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Based on the literature study,the thoughts and possible therapeutic mechanism in treating male infertility from the perspective of spleen and kidney by regulating intestinal flora were explored.Disturbance of intestinal flora is one of the important factors leading to the development of male infertility,and the spleen and kidney have certain similarities to intestinal flora in the physiological function and pathological changes.Moreover,tonifying the kidney and strengthening the spleen can regulate the intestinal flora by fostering the growth of beneficial bacteria,inhibiting the reproduction of pathogenic bacteria,and protecting the barrier of the intestinal mucosa.Therefore,the possible therapeutic mechanisms in treating male infertility with the prescriptions for tonifying the kidney and strengthening the spleen to regulate intestinal flora are as follows:inhibiting the expression of inflammatory factors to reduce the inflammatory reaction of testicular tissues;improving the antioxidant capacity to alleviate the damage of spermatozoa caused by oxidative stress,and improving the bad mood to alleviate the impact of psychological stress on the reproductive system.The exploration of the thoughts for treating male infertility from the perspective of spleen and kidney by regulating intestinal flora may provide a new entry point for modern Chinese medicine clinical treatment of male infertility.
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Objective:To evaluate an anticoagulation management method based on mobile health technology and artificial intelligence.Methods:The study was a single-center, prospective, randomized, controlled, non-inferiority clinical trial. From November 2017 to September 2018, 67 patients who received warfarin therapy after mechanical valve replacement were consecutively enrolled and randomized into two groups: 34 were randomized to intervention group and 33 to control group. The intervention group was managed via Anticlot Assistant and the control group was handled as routine care. Evaluations were performed at least 3 months after enrollment and ended on 30 September 2019. Non-inferiority was evaluated using one-sided tests with a non-inferiority margin set 11.0% for time in therapeutic range (TTR) and 10.0% for the percentage of international normalized ratio (INR) in the therapeutic range.Results:The mean TTR was (58.2±23.4)% in the intervention group and (54.8±23.6)% in the control (the difference: 3.4%; low limit of one-side 95% confidence interval for the difference: -6.4%; and P value for non-inferiority was 0.009). The percentage of INR in the therapeutic range was (55.4±21.9)% in the intervention group and (52.8±22.5)% in the control (the difference: 2.6%, low limit of one-side 95% confidence interval for the difference: -6.6%; and P value for non-inferiority was 0.012). Conclusion:The outcomes of patients managed via the anticoagulation management method base on mobile health technology and artificial intelligence are not inferior to those handled as routine care.
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@#Objective To verify the reliability of Anticlot Assistant, a patient self-management system for warfarin therapy assisted by artificial intelligence. Methods It was a single-center, prospective cohort study. The eligible 34 participants were recruited consecutively between November 29, 2017 to September 27, 2018 and managed by warfarin therapy via Anticlot Assistant. The recommendations of Anticlot Assistant were examined and verified by the doctors to ensure the security. Medical records were exported from the the background management system. An univariate analysis compared the outcomes between accepted and overridden records and a logistic regression model was built to determine independent predictors of the outcomes. The research team analyzed 153 medical records, which were from 18 participants and were input by 19 doctors. There were 97 records with doctor accepting the suggestion and 56 records with doctor rejecting the suggestion . Results When the doctors accepted the recommendations, the percentage of the next-test international normalized ratio (INR) in the therapeutic range was higher (64.95% vs. 44.64%, RR=2.298, 95%CI 1.173 to 4.499, P=0.014). The logistic regression analysis revealed that accepting the recommendations was an independent predictor for the next-test INR being in the therapeutic range after controlling potentially confounding factors (OR=2.446, 95%CI 1.103 to 5.423, P=0.028). Conclusion The algorithm of Anticlot Assistant is reasonable and reliable.
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Objective@#To explore the association between soil selenium levels and the risk of diabetes in Chinese adults aged 35-74 years.@*Methods@#Data for this study were derived from the China Chronic Diseases and Behavioral Risk Factors Surveillance 2010 survey. Selenium concentrations in soil were obtained from the Atlas of Soil Environmental Background Values in China. A two-level binary logistic regression model was used to determine the association between soil selenium concentrations and the risk of diabetes, with participants nested within districts/counties.@*Results@#A total of 69,332 participants aged 35-74 years, from 158 districts/counties were included in the analysis. Concentrations of selenium in soil varied greatly across the 158 districts/counties, with a median concentration of 0.219 mg/kg ( : 0.185-0.248). The results showed that both Quartile 1 (0.119-0.185 mg/kg) and Quartile 4 (0.249-0.344 mg/kg) groups were positively associated with diabetes compared to a soil selenium concentration of 0.186-0.219 mg/kg (Quartile 2), crude odds ratios ( s) (95% ) were 1.227 (1.003-1.502) and 1.280 (1.048-1.563). The values were 0.045 and 0.013, for Quartile 1 and Quartile 4 groups, respectively. After adjusting for all confounding factors of interest, the Quartile 1 group became non-significant, and the Quartile 4 group had an adjusted (95% ) of 1.203 (1.018-1.421) relative to the reference group (Quartile 2), the values was 0.030. No significant results were seen for the Quartile 3 group (0.220-0.248 mg/kg) compared to the reference group.@*Conclusion@#Excessive selenium concentrations in soil could increase the risk of diabetes among Chinese adults aged 35-74 years.
