Kidney-tonifying and Blood-activating Prescription Regulates Wnt/β-catenin Signaling Pathway to Improve Uterine Spiral Artery Remodeling in Mouse Model of Recurrent Miscarriage / 中国实验方剂学杂志

ObjectiveTo observe the effects of the kidney-tonifying and blood-activating prescription on the Wnt/β-catenin signaling pathway and uterine spiral artery remodeling in a mouse model of recurrent miscarriage and to explore its underlying mechanism. MethodA mouse model of normal pregnancy was established by mating CBA/J mice with BALB/c mice. A mouse model of recurrent miscarriage was established by mating CBA/J mice with DBA/2 mice. The modeled mice of recurrent miscarriage were randomized into model， dydrogesterone， and low- and high-dose Chinese medicine groups. The mice in normal pregnancy were used as the control group. Each group consisted of 10 mice， and the drug administration lasted for 14 days. After the treatment， the embryo absorption rate of each group was recorded. Hematoxylin-eosin （HE） staining was employed to observe the pathological morphology of the uterine decidua， and the physiological transformation rate of spiral arteries （SPA） was evaluated. Real-time polymerase chain reaction （Real-time PCR） and Western blot were performed to determine the mRNA and protein levels， respectively， of matrix metalloproteinases （MMP）-2， MMP-9， vascular endothelial growth factor （VEGF）， and Wnt/β-catenin signaling pathway. ResultCompared with the control group， the model group presented increased embryo absorption rate （P<0.05）， decreased physiological transformation rate of uterine SPA （P<0.05）， cellular swelling， degeneration， and disordered arrangement in the uterine decidua tissue， and down-regulated mRNA and protein levels of key factors involved in SPA remodeling （MMP-2， MMP-9， VEGF） and the Wnt/β-catenin signaling pathway （Wnt2， β-catenin， Cyclin D1， c-Myc） （P<0.05）. Compared with the model group， both the low- and high-dose Chinese medicine reduced embryo absorption rate （P<0.05）， increased SPA physiological transformation rate （P<0.05）， improved uterine decidua tissue morphology， and increased decidua vessel count. Furthermore， they up-regulated the mRNA and protein levels of MMP-2， MMP-9， VEGF， and proteins in the Wnt/β-catenin signaling pathway （P<0.05）. ConclusionRecurrent miscarriage is associated with impaired uterine spiral artery remodeling. The kidney-tonifying and blood-activating prescription can promote uterine spiral artery remodeling by activating the Wnt/β-catenin signaling pathway and promoting the expression of VEGF， MMP-2， and MMP-9， thus treating recurrent miscarriage.

Qihuang Yishen Granules （芪黄益肾颗粒） Combined with Chronic Disease Management of Traditional Chinese Medicine for Diabetic Kidney Disease Patients with Deficiency of both Qi and Yin：A Clinical Observation / 中医杂志

ObjectiveTo observe the effectiveness and safety of Qihuang Yishen Granules （芪黄益肾颗粒） combined with traditional Chinese medicine （TCM） chronic disease management on patients with diabetic kidney disease with deficiency qi and yin. MethodsTotally 140 patients diagnosed as diabetic kidney diseases with deficiency of both qi and yin were randomly divided into control group and trial group，with 70 cases in each group. Patients in the control group were treated with symptomatic treatment and routine chronic disease management. Patients in the trial group added Qihuang Yishen Granules and chronic disease management with TCM characteristics on the basis of symptomatic treatment. The course of treatment in both groups lasted for 6 months. The changes of laboratory indexes and chronic disease management level scores of the two groups of patients before treatment and after 3 and 6 months of treatment were compared， and their correlation were analyzed.The laboratory indexes of urinary protein and renal function related indicators such as 24-hour urinary protein quantification （24 hUTP）， serum creatinine （Scr）， blood urea nitrogen （BUN）， and estimated glomerular filtration rate （eGFR）， and control compliance rate， as well as blood glucose and lipid related indicators such as glycosylated hemoglobin （HbA1c）， low-density lipoprotein cholesterol （LDL-C）， triglyceride （TG） and control compliance rate were observed. The chronic disease management level scores included exercise，cognitive symptom management practice，communication with doctors， self-efficacy of symptom management，self-efficacy of disease commonness management. ResultsFinally，67 cases in the control group and 68 cases in the trial group completed the study. Compared with the group before treatment， the trial group had lower 24 hUTP and Scr， higher exercise score， total self-management score and all self-efficacy scale scores， higher TG at 3 months of treatment； at 6 months of treatment， the trial group had lower 24 hUTP， higher eGFR， and higher self-management scores and self-efficacy scale scores of all chronic diseases （P＜0.05）， and the control group had higher self-management total score （P＜0.05）. After 6 months of treatment， the trial group had lower 24 hUTP， Scr， LDL-C， and TG， higher eGFR， higher compliance rate of 24 hUTP， eGFR， LDL-C， and TG， and higher scores for all chronic disease management indexes compared with the control group （P＜0.05）. In terms of the correlation between laboratory indicators and chronic disease management level scores：there was a statistically significant difference in the correlation between 24hUTP and exercise，symptom management self-efficacy，and self-efficacy of disease commonness management （P＜0.05 or P＜0.01），all of which were negatively correlated. There was a statistically significant difference in the correlation between Scr and symptom management self-efficacy and self-efficacy of disease commonness management （P＜0.01），both of which were negatively correlated. There was a statistically significant difference in the correlation between eGFR and symptom management self-efficacy and self-efficacy of disease commonness management （P＜0.01），both of which were positively correlated. ConclusionQihuang Yishen Granules combined with chronic disease management of TCM can improve the level of proteinuria，renal function and lipid metabolism in patients with diabetic kidney disease with deficiency of both qi and yin，thus delaying the progress of diabetic kidney disease and also improve the level of chronic disease management of patients.

