Clinical Evidence Mapping of Chinese Patent Medicines Combined with Western Medicine in Treatment of Hypertension / 中国实验方剂学杂志

ObjectiveTo systematically collect， analyze， and evaluate the randomized controlled trials （RCT） of Chinese patent medicine combined with western medicine in the treatment of hypertension， map the evidence， and provide reference for the future clinical research and formulation of guidelines and policies. MethodThe relevant articles were retrieved from China Biology Medicine disc， China National Knowledge Infrastructure （CNKI）， VIP， Wanfang Data， PubMed， Embase， and Cochrane Library with the time interval from inception to December 31， 2022. The RCT of Chinese patent medicines combined with western medicine in the treatment of hypertension were included. The research characteristics and methodological quality were analyzed and evaluated. ResultA total of 330 RCTs of treating hypertension with Chinese patent medicines combined with Western medicine were included in this study， all of which were published in Chinese. These RCTs involved 88 Chinese patent medicines and 37 788 patients， and 46% of RCT had the sample size ≥100 patients. Eighty-seven percent of RCT showed the study period within 3 months. All the interventions in the RCTs were Chinese patent medicine + western medicine vs western medicine. Among the evaluation indicators， blood pressure， response rate， TCM syndrome score， endothelial cell function， and safety were mainly concerned. In terms of methodological quality， most articles did not mention the generation of random sequences， allocation concealment， or blinding method. The blinding evaluation of outcomes showed low risks of bias， and there was insufficient information to judge whether there was selective bias or other bias. ConclusionThere were many Chinese patent medicines used in combination with western medicine in the treatment of hypertension， and they were mainly taken orally. The existing RCT had problems such as small sample size， unclear clinical value positioning， imperfect design failing to reflect the value of Chinese patent medicines， unreasonable measurement indicators， and non-standard measurement methods. Future research should solve the above problems， improve the research quality， value， and authenticity， and enhance the reliability and extension of evidence.

GRADE Clinical Study Evidence Evaluation and Expert Consensus on Antihypertensive Chinese Patent Medicines Combined with Western Medicines for Treatment of Hypertension / 中国实验方剂学杂志

ObjectiveTo evaluate the quality of research and evidence related to antihypertensive Chinese patent medicines combined with western medicines for the treatment of hypertension， synthesize and update the evidence， form expert consensus， and provide evidence for clinical decision-making. MethodThe databases of China National Knowledge Infrastructure （CNKI）， WanFang Data Knowledge Service Platform （WanFang）， Vip Chinese Science and Technology Journal Database （VIP）， Chinese Biomedical Literature Service System （Sinomed）， National Library of Medicine （PubMed）， Cochrane Library， Web of Science， and US Clinical Trials Registry were searched for randomized controlled trials of antihypertensive Chinese medicine combined with western medicine for the treatment of hypertension from database construction to July 31， 2022. The quality of the literature was evaluated using the bias risk assessment tool in Cochrane Handbook 6.3. Evidence synthesis of main outcome indicators was performed using R software. The Grading of Recommendations Assessment， Development， and Evaluation profiler （GRADEprofiler） 3.6 was employed to evaluate the quality of evidence. Expert consensus was formed based on the Delphi method after two rounds of voting. Result64 pieces of literature were included， and the results of literature quality evaluation and risk of bias showed that 70.31% （45/64） of the studies indicated some risks， and 29.69% （19/64） indicated high risks. Compared with conventional western medicines， the combination of Chinese patent medicines with western medicines can significantly lower systolic pressure （SBP） and diastolic pressure （DBP）， increase the effective rate of antihypertensive， reduce the incidence of adverse reactions， endothelin-1， and traditional Chinese medicine syndrome scores. Egger's test showed that Songling Xuemaikang capsules reduced SBP and DBP. Tianma Gouteng granules reduced SBP and DBP and increased the effective rate of antihypertensive， and Xinmaitong capsules reduced SBP and increased the effective rate of antihypertensive， without significant publication bias. Songling Xuemaikang capsules increased the effective rate of antihypertensive， and Xinmaitong capsules decreased DBP， with significant publication bias. The results of the GRADE evidence quality evaluation showed that most evidence was at grades B and C. Finally， four strong recommendations and 14 weak recommendations were formed. ConclusionCompared with conventional western medicines for the treatment of hypertension， antihypertensive Chinese patent medicines combined with western medicines have advantages in reducing blood pressure and improving drug use safety， but they are mostly weak recommendations in terms of efficacy， and more high-quality evidence is needed.

