ABSTRACT
Breast cancer, as a heterogeneous disease, has different molecular subtypes. The most common molecular subtype is hormone receptor positive (HR +). Endocrine therapy is the predominant treatment for this subtype. The main treatment modality for HR +/human epidermal growth factor receptor 2-negative (HER2 -) metastatic breast cancer (MBC) is novel targeted agents combined with endocrine therapy. In this review, researches in endocrine clinical treatment of HR +/HER2 - MBC was reviewed to provide a new targeted therapy, including CDK4/6 inhibitors combined with endocrine therapy, the debate between CDK4/6 inhibitors combined with endocrine therapy and chemotherapy, new directions of CDK4/6 inhibitor combination, exploration of multiple treatment strategies after CDK4/6 inhibitor therapy progresses, histone deacetylase inhibitor combined with endocrine therapy, PI3K/Akt/mTOR pathway targeting drugs in combination with endocrine therapy, polyadenosine diphosphate ribose polymerase (PARP) inhibitors for gBRCA1/2 mutated breast cancer, novel targeted drugs, and multi-target/multi-combination therapy model.
ABSTRACT
Cancer stem cells (CSCs) are a class of cells with self-renewal, differentiation, and tumorigenic potential in tumors. It is currently believed that the resistance of CSCs to chemotherapy and radiotherapy is an important cause of tumor recurrence and metastasis. Researchers have found that related factors in many signaling pathways endow CSCs with the ability to adapt to changes in the microenvironment, including inflammatory factors, hypoxia, low pH, and a lack of nutrients. In recent years, the mechanism of CSCs' resistance to therapy has been studied, mainly including the drug efflux mediated by the ATP-binding cassette transporter, the effect of aldehyde dehydrogenase 1 (ALDH1) activity on tumor stem cells, the enhancement of DNA damage repair and degradation of reactive oxygen species, autophagy, activation of development-related pathways, stimulation of the microenvironment, and EMT. The targeting strategies for CSCs include targeting signaling pathway inhibitors, targeting multidrug resistance, DNA damage repair, ALDH, targeting the tumor microenvironment, immunotherapy, etc. In this review, the research progress in CSCs treatment resistance and related treatment strategies was reviewed.
ABSTRACT
Objective:To explore the effects of foraging exercise (FE) on depressive-like behaviors and expression of transforming growth factor-β1 (TGF-β1) in hippocampus of rats with ischemic stroke after chronic stress.Methods:The right middle cerebral artery occlusion (MCAO) model was used in 30 male adult clean grade SD rats by suture method.According to the body weight, rats were evenly divided into stroke group ( n=10) and chronic unpredictable mild stimulation (CUMS) group ( n=20). Rats of CUMS group received stress induction 1 week after operation and lasted for 3 weeks. Then, according to random number generator of SPSS 24.0 software, the depression rats were divided into post-stroke depression (PSD) group( n=10) and FE groups ( n=10). The FE group received free FE intervention for 4 weeks. Body weight, water maze test, novelty inhibition feeding test (NSFT) and sucrose preference test (SPT) were performed at the end of the 1st, 4th and 8th week, respectively. The expression of TGF-β1 in hippocampus was detected by Immunohistochemistry (IHC) and Western blot (WB), and the levels of TGF-β1 and TNF-α in serum were detected by ELISA. SPSS 24.0 software was used for statistical analysis. The behavioral data were compared by two factor repeated measurement analysis of variance. One way ANOVA was used for comparison among groups, and LSD test was used for further pairwise comparison. Results:(1) The interaction between group and time had statistical significance on body weight, latency and food intake of NSFT and sucrose preference index(SPI) ( F=2.936-12.098, all P<0.05). After 4 weeks, compared with the stroke group((343.80±19.34)g, (12.10±6.97)s, (0.75±0.09)%), the body weight((307.80±17.23)g, (305.30±24.39)g), and SPI((0.52±0.06)%, (0.53±0.07)%) of PSD group and FE group were lower and the NSFT latency((21.70±7.02)s, (22.40±0.84)s) was longer (all P<0.05). After 8 weeks, SPI in FE group was higher than that in PSD group ( P=0.045). There were significant differences in body weight of three groups, NSFT latency and SPI of PSD group and FE group, and food intake of stroke and FE group ( F=8.478-196.548, all P<0.05). There was no interaction between group and time in the water maze test. Main effect of time ( P=0.034) and main effect of group ( P<0.01) had statistical significance on escape latency. The escape latency after 4 weeks was longer than that after 1 week ( P=0.003). The latency of PSD group was longer than that of stroke group ( P=0.005), and latency of FE group was shorter than that of the PSD group ( P<0.01). The main effect of group had statistical significance in the number of crossing quadrant ( P<0.01). The number of crossing quadrant of FE group was less than that of PSD group ( P<0.01). (2) Immunohistoche mistry staining showed