Clinical value of frontal P-wave axis in chronic obstructive pulmonary disease / 中国医师杂志

Objective:To observe the correlation between the frontal P-wave axis and the severity of chronic obstructive pulmonary disease (COPD) and the prognosis evaluation system.Methods:Patients with COPD>45 years old who were followed up in the outpatient department of Hunan Chest Hospital from January to July 2022 were continuously selected as subjects. At the same time, the healthy people who examined in the health management center of our hospital were in the control group. Both groups of subjects completed electrocardiogram and pulmonary function tests. The level of frontal P-wave axis and the results of pulmonary function examination were recorded, and the differences of frontal P-wave axis between the COPD group and the control group were compared, so as to clarify the value of frontal P-wave axis in the diagnosis, disease severity and prognosis evaluation of COPD.Results:The level of forced expiratory volume in the first second/forced vital capacity(FEV1/FVC )in the COPD group was significantly lower than that in the control group, while the level of P-wave axis was significantly higher than that in the control group (all P<0.05). The receiver operating characteristic (ROC) curve of P-wave axis showed that the AUC of P-wave axis in predicting COPD was 0.96 ( P<0.001), the best cut-off value was 63.80, the sensitivity was 0.89, and the specificity was 0.93. There were significant difference in P-wave axis level, the forced expiratory volume in one second to forced vital capacity ratio (FEV 1%pred), body mass index (BMI) and BMI, airflow obstruction, dyspnea, and exercise capacity (BODE) index between groups according to the degree of airflow limitation (all P<0.05). Correlation analysis showed that P-wave axis level was positively correlated with BODE index ( r=0.77, P<0.001), and negatively correlated with pulmonary function FEV 1%pred ( r=-0.76, P<0.001). Conclusions:There is a good correlation between the level of frontal P-wave axis and the severity of COPD and the prognosis evaluation system, which has clinical application value.

Real-world Study of Medication Characteristics and Clinical Efficacy of Tenghuang Jiangu Tablets in Treatment of Knee Osteoarthritis in Remission Stage / 中国实验方剂学杂志