Evaluation of GRADE Clinical Research Evidence of Chinese Patent Medicine Combined with Western Medicine in Treatment of Hypertension with Dyslipidemia / 中国实验方剂学杂志

ObjectiveTo evaluate the effect of antihypertensive and lipid-regulating Chinese patent medicine combined with conventional Western medicine in the treatment of hypertension with dyslipidemia. To carry out the evidence synthesis of clinical research and provide evidence-based evidence support for clinical decision-making. MethodThe databases including China National Knowledge Infrastructure （CNKI），Wanfang Data Knowledge Service Platform （WF），VIP，SinoMed，Embase，PubMed，Web of Science （WOS），and the Cochrane Library were searched for randomized controlled trials （RCT） of all listed Chinese patent medicines in the treatment of hypertension with dyslipidemia from the establishment of the databases to April 15，2023. The literature was screened and extracted，and the risk of bias tool 2.0 （RoB2） was used to assess the quality and risk of bias of the methodology. Revman 5.4.1 software was used to analyze the outcome indicators. Grading of Recommendations Assessment，Development and Evaluation （GRADE） was applied to assess the quality of evidence formed by clinical research data. The inclusion and recommendation of Chinese patent medicines in the National Drug Catalogue for Basic Medical Insurance，Work-related Injury Insurance and Maternity Insurance （2022） and domestic guidelines and consensus were searched to form a bubble chart. ResultA total of 15 studies were included. The evaluation of the methodological quality of each study showed that the risk of bias stemmed from the lack of blinding and allocation concealment，and low sample size. The comprehensive analysis of clinical studies showed that Dengzhan Shengmai capsules combined with rosuvastatin and amlodipine besylate，Yindan Xinnaotong capsules combined with simvastatin and levamlodipine tablets，Xiaoshuan Tongluo capsules combined with nifedipine controlled release tablets and pravastatin sodium tablets，Xinshubao capsules combined with atorvastatin calcium tablets and irbesartan，Wenyading capsules combined with enalapril，and Jiangzhining tablets combined with conventional Western medicines were all superior to conventional Western medicines used in the control group in improving systolic blood pressure （SBP），diastolic blood pressure （DBP），cholesterol （TC），triglyceride （TG），low density lipoprotein cholesterol （LDL-C），and high density lipoprotein cholesterol （HDL-C）. There was no significant difference in the incidence of adverse reactions between the two groups. The GRADE evaluation of the main outcome indicators showed that the evidence quality of SBP and incidence of adverse reactions was graded as B，that of DBP as C，and that of total TC，TG，LDL-C，and HDL-C as D. The evaluation of Chinese patent medicines covered by medical insurance and recommended by guidelines and consensus showed that Yindan Xinnaotong soft capsules，Dengzhan Shengmai capsules and Xiaoshuan Tongluo capsules belonged to class B drugs of medical insurance，and were recommended for 7，6 and 3 times in the guidelines and consensus，respectively. ConclusionCompared with simple medicine treatment，Chinese patent medicine combined with conventional Western medicine has more advantages in improving blood pressure and blood lipid，and shows higher safety. Among them，Yindan Xinnaotong soft capsules，Dengzhan Shengmai capsules and Xiaoshuan Tongluo capsules have stronger clinical applicability and economy. All the trials included in this article adhered to the principle of randomization and reported the outcome measures. However，the quality of evidence in related clinical studies was low. In terms of trial design，large-sample，multi-center，blinded randomized controlled trials based on the consolidated standards of reporting trials （CONSORT） statement are still needed for comprehensive trial designs and reporting，to further improve the GRADE quality evaluation and guideline formulation under the guidance of evidence-based medicine，so as to provide higher quality evidence-based research evidence for clinical decision-making.

