Incidence, risk factors and clinical outcome of multidrug-resistant organisms after heart transplantation

BACKGROUND Transplant recipients commonly harbor multidrug-resistant organisms(MDROs),as a result of frequent hospital admissions and increased exposure to antimi-crobials and invasive procedures.AIM To investigate the impact of patient demographic and clinical characteristics on MDRO acquisition,as well as the impact of MDRO acquisition on intensive care unit(ICU)and hospital length of stay,and on ICU mortality and 1-year mortality post heart transplantation.METHODS This retrospective cohort study analyzed 98 consecutive heart transplant patients over a ten-year period(2013-2022)in a single transplantation center.Data was collected regarding MDROs commonly encountered in critical care.RESULTS Among the 98 transplanted patients(70%male),about a third(32%)acquired or already harbored MDROs upon transplantation(MDRO group),while two thirds did not(MDRO-free group).The prevalent MDROs were Acinetobacter baumannii(14%),Pseudomonas aeruginosa(12%)and Klebsiella pneumoniae(11%).Compared to MDRO-free patients,the MDRO group was characterized by higher body mass index(P=0.002),higher rates of renal failure(P=0.017),primary graft dysfunction(10%vs 4.5%,P=0.001),surgical re-exploration(34%vs 14%,P=0.017),mechanical circulatory support(47%vs 26%P=0.037)and renal replacement therapy(28%vs 9%,P=0.014),as well as longer extracorporeal circulation time(median 210 vs 161 min,P=0.003).The median length of stay was longer in the MDRO group,namely ICU stay was 16 vs 9 d in the MDRO-free group(P=0.001),and hospital stay was 38 vs 28 d(P=0.006),while 1-year mortality was higher(28%vs 7.6%,log-rank-χ2:7.34).CONCLUSION Following heart transplantation,a predominance of Gram-negative MDROs was noted.MDRO acquisition was associated with higher complication rates,prolonged ICU and total hospital stay,and higher post-transplantation mortality.

Effects of health concept model-based detailed behavioral care on mood and quality of life in elderly patients with chronic heart failure

BACKGROUND With the intensification of social aging,the susceptibility of the elderly population to diseases has attracted increasing attention,especially chronic heart failure(CHF)that accounts for a large proportion of the elderly.AIM To evaluate the application value of health concept model-based detailed behavioral care in elderly patients with CHF.METHODS This study recruited 116 elderly CHF patients admitted from October 2018 to October 2020 and grouped them according to the nursing care that they received.The elderly patients who underwent health concept model-based detailed behavioral care were included in a study group(SG;n=62),and those who underwent routine detailed behavioral nursing intervention were included as a control group(CG;n=54).Patients’negative emotions(NEs),quality of life(QoL),and nutritional status were assessed using the self-rating anxiety/depression scale(SAS/SDS),the Minnesota Living with Heart Failure Questionnaire(MLHFQ),and the Modified Quantitative Subjective Global Assessment(MQSGA)of nutrition,respectively.Differences in rehabilitation efficiency,NEs,cardiac function(CF)indexes,nutritional status,QoL,and nursing satisfaction were comparatively analyzed.RESULTS A higher response rate was recorded in the SG vs the CG after intervention(P<0.05).After care,the left ventricular ejection fraction was higher while the left ventricular end-diastolic dimension and left ventricular end systolic diameter were lower in the SG compared with the CG(P<0.05).The post-intervention SAS and SDS scores,as well as MQSGA and MLHFQ scores,were also lower in the SG(P<0.05).The SG was also superior to the CG in the overall nursing satisfaction rate(P<0.05).CONCLUSION Health concept model-based detailed behavioral care has high application value in the nursing care of elderly CHF patients,and it can not only effectively enhance rehabilitation efficiency,but also mitigate patients’NEs and improve their CF and QoL.