ObjectiveTo explore the medication characteristics and clinical efficacy of the Tenghuang Jiangu tablets in the treatment of knee osteoarthritis （KOA） in the remission stage in the real world，providing references for rational clinical use of this prescription. MethodBased on the "registration system of KOA treated with Tenghuang Jiangu tablets"，2 439 KOA cases in the remission stage were analyzed by SPSS 25.0，IBM SPSS Modeler18.0，and Apriori algorithm. To be specific，the age，body mass index （BMI），and course of treatment were described in the form of x̄±s. The information on gender，K-L grade，daily dose，and frequency of drug use was described by frequency analysis. The number of cases，course of treatment，daily dose，and drug use frequency of the single-use group and the combined-use group were described by frequency analysis，and the combination of drugs was described by frequency analysis and Apriori algorithm. Mann-Whitney U test was employed to compare the scores of Visual Analogue Scale （VAS），Western Ontario and McMaster Universities Osteoarthritis Index （WOMAC），pain，stiffness，and joint function between the single-use group and the combined-use group. ResultThe results of clinical treatment showed that 2 439 patients with KOA in the remission stage were treated with Tenghuang Jiangu tablets，with 1 432 （58.71%） in the single-use group and 1 007 （41.29%） in the combined-use group. The average daily dose of Tenghuang Jiangu tablets was （3.90±1.44） g，and the majority of the patients were at grade Ⅱ （54.47%）. The daily average daily dose of Tenghuang Jiangu tablets in the single-use group was （3.64±1.35） g，which was lower than that in the combined-use group ［（4.26±1.48） g，P<0.05］. In the combined use，the top three western medicines were glucosamine （270 times，14.68%），sodium hyaluronate （126 times，6.85%），and imrecoxib （116 times，6.31%），and the top three Chinese medicines were Huoxuezhitong capsules/tablets/ointments （31 times，1.69%），Biqi capsules （25 times，1.36%），and Maizhiling （23 times，1.25%）. As for the overall clinical efficacy，the VAS score was （5.13±0.93） score before treatment and （2.22±1.18） score after treatment （P<0.05），with an overall average decrease of （2.91±1.14） score， and the average decrease in the single-use group was （2.76±1.43） score， which was lower than that in the combined-use group ［（3.12±1.36） score，（P<0.01）］. The WOMAC score was （31.05±11.84） score before treatment and （13.55±9.91） score after treatment （P<0.05）. The overall average decrease was （17.50±11.79） score， and the average decrease in the single-use group and combined-use group was （16.39±11.14） score and （19.08±12.50） score，respectively （P<0.01）. The patients with KOA>grade Ⅱ accounted for 91.34%（1 308/1 432） and 93.55%（942/1 007） in the single-use group and combined-use group，respectively （χ2=80.026，P<0.05）. A total of 43.37%（621/1 432） of the patients in the single-use group had other complications，lower than that in the combined-use group ［54.92%（553/1 432），（χ2=20.087，P<0.01）］. ConclusionMore than half of the patients with KOA in the remission stage are treated with Tenghuang Jiangu tablets alone，and the combination therapy is mainly applied in patients with severe conditions or other complications. In relieving knee joint pain and improving joint stiffness and joint function，both the Tenghuang Jiangu tablets alone and the combination therapy are effective.

Tenghuang Jiangu Tablets Combined with Non-steroidal Anti-inflammatory Drugs for Osteoarthritis of Knee： A Real-world Study / 中国实验方剂学杂志

ObjectiveTo investigate the clinical efficacy of Tenghuang Jiangu tablets （THJGT） combined with oral non-steroidal anti-inflammatory drugs （NSAIDs） in the treatment of osteoarthritis of the knee and its applicable stage based on real-world data， and provide a basis for the rational clinical use of THJGT. MethodA total of 218 cases treated with THJGT combined with oral NSAIDs included in the "THJGT for knee osteoarthritis case registry" from September 2019 to January 2021 were selected as the observation group， and 126 cases treated with oral NSAIDs alone as the control group （CG）. The data of gender， age， body mass index， Kellgren-Lawrence grading scale （K-L scale） score， visual analogue score （VAS score）， Western Ontario and McMaster Universities Osteoarthritis Index （WOMAC） score， swelling grade， joint fear of cold score， back pain and weakness score， and occurrence of adverse events/reactions of the patients in both groups were used for the evaluation of efficacy with full analysis set. The propensity score matching method was used to exclude the influence of confounding factors between groups， and the sub-data sets were established， with which the repeated measures analysis of variance （ANOVA） was carried out to evaluate the efficacy. Visit points were at registration， 4 weeks and 8 weeks after registration. The data were statistically analyzed in Excel 2019 and SPSS 23.0. ResultThe proportion of females in the observation group was 66.06% （144/218）， which was higher than that （58.73%， 74/126） in the control group （χ2=1.846）. The average age in the observation group was （61.12±7.01） years， which was higher than that ［（59.38±5.99） years］ in the control group （W=19 918.50， P<0.05）. The remission rate in the observation group was 98.17% （214/218）. In the observation group， the proportions of the patients at K-L grades Ⅱ and Ⅲ were 64.22% （144/218） and 25.23% （55/218）， respectively. The effect analysis of the whole data set for enrollment and treatment for 8 weeks showed that the VAS score of the experimental group decreased by （3.27±1.24） points on average， which was better than that of the control group [（2.75±1.20）， W=34 179.00， P<0.05]. The average WOMAC score decreased （23.43±11.46） points， which was better than that of the control group [（16.71±8.86）， W=32 387.00， P<0.05]. The average swelling grade decreased （0.63±0.64）， which was better than the control group [（0.33±0.59）， W=33 847.50， P<0.05]. The average score of joint chills decreased （1.90±1.84）， points， which was better than that of control group [（1.40±1.28）， W=35 165.00， P<0.05]. The average lumbar acid fatigue score decreased by （2.02±1.64） points, which was better than that of the control group [（1.10±1.28）， W=32 986.50， P<0.05]. Efficacy analysis of subdata sets for enrollment， 4 weeks of medication and 8 weeks of medication showed that VAS scores of both groups showed a downward trend after treatment， and the improvement of experimental group was more significant than that of control group at 4 weeks， with statistical significance （P<0.05）. After treatment， the total WOMAC score of both groups showed a downward trend， and the improvement of experimental groups was more significant at 4 weeks and 8 weeks （P<0.05）. After treatment， swelling， cold fear grade and lumbar acid fatigue score of both groups showed a decreasing trend,， and the improvement of experimental group was more significant at 8 weeks （P<0.05）. The therapeutic effect analysis of patients in the attack stage and remission stage of the experimental group showed that the total WOMAC score of the two groups showed a downward trend after treatment， and the trend was basically the same， and there was no statistical difference between the two groups at enrollment， 4 weeks after treatment， and 8 weeks after treatment （t=1.675， t=2.068， t=2.364）. The total WOMAC score of the patients in remission stage in the experimental group with K-L grading between grade 0 and grade Ⅲ had statistical significance at 4 weeks after treatment compared with the time of entry （P<0.05， P<0.01）. Group of adverse event rate was 4.13% （9/218）， lower than the control group 10.32% （13/126） （χ2= 5.109， P<0.05）. ConclusionThe population receiving THJGT combined with oral NSAIDs is mostly female， old， in remission， and with K-L grades Ⅱ and Ⅲ. THJGT can enhance the anti-inflammatory and analgesic effects of oral NSAIDs and keep the drug effect in improving joint function and alleviating fear of cold， swelling， and back pain and weakness. The drug combination can be applied to patients in both attack and remission， and the clinical application should take patient's disease stage and degree of osteoarthritis into account. Furthermore， the combination has the potential to reduce the incidence of adverse events caused by NSAIDs.

