抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

ABCD
: Appropriate Blood pressure Control in Diabetes
ABI
: ankle–brachial index
ABPM
: ambulatory blood pressure monitoring
ACCESS
: Acute Candesartan Cilexetil Therapy in Stroke Survival
ACCOMPLISH
: Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension
ACCORD
: Action to Control Cardiovascular Risk in Diabetes
ACE
: angiotensin-converting enzyme
ACTIVE I
: Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events
ADVANCE
: Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation
AHEAD
: Action for HEAlth in Diabetes
ALLHAT
: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart ATtack
ALTITUDE
: ALiskiren Trial In Type 2 Diabetes Using Cardio-renal Endpoints
ANTIPAF
: ANgioTensin II Antagonist In Paroxysmal Atrial Fibrillation
APOLLO
: A Randomized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People
ARB
: angiotensin receptor blocker
ARIC
: Atherosclerosis Risk In Communities
ARR
: aldosterone renin ratio
ASCOT
: Anglo-Scandinavian Cardiac Outcomes Trial
ASCOT-LLA
: Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm
ASTRAL
: Angioplasty and STenting for Renal Artery Lesions
A-V
: atrioventricular
BB
: beta-blocker
BMI
: body mass index
BP
: blood pressure
BSA
: body surface area
CA
: calcium antagonist
CABG
: coronary artery bypass graft
CAPPP
: CAPtopril Prevention Project
CAPRAF
: CAndesartan in the Prevention of Relapsing Atrial Fibrillation
CHD
: coronary heart disease
CHHIPS
: Controlling Hypertension and Hypertension Immediately Post-Stroke
CKD
: chronic kidney disease
CKD-EPI
: Chronic Kidney Disease—EPIdemiology collaboration
CONVINCE
: Controlled ONset Verapamil INvestigation of CV Endpoints
CT
: computed tomography
CV
: cardiovascular
CVD
: cardiovascular disease
D
: diuretic
DASH
: Dietary Approaches to Stop Hypertension
DBP
: diastolic blood pressure
DCCT
: Diabetes Control and Complications Study
DIRECT
: DIabetic REtinopathy Candesartan Trials
DM
: diabetes mellitus
DPP-4
: dipeptidyl peptidase 4
EAS
: European Atherosclerosis Society
EASD
: European Association for the Study of Diabetes
ECG
: electrocardiogram
EF
: ejection fraction
eGFR
: estimated glomerular filtration rate
ELSA
: European Lacidipine Study on Atherosclerosis
ESC
: European Society of Cardiology
ESH
: European Society of Hypertension
ESRD
: end-stage renal disease
EXPLOR
: Amlodipine–Valsartan Combination Decreases Central Systolic Blood Pressure more Effectively than the Amlodipine–Atenolol Combination
FDA
: U.S. Food and Drug Administration
FEVER
: Felodipine EVent Reduction study
GISSI-AF
: Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation
HbA1c
: glycated haemoglobin
HBPM
: home blood pressure monitoring
HOPE
: Heart Outcomes Prevention Evaluation
HOT
: Hypertension Optimal Treatment
HRT
: hormone replacement therapy
HT
: hypertension
HYVET
: HYpertension in the Very Elderly Trial
IMT
: intima-media thickness
I-PRESERVE
: Irbesartan in Heart Failure with Preserved Systolic Function
INTERHEART
: Effect of Potentially Modifiable Risk Factors associated with Myocardial Infarction in 52 Countries
INVEST
: INternational VErapamil SR/T Trandolapril
ISH
: Isolated systolic hypertension
JNC
: Joint National Committee
JUPITER
: Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin
LAVi
: left atrial volume index
LIFE
: Losartan Intervention For Endpoint Reduction in Hypertensives
LV
: left ventricle/left ventricular
LVH
: left ventricular hypertrophy
LVM
: left ventricular mass
MDRD
: Modification of Diet in Renal Disease
MRFIT
: Multiple Risk Factor Intervention Trial
MRI
: magnetic resonance imaging
NORDIL
: The Nordic Diltiazem Intervention study
OC
: oral contraceptive
OD
: organ damage
ONTARGET
: ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial
PAD
: peripheral artery disease
PATHS
: Prevention And Treatment of Hypertension Study
PCI
: percutaneous coronary intervention
PPAR
: peroxisome proliferator-activated receptor
PREVEND
: Prevention of REnal and Vascular ENdstage Disease
PROFESS
: Prevention Regimen for Effectively Avoiding Secondary Strokes
PROGRESS
: Perindopril Protection Against Recurrent Stroke Study
PWV
: pulse wave velocity
QALY
: Quality adjusted life years
RAA
: renin-angiotensin-aldosterone
RAS
: renin-angiotensin system
RCT
: randomized controlled trials
RF
: risk factor
ROADMAP
: Randomized Olmesartan And Diabetes MicroAlbuminuria Prevention
SBP
: systolic blood pressure
SCAST
: Angiotensin-Receptor Blocker Candesartan for Treatment of Acute STroke
SCOPE
: Study on COgnition and Prognosis in the Elderly
SCORE
: Systematic COronary Risk Evaluation
SHEP
: Systolic Hypertension in the Elderly Program
STOP
: Swedish Trials in Old Patients with Hypertension
STOP-2
: The second Swedish Trial in Old Patients with Hypertension
SYSTCHINA
: SYSTolic Hypertension in the Elderly: Chinese trial
SYSTEUR
: SYSTolic Hypertension in Europe
TIA
: transient ischaemic attack
TOHP
: Trials Of Hypertension Prevention
TRANSCEND
: Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease
UKPDS
: United Kingdom Prospective Diabetes Study
VADT
: Veterans' Affairs Diabetes Trial
VALUE
: Valsartan Antihypertensive Long-term Use Evaluation
WHO
: World Health Organization