An Analysis of the Effects of Blood Pressure and Antihypertensive Drugs on Heart Disease

Background: The American College of Cardiology (ACC), American Heart Association (AHA) and other organizations announced a new hypertension guideline (2017 ACA/AHA Guideline) in November 2017. However, other organizations such as the European Society of Cardiology and European Society of Hypertension maintained their diagnostic thresholds. It is necessary to evaluate the effects of blood pressure (BP) and antihypertensive drugs on the probability of having heart disease (HD). Data and Methods: The effects of BP, antihypertensive drugs and other factors on the probability of undergoing HD treatment were analyzed. We used a dataset containing 83,287 medical check-up and treatment records obtained from 35,504 individuals in 5 fiscal years. The probit models were used in the study. Considering the possibility of endogeneity problems, different types of models were used. Results: We could not find evidence that a higher systolic BP increased the probability of undergoing HD treatment. However, diastolic BP increased the probability in most of the models. Taking antihypertensive drugs also increased the probability of undergoing HD treatment. Diabetes was another important risk factor. Conclusion: The results of this study did not support the new 2017 ACC/AHA Guideline. It is necessary to choose proper drugs and methods to reduce the risks of side effects. Limitations: The dataset was observatory, the data were obtained from just one medical society, and sample selection bias might exist.

TCMATHF:a bioinformatics platform to predict pharmacological action of drug and dynamic molecular changes against from myocardial infarction to heart failure

OBJECTIVE To investigate the characteristics and regulations of medication in different stages of disease by constructing a dynamic disease network and a cellular feature network spanning from myocardial infarction to heart failure.METHODS Based on transcrip⁃tome and single-cell sequencing data from a mouse model of left anterior descending coro⁃nary artery ligation,a dynamic early-middle-late network and cellular feature network were con⁃structed by integrating differential gene expres⁃sion trends and biological functions.The robust⁃ness of the perturbation effect of traditional Chi⁃nese medicine(TCM)on the disease network was calculated based on multi-target TCM,and we acquired the foundational data by analyzing the results of effectiveness.The predictive plat⁃form was scrutinized and assessed with regards to the functional attributes of FDA approveddrugs and compound prescriptions,in order to determine the primary stages of intervention and the drug patterns actions in the progression of heart failure.RESULTS In this study,we devel⁃oped a prediction and analysis platform for assessing the efficacy of drugs using a networkbased approach.The accuracy of the system was validated by FDA approved-drugs.It was found that blood-activating drugs,heat-clearing drugs,and phlegm-expelling drugs exhibited favorable intervention effects during the early to middle stages of the disease by investigating the effects of single herbs and TCM prescriptions on disease progression.Similarly,phlegm-expelling drugs,spirit-nourishing drugs,and diuretic showed better intervention effects during the mid⁃dle to late stages.These findings were consis⁃tent with the clinical use of drugs.Analysis of the clustering heatmap results of TCM prescriptions revealed that the formulas aimed at qi stagnation and blood stasis had a strong effect in early stage,while the formulas for qi and yin deficiency and cardiorenal yang deficiency had a strong effect in the middle to late stages.Furthermore,analysis of the single-cell feature network demon⁃strated that TCM had advantages in modulating the changes in fibroblasts,myofibroblasts,endo⁃thelial cells,and granulocytes during the patho⁃logical process.Additionally,most prescriptions exhibited strong perturbation effects on the fea⁃ture network of NK-T cells,granulocytes,macro⁃phages,and myofibroblasts.CONCLUSION This platform quantitatively evaluates the primary action stages and characteristics of TCM and for⁃mulas involved in the dynamic process of myo⁃cardial infarction to heart failure based on the effective prediction of the efficacy of TCM and FDA approved-drugs.It provides reference for the precise clinical application of TCM and formu⁃las with multiple targets and multiple pathways.

