective effect on Aβ25-35-induced PC12 cells apoptosis and it may be related to the improvement of cellular antioxidation capacity and mitochondrial damage.

OBJECTIVE： To evaluate the efficacy and safety of apremilast in the treatment of moderate-to-severe plaque psoriasis systematically. METHODS： Retrieved from PubMed， Embase， Cochrane Library， VIP， CNKI and CBM， RCTs about apremilast or apremilast combined with other drugs （trial group） versus placebo （control group） in the treatment of moderate- to-severe plaque psoriasis were collected. Meta-analysis was conducted by using Rev Man 5.3 statistical software after literature screening， data extraction and quality evaluation with bias risk evaluation tool of Cochrane System Evaluator Manual 5.1.0. RESULTS： Totally 7 studies were included， involving 2 332 patients. Results of Meta-analysis showed that case number of psoriasis assessment and severity index （PASI） decreased by 75％ （PASI 75％） [OR＝6.44，95％CI（4.90，8.45），P＜0.000 01]， PASI 90％ [OR＝8.13， 95％CI（4.65， 14.22）， P＜0.000 01] and sPGA 0 or 1 [OR＝3.89，95％CI（3.00，5.05），P＜0.000 01]， the incidence of ADR [OR＝1.87，95％CI（1.44，2.43）， P＜0.000 01] in trial group were significantly more or higher than control group. Subgroup analysis by apremilast dose showed that case number of 20 mg PASI 75％ [OR＝4.72，95％CI（2.77，8.05），P＜0.000 01]， 30 mg PASI 75％ [OR＝7.05，95％CI（5.13，9.69），P＜0.000 01]， 20 mg PASI 90％ [OR＝4.27，95％CI（1.80，10.09），P＝0.001]， 30 mg PASI 90％ [OR＝11.11，95％CI（5.27，23.43），P＜0.000 01]， 20 mg sPGA 0 or 1 [OR＝2.82，95％CI（1.51，5.26），P＝0.001]， 30 mg sPGA 0 or 1 [OR＝4.13，95％CI（3.10，5.50），P＜0.000 01]， the incidence of 30 mg ADR [OR＝1.94，95％CI（1.51，2.49），P＜0.000 01] in trial group were significantly more or higher than control group. There was no statistical significance in the incidence of serious ADR [OR＝1.27，95％CI（0.77，2.07），P＝0.35] or case number of ADR leading to withdrawal [OR＝1.48，95％CI（1.00，2.20），P＝0.05] between 2 groups. CONCLUSIONS： Apremilast is effective for moderate-to-severe plaque psoriasis in dose-dependent manner and improve the quality of life， but increase the incidence of ADR.

OBJECTIVE： To investigate the protective effect and its mechanism of thymoquinone （TQ） on myocardial fibrosis （MF） induced by lipopolysaccharide in rats. METHODS： Totally 40 male Wistar rats were randomly divided into control group， model group， TQ low-dose and high-dose groups [5， 10 mg/（kg?d）]， with 10 rats in each group. Except that control group was given constant volume of normal saline intraperitoneally， other groups were given LPS intraperitoneally to induce MF model， once a day， for consecutive 3 weeks. Since the first day of modeling， administration group was given relevant medicine intraperitoneally， once a day， for consecutive 3 weeks. After last medication， ELISA method was used to detect the contents of serum inflammation factors （IL-1β， IL-6， TNF-α） in rats. Cardiac mass parameters （HW/BM， LVW/BW） were weighed and calculated. HE staining was used to observe the histopathological changes of myocardial tissue. The contents or activities of oxidative stress indicators （MDA， SOD） and myocardial collagen indexes （HYP， Col-Ⅰ， Col-Ⅲ） were detected by chemical analysis， xanthine oxidase method or ELISA. mRNA expression of regulation genes （Col-Ⅰ， Col-Ⅲ， MMP-3， MMP-9， TGF-β1 and Smad3） related to myocardial fibrosis were determined by real-time fluorescence quantitative PCR. RESULTS： Compared with control group， there were swollen myocardial cells， disordered nuclei of different sizes and visible fiber hyperplasia in model group； the levels of serum inflammatory factors and LVW/BW， cardiac contents of MDA， HYP， Col-Ⅰand Col-Ⅲ， mRNA expression of Col-Ⅲ， TGF-β1 and Smad3 in model group were increased significantly （P＜0.05）， while SOD activity was decreased significantly （P＜0.05）. Compared with model group， the degree of myocardial fibrosis was improved in TQ groups to different extents； serum content of IL-1β and the contents of MDA， HYP and Col-Ⅰ in cardiac tissue in TQ low-dose group， serum contents of IL-1β， IL-6 and TNF-α， LVW/BW and the contents of MDA， HYP， Col-Ⅰ and Col-Ⅲ in cardiac tissue of TQ high-dose group as well as mRNA expression of Col-Ⅰ， Col -Ⅲ， TGF-β1 in TQ groups were decreased significantly （P＜0.05）. The activities of SOD in cardiac tissue were increased significantly in TQ groups （P＜0.05）. There was no statistical significance in other indexes among groups （P＞0.05）. CONCLUSIONS： TQ can protect against MF model rats to certain extent， the mechanism of which may be associated with the inhibition of inflammation reaction and oxidant stress reaction， and down-regulation of mRNA expression of Col-Ⅰ， Col-Ⅲ and TGF-β1.