Analysis of Mechanism of Yishen Huashi Granules for Improving Diabetic Nephropathy Based on Metabonomics and Transcriptomics / 中国实验方剂学杂志

ObjectiveIn this study， based on ultra-high performance liquid chromatography-mass spectrometry（UHPLC-MS/MS） and high-throughput transcriptome sequencing technology（RNA-seq）， we investigated the mechanism of Yishen Huashi granules in regulating serum metabolites and renal messenger ribonucleic acid（mRNA） expression to improve diabetic kidney disease（DKD）. MethodSD rats were randomly divided into normal group ， model group and Yishen Huashi granules group， with 8 rats in each group. The rat model of DKD was established by intraperitoneal injection of streptozotocin. Yishen Huashi granules group was given 5.54 g·kg-1·d-1 of Yishen Huashi granules by gavage， and the normal group and the model group were given the same amount of normal saline for 6 weeks. During the experiment， the body weight and blood glucose of rats were monitored， and the rats were anesthetized 24 hours after the last administration， blood was collected from the inferior vena cava， serum was separated， and renal function， blood lipid， and inflammatory indicators were detected. Kidney tissue of rats was fixed in neutral paraformaldehyde， and stained with hematoxylin-eosin（HE）， Masson and periodic acid-Schiff（PAS） to observe the renal pathological changes. UHPLC-MS/MS and RNA-seq were used to identify the changes of serum metabolism and the differences of renal mRNA expression， and real time fluorescence quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to detect the differential mRNA and protein expression in renal tissue to explore the common expression mechanism. ResultCompared with the normal group， rats in the model group showed a decrease in body weight， a significant increase in blood glucose， urinary microalbumin to urinary creatinine ratio（UACR）， blood urea nitrogen（BUN）， cystatin-C（Cys-C）， β2-microglobulin（β2-MG）， interleukin-6（IL-6）， triglyceride（TG） and total cholesterol（TC）， and a significant decrease in total superoxide dismutase（T-SOD）（P<0.01）. After the intervention of Yishen Huashi granules， all the indexes were improved to different degrees in rats（P<0.05， P<0.01）. Compared with the normal group， the model group showed renal mesangial stromal hyperplasia， fibrous tissue hyperplasia and tubular vacuolar degeneration. Compared with the model group， the renal pathology of rats in Yishen Huashi granules group was improved to a certain extent. A total of 14 target metabolites and 96 target mRNAs were identified， the target metabolites were mainly enriched in 20 metabolic pathways， including sphingolipid metabolism， glycerophospholipid metabolism， and the biosynthesis of phenylalanine， tyrosine and tryptophan. The target mRNAs were enriched to obtain a total of 21 differential mRNAs involved in the TOP20 pathways closely related to glycolipid metabolism. A total of 6 pathways， glycerophospholipid metabolism， arachidonic acid metabolism， purine metabolism， primary bile acid biosynthesis， ascorbic acid and uronic acid metabolism， and galactose metabolism， were enriched by serum differential metabolites and renal differential mRNAs， among them， there were 7 differential metabolites such as phosphatidylethanolamine（PE） and 7 differential mRNAs such as recombinant adenylate cyclase 3（ADCY3）. Seven differential metabolites had high predictive accuracy as verified by receiver operating characteristic（ROC） curve， and the results of Real-time PCR and Western blot were highly consistent with the sequencing results. ConclusionYishen Huashi granules can reduce UACR， BUN and other biochemical indexes， correct the disorder of glucose and lipid metabolism， and improve renal function of DKD rats. And its mechanism may be related to the regulation of the level of PE and other blood metabolites， and expression of Phospho1 and other mRNAs in the kidney， of which six pathways， including glycerophospholipid metabolism， may play an important role.

