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Increasing evidence suggests that a cyclic adenosine monophosphate (cAMP)-dependent intracellular signal drives the process of myelination. Yet, the signal transduction underlying the action of cAMP on central nervous system myelination remains undefined. In the present work, we sought to determine the role of EPAC (exchange protein activated by cAMP), a downstream effector of cAMP, in the development of the myelin sheath using EPAC1 and EPAC2 double-knockout (EPAC) mice. The results showed an age-dependent regulatory effect of EPAC1 and EPAC2 on myelin development, as their deficiency caused more myelin sheaths in postnatal early but not late adult mice. Knockout of EPAC promoted the proliferation of oligodendrocyte precursor cells and had diverse effects on myelin-related transcription factors, which in turn increased the expression of myelin-related proteins. These results indicate that EPAC proteins are negative regulators of myelination and may be promising targets for the treatment of myelin-related diseases.
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Microneedles is an efficient, safe and novel transdermal drug delivery technology that has attracted much attention in recent decades. Microneedles could break through the skin's stratum corneum barrier and have an especially significant effect on the transdermal delivery of water-soluble small molecules and biological macromolecules. In this paper, a rapid onset local anesthetic preparation of lidocaine hydrochloride was prepared based on dissolving microneedles, and related quality evaluations were carried out. The key quality indicators of prepared lidocaine hydrochloride dissolving microneedles such as drug loading amount, appearance morphology, mechanical properties, skin penetration performance, in vitro dissolution performance and local anesthetic efficacy were investigated with HPLC, SEM, texture analyzer, organic staining, histological section, in vitro dissolution test and pharmacodynamics experiments respectively. The drug loading of the dissolving microneedles array reached 68.19 ±1.55 mg, and the needle tip contained 3.57 ±0.21 mg. The microneedles has good needle shape and sufficient mechanical strength to penetrate into the skin, which is a prerequisite for the successful administration of the preparation. The in vitro dissolution time was 28.28 ±1.12 s. When applied to guinea pig back acupuncture model which was modified by guinea pig intradermal papules model, although the efficacy maintenance time was shorter than that of compound lidocaine cream, dissolving microneedles can be activated within 1 min, which was much faster than compound lidocaine cream. It is possible to increase the duration of drug efficacy by increasing the density of microneedles and preparing microneedles for sustained and controlled release in future studies. Lidocaine hydrochloride dissolving microneedles and its evaluation methods for local anesthesia were established systematically here for the first time. The rapid effect of anesthesia with lidocaine hydrochloride dissolving microneedles on the skin was worthy of further investigation.
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Objective To understand the situation and epidemic characteristics of imported falciparum malaria in Huai'an City from 2010 to 2016,so as to provide the evidence for formulating the prevention and control strategies of imported falci-parum malaria in the city. Methods The epidemic data of imported falciparum malaria in Huai'an City from 2010 to 2016 were analyzed by using the descriptive epidemiological method. Results A total of 308 malaria cases were reported in Huai'an City from 2010 to 2016 with the average annual incidence of 0.88/105. A total of 240 imported falciparum malaria cases were report-ed,of which 18 cases(7.50%)developed into severe illness,and 2 severe patients died. The cases were reported in every coun-ty(district),and the incidence rates of Qingpu District and Huai'an District were higher than the city average level. The cases occurred every month,so there was no significant seasonal variation in the reporting time of the cases. Most of the patients were young men and aged 30-49 years. The occupational distribution revealed that the patients were mainly farmers,workers and mi-grant workers. The main source of infection was from African countries. The median interval from symptom appearing to definite diagnosis was 1 day,and the longest interval was 236 days. Twenty-nine cases were diagnosed within 24 hours,accounting for 12.08%. Conclusions The epidemic situation of imported falciparum malaria in Huai'an City is grim. In order to consolidate the achievements of malaria eradication,it is necessary to further improve the multi-sectoral cooperation mechanism,strengthen the management of floating population and take effective measures to reduce the risk of imported falciparum malaria.
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Objective:To explore anti-platelet/anti-coagulation treatment and their influence on prognosis in advanced aged patients with acute coronary syndrome (ACS)complicated atrial fibrillation (AF)after percutaneous coronary intervention (PCI).Methods:A total of 204 advanced aged ACS + AF patients treated in our heart center were se-lected.All patients received CHA2 DS2 Vasc score assessment,male had score ≥2 scores and female had score ≥3 scores.A total of 160 cases received dual anti-platelet therapy combined anticoagulant treatment of warfarin,and they were randomly divided into low intensity group [n=80,international normalized ratio (INR)remained 1.8~2.3]and high intensity group (n=80,INR remained 2.3~2.8),both groups were followed up for 18 months.Inci-dence rates of major adverse cardiovascular and cerebrovascular events (MACCE),ischemic and hemorrhage events were observed.Results:Both groups were followed up for a mean 18 months,and there were no significant differ-ence in all-cause mortality,incidence rates of MACCE and fatal hemorrhage between two groups,P > 0.05 all.Compared with low intensity group,there were significant rise in incidence rates of severe hemorrhage (3.8% vs. 12.5%),P <0.05.Conclusion:Low intensity warfarin anticoagulant therapy can effectively reduce incidence rates of MACCE and ischemic events,and incidence rate of hemorrhage events is low in advanced aged ACS + AF pa-tients after PCI.
