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Neuropathic pain is a debilitating pathological condition that presents significant therapeutic challenges in clinical practice. Unfortunately, current pharmacological treatments for neuropathic pain lack clinical efficacy and often lead to harmful adverse reactions. As G protein-coupled receptors (GPCRs) are widely distributed throughout the body, including the pain transmission pathway and descending inhibition pathway, the development of novel neuropathic pain treatments based on GPCRs allosteric modulation theory is gaining momentum. Extensive research has shown that allosteric modulators targeting GPCRs on the pain pathway can effectively alleviate symptoms of neuropathic pain while reducing or eliminating adverse effects. This review aims to provide a comprehensive summary of the progress made in GPCRs allosteric modulators in the treatment of neuropathic pain, and discuss the potential benefits and adverse factors of this treatment. We will also concentrate on the development of biased agonists of GPCRs, and based on important examples of biased agonist development in recent years, we will describe universal strategies for designing structure-based biased agonists. It is foreseeable that, with the continuous improvement of GPCRs allosteric modulation and biased agonist theory, effective GPCRs allosteric drugs will eventually be available for the treatment of neuropathic pain with acceptable safety.
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Objective To analyze related factors for early neurological improvement after intravenous thrombolysis with alteplase in elderly patients with acute ischemic stroke (AIS).Methods Clinical data of elderly AIS patients with intravenous thrombolytic therapy within 4.5 hours of symptom onset were retrospectively analyzed.The demographic and clonical data were compared between improvement group and non-improvement group.Relevant factors for early neurological improvement after thrombolysis with a[teplase were analyzed by using multivariate logistic regression model.Results A total of 118 patients were included,of which 43 had early symptom improvement (36.44％).Multivariate logistic regression analysis showed that baseline NIHSS score(OR =1.098,95％CI=1.002-1.202,P=0.045),admission blood glucose(OR =1.377,95％CI=1.040-1.822,P =0.025),atrial fibrillation(OR =0.329,95 ％ CI =0.122-0.883,P =0.027) were significantly correlated with early symptom improvement after thrombolysis.Conclusions Baseline NIHSS score,admission blood glucose and atrial fibrillation are correlated with early neurological improvement after intravenous thrombolysis with alteptase in elderly AIS patients.
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Objective@#To analyze related factors for early neurological improvement after intravenous thrombolysis with alteplase in elderly patients with acute ischemic stroke(AIS).@*Methods@#Clinical data of elderly AIS patients with intravenous thrombolytic therapy within 4.5 hours of symptom onset were retrospectively analyzed.The demographic and clonical data were compared between improvement group and non-improvement group.Relevant factors for early neurological improvement after thrombolysis with alteplase were analyzed by using multivariate logistic regression model.@*Results@#A total of 118 patients were included, of which 43 had early symptom improvement(36.44%). Multivariate logistic regression analysis showed that baseline NIHSS score(OR=1.098, 95%CI=1.002-1.202, P=0.045), admission blood glucose(OR=1.377, 95%CI=1.040-1.822, P=0.025), atrial fibrillation(OR=0.329, 95%CI=0.122-0.883, P=0.027)were significantly correlated with early symptom improvement after thrombolysis.@*Conclusions@#Baseline NIHSS score, admission blood glucose and atrial fibrillation are correlated with early neurological improvement after intravenous thrombolysis with alteptase in elderly AIS patients.
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Objective To investigate the influencing factors of short-term outcome after intravenous thrombolysis in patients with acute ischemic stroke. Methods Patients with acute ischemic stroke treated with alteplase intravenous thrombolysis within 4.5 hours of onset at the Department of Neurology, the Second Hospital of Tianjin Medical University from January 2015 to October 2017 were enrolled retrospectively. According to the modified Rankin scale score at discharge or 14 d after thrombolysis, the clinical outcome was assessed,0-2 was defined as good outcome and >2 was defined as poor outcome. Multivariate logistic regression analysis was used to identify the independent risk factors for poor outcome after intravenous thrombolysis in patients with acute ischemic stroke. Results A total of 94 patients were enrolled,including 40(42.6％)with poor outcome.Multivariate logistic regression analysis showed that high baseline National Institutes of Health Stroke Scale(NIHSS)score(odds ratio[OR]1.344,95％ confidence interval[CI]1.157-1.562; P<0.001), advanced age (OR 1.082, 95％ CI 1.010-1.159; P=0.026), and high blood glucose level(OR 1.259,95％ CI 1.018-1.556;P=0.033)were the independent risk factors for poor outcome. Conclusion High baseline NIHSS score, advanced age, and high baseline blood glucose level were the independent risk factors for poor outcome in patients with acute ischemic stroke after alteplase intravenous thrombolysis.