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Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , China , Epidemiología , Diabetes Mellitus , Epidemiología , Dieta , Modelos Logísticos , Oportunidad Relativa , Factores de Riesgo , Selenio , Metabolismo , Suelo , QuímicaRESUMEN
Objective:To investigate the current situation of doctor-patient communication ability and analyze the reasons and countermeasures, so as to provide a reference for the ability cultivation.Methods:We collected the data with survey sampling techniques from 366 graduates of clinical medicine in Grade 2016 at Hubei University of Medicine through a self-designed questionnaire and field interview. Similarly, a total of 266 patients and their family members were asked to evaluate the doctor-patient communication ability of the graduates. Kolmogorov-Smimov Z test was adopted for the enumeration data with skewed distribution, while chi-square test was applied for the enumeration data with normal distribution. The significance level was shown as α=0.05 in the analyses. Results:The doctor-patient communication ability of clinical graduates was far from perfect. The overall matching rate of non-verbal skills (including 4 items of personal appearance, body language, speech rate, voice volume and eye contact) reached 63.5% (930/1 464), while the number dropped below 50% regarding their verbal communication, listening and comprehension skills, professionalism and medical ethics. Graduates of different genders showed different communicative abilities. The self-assessments of graduates differed from the evaluations of patients and their family members.Conclusion:We suggest to lay stress on the cultivation of interpersonal communicative skills of undergraduates; reinforce the education on doctor-patient communication ability, especially on medical ethics and professionalism; enhance continuing education on communicative ability of young doctors.
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Objective To investigate the effect of continual care on postoperative medication compliance of patients with osteoporotic vertebral compression fractures (OVCF) after vertebroplasty.Methods A retrospective case control study was performed to analyze the clinical data of 150 patients with OVCF who underwent vertebroplasty in Guizhou People's Hospital from January 2016 to May 2017.There were 38 males and 112 females,aged 47-88 years,with an average of 67.5 years.Seventy-five patients were given continual care such as telephone follow-up and home visit (continual care group).Seventy-five patients were given routine health education (routine care group) when they were discharged from hospital.Visual analogue scale (VAS) and Oswestry dysfunction index (ODI) before operation,1 day,1,3,6 and 12 months after operation,as well as medication compliance and vertebral re-fracture at 1,3,6 and 12 months after operation were compared between the two groups.Results The preoperative VAS of the routine care group was 6 (6-7),1 (0-1),1 (1-3),2 (1-3) and 3 (2-5) points at 1 day and 1,3,6 and 12 months after operation,respectively.The preoperative ODI was 21 (18-27),0 (0-0),2 (1-4),5 (3-7),7 (5-10),10 (7-14) points at 1 day,1,3,6 and 12 months after operation.In the continual care group,VAS was 7 (6-7) points before operation,0 (0-1),1 (0-1),1 (0-2) and 2 (1-3) points at 1 day,1,3,6 and 12 months after operation,respectively.ODI of the continual care group was 18 (22-28) points before operation,0 (0-1),2 (0-4),4 (1-5),4 (3-6) and 6 (4-9) at 1 day,1,3,6 and 12 months after operation.The VAS and ODI of the two groups were lower than those before operation,and the scores of the continual care group were lower than those of the routine care group at 1,3,6 and 12 months after operation (P < 0.05).The medication compliance rates of continual care group were 93%,89%,91% and 84% at 1,3,6 and 12 months after operation,while those of routine care group were 44%,40%,47% and 40% respectively (P <0.05).The incidence of vertebral re-fracture was 1%,1%,3% and 3% in continual care group and 3%,5%,5% and 7% in routine care group at 1,3,6 and 12 months after operation respectively (P < 0.05).Conclusion Continual care can improve the medication compliance of OVCF patients after treatment with vertebroplasty,relieve pain,improve the quality of life,and reduce the incidence of vertebral re-fracture,which is worthy of clinical promotion.