Vitamin D,selenium,and antidiabetic drugs in the treatment of type 2 diabetes mellitus with Hashimoto's thyroiditis

BACKGROUND Diabetes and thyroiditis are closely related.They occur in combination and cause significant damage to the body.There is no clear treatment for type-2 diabetes mellitus(T2DM)with Hashimoto's thyroiditis(HT).While single symptomatic drug treatment of the two diseases is less effective,combined drug treatment may improve efficacy.AIM To investigate the effect of a combination of vitamin D,selenium,and hypoglycemic agents in T2DM with HT.METHODS This retrospective study included 150 patients with T2DM and HT treated at The Central Hospital of Shaoyang from March 2020 to February 2023.Fifty patients were assigned to the control group,test group A,and test group B according to different treatment methods.The control group received low-iodine diet guidance and hypoglycemic drug treatment.Test group A received the control treatment plus vitamin D treatment.Test group B received the group A treatment plus selenium.Blood levels of markers of thyroid function[free T3(FT3),thyroid stimulating hormone(TSH),free T4(FT4)],autoantibodies[thyroid peroxidase antibody(TPOAB)and thyroid globulin antibody(TGAB)],blood lipid index[low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),triacylglycerol(TG)],blood glucose index[fasting blood glucose(FBG),and hemoglobin A1c(HbA1c)]were measured pre-treatment and 3 and 6 months after treatment.The relationships between serum 25-hydroxyvitamin D3[25(OH)D3]level and each of these indices were analyzed.RESULTS The levels of 25(OH)D3,FT3,FT4,and LDL-C increased in the order of the control group,test group A,and test group B(all P<0.05).The TPOAB,TGAB,TC,TG,FBG,HbA1c,and TSH levels increased in the order of test groups B,A,and the control group(all P<0.05).All the above indices were compared after 3 and 6 months of treatment.Pre-treatment,there was no divergence in serum 25(OH)D3 level,thyroid function-related indexes,autoantibodies level,blood glucose,and blood lipid index between the control group,test groups A and B(all P>0.05).The 25(OH)D3 levels in test groups A and B were negatively correlated with FT4 and TGAB(all P<0.05).CONCLUSION The combination drug treatment for T2DM with HT significantly improved thyroid function,autoantibody,and blood glucose and lipid levels.

The neuroprotective effects of the anti-diabetic drug linagliptin against Aβ-induced neurotoxicity

Impaired insulin signaling in Alzheimer’s disease（AD）brains：The insulin signaling pathway is a fundamental physiological mechanism that presents in nearly all vertebrate cells.However,sometimes cells stop responding properly to insulin stimulation.This condition is known as insulin resistance,which is a hallmark of two very common conditions,metabolic syndrome and type 2 diabetes（T2D）.

Mechanisms on Correlation between the Pericardium Meridian and Heart Effects of Electroacupuncture at Neiguan and Other Acupo

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Effects of exercise training on diastolic and systolic dysfunction in patients with chronic heart failure

BACKGROUND Chronic heart failure(CHF)is a complex syndrome characterized by a progressive reduction of the left ventricular(LV)contractility,low exercise tolerance,and increased mortality and morbidity.Diastolic dysfunction(DD)of the LV,is a keystone in the pathophysiology of CHF and plays a major role in the progression of most cardiac diseases.Also,it is well estimated that exercise training induces several beneficial effects on patients with CHF.AIM To evaluate the impact of a cardiac rehabilitation program on the DD and LV ejection fraction(EF)in patients with CHF.METHODS Thirty-two stable patients with CHF(age:56±10 years,EF:32%±8%,88%men)participated in an exercise rehabilitation program.They were randomly assigned to aerobic exercise(AER)or combined aerobic and strength training(COM),based on age and peak oxygen uptake,as stratified randomization criteria.Before and after the program,they underwent a symptom-limited maximal cardiopulmonary exercise testing(CPET)and serial echocardiography evaluation to evaluate peak oxygen uptake(VO2peak),peak workload(Wpeak),DD grade,right ventricular systolic pressure(RVSP),and EF.RESULTS The whole cohort improved VO2peak,and Wpeak,as well as DD grade(P<0.05).Overall,9 patients(28.1%)improved DD grade,while 23(71.9%)remained at the same DD grade;this was a significant difference,considering DD grade at baseline(P<0.05).In addition,the whole cohort improved RVSP and EF(P<0.05).Not any between-group differences were observed in the variables assessed(P>0.05).CONCLUSION Exercise rehabilitation improves indices of diastolic and systolic dysfunction.Exercise protocol was not observed to affect outcomes.These results need to be further investigated in larger samples.