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Objective:To explore anti-platelet/anti-coagulation treatment and their influence on prognosis in advanced aged patients with acute coronary syndrome (ACS)complicated atrial fibrillation (AF)after percutaneous coronary intervention (PCI).Methods:A total of 204 advanced aged ACS + AF patients treated in our heart center were se-lected.All patients received CHA2 DS2 Vasc score assessment,male had score ≥2 scores and female had score ≥3 scores.A total of 160 cases received dual anti-platelet therapy combined anticoagulant treatment of warfarin,and they were randomly divided into low intensity group [n=80,international normalized ratio (INR)remained 1.8~2.3]and high intensity group (n=80,INR remained 2.3~2.8),both groups were followed up for 18 months.Inci-dence rates of major adverse cardiovascular and cerebrovascular events (MACCE),ischemic and hemorrhage events were observed.Results:Both groups were followed up for a mean 18 months,and there were no significant differ-ence in all-cause mortality,incidence rates of MACCE and fatal hemorrhage between two groups,P > 0.05 all.Compared with low intensity group,there were significant rise in incidence rates of severe hemorrhage (3.8% vs. 12.5%),P <0.05.Conclusion:Low intensity warfarin anticoagulant therapy can effectively reduce incidence rates of MACCE and ischemic events,and incidence rate of hemorrhage events is low in advanced aged ACS + AF pa-tients after PCI.
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OBJECTIVE: To investigate the chemical constituents in the roots of Allium tuberosum. METHODS: Colum chromatography with different materials such as silica gel was used to isolate and purify the chemical constituents. Their structures were identified by spectroscopic analysis. RESULTS: Nine compounds were isolated from the roots of Allium tuberosum and their structures were identified as 4,8-dihydroxyacetophenone-8-O-ferulate(1), 4,8-dihydroxyacetophenone(2), 3,4,5-trimethoxybenzoic acid(3), 3,4,5-trimethoxycinnamic acid(4), buddlenol D(5), E-1,6,11-triene-4,5,9-trithiadodeca-9,9-dioxide(6), tianshic acid(7), daucosterol(8), and linoleic acid(9). CONCLUSION: Compound 1 is a new compound and compounds 2-5 are obtained from Allium tuberosumfor the first time.
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Objective To explore the expression level and influencing factors of CD4 +CD25 + regulatory cells(Treg)among male drug -abusers with syphilis.Methods 144 male drug -abusers with syphilis,41 male drug -abusers without syphilis,35 male non -drug abuser with syphilis and 35 male healthy volunteers were enrolled in this study.Expression levels of CD4 +CD25 +Treg of them were detected.A questionnaire interview was conducted among these participants, including drug abuse duration,drug types and abuse ways.Results The levels of Treg expression of drug -abusers with syphilis were significantly higher than that of drug -abusers without syphilis and non -drug abuser with syphilis (P <0.01 ).Despite of the stage of syphilis,types of drugs and abuse way,Treg expression levels with drug abuse duration of"above 1 -year"were significantly higher than those of "1 -year or below"(P <0.01 ).Treg expression levels were positively correlated to drug abuse duration (R2 =0.672,P <0.01)among patients.Among the participants,people both with traditional and new drugs were significantly higher than that with only traditional or new drug (P <0.01).In addition, people both with injecting and non -injecting abuse were significantly higher than that with one way of drug -abuse (P <0.01).Among those with drug abuse duration of "above 1 -year",Treg levels of drug -abusers with traditional drugs and injecting abuse way were remarkably higher than that with new drug and non -injecting abuse respectively (P <0.01). Conclusion Among male drug -abusers with syphilis,suppression of cellular immune function resulting from increased CD4 +CD25 +regulatory T cells is related to drug abuse duration,and is also influenced by drug types and abuse ways.
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Objective To construct the eukaryotic expression vector of pprI gene from Deinococcus radiodurans R1 and investigate its radioresistant effects in eukaryotic cells.Methods A recombinant vector pEGFP-c1-pprI was constructed by DNA recombinant technique.The empty vector pEGFP-c1 and the pEGFP-c1-pprI were transferred into human lung epithelial cells Beas-2B by LipofectamineTM 2000,respectively.Then the infected cells were screened in order to develop a cell line with stable expression of pprI gene.Cell survival rate was tested by clone-forming assay.Cell cycle distribution and apoptosis were detected by a flow cytometry.The fluorescence intensity of reactive oxygen species (ROS) was observed by a fluorescent microscope.γ-H2AX foci in the irradiated cell was detected by immunofluorescence.Results The eukaryotic expression plasmid of pprI prokaryotic gene was constructed and PprI fusion protein was expressed in human lung epithelial cells successfully,and the cell line (2BG) with a stable pprI gene expression was established.After irradiation,the cell survival fraction of 2BG cells was significantly higher than Beas-2B cells so that the value of D0 、Dq and N of the survival curve were increased.Moreover,the fluorescence intensity of ROS and the number of γ-H2AX foci in 2BG cells were also lower than those of B eas-2B cells(F =16.73,19.47,6.94,P ＜ 0.05).Between these two cell lines,the apoptosis rate and cell cycle G2 arrest also had significant difference (F =139.73,237.92,P ＜ 0.05).Conclusions The pprI gene from Deinococcus radiodurans RI can be stably expressed in the eukaryotic cells and it allows the transferred cells to have a radioresistant function.