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Objective To observe the effects of different energy of extracorporeal shock waves (ECSWs) on diabetic neuralgia in rats.Methods Fifty clean-grade healthy male Sprague-Dawley rats of both sexes,aged 8 weeks,weighing 180-200 g,were divided into 5 groups (n=10 each) using a random number table method:control group (group C),diabetic neuralgia group (group DN),low-energy ECSW group (group L + DN),medium-energy ECSW group (group M + DN),and high-energy ECSW group (group H+DN).Diabetic neuralgia models were established by intraperitoneally injecting streptozotocin (60 mg/kg) in DN,L+DN,M+DN and H+DN groups.ECSWs at 1,2 and 3 bar were applied during 4 consecutive weeks after successful establishment of the model once a week (T1-T4) in L+DN,M+DN and H+ DN groups,respectively.The mechanical paw withdrawal threshold (MWT),thermal paw withdrawal latency (TWL) and motor nerve conduction velocity (MNCV) were measured at T1-T4.Animals were sacrificed after the last measurement,and the sciatic nerve samples were obtained for determination of the expression of tumor necrosis factor-alpha (TNF-α) and interluekin-6 (IL-6) (by Western blot) and expression of TNF-α and IL-6 mRNA (by real-time polymerase chain reaction).Results Compared with group C,MWT,TWL and MNCV were significantly decreased at T1-T4,and the expression of TNF-α and IL-6 protein and mRNA was up-regulated in the other groups (P<0.05).Compared with group DN,MWT at T2-4 and TWL and MNCV at T3,4 were significantly increased,and the expression of TNF-α and IL-6 protein and mRNA was down-regulated in L+DN,M+DN and H+DN groups (P<0.05).Compared with group H+ DN,MWT at T2-4 and TWL and MNCV at T3,4 were significantly increased,and the expression of TNF-α and IL-6 protein and mRNA was down-regulated in L+DN and M+DN groups,and the expression of IL-6 mRNA was significantly down-regulated in group L+DN (P<0.05).Conclusion ECSWs can mitigate diabetic neuralgia in rats,and the low-and medium-energy ECSWs produce better efficacy,and the mechanism is related to inhibiting inflammatory responses.
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[Objective] The present study was to evaluate the association of serum total cholesterol level and prognosis in patients with acute left heart failure and associated mechanisms.[Methods] Sixty-eight patients due to acute episode of left heart failure prospectively enrolled,and baseline data and biochemical parameters were collected.After discharge,patients were follow-up for 1 month and they were divided into two groups (with and without cardiovascular events).Differences between groups were evaluated and the association of serum total cholesterol level and cardiovascular events were analyzed by logistic regression analysis.[Results] The mean age was 57.3 ± 12.6 years old and 52 cases were male patients accounting for 76.5 %.Among these patients,46 had a diagnosis of coronary heart disease (67.6 %),10 rheumatic heart disease (14.7 %),12 dilated cardiomyopathy (17.7%),38hypertension (55.9%) and 24 diabetes mellitus (35.3%).After 1 month's follow up,39 patients (57.4%) had experienced cardiovascular events,36 cases were re-hospitalized,and 3 died from heart failure.Compared to those with cardiovascular events,event free individuals were younger and were less likely smokers (P < 0.05).In addition,event free group had lower serum levels of N-terminal pro-BNP and C-reactive protein (P < 0.05) while serum levels of total cholesterol and albumin were significantly higher (P < 0.05).There was no significant difference in medication between these two groups.After adjusted for age,gender,smoking,systolic blood pressure,serum albumin level,diabetes,hypertension and medications,increased total cholesterol level was independently associated with better prognosis with odds ratio of 0.91 (95 % confidence interval 0.80-0.96).Further adjusted for C-reactive protein,the association was attenuated to non-significance,with odds ratio of 0.97 (95 % confidence interval 0.87-1.09).[Conclusion] Adequate serum total cholesterol level was beneficial for improving short-term cardiovascular outcomes in patients with left heart failure and the potential mechanisms might be related to cholesterol effects on improving nutritional status and anti-inflammation.