Prognostic effect of MyD88L265P gene mutation in cerebrospinal fluid in primary central nervous system lymphoma / 中华检验医学杂志

Objective:This study has investigated the value of detecting cerebrospinal fluid (CSF) MyD88L265P mutation and interleukin-10 (IL-10) levels in the prognosis of PCNSL.Methods:We retrospectively analyzed the clinical data, CSF characteristics (including cytology, cell counting, total protein, and the level of cytokine IL-10) and treatment process of 39 PCNSL patients newly diagnosed by surgery and pathology (18 males and 21 females, aged 40-73 years) from August 2013 to December 2016 in Hua Shan Hospital North. MyD88L265P mutation was detected by digital PCR in 39 paraffin-embedded tissues and 35 cerebrospinal fluid samples. Log-rank test was used for univariate analysis and Cox regression for multivariate analysis to establish the prognosis model of PCNSL which might be related to PCNSL first progress-free survival (PFS) and overall survival (OS).Results:The median age of the 39 PCNSL patients was 59 years old, with 30.8% (12/39) intraocular involvement. The mutation rate of MyD88L265P in tissues and cerebrospinal fluid was 74.4% (29/39) and 40.0% (14/35), respectively. 51.9% (14/27) patients were observed with MyD88L265P mutation in both tissues and CFS. Univariate analysis showed that intraocular involvement, high level of IL-10 in CFS (≥45 pg/ml), and MyD88L265P mutation in CFS are factors significantly influencing median progression-free survival (mPFS) of patients ( P<0.05). Patients with intraocular involvement had shorter OS than those without involvement which was statistically significant ( HR=6.5,95% CI 1.7-47.3, P<0.05). And multivariate analysis showed that intraocular involvement ( HR=2.4, 95% CI 1.3-7.8, P<0.05) and CFS MyD88L265P mutation ( HR=2.1, 95% CI 1.1-5.7, P<0.05) were independent prognostic factors for PFS. Conclusion:The presence of intraocular involvement and MyD88L265P mutation in CFS indicated poor prognosis of PCNSL patients. High CSF IL-10 level was not an independent factor affecting prognosis.

Study on the risk factors of type 1 gastric neuroendocrine tumor in 123 cases of autoimmune gastritis / 中华消化杂志