that compared with the stroke group, the expression of TGF-β1 was down-regulated in 3 areas of hippocampus of PSD group (CA1, CA3 and DG) ( t=5.449-9.353, all P<0.01). Compared with stroke group, the expression of TGF-β1 of CA1 ( t=7.433, P<0.01) in FE group was down-regulated, but was up-regulated in CA3 ( t=3.342, P<0.05) of FE group. Compared with the PSD group, the expression of TGF-β1 was up-regulated in CA3 and DG of FE group ( t=7.811, 8.790, both P<0.01). (3) Western blot results: Compared with stroke group, the expression of TGF-β1 in hippocampus of PSD group was down-regulated ( t=3.255, P<0.01). Compared with the PSD group, the expression of TGF-β1 in hippocampus of FE group was up-regulated ( t=2.906, P<0.05). (4) ELISA detection showed that compared with the stroke group, the levels of TGF-β1 decreased ( t=2.224, P<0.05), but TNF-α increased ( t=6.127, P<0.01) in PSD group.Compared with the PSD group, the expression of TGF-β1 in FE group increased significantly ( t=4.417, P<0.01). Conclusion:Foraging exercise can improve the depressive behavior symptoms of ischemic stroke rats after chronic stress, and its mechanism may be related to the increasing expression of TGF-β1, which can alleviate the inflammatory reaction in hippocampus.
ABSTRACT
OBJECTIVE To evaluate the efficiency of drug safet y supervision in China after issuing a series of new policies in 2018，and to provide the suggestions for optimizing the construction of drug safety supervision system in China and narrowing regional differences. METHODS The panel data of input-output indexes of 18 provinces in 7 administrative regions were collected from the official website of provincial drug regulatory departments ，the open platform of budget and final accounts and the official website of National Bureau of Statistics. Data envelopment analysis （DEA）model and Malmquist index were adopted to conduct an empirical analysis on the efficiency of drug safety supervision in China during 2019-2020. RESULTS & CONCLUSIONS DEA analysis showed that during 2019-2020，the overall technical efficiency （TE）of drug safety supervision in China was lower than 1.000，which didn ’t meet effective DEA. Only Liaoning ，Guangdong and Guangxi had TE of 1.000，indicating significant differences in efficiency of drug safety supervision in different regions. The results of Malmquist index analysis showed that the overall efficiency of drug safety regulation in China was declining ，among which insufficient regulatory capacity supported by technology and large loss of professional personnel were the main factors ，and the improvement of drug regulatory departments ’ management and supervision level could ensure the improvement of overall regulatory efficiency. The current scale of drug supervision in nearly half of provinces （8/18）was close to the optimal state. It is necessary to strengthen the infrastructure construction and pay attention to the training of professional talents to optimize the drug regulatory team ；strengthen the innovation of supervision technology and improve the construction of technological support system ；rationally allocate regulatory resources and balance regional regulation according to local conditions to improve the construction of drug safety supervision system in China.
ABSTRACT
Objective:To investigate the current application of colonoscopy at hospitals in China.Methods:From November 2019 to January 2020, an online questionnaire survey was conducted among gastroenterologists and colonoscopists in hospitals of different levels. The contents of questionnaire survey included basic information of colonoscopy at the respondent′s hospital, protocols and patient education of bowel preparation, implementation of colonoscopy quality control, and colonoscopists′ understanding of polypectomy techniques and post-polypectomy follow-up.Results:A total of 236 valid questionnaires were collected, involving 187 hospitals, and 143 (76.5%) had an annual operation capacity of more than 5 000 cases. In terms of bowel preparation, split-dosed polyethylene glycol electrolyte powder (PEG) was the most commonly used (60.4%, 113/187) and the most common volume of PEG was 3 L (67.4%, 126/187). Verbal (90.9%, 170/187) and written (79.7%, 149/187) instructions were given more often than other methods for patient education of bowel preparation. Antifoaming agent was routinely used in 124 (66.3%) hospitals. In terms of quality control, only 11.5% (20/174) hospitals implemented all four measures. In terms of polypectomy techniques, 98.1% (203/207) colonoscopists chose hot snare polypectomy or endoscopic mucosal resection for lesions of diameter>1 cm, while options varied for lesions of diameter<1 cm. The interval of follow-up after polypectomy recommended by colonoscopists was shorter than that by guidelines.Conclusion:Several problems are found in the survey in the application of colonoscopy in China, i. e., patient education of bowel preparation is not diversified; quality control of colonoscopy still needs to be strengthened; polypectomy techniques and follow-up after polypectomy need to be further standardized.
