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Effective treatments for neuropathic pain are lacking due to our limited understanding of the mechanisms. The circRNAs are mainly enriched in the central nervous system. However, their function in various physiological and pathological conditions have yet to be determined. Here, we identified circFhit, an exon-intron circRNA expressed in GABAergic neurons, which reduced the inhibitory synaptic transmission in the spinal dorsal horn to mediate spared nerve injury-induced neuropathic pain. Moreover, we found that circFhit decreased the expression of GAD65 and induced hyperexcitation in NK1R+ neurons by promoting the expression of its parental gene Fhit in cis. Mechanistically, circFhit was directly bound to the intronic region of Fhit, and formed a circFhit/HNRNPK complex to promote Pol II phosphorylation and H2B monoubiquitination by recruiting CDK9 and RNF40 to the Fhit intron. In summary, we revealed that the exon-intron circFhit contributes to GABAergic neuron-mediated NK1R+ neuronal hyperexcitation and neuropathic pain via regulating Fhit in cis.
Subject(s)
Rats , Animals , Posterior Horn Cells/pathology , Spinal Cord Dorsal Horn/metabolism , Neuralgia , Synaptic TransmissionABSTRACT
BACKGROUND@#Knee osteoarthritis (OA) is a major cause of disability among the older adults. Few treatments are safe and effective. Moxibustion is commonly used in treating knee OA in Chinese medicine (CM). CO Laser moxibustion device is a substitute for traditional moxibustion, which mimics the effects of traditional moxibustion. More data are needed to support its application in knee OA.@*OBJECTIVE@#ObjectiveThe trial aims to assess the effect and safety of CO laser moxibustion in patients with knee osteoarthritis compared with a sham control.@*METHODS@#This is a protocol for a multicenter, randomized, double-blind, placebo-controlled trial. A total of 392 participants were recruited and assigned to the CO laser moxibustion group and sham laser moxibustion group with a 1:1 ratio at 6 outpatient clinics in Shanghai, China. Participants in both groups received treatment at the affected knee(s) at the acupuncture point Dubi (ST 35) and an Ashi point. There were 3 sessions per week for 4 weeks, and an additional 20-week follow-up. Primary outcomes were changes in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores at week 4. Secondary outcomes were WOMAC function score, stiffness score and overall score, VAS pain, Short-Form heath survey (SF-36), and patients' global assessment. The serum levels of cytokines involved in progress of knee OA were explored. Safety was assessed during the whole trial. Masking effectiveness was assessed by both participants and treatment providers.This is a protocol for a multicenter, randomized, double-blind, placebo-controlled trial. A total of 392 participants were recruited and assigned to the CO laser moxibustion group and sham laser moxibustion group with a 1:1 ratio at 6 outpatient clinics in Shanghai, China. Participants in both groups received treatment at the affected knee(s) at the acupuncture point Dubi (ST 35) and an Ashi point. There were 3 sessions per week for 4 weeks, and an additional 20-week follow-up. Primary outcomes were changes in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores at week 4. Secondary outcomes were WOMAC function score, stiffness score and overall score, VAS pain, Short-Form heath survey (SF-36), and patients' global assessment. The serum levels of cytokines involved in progress of knee OA were explored. Safety was assessed during the whole trial. Masking effectiveness was assessed by both participants and treatment providers.@*DISCUSSION@#CO laser moxibustion device, designed as a substitute for CM moxibustion, is easy to use and control with no choking smoke and smell, and is a plausible method for double-blind research. This study would provide rigorous evidence for the effect and safety of CO laser moxibustion in treating knee OA (Trial registration No.: ISRCTN15030019).