Pharmacogenomic testing-based precision medicine in the elderly: Current status and prospects / 中华老年医学杂志

Comorbidities will inevitably lead to an increase in the number of medications used and adverse drug reaction events in elderly patients.Therefore, it is urgent to implement precision medicine in the elderly population.pharmacogenomic testing can increase the opportunity of individualized drug selection for elderly patients, reduce the risk of adverse drug reactions, reduce the cost-effectiveness ratio of medication, improve elderly patients' medication compliance, and thus reduce their readmission rate.Therefore, it is necessary to promote pharmacogenetic testing for elderly patients with comorbidities and polypharmacy, so as to provide measures for the implementation of personalized medicine in the elderly.

Relationships between Islet-Specific Autoantibody Titers and the Clinical Characteristics of Patients with Diabetes Mellitus

BackgroundDysimmunity plays a key role in diabetes, especially type 1 diabetes mellitus. Islet-specific autoantibodies (ISAs) have been used as diagnostic markers for different phenotypic classifications of diabetes. This study was aimed to explore the relationships between ISA titers and the clinical characteristics of diabetic patients.MethodsA total of 509 diabetic patients admitted to Department of Endocrinology and Metabolism at the Affiliated Hospital of Nantong University were recruited. Anthropometric parameters, serum biochemical index, glycosylated hemoglobin, urinary microalbumin/creatinine ratio, ISAs, fat mass, and islet β-cell function were measured. Multiple linear regression analysis was performed to identify relationships between ISA titers and clinical characteristics.ResultsCompared with autoantibody negative group, blood pressure, weight, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), visceral fat mass, fasting C-peptide (FCP), 120 minutes C-peptide (120minCP) and area under C-peptide curve (AUCCP) of patients in either autoantibody positive or glutamate decarboxylase antibody (GADA) positive group were lower. Body mass index (BMI), waist circumference, triglycerides (TGs), body fat mass of patients in either autoantibody positive group were lower than autoantibody negative group. GADA titer negatively correlated with TC, LDL-C, FCP, 120minCP, and AUCCP. The islet cell antibody and insulin autoantibody titers both negatively correlated with body weight, BMI, TC, TG, and LDL-C. After adjusting confounders, multiple linear regression analysis showed that LDL-C and FCP negatively correlated with GADA titer.ConclusionDiabetic patients with a high ISA titer, especially GADA titer, have worse islet β-cell function, but less abdominal obesity and fewer features of the metabolic syndrome.

Relationships between Islet-Specific Autoantibody Titers and the Clinical Characteristics of Patients with Diabetes Mellitus

BackgroundDysimmunity plays a key role in diabetes, especially type 1 diabetes mellitus. Islet-specific autoantibodies (ISAs) have been used as diagnostic markers for different phenotypic classifications of diabetes. This study was aimed to explore the relationships between ISA titers and the clinical characteristics of diabetic patients.MethodsA total of 509 diabetic patients admitted to Department of Endocrinology and Metabolism at the Affiliated Hospital of Nantong University were recruited. Anthropometric parameters, serum biochemical index, glycosylated hemoglobin, urinary microalbumin/creatinine ratio, ISAs, fat mass, and islet β-cell function were measured. Multiple linear regression analysis was performed to identify relationships between ISA titers and clinical characteristics.ResultsCompared with autoantibody negative group, blood pressure, weight, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), visceral fat mass, fasting C-peptide (FCP), 120 minutes C-peptide (120minCP) and area under C-peptide curve (AUCCP) of patients in either autoantibody positive or glutamate decarboxylase antibody (GADA) positive group were lower. Body mass index (BMI), waist circumference, triglycerides (TGs), body fat mass of patients in either autoantibody positive group were lower than autoantibody negative group. GADA titer negatively correlated with TC, LDL-C, FCP, 120minCP, and AUCCP. The islet cell antibody and insulin autoantibody titers both negatively correlated with body weight, BMI, TC, TG, and LDL-C. After adjusting confounders, multiple linear regression analysis showed that LDL-C and FCP negatively correlated with GADA titer.ConclusionDiabetic patients with a high ISA titer, especially GADA titer, have worse islet β-cell function, but less abdominal obesity and fewer features of the metabolic syndrome.