ABSTRACT
Objective:To explore the application value of creatinine correction method in estimating 24 h urinary iodine excretion of healthy adults.Methods:Healthy adults(half males and half females) aged 18 to 59 yesrs old in Tangshan City were selected as the research subjects. Random urine within 1 d, morning urine and 24 h urine samples of 5 d in a row of all subjects were collected to detect urinary iodine and creatinine concentrations. Twenty-four hours urinary iodine excretion was estimated by creatinine correction formula [24 h urinary iodine excretion estimated value(μg/d) = urinary iodine/creatinine concentration ratio (μg/g Cr) × 24 h urinary creatinine excretion (g Cr/d)]. The estimated value of 24 h urinary iodine excretion obtained from random urine within 1 d and continuous 5 d morning urine corrected by creatinine were studied by the coefficient of variation, and compared with the measured value of 24 h urinary iodine excretion.Results:The coefficient of variation of the estimated 24 h urinary iodine excretion of random urine within 1 d ranged from 8.8% - 20.2%, with an average value of 13.1%; the coefficient of variation of 24 h urinary iodine excretion estimated value from continuous 5 d morning urine and the 24 h urinary iodine excretion measured value ranged from 4.7% - 17.2% and 4.0% - 10.4%, and the average values were 10.1% and 6.4%, respectively. In the detection of random urine within 1 d, there was no significant difference between the 24 h urinary iodine excretion estimated value of the first, second, third, and forth time random urine and the 24 h urinary iodine excretion measured value ( P > 0.05). In the detection of continuous 5 d morning urine, there were no significant differences in the 24 h urinary iodine excretion estimated value of the first, second, third, forth and fifth day compared with the 24 h urinary iodine excretion measured value on the same day, respectively ( P > 0.05). Conclusions:When the daily creatinine excretion is accurately known, the estimated 24 h urine iodine excretion obtained by the creatinine correction method can better reflect the actual 24 h urinary iodine excretion. Further study on prediction criteria of creatinine excretion suitable for Chinese people will help to better detect the iodine intake of corresponding individuals.
ABSTRACT
Objective@#The active components and potential targets were predicted and confirmed to explore the possible mechanism of Wenpi decoction on ulcer colitis.@*Methods@#The traditional Chinese medicine integrated pharmacology platform (TCMIP) was used to construct the decoction-target-disease target network, and the key nodes were analyzed and screened. The function and pathway enrichment analysis were conducted to explore the biological processes, which Wenpi decoction may be involved in the treatment of ulcerative colitis.@*Results@#The study showed that there were 455 active ingredients and 3044 targets in Wenpi decoction. The 434 targets and multiple biological processes and metabolic pathways were involved, such as chemokine signaling pathways, estrogen signaling pathway, thyroid hormone signaling pathway, MAPK signaling pathway, and PI3K/Akt signaling pathway. These targets and pathways were consistent with the pathogenesis of ulcerative colitis reported in the literature. In addition, Wenpi decoction was potential to be applied in the treatment of tumor, endocrine and metabolic diseases.@*Conclusions@#This study provided a scientific basis for further studies on the mechanism of Wenpi decoction in the treatment for ulcer colitis.