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Objective To investigate the effect of dexmedetomidine on myocardial repolarization heterogeneity and the expression of Cx43 during ischemia-reperfusion and the role of Cx43 in the dexmedetomidine for inhibition of myocardial repolarization heterogeneity during ischemia-reperfusion in isolated rabbit hearts.Methods Eighteen healthy adult rabbits,weighing (2.0±0.5) kg,were randomly divided into three groups after Langendorff isolated heart perfusion model had been prepared and K-H fluid had been perfused and balanced 15 min.In the control group (group C),37℃ K-H fluid was continuously perfused and balanced for 150 min.In group IR,K-H fluid was stopped after perfusion continue filling for 15 min,and then made the cardiac stop for 60 min with the injection of Thomas solution 10 ml/kg while the heart was protected by the 4℃ Thomas solution around.Following the reperfusion of 4℃ Thomas solution 5 ml/kg was performed for 30 min and the heart was resuscitated by the perfusion of K-H fluid for 60 min.In dexmedetomidine group given (group DEX),dexmedetomidine was added in the K-H fluid and the Thomas solution 25 ng/ml.The other procedures were the same as those of group IR.The heart rate (HR),90% monophasic action potential duration (MAPD90) were recorded at the time of balance perfusion record 15 min (T0),continue perfusion 15 min/balance 30 min (T1),reperfusion 30 min/balance 120 min (T2) and reperfusion 60min/balance 150 min (T3).The transmural dispersion of repolarization (TDR) was calculated.To observe the cardiac reperfusion arrhythmia and rebeating time and recording.Detection expression of Cx43 in the left ventricular myocardial by Western blot and immunohistochemistry at T3.Results Group DEX cardiac resuscitation time was significantly shorter than that of group IR (P<0.05).In group DEX.Compared with T0,HR was significantly decreased and TDR was significantly increased in groups IR and DEX at T2、T3 (P<0.05).Compared with group IR,the TDR of group DEX was significantly decreased at T2、T3 (P<0.05).Compared with group C,the expression of Cx43 was decreased (P<0.05) and the distribution was not uniform in groups IR and DEX.Compared with group IR,the expression of Cx43 was decreased (P<0.05) and the distribution was improved in group DEX.Conclusion Dexmedetomidine could inhibits myocardial repolarization heterogeneity of ischemia-reperfusion injury,and thus play a stable cardiac conduction,reduce reperfusion arrhythmias,and its mechanism may be that dexmedetomidine could inhibits gap junctional uncoupling and inhibits expression and distribution of connexins decreased.
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Objective: To explore correlation among clinic blood pressure (CBP), ambulatory blood pressure (ABP) and cardiovascular diseases in diabetic populations.Methods: A total of 336 patients complicated with type 2 diabetes mellitus, who received 24h ambulatory blood pressure monitoring, were selected.According to complicated with coronary heart disease or stroke or not, they were divided into cardiovascular disease group (CVD group, n=122) and no cardiovascular disease group (NCVD group, n=214).Blood lipids, blood pressure, CBP and ABP etc.were compared between two groups;according to median of 24h mean SBP (122mmHg), they were divided into <122mmHg group (n=168) and ≥122mmHg group (n=168), incidence of cardiovascular diseases was compared between these two groups.Results: (1) Compared with NCVD group, there were significant rise in age, percentages of smoking and hypertension, and plasma hsCRP level in CVD group (P<0.05 or <0.01);for ambulatory blood pressure,there were significant rise in levels of 24h mean SBP(mSBP) [(119.8±8.7)mmHg vs.(124.4±9.6) mmHg], daytime SBP (dSBP)[(121.4±9.3) mmHg vs.(128.0±10.3) mmHg] and nighttime SBP(nSBP) [(114.4±4.2) mmHg vs.(120.8±4.7) mmHg] in CVD group, P<0.01 all;there was no significant difference in CBP between two groups;(2) compared with <122mmHg group, there were significant rise in percentages of stroke (20.2% vs.25.0%) and total cardiovascular diseases (32.7% vs.39.9%) in ≥122mmHg group, P<0.01 both;(3) Logistic regression analysis indicated that diabetic patients no matter complicated with hypertension or not, 24h mean SBP was always an independent risk factors of diabetic patients complicated cardiovascular diseases (OR=1.83, 1.36, P<0.05 all).Conclusion: ABP is superior to CBP in predicting cardiovascular risk in patients with diabetes, and 24h mean SBP may be a good ABP index to predict cardiovascular risk.
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Objective To investigate the role of potassium channel in remifentanil-induced prolongation of monophasic action potential duration (MAPD) in the myocardium of rabbits.Methods Eighteen adult rabbit hearts successfully perfused in a Langendorff apparatus were randomly divided into 3 groups (n =6 each) using a random number table:control group (group C),remifentanil group (group R),and K+ channel blocker tetraethylammonium group (group T).After 15 min stabilization with K-H solution,group C was continuously perfused with K-H solution for 60 min,and R and T groups were perfused with KH solution containing 12 ng/ml remifentanil and 10 ng/ml tetraethylammonium,respectively,for 60 min.At 15 min of stabilization,and 15,30 and 60 min of perfusion,heart rate,MAPD of all the three layers of the myocardium in the anterior wall of the left ventricular was recorded.MAPD at 50% and 90% repolarization (MAPD50,MAPD90) were calculated.Results Compared with group C,heart rate was significantly decreased,MAPD50 and MAPD90 were prolonged in R and T groups (P <0.05).Conclusion The mechanism by which remifentanil prolongs MAPD in the myocardium of rabbits is associated with blockade of the potassium channels.