Construction of Clinical Pharmacist Performance Appraisal System under the New “National Examination ” Situation / 中国药房

OBJECTIVE：To prov ide reference for mobilizing the work enthusiasm of clinical pharmacists ，and further promoting the strategic objectives of performance appraisal in three-level public hospitals （“National examination ”for short ）. METHODS：A department performance appraisal team was established ，and a key performance indicator system consisting of 4 first-level indicators and 9 second-level indicators was constructed by using literature retrieval and expert consultation. The performance distribution method of double assessment of performance score and performance score was established ，and a performance publicity and feedback performance mechanism was formed. Relevant data were collected to compare the core work indicators of clinical pharmacists ，use intensity of antibiotics ，compliance rate of essential drugs in our hospital from Apr. to Dec. 2019（before implementation ）and Apr. to Dec. 2020（after implementation ）. RESULTS ：After the implementation of performance appraisal scheme ，the total number of medication recommendations of clinical pharmacists increased from 1 192 to 5 226，with an increase of 338.42％；the number of medication suggestions received increased from 846 to 4 855，with an increase of 473.88％； and the rate of drug suggestions received increased from 70.97％ to 92.90％；the number of pharmaceutical consultation increased from 195 to 1 284，with an increase of 558.46％；the number of drug counseling increased from 1 203 to 2 719，increasing by 126.02％. Form Apr. to Dec. 2020，the number of patient safety medication evaluation forms reached 660. The antibiotics use density（AUD）in clinical departments of 13 clinical pharmacists were decreased to different extent after the implementation of performance appraisal scheme ，the decine rate was 92.31％（12/13），and the compliance rate was 69.23％（9/13）；utilization rate of essential medicine among outpatients of 11 clinical pharmacists ’clinical departments had achieved positive growth ，and those among inpatients of 2 clinical pharmacists ’clinical departments had achieved positive growth. CONCLUSIONS ：The performance appraisal system of clinical pharm acists formulated by our hospital links the “National examination ”index with the performance ， appraisal of clinical pharmacists ，which can provide ideas for No.2018sxzx57，No.2020jyxm2328，No.2020jyxm2307） the performance appraisal of three-level public hospitals and help to promote the high-quality and sustainable development of hospital pharmaceutical care.

Protective effect of adrenomedullin on hyperoxia-induced lung injury / 中国当代儿科杂志

OBJECTIVES@#To study the role of adrenomedullin (ADM) in hyperoxia-induced lung injury by examining the effect of ADM on the expression of calcitonin receptor-like receptor (CRLR), receptor activity-modifying protein 2 (RAMP2), extracellular signal-regulated kinase (ERK), and protein kinase B (PKB) in human pulmonary microvascular endothelial cells (HPMECs) under different experimental conditions.@*METHODS@#HPMECs were randomly divided into an air group and a hyperoxia group (@*RESULTS@#Compared with the air group, the hyperoxia group had significant increases in the mRNA and protein expression levels of ADM, CRLR, RAMP2, ERK1/2, and PKB (@*CONCLUSIONS@#ERK1/2 and PKB may be the downstream targets of the ADM signaling pathway. ADM mediates the ERK/PKB signaling pathway by regulating CRLR/RAMP2 and participates in the protection of hyperoxia-induced lung injury.

Feasibility of computed tomography-guided irreversible electroporation for porcine kidney ablation

Objective: The objective was to evaluate the feasibility and safety of computed tomography (CT)-guided percutaneous irreversible electroporation (IRE) in porcine kidneys. Materials and Methods: Under CT guidance, two monopole probes were used to precisely puncture through the renal parenchyma into the renal hilum in nine anesthetized adult Bama miniature pigs. After which, IRE ablation was performed. Biochemical and pathological examinations were carried out 2 h, 2, 7, and 14 days after the procedure. Results: All procedures were performed successfully without any serious complications such as bleeding, infection, or death. All pigs survived until the end of the study. Pathological examinations showed that cells in the ablation area were dead within 2 days after the procedure, whereas the vascular endothelium showed only slight damage. After 2 days, endothelialization ensued and regrowth of smooth muscle cells was observed after 14 days. Hemogram tests indicated a transient increase but gradually returned to baseline levels 14 days after the procedure. Conclusion: IRE was essentially safe, however further studies on tumor ablation using several different animal models are needed