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Objective To summarize the experience of transcatheter aortic valve implantation (TAVI) in the treatment of severe aortic stenosis (AS) with VENUS-A valve. Methods Retrospectively collected and analyzed the baseline characteristics,preoperative assessment, surgery details,early and mid-term clinical outcome of 10 patients who underwent TAVI. Results From April 2016 to April 2017,10 patients with severe AS were treated with TAVI at the Guangdong General Hospital. The median age was 75 (65,81)years old and 5(5/10)were males. The median Society of Thoracic Surgery score was 5% (2%,11%). TAVI was successful in 10 patients (10/10),and percutaneous coronary intervention was performed in two cases (2/10) at the same time. The median operation time was 190 (150,225) minutes,the ICU monitoring time was 113 (49, 231) hours,and the hospital stay was 12 (6,25) days. After the procedure,the mean aortic-valve gradient reduced to 10(6,21)mmHg(1 mmHg=0.133 kPa). There was minimal or mild marginal periprosthetic leak in five patients(5/10)and moderate leak in one patient(1/10). During the 30 days of follow up,one patient(1/10)die due to perioperative myocardial infarction and ventricular fibrillation. One patient(1/10)was implanted with a permanent pacemaker for severe arrhythmia. Two patients(2/10)occurred vascular complications. The median follow-up was 3(1,15)months. One patient had syncope at 6 months post operation with R-R interval up to 7 seconds and he was implanted with a permanent pacemaker. There was no death,stroke,surgical surgery intervention and rehospitallization due to heart failure during the follow up. Conclusions It is feasible,safe and effective to use VENUS-A valve for TAVI treatment in serve AS.
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Objective To explore the feasibility of applying ATP bioluminescence technology to disinfection quality monitoring of the flexible endoscope.Methods Totally 30 flexible endoscopes used repeatedly from October 2014 to March 2015 were randomly selected,and had the disinfection quality monitored by ATP bioluminescence technology and bacterial culture method respectively.Parallel comparison was carried out to evaluate the feasibility of applying ATP bioluminescence technology to disinfection quality monitoring of the flexible endoscope.Results ATP bioluminescence technology showed that the qualification rate of the disinfection was 93.3％,and bacterial culture method found it was 96.7％.The two methods proved the outer surface of the endoscope had the disinfection acceptable while the biopsy hole and intracavity not.There was no significant correlation between the two methods while high consistency between the detection results by the two methods.Conclusion ATP bioluminescence technology can be used for preliminary screening in field,instant and daily monitoring of the medical flexible endoscope,which assists bacterial culture method in disinfection quality monitoring of the flexible endoscope.
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Objective To summarize the experience of transcatheter aortic valve implantation (TAVI) in the treatment of severe aortic stenosis (AS) with VENUS-A valve. Methods Retrospectively collected and analyzed the baseline characteristics,preoperative assessment, surgery details,early and mid-term clinical outcome of 10 patients who underwent TAVI. Results From April 2016 to April 2017,10 patients with severe AS were treated with TAVI at the Guangdong General Hospital. The median age was 75 (65,81)years old and 5(5/10)were males. The median Society of Thoracic Surgery score was 5% (2%,11%). TAVI was successful in 10 patients (10/10),and percutaneous coronary intervention was performed in two cases (2/10) at the same time. The median operation time was 190 (150,225) minutes,the ICU monitoring time was 113 (49, 231) hours,and the hospital stay was 12 (6,25) days. After the procedure,the mean aortic-valve gradient reduced to 10(6,21)mmHg(1 mmHg=0.133 kPa). There was minimal or mild marginal periprosthetic leak in five patients(5/10)and moderate leak in one patient(1/10). During the 30 days of follow up,one patient(1/10)die due to perioperative myocardial infarction and ventricular fibrillation. One patient(1/10)was implanted with a permanent pacemaker for severe arrhythmia. Two patients(2/10)occurred vascular complications. The median follow-up was 3(1,15)months. One patient had syncope at 6 months post operation with R-R interval up to 7 seconds and he was implanted with a permanent pacemaker. There was no death,stroke,surgical surgery intervention and rehospitallization due to heart failure during the follow up. Conclusions It is feasible,safe and effective to use VENUS-A valve for TAVI treatment in serve AS.