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Objective To study the effects of dexmedetomidine on the monophasic action po-tential duration and the transmural dispersion of repolarization during ischemia-reperfusion of isolated rabbit hearts and thus explore its effect on myocardial ischemia-reperfusion electrophysiological char-acteristics.Methods Eighteen healthy adult rabbits,weighing (2.0±0.5)kg,were randomly divided into 3 groups after successful preparation of Langendorff isolated heart perfusion model and 1 5 min perfusion and balance of K-H fluid.In the control group (group C),37 ℃ K-H fluid was continuously perfused and balanced for 1 50 min.In the ischemia/reperfusion group (group IR),K-H fluid was stopped after continuous perfusion and balance for 1 5 min and cardiac arrest was induced for 60 min with the injection of Thomas solution (4 ℃,10 ml/kg)while the heart was protected by the low tem-perature Thomas solution (4 ℃)around it.Reperfusion of Thomas solution (4 ℃,5 ml/kg)was performed for 30 min and the heart was resuscitated by the perfusion of K-H fluid for 60 min.In dexmedetomidine group (group DEX),dexmedetomidine (25 ng/ml)was added in the K-H fluid and the Thomas solution.Other procedures were same as in group IR.Heart rate(HR),monophasic ac-tion potential amplitude (MAPA)of the three layers of heart [endocardium (Endo),myocardium (Mid)and epicardium (Epi)],0 phase maximal increase rate (Vmax),90% monophasic action po-tential duration (MAPD90 )and transmural dispersion of repolarization (TDR)were recorded at the time of continuous balance perfusion 1 5 min(T0 ),continuous perfusion 1 5 min/balance 30 min(T1 ), reperfusion 30 min/balance 120 min(T2 )and reperfusion 60 min/balance 1 50 min(T3 ).Cardiac ar-rhythmia and resuscitation time at cardiac reperfusion were observed,without using drugs to restore normal cardiac rhythm.Results In group DEX,cardiac resuscitation time was significantly shorter (1 6.67±3.78)s than that in group IR (46.33±7.29)s (P <0.05);At T2 ,in group IR,arrhythmia was seen in 6 rabbits and normal cardiac rhythm was restored within 2 min in two rabbits,while in group DEX,arrhythmia was seen in 2 rabbits and normal cardiac rhythm was restored within 2 min in one rabbit,without the use of any drugs.When compared with T0 ,HR was slower at T2 and T3 in group IR and at T1-T3 in group DEX (P <0.05);Compared with T1 ,HR was slower at T2 and T3 in group DEX (P <0.05);Compared with T2 and group C,HR was slower at T3 in group DEX;At T1-T3 ,HR in group DEX were significantly slower than that in group IR (P <0.05).Compared with T0 ,MAPD90 of Mid at T1 and Epi,Mid,Endo at T2 and T3 in group DEX were significantly extend-ed (P <0.05);Compared with T1 ,MAPD90 of Epi,Mid,Endo in group DEX were significantly ex-tended at T3 ;MAPD90 of Mid in group DEX was significantly longer than that in group C at T3 (P <0.05);At T2 and T3 ,MAPD90 of Epi,Mid,Endo in group DEX were longer than that in group IR (P <0.05).Compared with T0 and group C,TDR at T2 and T3 in group IR and at T1-T3 in group DEX significantly increased (P <0.05),while TDR in group DEX were less than that in group IR at T2 and T3 (P <0.05).Conclusion Dexmedetomidine appeared to prolong MAPD and restrain the dis-proportion of resuscitation of myocardial ischemia-reperfusion injury.Dexmedetomidine could have the effect of stabilizing myocardial ischemia-reperfusion electrophysiological characteristics.
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OBJECTIVETo observe the long-term therapeutic efficacy of standardized specific subcutaneous immunotherapy on persistent allergic rhinitis in children. METHODSFrom Jan. 2007 to Aug. 2009, 236 children with persistent allergic rhinitis were divided into two groups, which 120 cases underwent standardized house dust mite allergen subcutaneous specific immunotherapy (SCIT), another 116 cases accepted a serious of steroids nasal spray and oral antihistamine (control group). The efficacy of the patients was evaluated by using the visual analog scale (VAS) and Rhino conjunctivitis quality of life questionnaire (RQLQ).RESULTSAfter patients underwent 3-years SCIT, the VAS score was 2.3±0.7, 2.4±0.6, 1.6±0.4, 1.9±0.5, and the RQLQ score was 7.7±1.6, 7.4±1.1, 4.3±0.7, 4.1±0.9, respectively, at the follow-up period of 3 month, 1 year, 3 years and 5 years, and both scores were significantly lower than the score of pre-treatment (P0.05). No serious adverse events occurred in all treatments.CONCLUSIONThe standardized specific immunotherapy has the long-term efficacy for dust mite positive children with persistent allergic rhinitis. It demonstrated a similar effect in both single dust mite positive patients and multiple allergens positive patients.