Relationships between Islet-Specific Autoantibody Titers and the Clinical Characteristics of Patients with Diabetes Mellitus

Background@#Dysimmunity plays a key role in diabetes, especially type 1 diabetes mellitus. Islet-specific autoantibodies (ISAs) have been used as diagnostic markers for different phenotypic classifications of diabetes. This study was aimed to explore the relationships between ISA titers and the clinical characteristics of diabetic patients. @*Methods@#A total of 509 diabetic patients admitted to Department of Endocrinology and Metabolism at the Affiliated Hospital of Nantong University were recruited. Anthropometric parameters, serum biochemical index, glycosylated hemoglobin, urinary microalbumin/creatinine ratio, ISAs, fat mass, and islet β-cell function were measured. Multiple linear regression analysis was performed to identify relationships between ISA titers and clinical characteristics. @*Results@#Compared with autoantibody negative group, blood pressure, weight, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), visceral fat mass, fasting C-peptide (FCP), 120 minutes C-peptide (120minCP) and area under C-peptide curve (AUCCP) of patients in either autoantibody positive or glutamate decarboxylase antibody (GADA) positive group were lower.Body mass index (BMI), waist circumference, triglycerides (TGs), body fat mass of patients in either autoantibody positive group were lower than autoantibody negative group. GADA titer negatively correlated with TC, LDL-C, FCP, 120minCP, and AUCCP.The islet cell antibody and insulin autoantibody titers both negatively correlated with body weight, BMI, TC, TG, and LDL-C. After adjusting confounders, multiple linear regression analysis showed that LDL-C and FCP negatively correlated with GADA titer. @*Conclusion@#Diabetic patients with a high ISA titer, especially GADA titer, have worse islet β-cell function, but less abdominal obesity and fewer features of the metabolic syndrome.

Bone morphogenetic protein 7 regulates insulin signal transduction in mice / 中华内分泌代谢杂志

Objective To analyze the effects of bone morphogenetic protein 7 (BMP 7) on insulin signaling pathway in mice and its involved molecular mechanisms. Methods To increase BMP7 expression in liver, adenovirus bearing BMP7 was injected into mice via tail vein. The impact of BMP7 overexpression on glucose metabolism was assayed by glucose tolerance test and insulin tolerance test. The levels of proteins involved in insulin signaling pathway and c-Jun N-terminal kinase ( JNK) signaling pathway were analyzed by Western blot. Results The blood glucose level was increased by BMP7 overexpression (P>0. 05), while the glucose tolerance and insulin tolerance were decreased by BMP7. The p-Akt and p-GSK3βin liver and epididymal white adipose tissue (WAT) were reduced in the BMP7-overexpressed mice (P>0. 01), indicating insulin signal transduction was inhibited. In gastrocnemius muscle, the insulin signal transduction was not altered by BMP7. Mechanistically, the JNK pathway was activated by BMP7 in liver and epididymal WAT (P>0. 01), while the JNK pathway in skeletal muscle was not changed. Conclusions In mice, BMP7 elevated blood sugar and decreased glucose and insulin tolerance. BMP7 inhibited the insulin signaling pathway in liver and WAT. These inhibitory effects on insulin signaling pathway was likely to be achieved by an activating JNK signaling pathway.

Simultaneous determination of fourteen constituents in Yangxue Qingnao Granules by LC-MS/MS / 中成药

AIM To establish an LC-MS/MS method for the simultaneous content determination of paeoniflorin,albiflorin,neochlorogenic acid,chlororogenic acid,catechin,epicatechin,ethyl gallate,danshensu,ferulic acid,caffeic acid,gallic acid,protocatechuic acid,protocatechualdehyde and rosmarinic acid in Yangxue Qingnao Granules (Angelicae sinensis Radix,Chuanxiong Rhizoma,Paeoniae Radix Alba,etc.).METHODS The analysis of methanol extract of this drug was performed on a 20 ℃ thermostatic Waters Symmetry Shield RP C18 column (3.9 mm × 150 mm,5 μm),with the mobile phase comprising of acetonitrile-water (containing 0.1％ formic acid) flowing at 0.4 mL/min in a gradient elution manner.RESULTS Fourteen constituents showed good linear relationships within their own ranges,whose average recoveries were 85.5％-107.0％ with the RSDs of 2.0％-5.0％.CONCLUSION This simple,sensitive,accurate and reproducible method can be used for the quality control of Yangxue Qingnao Granules.