8-prenylnaringenin (8-PN) is a potent estrogen with high medicinal values. It also serves as an important precursor for many prenylated flavonoids. Microbial synthesis of 8-PN is mainly hindered by the low catalytic activity of prenyltransferases (PTS) and insufficient supply of precursors. In this work, a SfN8DT-1 from Sophora flavescens was used to improve the efficiency of (2S)-naringenin prenylation. The predicted structure of SfN8DT-1 showed that its main body is comprised of 9 α-helices and 8 loops, along with a long side chain formed by nearly 120 amino acids. SfN8DT-1 mutants with different side-chain truncated were tested in Saccharomyces cerevisiae. A mutant expressing the truncated enzyme at K62 site, designated as SfND8T-1-t62, produced the highest 8-PN titer. Molecular docking of SfN8DT-1-t62 with (2S)-naringenin and dimethylallyl diphosphate (DMAPP) showed that K185 was a potentially crucial residue. Alanine scanning within a range of 0.5 nm around these two substrates showed that the mutant K185A may decrease its affinity to substrates, which also indicated K185 was a potentially critical residue. Besides, the mutant K185W enhanced the affinity to ligands implied by the simulated saturation mutation, while the saturated mutation of K185 showed a great decrease in 8-PN production, indicating K185 is vital for the activity of SfN8DT-1. Subsequently, overexpressing the key genes of Mevalonate (MVA) pathway further improved the titer of 8-PN to 31.31 mg/L, which indicated that DMAPP supply is also a limiting factor for 8-PN synthesis. Finally, 44.92 mg/L of 8-PN was produced in a 5 L bioreactor after 120 h, which is the highest 8-PN titer reported to date.
Dimethylallyltranstransferase/metabolism* ; Flavonoids/metabolism* ; Molecular Docking Simulation ; Prenylation ; Saccharomyces cerevisiae/metabolism* ; Sophora/metabolism*

OBJECTIVE： To evaluate the therapeutic efficacy and safety of 2 kinds of selective Janus kinase 1 （JAK-1） inhibitor Upadacitinib and Filgotinibfor in the treatment of rheumatoid arthritis， and to provide evidence-based reference for clinical treatment. METHODS： Retrieved from PubMed， Medline， Embase， the Cochrane library， CBM， CJFD， Wanfang database and VIP， RCTs about placebo （control group） versus Upadacitinib or Filgotinibfor （trial group） in the treatment of rheumatoid arthritis on the basis of methotrexate or other antirheumatic drugs were collected during the establishment of the database to Jan. 2019. Meta-analysis of therapeutic efficacy [the proportion of patients with remission rate of 20％ （ACR20）， ACR50， ACR70 according to the criteria of American Rheumatism Association， the proportion of patients with 28-joint disease activity score （DAS28）＜3.2] and safety [the incidence of adverse event （AE）， severe adverse event （SAE）， infection， severe infection， herpes zoster， liver injury] were conducted by using Rev Man 5.3 software after data extraction and quality evaluation with Cochrane system evaluator manual 5.1.0. RESULTS： A total of 8 RCTs were included， involving 2 738 patients. Meta-analysis showed that the proportion of patients with ACR20 [OR＝3.37，95％CI（2.80，4.05），P＜0.001]， ACR50 [OR＝3.78，95％CI（2.98，4.78），P＜0.001] and ACR70 [OR＝4.31，95％CI（3.05，6.09），P＜0.001]， the proportion of patients with DAS28＜3.2 [OR＝3.86，95％CI（2.98，5.00），P＜0.001]， the incidence of AE [OR＝1.33，95％CI（1.11，1.61）， P＝0.002]， the incidence of infection [OR＝1.43，95％CI（1.12，1.81），P＝0.004] in trial group were significantly higher than control group； there was no statistical significance in other indexes （P＞0.05）. CONCLUSIONS： JAK-1 inhibitors Upadacitinib and Filgotinib can improve the effect indexes of ACR20， ACR50 and ACR70 and the proportion of patients with DAS28＜3.2 of rheumatoid arthritis patients； it can not increase the incidence of SAE， severe infection， herpes zoster， liver injury， but can increase the risk of AE and infection.

Whether habit stimulation is effective in DOC patient arousal has not been reported. In this paper, we analyzed the responses of DOC patients to habit stimulation. Nineteen DOC patients with alcohol consumption or smoking habits were recruited and 64-channel EEG signals were acquired both at the resting state and at three stimulation states. Wavelet transformation and nonlinear dynamics were used to extract the features of EEG signals and four brain lobes were selected to investigate the degree of EEG response to habit stimulation. Results showed that the highest degree of EEG response was from the call-name stimulation, followed by habit and music stimulations. Significant differences in EEG wavelet energy and response coefficient were found both between habit and music stimulation, and between habit and call-name stimulation. These findings prove that habit stimulation induces relatively more intense EEG responses in DOC patients than music stimulation, suggesting that it may be a relevant additional method for eliciting patient arousal.
Adult ; Alcohol Drinking ; physiopathology ; Brain ; physiopathology ; Consciousness Disorders ; physiopathology ; therapy ; Electroencephalography ; Female ; Habits ; Humans ; Male ; Middle Aged ; Music ; Names ; Nonlinear Dynamics ; Physical Stimulation ; Rest ; Smoking ; physiopathology ; Speech ; Treatment Outcome ; Wavelet Analysis