Objective:To investigate the risk factors of type 1 gastric neuroendocrine tumor (g-NET) in patients with autoimmune gastritis(AIG).Methods:From September 1, 2016 to February 28, 2022, 123 patients with AIG visited the First Affiliated Hospital of Zhengzhou University were retrospectively enrolled, including 37 cases with type 1 g-NET and 86 cases without type 1g-NET. The clinical data, serological indicators, and endoscopic manifestation of all the patients were analyzed, including the age at the time of AIG diagnosis (hereinafter referred to as the age at diagnosis), levels of gastrin 17 and pepsinogen Ⅰ (PGⅠ), presence or absence of gastric fundus and gastric body polyps, etc. The independent risk factors of type 1 g-NET in AIG patients were analyzed by univariate and multivariate logistic regression. The receiver operating characteristic curve (ROC) was plotted to analyze the optimal cut-off value, sensitivity and specificity of the independent risk factors in predicting type 1 g-NET in AIG patients. Independent sample t test, Mann-Whitney U test and chi-square test were used for statistical analysis. Results:Compared with those of the AIG patients without type 1 g-NET, the age at diagnosis of AIG patients with type 1 g-NET was younger ((57.49±11.16) years old vs. (48.49±10.96) years old), the level of gastrin 17 was higher (200.21 ng/L, 121.85 ng/L to 244.40 ng/L vs. 244.40 ng/L, 182.50 ng/L to 248.02 ng/L), and the proportion of patients with gastric fundus and gastric body polyps was higher(18.6%, 16/86 vs. 56.8%, 21/37), and the differences were statistically significant( t=-4.13, Z=-3.06, χ2=17.90; P<0.001, =0.002 and <0.001). The results of univariate logistic analysis showed that the age at diagnosis ( OR=0.931, 95% confidence interval (95% CI)0.895 to 0.967), gastrin 17( OR=1.012, 95% CI 1.005 to 1.019), PGⅠ( OR=0.974, 95% CI 0.950 to 0.998)and gastric fundus and gastric body polyps( OR=5.742, 95% CI 2.461 to 13.399)were the influencing factors of type 1 g-NET in AIG patients ( P<0.001, =0.001, =0.033 and <0.001). The results of multivariate logistic regression analysis indicated that the age at diagnosis( OR=0.921, 95% CI 0.881 to 0.964), gastrin 17( OR=1.011, 95% CI 1.001 to 1.020), gastric fundus and gastric body polyps( OR=7.696, 95% CI 2.710 to 21.857)were the independent risk factors of type 1 g-NET in AIG patients ( P<0.001, =0.024 and <0.001). The results of ROC analysis demonstrated that the optimal cut-off values for the age at diagnosis and gastrin 17 in predicting type 1 g-NET were 56.50 years old and 206.40 ng/L, respectively; with sensitivity of 83.8% and 70.3%, respectively, and specificity of 54.7% for both ( P<0.001 and=0.003). Conclusion:The age at diagnosis< 56.50 years old, gastrin 17>206.40 ng/L and the presence of gastric fundus and gastric body polyps are independent risk factors of type 1 g-NET in AIG patients.

Development of platelet change characteristics and antithrombotic strategies after transcatheter aortic valve replacement / 中国综合临床

Transcatheter aortic valve implantation (TAVI) is an emerging, minimally invasive surgical procedure for the safe and effective treatment of aortic valve lesions,and with the advancement of medical research and surgical techniques, the population for TAVI is gradually expanding,but, the characteristics of platelet changes after TAVI and the best antithrombotic strategy in the perioperative period are not conclusive. We review the characteristics of platelet changes and related factors after TAVI, and the outcomes of clinical studies related to different antithrombotic treatments in the perioperative period, in order to discuss the individualized antithrombotic strategy after TAVI.

Effect of CYP2C19 gene polymorphism on clopidogrel concentration, platelet inhibition rate and safety in patients after PCI / 药学实践杂志

Objective To explore the effect of CYP2C19 gene polymorphism on clopidogrel plasma concentration, rate of platelet inhibition and safety. Methods We screen the patients who took clopidogrel after PCI in our hospital, according to the inclusion and exclusion criteria. Blood samples were collected on the 6th day after clopidogrel administration. Clopidogrel blood concentration was determine by RP-HPLC. The CYP2C19 genotype was detected by non-amplified immune hybridization. The rate of platelet inhibition was evaluated by the thromboelastogram. The results were analyzed by SPSS 20.0 software. Results A total of 87 patients were recruited, including 46 males and 41 females. Among them, 34 cases were fast metabolism. 38 cases were medium metabolism. 15 cases were slow metabolism. The result showed that there was no significant difference in drug concentration between fast and intermediate metabolism(P=0.667). There was a significant difference in drug concentration between slow metabolism and fast metabolism or medium metabolism(P<0.05). Analysis of variance and chi-square test showed that CYP2C19 gene polymorphism has a significant effect on clopidogrel platelet inhibition rate and safety (P<0.05). Conclusion Guiding clopidogrel clinical medication based on CYP2C19 genotype alone does not necessarily achieve better therapeutic effects. CYP2C19 genotype detection and blood concentration monitoring can be combined to guide the clinical individualized administration of clopidogrel

The relationship between cognitive function and the enlargement of peripheral vascular space in patients with acute ischemic stroke / 中华行为医学与脑科学杂志