Correlation between heteroplasmy level of the 5178C＞A mutation in the ND2 gene of mitochondria DNA and essential hypertension in middle-aged and elderly adults / 中华老年医学杂志

Objectives To explore the correlation between the heteroplasmy level of mt5178C＞A mutation in ND2 gene of mitochondria DNA and essential hypertension(EH)in middle-aged and elderly adults.Methods EH patients and normotensive controls were recruited consecutively from 2014-2015 from general population.Demographics,clinical characteristics and blood leukocytes were collected.The mt5178C＞A mutation heteroplasmy level was quantified by the rapid and sensitive realtime polymerase chain reaction(PCR) method for each participant.Results A total of 108 EH patients and 109 controls were recruited.The mt5178C＞A mutation heteroplasmy level was(42 ± 11％)in EH patients and (54± 13)％ in control subjects,with statistically significant difference between the two groups(P＜0.01).Using a two-step cluster analysis,the mt5178C＞A heteroplasmy level exceeding 44％ was associated with a decreased risk of EH(OR=0.18,95％,CI:0.10-0.31,P＜0.01).Correlation analysis showed mt5178C＞ A heteroplasmy level was significantly negatively correlated with both systolic blood pressure (r =-0.38,P＜ 0.001) and diastolic blood pressure (r =-0.49,P＜ 0.01)in 109 controls.Logistic regression analysis demonstrated that in single-factor analysis,mt5178C ＞ A heteroplasmy level (OR =0.82,95 ％ CI:0.77 0.87,P ＜ 0.01) was protective factor for EH,however,BMI(OR=1.30,95％CI:1.12-1.45,P＜0.01),total cholesterol(OR=2.13,95％CI:1.39-3.28,P=0.00),triglyceride(OR=7.62,95％CI:3.45-16.84,P＜0.01)and blood urea nitrogen(OR =1.35,95 ％ CI,P =0.03) were risk factors for EH.And a multiple logistic regression analysis showed that mt5178C＞ A heteroplasmy level (OR =0.83,95 ％ CI:0.78-0.89,P＜ 0.01) was independent protective factor for E H,however,only total cholesterol (OR =2.17,95 ％ CI:1.58-2.98,P =0.02) and low density lipoprotein cholesterol (OR =0.06,95％ CI:0.01-0.83,P =0.04) were independent risk factors for EH,and the P at critical 0.05 value.Conclusions Mitochondrial ND2 gene 5178C＞ A mutation heteroplasmy level exerts protective role against EH in middle-aged and elderly adults in Chinese population.

Effect of Quality Control Circle on the Reasonable Ratio of Emergency Orthopedics Prescriptions / 中国药师

Objective:To study the effect of quality control circle(QCC)on the reasonable ratio of clinical prescriptions. Methods:The dispensed prescriptions in orthopedic emergency department were reviewed in our hospital,and the reasons of unreasonable prescriptions were analyzed. According to the QCC technique,the activities were implemented,the standardized work process was made out and the results were studied. Results:After the six-month QCC activities,the unreasonable ratio of emergency orthopedics prescriptions was reduced from 70% to 21% ,and the target yield rate was 140% and the improvement rate was 70% . Conclusion:The QCC has obvious effect on the improvement of reasonable ratio of emergency orthopedics prescriptions.