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Objective To investigate the effects of traditional Chinese medicine colquhounia root tablet on the expression of tight junction protein claudin-2 and ZO-1 in bronchial epithelium tissues of rats with acute lung injury (ALI), and to study the mechanism of protective effect of colquhounia root tablet on ALI. Methods Twenty-four healthy male Sprague-Dawley (SD) rats were randomly divided into control group, ALI group and colquhounia root tablet pretreatment group, with 8 rats in each group. The model of ALI was reproduced by intravenous injection of oleic acid 0.04 mL/kg, and the rats in cont rol group were given the same amount of normal saline (NS) instead. The rats in colquhounia root tablet pretreatment group were intragastric administrated with colquhounia root tablet of 600 mg·kg-1·d-1 (2 mL) for 10 days before model reproduction, and the rats in control group and ALI group were given the same amount of NS. At 4 hours after model reproduction, the blood was drawn from abdominal aorta, and bronchoalveolar lavage fluid (BALF) was collected for determination of protein content in plasma and BALF, and the lung permeability index (LPI) was calculated. The rats were sacrificed to collect lung tissues for determination of lung wet/dry weight ratio (W/D), the changes in pathology of lung tissue were observed after hematoxylin and eosin (HE) staining with light microscope, and lung injury score (LIS) was evaluated. The immunohistochemic al staining was used to detect the expression and localization of claudin-2 and ZO-1 in bronchial epithelium tissues. The protein expressions of claudin-2 and ZO-1 in bronchial epithelium tissues were determined by Western Blot. Results Compared with control group, the lung injury in ALI group was more obvious including cellular edema and structural disorder of intercellular connection by optical microscope, and LIS, W/D ratio, and LPI were significantly increased (LIS: 3.81±0.42 vs. 0.40±0.08, W/D: 7.68±0.64 vs. 4.44±0.39, LPI: 0.89±0.15 vs. 0.38±0.05, all P < 0.01). Claudin-2 and ZO-1 were mainly expressed in the bronchial epithelium cell, and the expression degrees were significantly weakened in ALI group as compared with control group. It was shown by Western Blot results that compared with control group, the protein expressions of claudin-2 and ZO-1 were significantly down-regulated in ALI group [claudin-2 protein (gray value): 0.43±0.31 vs. 2.16±1.33, ZO-1 protein (gray value): 1.25±0.41 vs. 2.82±0.76, both P < 0.01]. Compared with ALI group, colquhounia root pretreatment could effectively diminish the degree of ALI (LIS: 1.22±0.39 vs. 3.81±0.42, W/D: 4.62±0.84 vs. 7.68±0.64, LPI: 0.46±0.07 vs. 0.89±0.15, all P < 0.01), and the protein expressions of claudin-2 and ZO-1 were significantly up-regulated [claudin-2 protein (gray value): 2.98±0.91 vs. 0.43±0.31, ZO-1 protein (gray value): 2.35±0.51 vs. 1.25±0.41, both P < 0.01]. Conclusion Administration of colquhounia root table could attenuate lung injury induced by oleic acid with improving epithelial barrier function via up-regulate the expression claudin-2 and ZO-1, which play a protective effect on the lung of rats with ALI.