Excellent effects and possible mechanisms of action of a new antibody–drug conjugate against EGFR-positive triple-negative breast cancer

Background:Triple-negative breast cancer(TNBC)is the most aggressive subtype and occurs in approximately 15%–20%of diagnosed breast cancers.TNBC is characterized by its highly metastatic and recurrent features,as well as a lack of specific targets and targeted therapeutics.Epidermal growth factor receptor(EGFR)is highly expressed in a variety of tumors,especially in TNBC.LR004-VC-MMAE is a new EGFR-targeting antibody–drug conjugate produced by our laboratory.This study aimed to evaluate its antitumor activities against EGFR-positive TNBC and further studied its possible mechanism of antitumor action.Methods:LR004-VC-MMAE was prepared by coupling a cytotoxic payload(MMAE)to an anti-EGFR antibody(LR004)via a linker,and the drug-to-antibody ratio(DAR)was analyzed by HIC-HPLC.The gene expression of EGFR in a series of breast cancer cell lines was assessed using a publicly available microarray dataset(GSE41313)and Western blotting.MDA-MB-468 and MDA-MB-231 cells were treated with LR004-VC-MMAE(0,0.0066,0.066,0.66,6.6 nmol/L),and the inhibitory effects of LR004-VC-MMAE on cell proliferation were examined by CCK-8 and colony formation.The migration and invasion capacity of MDA-MB-468 and MDA-MB-231 cells were tested at different LR004-VCMMAE concentrations(2.5 and 5 nmol/L)with wound healing and Transwell invasion assays.Flow cytometric analysis and tumorsphere-forming assays were used to detect the killing effects of LR004-VC-MMAE on cancer stem cells(MDA-MB-468 and MDA-MB-231 cells).The mouse xenograft models were also used to evaluate the antitumor efficacy of LR004-VC-MMAE in vivo.Briefly,BALB/c nude mice were subcutaneously inoculated with MDA-MB-468 or MDAMB-231 cells.Then they were randomly divided into 4 groups(n=6 per group)and treated with PBS,naked LR004(10 mg/kg),LR004-VC-MMAE(10 mg/kg),or doxorubicin,respectively.Tumor sizes and the body weights of mice were measured every 4 d.The effects of LR004-VC-MMAE on apoptosis and cell cycle distribution were analyzed by flow cytometry.Western blotting was used to detect the effects of LR004-VC-MMAE on EGFR,ERK,MEK phosphorylation and tumor stemness marker gene expression.Results:LR004-VC-MMAE with a DAR of 4.02 were obtained.The expression of EGFR was found to be significantly higher in TNBC cells compared with non-TNBC cells(P<0.01).LR004-VC-MMAE inhibited the proliferation of EGFRpositive TNBC cells,and the ICvalues of MDA-MB-468 and MDA-MB-231 cells treated with LR004-VC-MMAE for 72 h were(0.13±0.02)nmol/L and(0.66±0.06)nmol/L,respectively,which were significantly lower than that of cells treated with MMAE[(3.20±0.60)nmol/L,P<0.01,and(6.60±0.50)nmol/L,P<0.001].LR004-VC-MMAE effectively inhibited migration and invasion of MDA-MB-468 and MDA-MB-231 cells.Moreover,LR004-VC-MMAE also killed tumor stem cells in EGFR-positive TNBC cells and impaired their tumorsphere-forming ability.In TNBC xenograft models,LR004-VC-MMAE at 10 mg/kg significantly suppressed tumor growth and achieved complete tumor regression on day 36.Surprisingly,tumor recurrence was not observed until the end of the experiment on day 52.In a mechanistic study,we found that LR004-VC-MMAE significantly induced cell apoptosis and cell cycle arrest at G/M phase in MDAMB-468[(34±5)%vs.(12±2)%,P<0.001]and MDA-MB-231[(27±4)%vs.(18±3)%,P<0.01]cells.LR004-VC-MMAE also inhibited the activation of EGFR signaling and the expression of cancer stemness marker genes such as Oct4,Sox2,KLF4 and EpCAM.Conclusions:LR004-VC-MMAE showed effective antitumor activity by inhibiting the activation of EGFR signaling and the expression of cancer stemness marker genes.It might be a promising therapeutic candidate and provides a potential therapeutic avenue for the treatment of EGFR-positive TNBC.