Objective:To investigate the relationship between the enlarged of peripheral vascular space and cognitive function in patients with acute ischemic stroke.Methods:Totally 223 patients with first-episode acute cerebral infarction were selected from the department of neurology in Hebei general hospital from September 2016 to December 2018, who completed the test of cognitive function. All patients were divided into cognitive impairment group( n=67)and normal cognitive group( n=156)according to the score of MoCA.The risk factors of cognitive function and the relationship between the enlargement of perivascular space and cognitive function were analyzed by SPSS 21.0. Results:Age, history of coronary heart disease, Hcy, Fib, BG-EPVS and CSO-EPVS were statistically significant different in cognitive impairment group and normal cognitive group(all P<0.05). Age ( B=0.067, OR=1.070, 95% CI=1.035-1.106, P<0.05), Hcy( B=0.032, OR=1.033, 95% CI=1.007-1.060, P=0.013), and BG-EPVS( B=0.720, OR=2.055, 95% CI=1.041-4.055, P=0.038)were independent risk factors for cognitive impairment.The degree of BG-EPVS in the cognitive impairment group was negatively correlated with the total MoCA score( r=-0.332, P<0.05), visual space and execution( r=-0.256, P<0.01), attention( r=-0.256, P<0.01), language( r=-0.182, P<0.05)and orientation( r=-0.370, P<0.05). Conclusion:EPVS, especially BG-EPVS, can be used as an indicator to evaluate the early cognitive function of AIS patients.

Correlation of total magnetic resonance imaging burden with homocysteine in patients with cerebral small vessel disease / 中华行为医学与脑科学杂志

Objective:To explore the relationship between total MRI burden and serum homocysteine (Hcy) in patients with cerebral small vessel disease(CSVD), and to provide clues for disease prevention and treatment.Methods:A total of 370 inpatients with CSVD from the neurology department of hospital were consecutively enrolled from September 2016 to December 2018.The clinical data, including serum homocysteine(Hcy) levels were collected.Brain MRI data were collected, including the severity of white matter hyperintensities(WMH), lacune infarcts(LI), cerebral microbleeds(CMBs), and enlarged perivascular spaces(ePVS) to evaluate the total load of CSVD.SPSS21.0 was applied to analyze the association between total CSVD burden and Hcy.Results:(1)Compared with the patients with lower Hcy levels, the higher Hcy group had heavier total burdens of CSVD( P<0.01). (2)According to the total MRI burden scores of CSVD, all patients were further divided into low burden group(106 cases) and moderate-high burden group(264 cases). Multivariate logistic regression analysis showed that Hcy( OR=1.026, 95% CI: 1.003-1.049, P=0.026) was risk factor for increasing CSVD burden and hyperhomocysteinemia was a stronger predictor for total MRI burdens of CSVD( OR=3.202, 95% CI: 1.947-5.268, P<0.001). Conclusion:Serum Hcy can be an independent risk factor for the total MRI burdens of CSVD.This finding provides a promising clue for the prediction and clinical management of CSVD.

Research advances of fentanyl and fentanyl-related substances / 中国药科大学学报

@#Fentanyl and fentanyl-related substances are a series of synthetic and powerful anesthetics represented by fentanyl. In recent years,the abuse and trafficking of these substances in many countries around the world are serious which poses a great threat to people"s health and social stability. This paper focuses on the abuse,pharmacological and toxicological action,detection methods and control of fentanyl and fentanyl-related substances and aims to enhance people"s understanding of their basic properties,current research and control so as to provide references for future research.

Homocysteine and cerebral small vessel disease / 国际脑血管病杂志

Homocysteine participates in the methionine cycle in the body and is excreted by the kidneys. Its abnormal elevation increases the risk of cerebrovascular disease. Studies in recent years have shown that hyperhomocysteinemia is closely related to cerebral small vessel diseases and is an independent risk factor for ischemic stroke and cognitive impairment. Because hyperhomocysteinemia is largely reversible, the significance of drug intervention in the prevention and treatment of cerebrovascular disease has gradually been confirmed. This article reviews the relationship between homocysteine and cerebral small vessel diseases in order to provide a reference for the prevention of stroke and dementia.

Role of neurovascular dysfunction in vascular cognitive impairment and Alzheimer's disease / 国际脑血管病杂志

The neurovascular unit consists of neurons, glial cells and cerebral blood vessels. Each eomponent synergistically regulates vasomotion and maintains the blood-brain barrier function to maintain the microenvironment homeostasis and ensure normal brain function. Cognitive impairment, especially in the advanced stage of dementia, places heavy economic and mental burdens on society and families. From the perspective of holistic view, this article expounds the role of neurovascular dysfuntion in the two major causes of cognitive impairment, including Alzheimer's disease and vascular cognitive impairment, and aims to provide possible clues for early prevention and treatment of these diseases.

Lacunar stroke and vascular cognitive impairment / 国际脑血管病杂志

Lacunar stroke is a common ischemic cerebral small vessel disease. It can cause vascular cognitive impairment. Many studies have shown that the number, location, and course of lacunar stroke are closely associated with vascular cognitive impairment. This article reviews the related studies of lacunar stroke and vascular cognitive impairment.