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Objective To investigate the correlation between serum Klotho protein level with vascular calcification in the pa-tients with chronic kidney disease (CKD) .Methods One hundred and seven inpatients with CKD in the nephrology department of the hospital from January 2014 to December 2014 were selected and 20 age-and sex-matched persons undergoing healthy physical examination served as the control group .Serum Klotho ptotein level was measured by ELISA .Abdominal aortic calcification(AAC) was assessed by abdominal lateral X-rays .Meanwhile the brachial arterial flow-mediated dilatation (FMD) and carotid intima-media thickness (cIMT) were determined by the color Doppler ultrasound .The difference of serum Klotho protein levels were compared between the CKD patients and healthy people .The relationship between the serum Klotho protein level with CKD-mineral and bone disorder (CKD-MBD) and vascular dysfunction such as vascular calcification ,.endothelial dysfunction and cIMT was investigated and its clinical significance was analyzed .Results Serum Klotho protein level and FMD in the CKD group were significantly lower than those in the control group ,while the cIMT and AAC scores were significantly higher than those in the control group .Serum Klotho level was significantly decreased along with the progression of CKD .Serum Klotho protein level were negatively correlated with the age(r= -0 .348 ,P< 0 .01) ,log iPTH (r= -0 .366 ,P< 0 .01) ,cIMT (r= -0 .192 ,P< 0 .05) and AAC score (r= -0 .251 ,P<0 .01) ,and positively correlated with eGFR (r=0 .387 ,P<0 .01) ,1 ,25-dihydroxyvitamin D3 level (r=0 .311 ,P<0 .01) and FMD (r=0 .190 ,P<0 .05) in the CKD patients .The Klotho protein level in the patients with FMD ≥6 .0 ,cIMT<1 .0 mm and AAC score=0 were significantly higher than those in the patients with FMD <6 .0 ,cIM T≥1 .0 mm and AAC score >0 . The multivariate Logistic regression analysis showed that age (OR=3 .63 ,95% CI:1 .75 -8 .89 ,P=0 .002) ,MBP (OR=2 .98 , 95% CI:1 .45-7 .69 ,P=0 .009) ,albuminuria (OR= 1 .97 ,95% CI:1 .16 -3 .73 ,P= 0 .022) ,serum Klotho protein level (OR=0 .60 ,95% CI:0 .39-0 .98 ,P=0 .007) were the independent predictive factors of vascular calcification .Conclusion Serum Klotho protein level in the CKD patients is significantly decreased along with CKD progression ;serum Klotho protein level decrease is an independent predictive factor of vascular calcification .
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Objective To investigate the sleep quality and the risk factors for sleep disorders in population at high-risk for stroke:.Methods A cross-sectional survey was conducted in population at highrisk for stroke:in Water Park and Wangdingdi Communities,Nankai District,Tianjin in March 2016.The residents were divided into either a good sleep group or a sleep disorder group according to the Pittsburgh Sleep Quality Index (PSQI).Multivariate logistic regression analysis was used to determine the risk factors affecting sleep quality.They also divided into a stroke history group and a non-stroke history group according to the high-risk population with or without previous history of stroke.The sleep quality was compared between the 2 groups,and the correlation between sleep disorders and stroke outcomes was analyzed.Results A total of 565 residents at high-risk for stroke were enrolled in the study,and 178 01.5％) had sleep disorders.The age in the sleep disorder group was significantly older than that in the good sleep group (66.70 ±8.97 years vs.62.87 ±9.46 years;t =4.540,P＜0.001).The proportions of female (68.0％ vs.49.1％;x2 =16.190,P ＜ 0.001),hypertension (69.7％ vs.57.9％;x2 =7.154,P =0.005),ischemic heart diseases (48.9％ vs.35.4％;x2 =9.253,P =0.002),history of previous stroke or transient ischemic attack (TIA) (30.9％ vs.18.9％;x2 =10.080,P =0.001),and carotid plaques (71.9 vs.53.7％;x2 =16.688,P ＜0.001) in the sleep disorder group were higher than those in the good sleep group.Multivariate logistic regression analysis showed that after adjusting for age and sex,the history of previous stroke or TIA (odds ratio [OR] 1.712,95％ confidence interval [CI] 1.105-2.653;P =0.016),and carotid plaques (OR 1.583,95％ CI 1.003-2.498;P =0.048) were the dependent risk factors for sleep disorders.The total score of PSQI in patients with previous stroke was significantly higher than that in patients without previous stroke (7.25 ±4.71 vs.6.13 ±4.20,t =-2.578,P =0.010).The sleep latency score (1.24 ± 1.06 vs.0.95 ± 1.02;t =-2.868,P =0.004) and sleep disorder score (1.23 ± 0.63 vs.1.07 ± 0.61;t =-2.622,P =0.009) in patients with previous stroke history were significantly higher than those without.According to the modified Rankin Scale scores,the patients with a history of stroke were divided into a good outcome group (0-2) and a poor outcome group (＞2),including 105 (82.0％) and 23 patients (18.0％),resectively.The proportion of patients with sleep disorders (78.3％ vs.35.2％;x2 =14.251,P＜0.001) and the PSQI score (median and four percentile interval:6 [3-8] vs.12 [8-18];Z =-4.392,P ＜0.001) in the poor outcome group were significantly higher than those in the good outcome group.Conclusions The incidence of sleep disorder is high in the high-risk population,the previous stroke or TIA history and carotid plaques are the independent risk factors for sleep disorder in the high-risk population,and sleep disorder is associated with the poor outcomes of strokes.Therefore,attention should be paid to the sleep quality of this stroke high-risk population and control the risk factors of causing sleep disorders,especially for those with a history of stroke.This will help reduce the risk of stroke.