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Objective To investigate the influencing factors of successfully switching to sequential ventilation in patients with prolonged weaning due to acute respiratory failure (ARF) after thoracolaparotomy based on the initial rapid shallow breathing index (RSBI) at 60 min after spontaneous breathing trial (SBT), namely, the f/VT optimal value range of 80-120 times/ (min · L), thus providing the basis for determining the ideal timing of weaning in clinical practice.Methods A prospective observational study of sequential ventilation [RSBI during the initial SBT (60 min), 80-120 breaths/ (min · L)] was carried out in 42 patients on mechanical ventilation (≥ 48 h) due to post-thoracolaparotomy ARF in the ICUs.According to the duration of the mechanical ventilation, the patients were divided into 2 groups : successfully prolonged weaning group (≥ 7 days, n =24) and refractory weaning group (＜ 7 days, n =18).The patients with cardiac failure, aged less 18 or over 80, with hepatic dysfunction, or those needing gastrointestinal decompression after esophageal surgery or upper abdomen surgery were excluded.The demographics, APACHE Ⅱ scores and duration of mechanical ventilation of both groups were recorded, and the respiratory work and oxygen metabolism variables before the switch to sequential ventilation (within 24 hours after admission to ICU) and at the time of switching (24 hours in the ICU after admission) were recorded, respectively: clinical puhnonary infection score (CPIS), assessment of cough severity, pH, PaO2, PaCO2 and PaO2/FiO2;hemodynamic and microcirculation-related variables: HR, MAP, fluid balance, BNP and Lac;endocrine and metabolism variables : Hb, ALB and random serum cortisol (COR).The clinical features and the changes of the above-mentioned variables before and at the time of switching were compared between both groups.The independent sample t test was used for the single factor comparison and Mann-Whitney U test was applied to the non-normal distributions.The Fisher exact probability test was used for the single factor comparison of ranked data such as categorical variables.Results There were no significant differences in age, gender and severity of disease between two groups (P ＞ 0.05);the successfully prolonged weaning group had longer duration of invasive mechanical ventilation and ICU stay compared with the refractory weaning group (P ＜ 0.05).There were significant differences in cough severity, PaCO2, pH, HR and fluid balance between two groups before switching (P ＜ 0.05).Compared with those before switching, in the refractory weaning group there were marked decrease in Lac (P ＜ 0.05), obvious increase in cough severity, pH, Hb and ALB (P ＜ 0.05), but there was no significant difference in COR (P ＞ 0.05);while in the successfully delayed weaning group, there were significant decrease in CPIS, PaCO2, HR, MAP, BNP, fluid balance and Lac (P ＜ 0.05), and cough severity, pH, ALB and COR showed an upward trend (P ＜ 0.05).Conclusions The key of successful sequential ventilation is within the values of RSBI ranging from 80 to 120 times/ (min · L) during the initial SBT (60 min) selected as the switching point in patients with prolonged weaning after thoracolaparotomy.The major influencing factors for determining the ideal timing of switching include the matching status between respiratory endurance and respiratory work, the balance between myocardial strength and both cardiac preload and afterload, the severe disease associated with adrenal insufficiency, and malnutrition.
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<p><b>OBJECTIVE</b>To observe the effects of poly(ADP-ribose)polymerase (PARP) inhibitor AG014699 alone and combined with docetaxel (DTX) or carboplatin (CBP) on the proliferation of triple-negative breast cancer cell line MDA-MB-231 and to investigate whether PARP inhibitor AG014699 combined with chemotherapy could play a synergistic antitumor effect.</p><p><b>METHODS</b>MDA-MB-231 cells were treated by PARP inhibitor AG014699 alone or combination with DTX or CBP. Cell proliferation was measured by cell counting kit-8 assay. The combined effect was evaluated by q value less than 0.85, in the range of 0.85 and 1.15, more than 1.15, which respectively meant that the combined effect of the drugs was antagonistic, additive, and synergistic.</p><p><b>RESULTS</b>Treatment with PARP inhibitor AG014699, DTX, or CBP alone inhibited the proliferation, induced apoptosis and blocked the cell cycle. The cell viability of AG014699 (10 µmol/L) combined with DTX (10(-8), 10(-7), 10(-6), 10(-5) mol/L) or CBP (10(-5), 10(-4) mol/L) were lower than that of the drug used alone, and q value was between 0.85 and 1.15, suggesting the combined effect was additive. The cell viability of AG014699 (10 µmol/L) combined with CBP (10(-3) mol/L) was lower than that of the drug used alone, and q value was more than 1.15, suggesting the combined effect was synergetic. A combination of PARP inhibitor AG014699 and DTX or CBP promoted apoptosis and increased the proportion of G2/M stage cells.</p><p><b>CONCLUSION</b>PARP inhibitor AG014699 combined with DTX or CBP can remarkably inhibit MDA-MB-231 cell proliferation, showing additive or synergistic antitumor effects.</p>
Subject(s)
Female , Humans , Antineoplastic Combined Chemotherapy Protocols , Apoptosis , Carboplatin , Pharmacology , Cell Line, Tumor , Cell Proliferation , Cell Survival , Enzyme Inhibitors , Pharmacology , Indoles , Pharmacology , Triple Negative Breast Neoplasms , PathologyABSTRACT
This study was purposed to establish a new quick and simple diagnostic method with high sensitivity and good specificity for idiopathic thrombocytopenic purpura (ITP) and to evaluate its significance. 240 platelet lysates (from patients with ITP, leukemia, MDS, and healthy adults, each of 60 cases) were randomly assigned to training set (120 cases) or validation set (120 cases), all of them were detected by surface enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF-MS), in order to identify the differentially expressed protein, the diagnostic model was established by means of artificial neural network (ANN), and was validated by blind test with SPSS 17.0. The results showed that 5 marked proteins significantly differentially expressed (P < 0.01), m/z of highly expressed proteins were 2234.30, 3476.36, and 7526.29, m/z of low expressed proteins were 4990.02 and 5152.39, respectively. The sensitivity and specificity of diagnostic model were 80.6% and 77.3% respectively. The area under the ROC curve consisting of the output value of artificial neura1 network was 0.837. Efficacy of the model was validated by means of blinded test. It is concluded that the ANN model is useful for clinical diagnosis of ITP on the basis of platelet protein fingerprint spectrum.