ABSTRACT
Objective@#To evaluate the clinical value of a commercial low-residue diet (LRD) for bowel preparation of colonoscopy.@*Methods@#This study was a prospective, endoscopist-blind, and randomized controlled trial. Participants were randomly assigned to two groups according to administration of LRD: the experimental group and the control group. Bowel preparation quality, compliance and tolerability of the two groups were compared.@*Results@#A total of 61 patients were enrolled, with 32 in the experimental group and 29 in the control group. The outcomes were as follows: Boston Bowel Preparation Scale (BBPS) (7.8±1.0 VS 7.1±1.3, P=0.037), the rate of bowel preparation adequacy (87.5% VS 79.3%, P=0.388), compliance rate of dietary restriction (78.1% VS 55.2%, P=0.057), preparation completion rate (93.8% VS 93.1%, P=0.919), cecal intubation rate (both were 100.0%) and cecum arrival time (9.1±2.9 min VS 9.8±3.7 min, P=0.417), incidence of adverse (3.1% VS 3.4%, P=0.944), and hunger rate before colonoscopy (34.4% VS 48.3%, P=0.102).@*Conclusion@#The LRD for bowel preparation of colonoscopy significantly improves BBPS, but its effect on improving the bowel preparation adequacy, patient compliance and tolerability needs to be confirmed by further larger-scale trials.
ABSTRACT
Objective To evaluate the clinical value of a commercial low-residue diet (LRD) for bowel preparation of colonoscopy. Methods This study was a prospective, endoscopist-blind, and randomized controlled trial. Participants were randomly assigned to two groups according to administration of LRD:the experimental group and the control group. Bowel preparation quality, compliance and tolerability of the two groups were compared. Results A total of 61 patients were enrolled, with 32 in the experimental group and 29 in the control group. The outcomes were as follows:Boston Bowel Preparation Scale ( BBPS) (7. 8±1. 0 VS 7. 1±1. 3, P=0. 037), the rate of bowel preparation adequacy (87. 5％ VS 79. 3％, P=0. 388), compliance rate of dietary restriction (78. 1％ VS 55. 2％, P=0. 057), preparation completion rate (93. 8％ VS 93. 1％, P=0. 919), cecal intubation rate (both were 100. 0％) and cecum arrival time (9. 1± 2. 9 min VS 9. 8±3. 7 min, P=0. 417), incidence of adverse (3. 1％ VS 3. 4％, P=0. 944), and hunger rate before colonoscopy (34.4％ VS 48.3％, P=0.102). Conclusion The LRD for bowel preparation of colonoscopy significantly improves BBPS, but its effect on improving the bowel preparation adequacy, patient compliance and tolerability needs to be confirmed by further larger-scale trials.
ABSTRACT
Objective To investigate the risk factors of cognitive impairment associated with early post－acute stroke seizures (EPASS). Methods One hundred and sixty－eight eligible patients were recruited in the study. Patients were divided into cognitive impairment group and non－cognitive disorder group according to MMSE. General clinical data, severity of the stroke, location and extent of infarction, characteristics of epileptic seizures were compared between the two groups. Multivariate Logistic regression analysis was utilized to investigate the independent risk factors of EPASS related cognitive impairment. Results Multivariate logistic regression analysis showed that moderate to severe stroke (OR=4.386, P=0.006), cortical infarction (OR=6.430, P=0.012), general tonic clonic seizure (OR=8.189, P=0.004), seizure frequency≥1 time per day (OR=12.818, P＜0.001) were the independent risk factors for cognitive impairment in EPASS. Conclusions Patients with moderate to severe stroke, cortical infarction, general tonic clonic seizure and seizure frequency≥1 time per day may have a higher risk of cognitive impairment.
ABSTRACT
Objective To analyze the risk factors of delayed post-polypectomy bleeding ( DPPB) of colonoscopy. Methods The data of 459 patients who underwent colonoscopic polypectomy between January 2014 and May 2017 were summarized, and the risk factors of DPPB were analyzed. Results Among the 459 patients, a total of 572 polyps were removed, and DPPB occurred in 27 patients with 42 polyps. Univariate analysis revealed that gender (male 85. 2%), number of polyps removed (≥3 polyps, 59. 3%), complicated with hyperlipidemia (29. 6%), polyps′diameter (≥10 mm, 66. 7%), morphology (pedunculated, 81. 0%), pathological type ( adenoma, 95. 2%), and excision method ( endoscopic mucosal resection, 90. 5%) were significantly correlated with DPPB ( all P＜0. 05). Logistic regression analysis showed that gender, with hyperlipidemia, number of polyps removed, polyps′ size, and morphology were independent risk factors of DPPB (P＜0. 05). Conclusion The risk factors of DPPB include male, complicated with hyperlipidemia, excision of more than 3 polyps, more than 10 mm in diameter, and pedunculated morphology.