Liraglutide promotes proliferation and migration of cardiac microvascular endothelial cells through PI3K/Akt and MAPK/ERK signaling pathways / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of liraglutide, an analogue of glucagon-like peptide-1, on the proliferation and migration of cardiac microvascular endothelial cells (CMECs) and explore the mechanism.</p><p><b>METHODS</b>In vitro cultured CMECs of SD rats were purified by differential adhesion method and identified immunocytochemically using CD31 antibody and factor VIII. MTT assay was performed to assess the proliferation of the first-generation cells exposed to different concentrations (0-1000 nm/L) of liraglutide. Western blotting was used to detect the activation of PI3K/Akt and MAPK/ERK signaling pathways. BrdU fluorescent labeling and scratch assay were performed to observe the proliferation and migration of CMECs following liraglutide treatment, and PI3K/Akt and MAPK/ERK pathway inhibitors LY294002 and PD98059, respectively, were used to further confirm the role of these signaling pathways in regulating the proliferation and migration of CMECs.</p><p><b>RESULTS</b>Immunocytochemical staining demonstrated a proportion of double positive cells exceeding 95%. The cells exhibited a logarithmic growth 48 h after plating. Liraglutide exposure concentration-dependently promoted the proliferation of CMECs with the optimal concentration of 100 nmol/L (P<0.05). Liraglutide exposure of the cells for 24 h significantly increased the levels of intracellular phosphorylated Akt and ERK (P<0.05), but pretreatment of the cells with Akt and ERK signaling pathway inhibitors 1 h before liraglutide obviously reversed such effect (P<0.05). BrdU and scratch assay showed that 100 nmol/L liraglutide significantly promoted the proliferation and migration of CMECs (P<0.05), but such effects were obviously suppressed by Akt and ERK inhibitors (P<0.05).</p><p><b>CONCLUSION</b>Liraglutide promotes the proliferation and migration of CMECs in vitro via PI3K/Akt and MAPK/ERK signaling pathways.</p>

Mitochondrial DNA mutation associated with hypertension in tRNA(Ile) and tRNA(Gln) genes / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the relationship between mitochondrial DNA (mtDNA) mutations and hypertension.</p><p><b>METHODS</b>Clinical data of two pedigrees with maternally transmitted hypertension was collected. Whole mtDNA sequence was analyzed.</p><p><b>RESULTS</b>The family members on the maternal side presented with various levels of hypertension, with the onset age ranging from 44 to 55 years old. Analysis of the mtDNA sequence of the two families members showed all patients have carried a matrilineal 4329C> G mutation of the tRNA(Ile) and tRNA(Gln) genes. The same mutation was not found in 366 healthy controls. The 4329C site of mtDNA is highly conserved across species, and has been associated with the fidelity of amino acid accept arm of the tRNAs, as well as functionality and stability in the formation of tRNAs.</p><p><b>CONCLUSION</b>The 4329C> G point mutation in tRNA(Ile) and tRNA(Gln) probably has contributed to the pathogenesis of hypertension, possibly in association with other modifying factors.</p>

Age-related changes in transient outward potassium current of rat ventricular myocyte / 生理学报

The study aimed to investigate the age-related changes and drug reactions of transient outward potassium current (Ito) of ventricular myocytes. Twenty-eight Sprague Dawley rats were divided into young (3-5 months), adult (13-15 months) and aged (22-24 months) groups, and Ito currents of isolated myocytes from each group were recorded respectively by patch-clamp. The perfusion of 2.0 mmol/L 4-AP or 1.0 μmol/L isoproterenol was added respectively in each group, and the changes of Ito were observed. In comparison with young and adult groups, Ito densities of ventricular myocytes in aged group was significantly increased, the curve of steady-state activation of Ito shifted to the left, the close-state inactivation rate significantly decreased, and recovery rate from the steady-state inactivation became quicker. However, no significant changes could be detected for the Ito steady-state inactivation of ventricular myocytes in aged group. The similar responsiveness to 4-AP was observed in all three groups, but the responsiveness to isoproterenol was weaker in the aged group (55.9%) than in the other two groups (127.5% and 125.8%). In conclusion, the results show that Ito of rat ventricular myocyte of aging heart has increased current density and decreased response to isoproterenol.