Subject(s)
Adult , Humans , Case-Control Studies , Neural Networks, Computer , Peptide Mapping , Proteome , Proteomics , Purpura, Thrombocytopenic, Idiopathic , Diagnosis , Genetics , Metabolism , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , MethodsABSTRACT
In this paper, microscopic identification method was adopted to observe the microscopic characters of ten batches of Medicago sativa seeds. And M. sativa seeds were identificated by TLC method in contrast to trigonelline and stachydrine hydrochloride. The impurities, moisture, ash, sour insoluble ash were detected based on Chinese Pharmacopoeia 2010 version (Vol I ). An HPLC method was also established for determination of trigonelline in the M. sativa seeds. The contents of impurities, moisture, ash, sour insoluble ash should not exceed 5%, 10%, 6%, and 2%, respectively. The content of trigonelline should be not less than 0.795 6 mg x g(-1). The experimental methods were accurate and reliable, and can be used as the quality control of the seeds of M. sativa.
Subject(s)
Alkaloids , Reference Standards , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Reference Standards , Medicago sativa , Chemistry , Quality Control , Seeds , ChemistryABSTRACT
@#BACKGROUND: Current studies on CD62P have focused mainly on cardiovascular diseases, while only few studies have evaluated the effects of CD62P on the development of sepsis and the association between endothelial cell injury with inflammation and coagulation. This study attended to explore the association between endothelial cell injury with inflammation and coagulation by evaluating the expression of soluble CD62P (s-CD62P) in plasma and its mechanism in patients with sepsis, thus to provide the evidence of effective treatment of sepsis with anti-adhesion therapy targeted CD62P. METHODS: A total of 70 critically ill patients with systemic inflammatory response syndrome (SIRS) admitted to intensive care unit (ICU) between September 2009 and February 2010 were enrol ed for a prospective and control study. According to the diagnostic criteria of sepsis/SIRS, the patients were divided into two groups: a sepsis group (n=38) and a SIRS group (n=32). Another 20 healthy volunteers served as a control group. Patients in the sepsis group and SIRS group were matched by clinical signs of high blood pressure, diabetes and its complications. The demographics of the patients including age, sex, body mass index (BMI), smoking and alcohol addict were compared among the groups. Six mL peripheral blood samples were collected within 24-hour admission in ICU for enzyme-linked immunosorbent assay (ELISA) to detect the plasma levels of s-CD62P, TNF-α, and hs-CRP. And variables of coagulation function such as platelet (PLT), prothrombin (PT), activated partial thromboplastin time (APTT), D-dimer and antithrombin-III (AT-III) were analyzed during 24 hours after admission to ICU. Meanwhile sequential organ failure assessment (SOFA) score of critically ill patients was evaluated. Data were expressed as mean±standard deviation and were statistical y analyzed by using SPSS 17.0 statistical software. The differences in plasma levels of s-CD62P of patients in each group were analyzed by ANOVA and the Kruskal-Wallis test. The relations between s-CD62P and inflammatory cytokines as well as with coagulation were determined by Pearson's product moment correlation coefficient analysis. Changes were considered as statistically significant if P value was less than 0.05. RESULTS: Compared with the control group and SIRS group, the sepsis group demonstrated significantly higher levels of s-CD62P, TNF-α and highly sensitive C-reactive protein (hs-CRP) (P<0.05). The plasma levels of D-dimer, PT, and APTT in the sepsis and SIRS groups were significantly higher than those in the