Enlarged perivasc ular spaces and its clinical significance / 国际脑血管病杂志

A number of studies have shown that the enlarged perivascular spaces (EPVS) are associated with various diseases such as cerebral small vessel disease,Alzheimer's disease,post-stroke depression,and post-stroke cognitive impairment.This article reviews the imaging features,pathophysiological mechanisms and clinical significance of EPVS.

Arterial spin labeling magnetic resonance imaging of patients with cognitive impairment / 国际脑血管病杂志

A growing number of clinical studies have shown that arterial spin labeling (ASL) magnetic resonance imaging has its unique value in the diagnosis and treatment of dementia. This article reviews the application principles and imaging manifestations of ASL in patients with different types of cognitive impairment, such as vascular cognitive impairment and Alzheimer's disease.

An improved method of exploring and extracting dorsal root ganglions in rats by reversely along the nerve traveling pathway / 中国比较医学杂志

Objective To explore a new efficient extraction method of dorsal root ganglions(DRGs)of rats by exploring and extracting DRGs reversely along the nerve traveling pathway. Methods The DRGs were extracted by the traditional method of opening the intervertebral foramina and the new method, extracting DRGs reversely along the nerve traveling pathway,respectively. The time consuming and the number of intact DRGs obtained with these two method were compared. Results The number of intact DRGs(L3-5segments,both sides)extracted from each rat with the traditional method was(3.08 ± 1.31),and the average time consuming of each DRG was(5.58 ± 1.21)min. As for the new method ,the number of intact DRGs extracted from each rat was(4.29 ± 1.08), and the average time consuming was(1.69 ± 0.91)min,significantly better than that of the traditional method(P < 0.05 for both). Conclusions The new method of exploring and extracting DRGs reversely along the nerve traveling pathway is more efficient for obtaining intact DRGs of rats,providing more useful tissue materials for subsequent culture and morphological studies of DRG cells.

Effect of Electro-acupuncture on Behavior Alterations in Mice with Isoflurane-induced Alzheimer's Disease and Its Mechanism / 广州中医药大学学报

Objective To investigate the effect of electro-acupuncture on behavior alterations,the expression of amyloid precursor protein(APP),amyloid β-protein(Aβ) proteins and neuroapoptosis in the cerebral cortex in the APPswe/PS1dE9 double transgenic mice with Alzheimer's disease (AD) induced by isoflurane.Methods Sixmonth-old AD mice and wild-type mice at the same age were randomly divided into wile-type control group,AD group,isoflurane group,electro-acupuncture group (N =8).The mice were given pretreatment with electro-acupuncture at Baihui(GV20) acupoint and Yongquan(KI 1) acupoint once a day for 3 successive days,15 min each time.And then the mice in electro-acupuncture group and isoflurane group were exposed to a box full of 1.2％ isoflurane for 4 hours.Morris water maze was used to test the learning and memory abilities of the mice,Western blotting method was used to detect the expression of APP-C83,APP-C99 and Aβ,and terminal deoxynucleotidyl transferase(TdT)-mediated dUTP nick end labeling(TUNEL) was used to detect neuroapoptosis in the cerebral cortex.Results The escape latency of AD group was longer than that of wild-type mice group(P＜0.05),and the latency of isoflurane group was longer than that of AD group (P ＜ 0.05),while the latency of electro-acupuncture group was shorter than that of isoflurane group(P ＜ 0.05).The percentage of retention time in the target quadrant and the times for crossing the target quadrant in isoflurane group were lower than those of AD group (P ＜ 0.05),but were higher in electro-acupuncture group than those in isoflurane group (P ＜ 0.05).APPC83 expression level in isoflurane group was significantly lower than that in AD group (P ＜ 0.05),while APP-C83 expression level in electro-acupuncture group was higher than that in isoflurane group (P ＜ 0.05).APP-C99 expression level in isoflurane group was significantly higher than that in AD group (P ＜ 0.05),and APP-C99 expression level in electro-acupuncture group was lower than that in isoflurane group (P ＜ 0.05).The cortical apoptosis index in isoflurane group was significantly higher than that in AD group (P ＜ 0.05),and the cortical apoptosis index in electro-acupuncture group was lower than that in isoflurane group (P ＜ 0.05).The expression level of Aβ in AD group,isoflurane group and electro-acupuncture group was significantly higher than wild-type control group (P ＜ 0.05).Conclusion Electro-acupuncture can relieve the AD-like neurotoxicity induced by isoflurane and inhibit the decline of learning and memory abilities of AD mice,and the mechanism is probably related with suppressing the overexpression of APP-C99 and reducing the production and accumulation of Aβ,thereby alleviating the neuroapoptosis.