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Current clinically available treatments for rheumatoid arthritis (RA) fail to cure the disease or unsatisfactorily halt disease progression. To overcome these limitations, the development of therapeutic DNA vaccines and boosters may offer new promising strategies. Because type II collagen (CII) as a critical autoantigen in RA and native chicken type II collagen (nCCII) has been used to effectively treat RA, we previously developed a novel therapeutic DNA vaccine encoding CCII (pcDNA-CCOL2A1) with efficacy comparable to that of the current "gold standard", methotrexate(MTX). Here, we systemically evaluated the safety and immunogenicity of the pcDNA-CCOL2A1 vaccine in normal Wistar rats. Group 1 received only a single intramuscular injection into the hind leg with pcDNA-CCOL2A1 at the maximum dosage of 3 mg/kg on day 0; Group 2 was injected with normal saline (NS) as a negative control. All rats were monitored daily for any systemic adverse events, reactions at the injection site, and changes in body weights. Plasma and tissues from all experimental rats were collected on day 14 for routine examinations of hematology and biochemistry parameters, anti-CII IgG antibody reactivity, and histopathology. Our results indicated clearly that at the maximum dosage of 3 mg/kg, the pcDNA-CCOL2A1 vaccine was safe and well-tolerated. No abnormal clinical signs or deaths occurred in the pcDNA-CCOL2A1 group compared with the NS group. Furthermore, no major alterations were observed in hematology, biochemistry, and histopathology, even at the maximum dose. In particularly, no anti-CII IgG antibodies were detected in vaccinated normal rats at 14 d after vaccination; this was relevant because we previously demonstrated that the pcDNA-CCOL2A1 vaccine, when administered at the therapeutic dosage of 300 µg/kg alone, did not induce anti-CII IgG antibody production and significantly reduced levels of anti-CII IgG antibodies in the plasma of rats with established collagen-induced arthritis (CIA). This is the first study demonstrating the safety and immunogenicity of a DNA vaccine encoding CCII for treating RA in normal rats. These results may support the use of this novel therapeutic DNA vaccine for the treatment of RA in the future.
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Artritis Experimental/terapia , Artritis Reumatoide/terapia , Autoantígenos/inmunología , Colágeno Tipo II/inmunología , Vacunas de ADN/uso terapéutico , Animales , Anticuerpos/sangre , Formación de Anticuerpos/inmunología , Autoantígenos/genética , Pollos , Colágeno Tipo II/genética , Femenino , Masculino , Ratas , Ratas Wistar , Vacunas de ADN/efectos adversos , Vacunas de ADN/inmunologíaRESUMEN
A major challenge in the development of effective therapies for rheumatoid arthritis (RA) is finding a method for the specific inhibition of the inflammatory disease processes without the induction of generalized immunosuppression. Of note, the development of therapeutic DNA vaccines and boosters that may restore immunological tolerance remains a high priority. pcDNA-CCOL2A1 is a therapeutic DNA vaccine encoding chicken type II collagen(CCII). This vaccine was developed by our laboratory and has been shown to exhibit efficacy comparable to that of the current "gold standard" treatment, methotrexate (MTX). Here, we used enzyme-linked immunosorbent assays with anti-CII IgG antibodies, quantified the expression levels of Th1, Th2, and Th3 cytokines, and performed flow cytometric analyses of different T-cell subsets, including Th1, Th2, Th17, Tc, Ts, Treg, and CD4(+)CD29(+)T cells to systemically evaluate humoral and cellular immune responses to pcDNA-CCOL2A1 vaccine in normal rats. Similar to our observations at maximum dosage of 3 mg/kg, vaccination of normal rats with 300 µg/kg pcDNA-CCOL2A1 vaccine did not induce the production of anti-CII IgG. Furthermore, no significant changes were observed in the expression levels of pro-inflammatory cytokines interleukin (IL)-1α, IL-5, IL-6, IL-12(IL-23p40), monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, regulated on activation in normal T-cell expressed and secreted (RANTES), receptor activator for nuclear factor-κB ligand (RANKL), and granulocyte colony-stimulating factor (G-CSF) or anti-inflammatory cytokines IL-4 and IL-10 in vaccinated normal rats relative to that in controls(P > 0.05). However, transforming growth factor (TGF)-ß levels were significantly increased on days 10 and 14, while interferon (IFN)-γ and tumor necrosis factor (TNF)-α levels were significantly decreased on days 28 and 35 after vaccination(P < 0.05). Similarly, there were no significant differences in the percentages of Tc, Ts, Th1/Th2, and Th17 cells between the 2 groups(P > 0.05), with the exception of Treg cells, which were significantly reduced on days 14 and 21 after vaccination (P < 0.05), and CD4(+)CD29(+)T cells, which were significantly increased on days 7 and 14 after vaccination(P < 0.05).Taken together, these results suggested that pcDNA-CCOL2A1 vaccine did not markedly affect the balance of immune system components in vaccinated normal rats, indicating that this DNA vaccine may have clinical applications in the treatment of RA.