Pharmacological Effects of Botanical Drugs on Myocardial Metabolism in Chronic Heart Failure

Although there have been significant advances in the treatment of heart failure in recent years,chronic heart failure remains a leading cause of cardiovascular disease-related death.Many studies have found that targeted cardiac metabolic remodeling has good potential for the treatment of heart failure.However,most of the drugs that increase cardiac energy are still in the theoretical or testing stage.Some research has found that botanical drugs not only increase myocardial energy metabolism through multiple targets but also have the potential to restore the balance of myocardial substrate metabolism.In this review,we summarized the mechanisms by which botanical drugs(the active ingredients/formulas/Chinese patent medicines)improve substrate utilization and promote myocardial energy metabolism by activating AMP-activated protein kinase(AMPK),peroxisome proliferator-activated receptors(PPARs)and other related targets.At the same time,some potential protective effects of botanical drugs on myocardium,such as alleviating oxidative stress and dysbiosis signaling,caused by metabolic disorders,were briefly discussed.

Why Don’t We Adequately Identify and Manage Adverse Drug Reactions despite Having the Needed Information?

Importance/Objective: Adverse Drug Reactions (ADRs) are unavoidable, but recognizing and addressing ADRs early can improve wellness and prevent permanent injury. We suggest that available medical information and digital/electronic methods could be used to manage this major healthcare problem for individual patients in real time. Methods: We searched the available digital applications and three literature databases using the medical subject heading terms, adverse drug reaction reporting systems or management, filtered by clinical trial or systemic reviews, to detect publications with data about ADR identification and management approaches. We reviewed the reports that had abstract or summary data or proposed or implemented methods or systems with potential to identify or manage ADRs in clinical settings. Results: The vast majority of the 481 reports used retrospectively collected data for groups of patients or were limited to surveying one population group or class of medication. The reports showed potential and definite associations of ADRs for specific drugs and problems, mostly, but not exclusively, for patients in hospitals and nursing homes. No reports described complete methods to collect comprehensive data on ADRs for individual patients in a healthcare system. The digital applications have ADR information, but all are too cumbersome or incomplete for use in active clinical settings. Several studies suggested that providing information about potential ADRs to clinicians can reduce these problems. Conclusion and Relevance: Although investigators and government agencies agree with the need, there is no comprehensive ADR management program in current use. Informing the patient’s healthcare practitioners of potential ADRs at the point of service has the potential for reduction of these complications, which should improve healthcare and reduce unneeded costs.

Effect of Ultrasound-Guided Transversus Abdominis Plane Block Combined with Lornoxicam on Pain and Recovery Quality After Abdominal Surgery in Patients with Drug Addiction