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Objective To investigate the change and correlation between hard-tissue and soft-tissue in patients with class III malocclusion after premolar extraction treatment. Methods Thirty-four adult patients with skeletal classⅢmalocclusion who met the including criteria were included in this retrospective study. The lateral cephalographs were traced and analysed before and after the treatment. Results After orthodontic treatment,the values of long axis of upper incisors and S-N angle (U1-SN) and long axis of lower incisors-mandibular plane (L1-MP) were decreased, and the angle of man-dibular plane (MP-FH) was increased (P<0.01). The SL line was used as a reference, the protrusion of upper incisor (UI-SL) and upper lips (UL-SL) was decreased, and the protrusion of lower incisors (LI-SL) and lower lips (LL-SL) was also de-creased after orthodontic treatment (P<0.05 or P<0.01). There was no significant difference in the relevant measurements of chin. The retraction of upper incisor (△UL-SL) was the only measurement that was positively correlated with upper lip re-traction (△UI-SL). The retraction of upper incisor (△UI-SL) and lower incisor (△LI-SL) were positively correlated with the lower lip retraction (△LL-SL). There was a positive correlation between△UI-SL and△LL-SL. Conclusion The soft-tissue profile improved significantly after four premolars extraction. The change of soft-tissue profile was moderate correlated with hard-tissue.
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Objective To optimize the method for total DNA extraction and RAPD analysis of Nervilia fordii (NF),and to study the genetic diversity of different breeds of NF,the substitute of NF and the fake of NF at molecular level.Methods We used low-pH extraction medium with high salt to extract total DNA,and used randomly amplified polymorphic DNAs (RAPD) to select polymorphism primer from 49 random primers.Twenty-two kinds of NF samples were analyzed by RAPD,and classified by SPSS.Genetic diversity were estimated by Shonnon's index and Nei's index.Results A higher puritiy of DNA can be obtained from fresh HF than that from medical materials.We selected 19 polymorphism primers for the cluster analysis of fresh NF and dried medical material.For medical materials of NF,the distance of amplification band of small-leave breed is close to that of middle-size leave breed,but is far away from that of,big-leave breed and Nervilia plicata.For the fresh materials of NF,there breeds of Nervilia fordii can be classified into one kind,the distance of fresh NF band is far from that of Nervilia plicata,Pachyrhizus erosus and the cultured breed,and more far awary from that of Plantago asiatica and Centella asiatica.Shonnon's genetic diversity is 0.463,Nei's genetic diversity is 0.267.Intra-population genetic variation is obvious compared to iner-population genetic variation.The estimated gene flow from Gst (Nm) is 0.94.Conclusion The molecular difference in different breeds of Nervilia Fordii can be used to identify Nervilia Fordii.The genetic diversity of Nervilia fordii is mainly caused by the geography environment.
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Objective To set up the electrochemical determination method for puerarin in Radix Puerariae.Methods The electrochemical behavior and content determination of puerarin were investigated by using coulomb array detector.Results In phosphate buffer with PH 4.32,puerarin showed good linearity in the range of 0.16 ng～ 162 ng.The regression equation was A=1444.7C+ 88.635,r=0.9998(n=7),the average recovery was 96.88 %,and RSD was 0.08 %.Conclusion This method is simple and rapid,and the result is accurate and reliable.It can be used for the determination of puerarin content and biological samples.