control group, while the platelet count and the activity of AT-III were obviously lower (P<0.05). In the sepsis group, the plasma levels of hs-CRP and TNF-α were positively correlated with PT, APTT, and D-dimer, and negatively correlated with AT-III and PLT (P<0.05). The plasma levels of s-CD62P were significantly correlated with the plasma levels of TNF-α, hs-CRP, D-dimer, PT, and APTT, whereas they were correlated negatively well with PLT and AT-III (P<0.05). CONCLUSIONS: The concentration of plasma s-CD62P is elevated as a early biomarker in patients with sepsis, and it serves as one of the pathogenic factors responsible for endothelial cell damage. Coagulation and mediators of inflammation promote each other, aggravating the severity of sepsis. Plasma s-CD62P may be an important factor for the development of coagulation and inflammatory reaction.
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Objective To observe the clinical findings about the endothelial cell injury related to the genesis of inflammatory cytokines and coagulation.Methods A total of 70 critically ill patients with SIRS (systemic inflammatory response syndrome) admitted to intensive care unit (ICU) between September 2009 and February 2010 were enrolled for a prospective and control study.According to diagnostic criteria of Sepsis/SIRS,the patients were divided into two groups:sepsis group (n =38) and SIRS group (n =32),and another 20 healthy volunteers served as control group.Patients in the sepsis group and SIRS group were matched by clinical signs of high blood pressure,diabetes and its complications.The demographics of patients including age,sex,body mass index (BMI),smoking and alcohol addict were comparable among the different groups.The 6 ml peripheral blood samples were collected within 24 h after admission to ICU for enzyme-linked immunosorbent assay (ELISA) to detect the plasma levels of s-CD62P,TNF-α,and hsCRP.And variables of coagulation function such as platelet (PLT),prothrombin time (PT),activated partial thromboplastin time (APTT),D-dimer and antithrombin-Ⅲ (AT-Ⅲ) were analyzed during 24 h after admission to ICU.Meanwhile sequential organ failure assessment (SOFA) score of critically ill patients was evaluated.Data were expressed in mean ± standard deviation and were statistically analyzed by using SPSS 17.0 statistical software.The differences in plasma levels of s-CD62P of patients in each group were analyzed by ANOVA and Kruskal Wallis test.The relationship between s-CD62P and inflammatory cytokines as well as with coagulation were determined by Pearson correlation analysis.Changes were considered as statistically significant if P value was less than 0.05.Results ① Compared with control group and SIRS group,the levels of s-CD62P,TNF-α and high sensitive C-reactive protein (hs-CRP) were significantly higher in sepsis group (P ＜ 0.05).② The plasma levels of D-dimer,PT,APTT in sepsis group and SIRS group were significantly higher than those in control group,while the platelet count (PLT) and the activity of AT-Ⅲ were obviously lower (P ＜ 0.05).③ In sepsis group,the plasma levels of hs-CRP and TNF-α positively correlated with PT,APTT,D-dimer,and negatively correlated with AT-Ⅲ,PLT (P ＜ 0.05).④ Plasma levels of s-CD62P were significantly correlated with plasma levels of TNF-α,hs-CRP,D-dimer,PT,APTT,whereas correlated negatively well with PLT,AT-Ⅲ (P ＜ 0.05).Conclusions The plasma s-CD62P concentration is elevated as a early biomarker in patients with sepsis,and it acted as one of pathogenic factors responsible for endothelial cell damage.Coagulation and mediators of inflammation promotes each other,aggravating the severity of the sepsis.The plasma s-CD62P may be the important factor associated with initiation of coagulation development and inflammatory reaction.