Objective:This paper aims to analyze the analgesic effect of ultrasound-guided transversus abdominis plane block(TAPB)combined with non-steroidal anti-inflammatory analgesic drug lornoxicam on abdominal surgery in patients with a history of drug addiction.Methods:32 patients aged 18-60 who underwent lower abdominal surgery in the First People's Hospital of Liangshan Yi Autonomous Prefecture and Butuo County People's Hospital of Liangshan Yi Autonomous Prefecture from January 2022 to March 2023 were selected,the patients must have drug abuse history for more than 1 year,with a history of drug withdrawal and relapse.The patients were divided into observation group and control group by the envelope method,with 16 cases in the observation group and 16 cases in the control group.Two groups of patients underwent ultrasound-guided bilateral transversus abdominis plane block after the operation.The observation group was treated with dexmedetomidine hydrochloride 1μg/kg+0.25%ropivacaine hydrochloride 40ml,and the control group was treated with 40ml 0.9%sodium chloride injection,the two groups of patients returned to the ward after operation and given intravenous infusion of lornoxicam for relieving the pain.The visual analogue scale(VAS)score of postoperative pain,the times of rescue analgesia,the time of postoperative anal exhaust,the time of ambulation,nausea and vomiting,withdrawal symptoms,related adverse reactions,and hospitalization days were compared between the two groups.Results:The VAS score of postoperative pain in the observation group was significantly lower than that in the control group,P<0.05.Patients in the observation group used less postoperative rescue analgesics than those in the control group,P<0.05.For postoperative anal exhaust time,the difference between the two groups of patients was relatively small,and the time in the observation group was shorter,P>0.05.The time to get out of bed and the length of hospital stay were not significantly different between the control group and the observation group,P>0.05.The withdrawal symptoms of the patients in the observation group were better,P<0.05,nausea and vomiting,and other adverse reactions were lower in the control group,P<0.05.Conclusion:Ultrasound-guided transversus abdominis plane block combined with lornoxicam can be used to relieve pain in abdominal surgery for patients with drug addiction,which can effectively improve the therapeutic effect of patients and reduce the number of postoperative rescue analgesia.Thus,it has high clinical application value.

Research on the Intervention Effect of Vibroacoustic Therapy in the Treatment of Patients with Depression

Research purpose:This study implemented somatosensory music therapy on patients with depressive disorders,and explored the effects of somatosensory music therapy on the degree of depression,positive and negative emotions,intuitive stress and autonomic nervous function of patients.Research method:We collected 66 patients diagnosed with depression from the Department of Psychological Medicine of Henan Provincial People’s Hospital,and divided them into a control group and an intervention group according to the random number table,with 33 people in each group.The control group received routine psychiatric treatment and nursing.On the basis of the control group,the intervention group received somatosensory music therapy 3 times a week,30 min each time,for 4 consecutive weeks.The Hamilton Depression Scale,Positive and Negative Emotion Scale,Perceived Stress Scale,and Heart Rate Variability Index were collected and analyzed at baseline(T0),2 weeks after treatment(T1)and 4 weeks after treatment(T2).Research results:After 4 weeks of treatment,the HAMD scores of the two groups decreased to varying degrees,and the difference between the groups was statistically significant(p<0.05).After 4 weeks of treatment,the scores of positive emotions in both groups increased to varying degrees,and the scores of negative emotions increased to varying degrees.The scores decreased to varying degrees,and there were statistically significant differences between the positive and negative emotion groups(p<0.05).After 4 weeks of treatment,the CPSS scores of the two groups decreased to varying degrees,and the difference between the two groups was statistically significant(p<0.05).Analyzing the main effect of intervention factors alone,after 4 weeks of treatment,SDNN and RMSSD indexes all increased to varying degrees,and the degree of increase in the intervention group was greater than that in the control group,and the difference between the groups was statistically significant(p<0.05).Research conclusion:assisting somatosensory music therapy for patients with depressive disorders can improve depressive symptoms,increase positive emotions,reduce negative emotions,and reduce perceived stress.These are beneficial to restore the balance of autonomic nervous system,and are effective for the treatment of depression.