ABSTRACT
Objective To evaluate the mid-to-long term therapeutic effect of endoscopic pneumatic dilation for achalasia of cardia (AC).Methods Endoscopic pneumatic dilation was used in 45 AC patients, with follow-up of 2-12 years. Eckardt score and Stooler grading were used before and after the operation for evaluation of curative effect of dilation. Results The operation success rate was 97. 8%( 44/45) and the effective remission rate was 93. 2%( 41/44 ). No massive hemorrhage, perforation or other serious complications occurred.The longest follow-up time was up to 144 months.Ten cases were followed up for over 60 months. Patients′symptoms relieved significantly (P＜0. 01). Eckardt scores in 24 months and 60 months after operation significantly decreased compared with those before the operation ( P＜0. 01). But Eckardt score in 60 months was higher than that in 24 months ( P＜0. 01). The length of the disease history was positively related to post-operative scores, and negatively related to efficacy ( P＜0. 01). Conclusion Endoscopic balloon dilation is a satisfactory therapy to AC with good efficacy and safety.
ABSTRACT
Objective To investigate the diagnostic value of endoscopic ultrasonography(EUS)for esophageal submucosal tumor(SMT). Methods Clinical data of 388 patients with esophageal SMT, who underwent EUS and endoscopic treatment in Tianjin Medical University General Hospital were collected from May 2010 to September 2016. The golden standard for the origin of esophageal SMT was the diagnosis during endoscopic treatment, and the golden standard of pathological type was the combination of postoperative pathological and immunohistochemical findings. The diagnostic accuracy of EUS for esophageal SMT was evaluated. Results The conventional endoscopy revealed that 31.70%(123/388)and 43.81%(170/388)esophageal SMTs were located in the middle and lower segments of esophagus,respectively. The diagnostic consistency of EUS for the origin of lesion was 71.51%(251/351), while the diagnostic consistency of EUS for lesion originated from the muscularis mucosae, submucosa and muscularis propria layer was 92.90%(170/183), 34.38%(11/32), and 51.47%(70/136), respectively. The diagnostic consistency of EUS for the type of lesion was 81.00%(260/321), while the diagnostic consistency of leiomyoma, esophageal cyst, and lipoma were 88.42%(252/285), 14.81%(4/27), and 80.00%(4/5), respectively. Conclusion EUS can preliminarily diagnose the origin and pathological type of esophageal SMT,but there are limitations on the diagnosis of uncommon lesions,which need combination of pathological and immunohistochemical findings.
ABSTRACT
Objective:To explain the present status of licensed pharmacists in China, and put forward suggestions for perfecting the system by a problem-focused method. Methods: The data from Certification Center for Licensed Pharmacists of CFDA and 2535 pieces of questionnaire from nationwide were reviewed, and the practice registration, distribution, educational background, qualifica-tions and the other status were analyzed. Results:Generally, the development of licensed pharmacists in China was promising. Howev-er, there were still some problems existing in China such as the lower registration rate compared with some countries abroad, the une-ven distribution inside, and the unclear duty understanding. Conclusion:It is proposed to formulate relevant policies to strengthen re-gional guidance, improve registration rate, distinguish the content of continuing education and so on in order to promote the quality of licensed pharmacists in China.
ABSTRACT
Objective To understand whether it had differences in bile culture and drug susceptibility test between patients with community-acquired acute cholecystitis and patients with community-acquired acute cholangitis at present.Methods 169 patients with community-acquired acute cholecystitis and the 97 patients with community-acquired acute cholangitis in our department were selected prospectively,in which 16 patients suffered from both community-acquired acute cholecystitis and community-acquired acute cholangitis.Bile sample was extracted in operations and delivered to perform aerobic culture and drug sensitivity test.The bile samples coming from cholecyst were divided into group A,while the bile samples coming from bile duct were divided into group B.Results The positive rates of bile culture in group A and group B were separately 24.9% and 64.9%(P0.05).Conclusion Some difference exist in the results of bile culture between patients with community-acquired acutecholecystitis and patients with community-acquired acute cholangitis,but the main bacteria of the both two types of biliary tract infection are Escherichia coli and Klebsiella pneumonia.The drug resistance is serious in the both infections,and the most sensitive antibiotics to gram negative bacteria include amikacin,ertapenem,imipenem,piperacillin/tazobactam,and the most sensitive antibiotics to gram positive bacteria include tigecycline,linezolid in the both infections.