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<p><b>OBJECTIVE</b>To compare the therapeutic effects of pleural perfusion of NDP and cDDP in non-small cell lung cancer (NSCLC) patients with malignant pleural effusion, their quality of life and toxic side effects.</p><p><b>METHODS</b>Sixty-eight NSCLC patients with malignant pleural effusion after chest drainage were randomly divided into two groups according to the pathological types: 34 cases in the NDP (Group A) and cDDP groups (Group B), 34 cases each. They were treated with NDP (40 mg/m(2)) and dexamethasone (10 mg) dissolved in 40 ml normal saline, or cDDP (40 mg/m(2)) and dexamethasone (10 mg) dissolved in 40 ml of normal saline, respectively, through pleural perfusion weekly for 2-4 weeks. Routine and symptomatic treatment was used in all the patients. The therapeutic effects, life quality and toxic side effects were evaluated.</p><p><b>RESULTS</b>The response rates of groups A and B were 88.23% and 61.7%, respectively, (P < 0.01). The rates of toxic side effects in groups A and B were 39.6% and 41.9%, respectively, (P > 0.05). However, the rates of gastrointestinal side effects of the two groups were 5% and 12.9%, respectively, (P < 0.05). The Karnofsky scores of group A were higher than that in group B (P < 0.05). The survival time of group A was significantly longer than that of group B.</p><p><b>CONCLUSION</b>Pleural perfusion with NDP is a good treatment method with milder toxicity for patients with malignant pleural effusion caused by NSCLC.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Carcinoma, Non-Small-Cell Lung , Cisplatin , Dexamethasone , Drainage , Follow-Up Studies , Lung Neoplasms , Neutropenia , Organoplatinum Compounds , Pleural Effusion, Malignant , Drug Therapy , General Surgery , Quality of Life , Survival Rate , VomitingABSTRACT
Objective To evaluate protective effects of recombinant human thioredoxin(TRX) in myocardial injury of mice with viral myocarditis. Methods We established viral myocarditis models by intraperitoneal injection with 0.1 ml 100TCID50 Coxsackie virus 3m(CVB3m), along with tail vein injection of recombinant human TRX (2 mg/kg) for protection. The control group was given equivalent volume of normal saline. The mice were killed 7 days following the injections. Serum lactate dehydrogenase (LDH) activity was determined and myocardial injury was examined with light microscopy. Results The somm LDH activity in Coxsackie virns-infected mice [(3130.50±390.57)U/L] was higher than that of animals in the control group[ (1617.86±155.42)U/L] and that of TRX protection group[ (1959.43±540.75)U/L], the difference being statistically significant (P<0.05); there was no significant difference between TRX protection group and the control group(P 0.05). Light microscopy showed that five of the eight Coxsackie rims-infected mice had myocardial lesions, including focal myocardial necrosis and inflammatory infiltration. There was no myocardial injury in the TRX protection group. Conclusions Recombinant human TRX can lessen myocardial injuries induced by infection with CVB3m, and so can protect myocardium.
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<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of live combined Bifidobacterium, Lactobacillus and Enterococcus capsules in treatment of irritable bowel syndrome.</p><p><b>METHODS</b>Eighty-five patients [male 32, female 53; age (45.31+/-11.72) years] were given live combined Bifidobacterium, Lactobacillus and Enterococcus capsules 1260 mg/d t.i.d.x4 weeks. Syndrome scales were used to evaluate the efficacy in gastrointestinal syndrome. Fecal flora was also measured before and after the treatment. Six bacteria were cultured and the colony forming units were counted in stool. SPSS was used for data analysis.</p><p><b>RESULTS</b>Seventy-four patients finished the follow-up. No side-effect was found. For treatment of irritable bowel syndrome, the effective rate of live combined Bifidobacterium, Lactobacillus and Enterococcus capsules was 56.8% in the second week, 74.3% in the fourth week and 73.0% in the sixth week. Single symptom was improved, especially in abdominal pain and stool character. The probiotica containing live combined Bifidobacterium, Lactobacillus and Enterococcus could increase bifidobacterium count (P<0.01) and lactobacillus count (P<0.05); decrease bacteroides count (P<0.05) and enterococci count (P<0.01); No obvious changes were observed in clostridium difficile colonitis and enterobacteriaceae (P>0.05).</p><p><b>CONCLUSION</b>The result of the study indicated that the administration of live combined Bifidobacterium, Lactobacillus and Enterococcus improved the symptom of irritable bowel syndrome and that there was a gradual increase of this effect. Thereafter conditions remained stable for 2 weeks. That improvement may be associated with alterations in gastrointestinal flora.</p>