Three-dimensional aspects of formulation excipients in drug discovery:a critical assessment on orphan excipients,matrix effects and drug interactions

Formulation/pharmaceutical excipients play a major role in formulating drug candidates,with the objectives of ease of administration,targeted delivery and complete availability.Many excipients used in pharmaceutical formulations are orphanized in preclinical drug discovery.These orphan excipients could enhance formulatability of highly lipophilic compounds.Additionally,they are safe in preclinical species when used below the LD50 values.However,when the excipients are used in formulating compounds with diverse physico-chemical properties,they pose challenges by modulating study results through their bioanalytical matrix effects.Excipients invariably present in study samples and not in the calibration curve standards cause over-/under-estimation of exposures.Thus,the mechanism by which excipients cause matrix effects and strategies to nullify these effects needs to be revisited.Furthermore,formulation excipients cause drug interactions by moderating the pathways of drug metabolizing enzymes and drug transport proteins.Although it is not possible to get rid of excipient driven interactions,it is always advised to be aware of these interactions and apply the knowledge to draw meaningful conclusions from study results.In this review,we will comprehensively discuss a)orphan excipients that have wider applications in preclinical formulations,b)bioanalytical matrix effects and possible approaches to mitigating these effects,and c)excipient driven drug interactions and strategies to alleviate the impacts of drug interactions.

Methodological challenges to control for immortal time bias in addressing drug effects in type 2 diabetes

There are multiple biases in using observational studies to examine treatment effects such as those from prevalent drug users, immortal time and drug indications. We used renin angiotensin system(RAS) inhibitors and statins as reference drugs with proven efficacies in randomized clinical trials(RCTs) and examined their effectiveness in the prospective Hong Kong Diabetes Registry using adjustment methods proposed in the literature. Using time-dependent exposures to drug treatments yielded greatly inflated hazard ratios(HR) regarding the treatment effects of these drugs for cardiovascular disease(CVD) in type 2 diabetes. These errors were probably due to changing indications to use these drugs during follow up periods, especially at the time of drug commencement making time-dependent analysis extremely problematic. Using time-fixed analysis with exclusion of immortal time and adjustment for confounders at baseline and/or during follow-up periods, the HR of RAS inhibitors for CVD was comparable to that in RCT. The result supported the use of the Registry for performing pharmacoepidemiological analysis which revealed an attenuated low low-density lipoprotein cholesterol related cancer risk with RAS inhibitors. On the other hand, time-fixed analysis with including immortal time and adjustment for confounders at baseline and/or during follow-up periods, the HR of statins for CVD was similar to that in the RCT. Our results highlight the complexity and difficulty in removing these biases. We call for validations of the methods to cope with immortal time and drug use indications before applying them to particular research questions, so to avoid making erroneous conclusions.

Preventive Effects of Five Drugs on Mycoplasma Pneumonia of Swine (MPS)

The paper was to explore the preventive effects of five drugs on mycoplasma pneumonia of swine （MPS） and to provide reference for clinical medication of pig farms in Hainan Province. A total of 444 health piglets were randomly divided into 6 groups, including five medication groups （72 piglets in group A, 74 pig- lets in group B, 72 piglets in group C, 76 piglets in group D, 76 piglets in group E） and one control group （74 piglets）. The piglets in experimental groups were treated drugs once a day for successive 5 days at 30, 60, 90, 120 and 150 of age. The piglets in control group were free of medication. At 70 and 140 days of age, 15 piglets of each group were randomly selected to collect their blood sermn. The Mycoplasma hyopneumoniae （M-Hyo） antibodies in serum were measured by en- zyme-linked immunosorbent assay （ELISA）. During the experiment, the incidence rates of respiratory disease, lung lesion, feed conversion rate, average daily gain （ADG）, and mortality rate of pigs were also observed and recorded. The results showed that the five drugs had significant difference in preventative effects. Group C （Zhiyuanjing group） received the best preventive effect and the highest economic benefits. Compared with control group, the ADG and feed conversion rate in group C were increased by 7.53% and 9.09%, respectively; the incidence rate of respiratory disease was reduced by 13.44% and lung lesion was alleviated by 81.43% ; and the earnings of each pig could rise by 132.70 yuan. The preventative effect and economic benefit of the drugs was sequenced by Chansu Kechuanling and Bingchan Kechuanwang. Wante Feilin and amoxicillin had weaker preventive effects against MPS but greatly influenced growth performance of pigs, so they should be used alternatively with other drugs.