ABSTRACT
Objective To investigate the mechanism of bone morphogenetic protein 4(BMP4) in the genesis of Barrett′s esophagus.Methods Human esophageal epithelial cell (HEEC) and MRC-5 were cultured.The effects of different concentration of BMP4 and different pH value of hydrochloric acid or glycocholic acid on the expression of caudal-related homeobox transcription factor 2(CDX2) in HEEC were detected by real time polymerase chain reaction.The effects of different pH value of hydrochloric acid or glycocholic acid on BMP4 expression in MRC-5 were also investigated.Independent sample t test was performed for statistical analysis.Results After HEEC stimulated by BMP4 at 0.1, 1.0, 10.0 and 100.0 ng/mL, the relative quantity expressions of CDX2 were 1.617±0.246, 2.489±0.455, 5.629±0.449 and 13.670±1.689, respectively, which were higher than those of control group (1.000±0.043, 1.029±0.094, 1.001±0.002 and 1.049±0.051, respectively), and the differences were statistically significant (t=2.47, 3.14, 10.31, 7.47;all P<0.05).After MRC-5 stimulated by acid at pH four or five, or glycocholic acid at pH four or five, the relative quantity expressions of BMP4 were 2.430±0.105, 2.394±0.145, 125.900±12.620 and 2.128±0.215, respectively, which were higher than those of control group(1.025±0.095, 0.999±0.007, 1.060±0.138 and 0.893±0.110,respectively), and the differences were statistically significant (t=9.94, 9.59, 9.89, 5.11;all P<0.01).Conclusion BMP4 can increase the expression of CDX2 in HEEC, which promote the genesis of Barrett′s esophagus.
ABSTRACT
Objective To analyze the current status of bacterial spectrum and drug resistance in community-acquired biliary tract infection to provide a basis for clinical medication .Methods The patients with community-acquired biliary tract infection (ex-periment group) and the patients with biliary tract diseases without biliary tract infection (control group) derived from the native ar-ea treated in this hospital from September 2014 to January 2016 were selected .The bile juice was intraoperatively extracted for con-ducting the bacterial culture and drug susceptibility test .Results Thirteen specieses (60 strains) of bacteria were isolated in the ex-periment group .The top 3 specieses were Escherichia coli (35 .0% ) ,Klebsiella pneumonia (21 .7% ) and Enterobacter cloacae (10 .0% ) .Eight specieses (13 strains) of bacteria were isolated in the control group .The top 3 specieses were Escherichia coli (30 .8% ) ,Klebsiella pneumonia(15 .4% ) and Lactococcus garvieae (15 .4% ) .The proportions of drug resistant strains in the two groups were 95 .0% and 84 .6% respectively (P>0 .05) .The proportions of multiple drug resistant strains in the two groups were 30 .0% and 7 .7% respectively(P>0 .05) .The occurrence rates of multiple drug resistance in the top 3 specieses of bacteria in the experiment group were 61 .9% ,7 .7% and 16 .7% respectively .Conclusion The bacterial spectra of community-acquired acute bili-ary tract infection in the native area are dominated by Gram negative bacteria .The total bacterial drug resistance is serious ,but the drug resistance situation in different bacteria pathogens is different .
ABSTRACT
@#Objective To investigate the effect of Ser473-Akt phosphorylation in the protection of atorvastatin to cerebral ischemia-re-perfusion (I/R) injury in rats. Methods Forty male Sprague-Dawley rats were randomly divided into normal group (n=10), sham group (n=10), I/R group (n=10) and intervention group (n=10). A model of cerebral ischemia-reperfusion in rats was establishied, with ischemia for 2 hours and reperfusion for 72 hours. The normal group and the sham group received no injury. I/R group was administered with normal saline only, and the intervention group received atorvastatin 10 mg/kg prepared with normal saline at palinesthesia, 24 and 48 hours after reperfu-sion. All rats were sacrificed 72 hours after reperfusion. HE staining and TUNEL staining were performed in the brain specimens. The ex-pression of Akt and Ser473-Akt in the prefrontal cortex of the brain were detected with Western blotting. Results Compared with I/R group, 72 hours after reperfusion, the damage of nerve cells significantly lessened in the intervention group;the apoptosis positive cells significant-ly reduced in the intervention group (t=-6.014, P<0.001). The expression of Ser473-Akt in prefrontal cortex was higher in I/R group than in the normal group and the sham group (t>20.327, P<0.001), and was higher in the intervention group than in I/R group (t=3.649, P=0.007). Conclusion The Ser473-Akt phosphorylation plays an important role in the protection of atorvastatin in nerve cell through anti-apoptosis of nerve cells, and reducing cerebral I/R injury.