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Artritis Reumatoide/tratamiento farmacológico , Colágeno Tipo II/inmunología , Inmunidad Celular/inmunología , Inmunidad Humoral/inmunología , Vacunas de ADN/inmunología , Vacunas de ADN/uso terapéutico , Animales , Pollos , Femenino , Factor Estimulante de Colonias de Granulocitos/metabolismo , Interferón gamma/metabolismo , Interleucina-10/metabolismo , Interleucina-4/metabolismo , Masculino , Ratas , Factor de Crecimiento Transformador beta/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
AIM:To study the effect of remifentanil on monophasic action potential and transmural dispersion of repolarization (TDR) in the 3-layer myocardium of isolated rabbit hearts .METHODS:Adult rabbits (n=18, 2.0 ~2.5 kg) were used to isolate the hearts for preparing Langendorff perfusion model .The hearts were randomly divided into 3 groups after perfusion with K-H solution for 15 min: the perfusion in control group ( C group ) continued for 60 min; the hearts in remifentanil group ( R group ) were perfused with 12 μg/L remifentanil K-H solution for 60 min; the hearts in remifentanil+aminophylline group ( RA group ) were given 60-min perfusion of 12 μg/L K-H remifentanil +30 mg/L aminophylline .The HR and 3 layers of myocardial monophasic action potential ( MAP) in the left ventricular anterior wall were recorded at time points after balanced infusion for 15 min ( T0 ) , and continued perfusion for 15 min ( T1 ) , 30 min ( T2 ) and 60 min ( T3 ) .The monophasic action potential duration of repolarization at 90%( MAPD90 ) and the transmural dispersion of repolarization (TDR) were calculated.The early afterdepolarization, delay afterdepolarization and arrhythmia were also observed.RESULTS:In R group, slower HR and prolonger MAPD90 and TDR at T1 ~T3 were observed as com-pared with those at T0(P<0.05).R group showed slower HR and longer MAPD 90 and TDR than C group and RA group (P<0.05).CONCLUSION:Remifentanil slows the HR, extends the MAPD90 and increases the TDR, thus being prone to induce reentry.Aminophylline makes HR faster and MAPD90 shorter, thereby reducing the TDR.
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Objective To investigate the effects of hypothermia combined with dexmedetomidine on myocardial monophasic action potentials (MAPs) in isolated rabbit hearts.Methods Adult rabbits,weighing 2.0-2.5 kg,were heparinized and anesthetized with pentobarbital sodium 30 mg/kg.Their hearts were rapidly removed and retrogradely perfused in a Langendorff apparatus at 37 ℃.Eighteen hearts were randomly divided into 3 groups (n =6 each) using a random number table:control group (group C),hypothermia group (group H),and hypothermia+dexmedetomidine group (group HD).The hearts were continuously perfused for 60 min with 37 ℃ K-H solution in group C,with 32 ℃ K-H solution in group H,or with 32 ℃ K-H solution containing dexmedetomidine 25 ng/ml in group HD.At the end of equilibration (T0) and at 15,30 and 60 min of perfusion with K-H solution,HR and MAPs of left ventricular epicardium,mid-myocardium and endocardium were recorded.MAP duration at 50% repolarization (MAPD50) and at 90% repolarization (MAPD90),monophasic action potential amplitude (MAPA) and maximal velocity (Vmax) were calculated.Results Compared with group C,HR was significantly decreased,and MAPD50 and MAPD90 were prolonged at each time of perfusion with K-H solution in H and HD groups.There was no significant difference in HR,MAPD50 and MAPD90 between H group and HD group.There was no significant difference in MAPA and Vmax between the three groups.Conclusion Hypothermia combined with dexmedetomidine can lead to prolongation of myocardial repolarization,and dexmedetomidine exerts no effect on hypothermia-induced change in MAPs in isolated rabbit hearts.