Combined effects of hypertension and angiotensin Ⅱ on the risk of coronary heart disease:a population-based prospective cohort study among Inner Mongolians in China

Objective To investigate the combined effects of hypertension and angiotensinⅡon the risk of coronary heart disease(CHD)on the basis of a 10-year prospective study in an Inner Mongolian population of China.Methods Based on a cross-sectional survey,a prospective cohort study was conducted from June 2003 to July 2012 among 2,530 Mongolian people.

The Effects of Antiretroviral Drugs on the Absorbance Characteristics of HIV-Infected Blood

In the twenty first century research works, there may be a need to achieve a more reliable research result through a synergy between engineers and biological researchers. The peak absorbance data for various interacting systems were measured. These were used to show that the antiretroviral drug has the effect of increasing the peak absorbance values of both the uninfected and infected blood components, i.e., the drugs are made able to increase the light absorption capacity of the blood cells. For drug 2 that contains three components including Efavirenz, the drug effect on lymphocytes was increased by about 38% for patients that had been on antiretroviral drug treatment. Mathematical models were proposed and used in determining the coating effectiveness of antiretroviral drugs in the presence and absence of HIV. The use of the findings of this work by pharmaceutical industries may help in the search for more effective antiretroviral drugs for the treatment of HIV patients.

Intercalation of Ciprofloxacin in Naturally Occurring Smectite from Bana: Potentiality as Drug Delivery System and Antimicrobial Effects on <i>Escherichia coli</i>and <i>Staphylococcus aureus</i>

Ciprofloxacin (CFX) was loaded on Bana clay (Cameroon) and CFX loaded-clays have been evaluated as drug delivery system. Raw clays and CFX loaded compounds have been characterized by some physico-chemicals methods. In vitro release studies have been done in gastric and phosphate buffer experimental mediums;bacteriological studies have been made up on Escherichia coli and Staphylococcus aureus. X-ray diffractometry patterns of loaded compounds show a basal spacing increasing due to CFX intercalation. On Fourier-Transformed Infrared spectrometry spectra, appearance of CFX characteristic bands and shifting of certain bands already presents on clay confirmed CFX intercalation. After 96 h of CFX released from release mediums, prolonged and continue profiles have been observed. Diffusion tests displayed an inhibition radius of ~2 cm on gelose seeded with Escherichia coli and Staphylococcus aureus due to CFX. The overall results show a modified release of ciprofloxacin with an effective antibacterial activity, giving the way for a new ciprofloxacin drug delivery system using Bana clay as carrier.

Late Protective Effects of the Anticalmodulin Drug Fluphenazine on Carbon Tetrachloride-induced Liver Necrosis

Fluphenazine (FP) treatment (50mg/kg bw, ip in saline) 30 min before or 6 or 10 h after CCl4 administration (1 ml/kg ip in olive oil) significantly prevented the liver necrosis produced by the hepatotoxin at 24 h. FP had enhancing effects on the covalent binding of CCl4 reactive metabolites to cellular constituents and on CCl4 induced lipid peroaldation.FP lowered bOdy temperature of the CCl4-poisoned animals during the 24 h observation period. The obtained results are compatible but do not prove the hypothesis that calmodulin (CaM) had participation in late occurring events preceding necrosis. FP lowering action on body temperature, however, might also play a role in the effects of this drug on the onset of CCl4 induced liver necrosis. FP levels in liver tissue as determined by gas chromatography-mass spectrometry evidenced the presence of the drug in amounts suffi cient to inhibit CaM and that suggests that not all preventive effects of FP are due to its indirect actions on the central nervous system via decreased body temperature