ABSTRACT
Objective To investigate the association between norepinephrine transporter (NET)gene polymorphism and decision-making processing in patients with cerebral infarction.Methods A total of 145 patients with cerebral infarction and 188 normal controls were enrolled in our study.In all subjects,the polymerase chain reaction (PCR) for NET-T182C/G1287A polymorphism assay,gel electrophoresis,image analysis and enzymatic reaction,gene sequencing methods were used.The relationships of NET T182C/G1287A genotypes and alleles with decision-making processing were analyzed in patients with cerebral infarction.All participants completed six kinds of choice situational problems.Results There were significant differences in genotype and allele frequencies of T182C and G1287A polymorphism in NET between the patients with cerebral infarction and control group(for NET-T182C:genotype,x2 =4.437,P=0.049,allele frequency,x2=4.363,P=0.037,OR=0.625,95％CI:0.436-0.895;for NET-G1287A:genotype,x2=8.435,P=0.038,allele frequency,x2=2.765,P=0.036,OR=1.520,95％CI:1.053-2.193).The cerebral infarction patients with three NET-T182C genotypes and T/C alleles all completed six choice scenarios,and the scheme selection probability had no significant difference (all P＞0.05).In high-risk and no-risk loss situation (scenario 4),the scheme selection probability had significant difference in cerebral infarction patients with NET-G1287 A genotypes and G/A alleles (P＜0.05 and 0.05,OR=1.657,95％CI:1.149-2.390),and the patients with GG genotype tended to choose high-risk loss scheme,and the probability was obviously lower than that patients with other two genotypes,the patients with G allele tended to choose high-risk loss scheme,and the probability was obviously lower than that in patients with A allele (all P＜0.05).In other five choice scenarios,the scheme selection probability had no significant difference between the patients (all P ＞0.05).Conclusions NET-G1287A polymorphism may be associated with decision-making processing in patients with cerebral infarction.In the high-risk and no-risk loss condition,patients with GG genotype and G allele have more loss risk aversion.
ABSTRACT
Objective To investigate the relationship between methylenetetrahydrofotate reductase (MTHFR)C677T polymorphisms and H-type hypertension and increased plasma homocysteine (Hcy) levels. Methods From September 2013 to June 2014,4 012 permanent residents aged ≤30 year from 12 natural villages or communities in 6 regions of Hunan province were extracted according to the cluster random sampling method. Using computer random number table,571 residents were randomly selected as the research objects. According to the blood pressure and Hcy levels,571 residents were divided into 3 groups:a common hypertension group (n = 190),an H-type hypertension group (n = 94),and a normal blood pressure group (n = 287 ). Amplification refractory mutation system-polymerase chain reaction (ARMS-PCR)method was used to detect the MTHFR C677T polymorphisms in all the research objects and the penotyping was performed. Hcy levels were detected at the same time. Results There were significant differences in recessive model (CC + CT,TT)genotype frequencies among the H-type hypertension group (n = 66[70. 2%],n = 28[29. 8%]),common hypertension group (n = 156[82. 1%],n = 34[17. 9%]), and normal blood pressure group (n = 235[81. 9%],n = 52[18. 1%])(χ2 = 6. 797,P = 0. 033),and there were no significant differences in CC,CT,and TT genotype frequencies among the 3 groups (P >0. 05). In the recessive model,there were significant differences in TT genotype frequencies between the H-type hypertension group and the normal blood pressure group or the common hypertension group (χ2 = 5. 812,P = 0. 016;χ2 = 5. 212,P = 0. 022). There was no significant difference in TT genotype frequencies between the common hypertension group and the normal blood pressure group (P > 0. 05). The CC + CT and TT genotype Hcy levels of the MTHFR C677T recessive model in the H-type hypertension group were 17. 1 ±1. 6 and 19. 0 ±2. 9 μmol/ L respectively. There was significant difference between the genotypes (t = - 3. 115,P = 0. 004). The logistic regression analysis of MTHFR C677T recessive model genotype showed that after adjusting for sex and age,the residents with recessive model TT genotype had higher risk of H-type hypertension (OR,1. 946,95% CI 1. 172 -3. 232,P = 0. 01). Conclusion The TT MTHFR C677T gene mutation in this population may be an important genetic factor for the increased Hcy levels and the onset of H-type hypertension.