Extremely low warfarin dose in patients with genotypes of CYP2C9*3/*3 and VKORC1-1639A/A / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Patients with the genotypes of both CYP2C9*3/*3 and VKORC1-1639 A/A are expected to require the lowest dose of warfarin, and to have a greatly increased risk of bleeding. The experience for the dosing of warfarin in such extremely rare cases has been seldom reported.</p><p><b>METHODS</b>Demographic and clinical data from two cases with stable low dose of warfarin in China were studied by resequencing the corresponding gene segments in their whole blood DNA. The potential clinical value of the pharmacogenetic algorithm for them was evaluated by calculating the stable dose of warfarin in pharmacogenetic algorithm developed by International Warfarin Pharmacogenetics Consortium.</p><p><b>RESULTS</b>Both cases (68-year-old female and 50-year-old male) were diagnosed as chronic nonvalvular atrial fibrillation needing warfarin treatment, with target international normalized ratio (INR) 2 to 3. Case 1 had stable warfarin dose of 0.625 mg/d and case 2 1.25 mg/d. They needed more than 1 month to stabilize their anticoagulation. Exceeding INR values were recorded for them when the dose of warfarin was no more than 2 mg/d. Hemorrhagic complication appeared in case 1 when the dose was titrated from 2.5 to 1.25 mg/d. No concomitant medicine to increase or decrease the INR value was recorded for them. Genotyping CYP2C9 and VKORC1 showed both patients were the carriers of the homozygous alleles -CYP2C9*3/*3 and VKORC1-1639 A/A. Their stable doses of warfarin calculated by the pharmacogenetic dose algorithm (0.672 mg/d for case 1 and 1.16 mg/d for case 2) were comparable with their actual stable therapeutic doses.</p><p><b>CONCLUSIONS</b>Two Chinese with the rare genotypes of both CYP2C9*3/*3 and VKORC1-1639 A/A were found to require the extremely low dose of warfarin. The pharmacogenetic algorithm incorporating the variances of VKORC1 and CYP2C9 genotypes, as well as the non-genetic factors could predict their stable dose of warfarin with high accuracy.</p>

Psychological Nursing for Anxiety-depression in Inpatients due to Cardiovascular Diseases / 中国康复理论与实践

@# ObjectiveTo explore the effect of the individualized intervention for the anxiety-depression after cardiovascular diseases. Methods80 inpatients with cardiovascular diseases were surveyed with Hospital Anxiety and Depressions Scale (HAD). The patients with anxiety-depression received individualized psychological intervention. Results14 of them suffered anxiety-depression. 13 cases recovered after the intervention. ConclusionThe individualized psychological intervention can improve anxiety-depression in the inpatients with cardiovascular diseases.

Construction of pSG5/TRIF and its expression in Huh7 cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To construct the plasmid pSG5/TRIF and investigate its expression in Huh7 cells.</p><p><b>METHODS</b>The plasmid pCX4pur/Myc-TRIF was digested with Not I and the digestion product was blunted followed by further digestion with EcoR I to obtain the insert Myc-TRIF. pSG5 was digested sequentially with Sma I and EcoR I. All the digested products were analyzed with agarose gel electrophoresis. The products with the expected size were extracted and ligated, and the positive clones were screened by ampicillin and amplified. The recombinant pSG5/TRIF was extracted, purified, and identified by restriction endonuclease BamH I and agarose gel electrophoresis. The recombinant plasmids were transfected into Huh7 cells with FuGene 6 reagents and into Huh7 cells previously infected with recombinant vaccinia virus (rVV) via Lipofectin. Immunofluorescence and Western blotting were performed to detect the expression of the recombinant plasmids, and the transfection efficiency with different transfection reagents was compared.</p><p><b>RESULTS</b>BamH I digestion resulted in a fragment with the expected size. Immunofluorescence staining showed successful expression of Myc-TRIF protein in Huh7 cells, and the transfection efficiency was enhanced in Huh7 cells previously infected with rVV. SDS-PAGE analysis showed that the relative molecular mass of the expressed product by pSG5/Myc-TRIF was about 100 ku, and prior infection of the cells with rVV obviously increased transfection efficiency, as was consistent with the results of immunofluorescence.</p><p><b>CONCLUSION</b>pSG5/Myc-TRIF is successfully constructed and expressed in Huh7 cells. The expression efficiency can be increased by prior infection of the cells with rVV.</p>