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Objective To evaluate the effect of aminophylline on monophasic action potential (MAP) during remifentanil-induced negative chronotropic effect in the isolated rabbit hearts.Methods Eighteen healthy adult rabbits,weighing 2.0-2.5 kg,wereused in the study.Their hearts were excised and retrogradely perfused in a Langendorff apparatus.After 15 min of stabilization with K-H solution,the isolated hearts were randomly divided into 3 groups (n =6 each) using a random number table:control group (group C),remifentanil group (R group),and remifentanil + aminophylline group (RA group).Group C was perfused with 37 ℃ K-H solution for 60 min.Group R was perfused with K-H solution containing remifentanil 12 ng/ml for 60 min.Group RA was perfused with K-H solution containing remifentanil 12 ng/ml and aminophylline 30 μg/ml for 60 min.At 15 min of stabilization and 15,30 and 60 min of perfusion,HR and MAP in the myardium of left ventricle were recorded:MAP duration at 90% and 50% repolarization (MAPD90,MAPD50) was calculated.The early after depolarization,delay after depolarization and arrhythmia were recorded.Results Compared with group C,HR was significantly decreased at 15,30 and 60 min of perfusion,and MAPD50 and MAPD90 were prolonged in goup R,and HR was increased in group RA.HR was significantly higher,and MAPD50 and MAPD90 were shorter in RA group than in group R.No early after depolarization,delay after depolarization or arrhythmia developed in each group.Conclusion Aminophylline antagonizes remifentanil-induced negative chronotropic effect through shortening monophasic action potential duration in the myocardium of left ventricle of the isolated rabbit hearts.
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Low-dose methotrexate (MTX), a traditional folate antagonist and disease-modifying antirheumatic drug administered weekly either alone or as combination therapy, is widely accepted as the gold standard in rheumatoid arthritis (RA) treatment. Although its mechanism of action in RA is still poorly understood, MTX potentially acts via antiproliferative, anti-inflammatory, and/or immunosuppressive means. The therapeutic mechanisms and efficacy of low-dose MTX and the oral tolerance protein natural chicken type II collagen (nCCII) were compared in vitro and in vivo using an established collagen-induced arthritis (CIA) rat model. We used clinical visual scoring, radiographic X-ray analysis, histopathological examination, and sera anti-CII IgG measurements to determine the severity of disease with and without treatment. Low-dose MTX had significant clinical therapeutic efficacy against established CIA. Similar to nCCII, MTX mediated CIA by specific immunotolerant effects and not by nonspecific immunosuppression. The mechanism underlying the therapeutic efficacy could be at least partially attributed to the increased production of CD4+CD25+ Treg cells. These cells specifically downmodulated the T lymphocyte proliferative response to CCII but not PHA, induced a Th1-to-Th2 shift, downregulated Th1 cytokines, and upregulated both Th2 and Th3 cytokines. To the best of our knowledge, this is the first demonstration that low-dose MTX probably serves as a potent inducer of specific immunotolerance but not of nonspecific immunosuppression in the treatment of RA.
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Antirreumáticos/uso terapéutico , Artritis Experimental/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Citocinas/metabolismo , Metotrexato/uso terapéutico , Linfocitos T Colaboradores-Inductores/inmunología , Linfocitos T Reguladores/inmunología , Animales , Antirreumáticos/administración & dosificación , Artritis Experimental/inmunología , Artritis Experimental/patología , Artritis Reumatoide/inmunología , Recuento de Linfocito CD4 , Colágeno Tipo II/inmunología , Femenino , Tolerancia Inmunológica , Activación de Linfocitos , Metotrexato/administración & dosificación , Ratas , Ratas Wistar , Linfocitos T Colaboradores-Inductores/efectos de los fármacos , Células TH1/efectos de los fármacos , Células TH1/inmunología , Células Th2/efectos de los fármacos , Células Th2/inmunologíaRESUMEN
Objective To compare the effects of upstream versus downstream tirofiban on tissure level perfu-sion and troponin Ⅰ release in high-risk non-ST-segment elevation acute coronary patients treated with percutaneous coronary intervention. Methods We randomized 138 non-ST-segment elevation acute coronary syndrome patients un-dergoing PCI to receive upstream(in the coronary care unit) and downstream(just prior to PCI) tirofiban. We com-pared the effects between the two drug regimens on tissue-level peffusion using Thrombolysis In Mycardial Infarction (TIMI) fram count,the TIMI myocardial perfusion grade(TMPG) and cardiac tropinin Ⅰ (cTn Ⅰ) release before and after PCI. Results There was no significant difference between two groups in TIMI 3 flow(P>0.05). High percent-age of TMPG 3 perfusion were observed in upstream tirofiban group than in downstream tirofiban group (P < 0.05). Post-procedual cTnI elevation was significantly less frequent among patients in the upstream group (P < 0.05). The cTnI level after PCI was significantly lower with upstream tirofiban compared with downstream tirofiban group (P<0.05). Conclusion Among high-risk non-ST-segment elevation ACS patients treated with an early invasive strategy, upstream tirofiban is associated with improved tissue-level perfusion and attenuated myocardial damage.