### 1.1 Principles

The 2013 guidelines on hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology …

/pdf/2013-esh-esc-guidelines-for-the-management-of-arterial-4ydvs5ifsx.pdf

2013 ESH/ESC Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).

http://www.klinikaikozpont.u-szeged.hu/pedia/images/pdf/CME_TEL/Full-Text/25.pdf

The Hallmarks of Aging

The mediators and cellular effectors of inflammation are important constituents of the local environment of tumours. In some types of cancer, inflammatory conditions are present before a malignant change occurs. Conversely, in other types of cancer, an oncogenic change induces an inflammatory microenvironment that promotes the development of tumours. Regardless of its origin, 'smouldering' inflammation in the tumour microenvironment has many tumour-promoting effects. It aids in the proliferation and survival of malignant cells, promotes angiogenesis and metastasis, subverts adaptive immune responses, and alters responses to hormones and chemotherapeutic agents. The molecular pathways of this cancer-related inflammation are now being unravelled, resulting in the identification of new target molecules that could lead to improved diagnosis and treatment.

/pdf/cancer-related-inflammation-ltml0xgfd3.pdf

Cancer-related inflammation.

Evaluating complex interventions is complicated. The Medical Research Council9s evaluation framework (2000) brought welcome clarity to the task. Now the council has updated its guidance

https://www.bmj.com/content/bmj/337/bmj.a1655.full.pdf

Developing and evaluating complex interventions: The new Medical Research Council guidance

Prognosis of Transient Ischemic Attack and Stroke

We thank Dr Weber and colleagues for their interest in our paper. We fully agree, and acknowledged in our paper, that coding accuracy is likely to differ between healthcare systems and the sensitivity of coding in identifying all incident stroke is expected to be higher in countries with higher hospitalisation rates, such as in Germany. In countries with good quality coding data, there is no doubt that nationwide analyses based on administrative coding can inform clinical practice. Nevertheless, it is important to recognise that changes of coding accuracy over time, even in countries with relatively good coding accuracy to begin with, may still introduce biases especially for studies looking at apparent trends in stroke incidence or severity. There can also be serious shortcomings in using routine coding data to identify strokes that occur during a hospital admission for another reason, which can lead, for example, to substantial underestimation of operative/procedural risks. We also agree that ICD-10 code I64 (‘stroke, not specified as haemorrhage or infarction’) should be rarely used in studies focusing on ischaemic stroke, although I64 has been widely used in previous studies using ‘Big Data’ approaches. As rightly pointed out by Dr Weber and colleagues and also reported in our paper, brain imaging rates have increased substantially over the last couple of decades resulting in a significant decrease of the use of I64 in patients with definite strokes in more recent years (61.9% in 2002–2005 vs. 15.3% in 2014–2017). Therefore, completely excluding patients with otherwise unknown strokes (i.e. I64) could overestimate the incidence change over time. Whilst it is important to acknowledge differences in coding practices between countries, it is also crucial to recognise that, in the current stroke literature using ‘Big Data’ approaches, the validity and generalisability of some studies can be undermined by the frequent lack of reporting details on how administrative coding data were acquired, searched and applied. Ideally, researchers publishing such work should also include an up-todate validation of the validity of their coding data against a clinical gold standard. Joint efforts between the stroke physicians and the ‘Big Data’ community are still required to improve coding accuracy as well as to optimise reporting standards across countries.

https://journals.sagepub.com/doi/pdf/10.1177/2396987319896679

Re: Author response regarding the Letter to the Editor about the article 'Temporal trends in the accuracy of hospital diagnostic coding for identifying acute stroke: A population-based study'. European Stroke Journal 2019 Oct 14. DOI: 10.1177/2396987319881017.

In Response: We thank Saber for the letter relating to our recent article on the risks, time course, and outcome of intracerebral hemorrhage, extracranial bleeds, and recurrent ischemic events in patients with transient ischemic attack or ischemic stroke from 2 cohorts who were prescribed antiplatelet agents. Consistent with earlier systematic reviews, we found that an increasing burden of cerebral microbleeds was associated with an increased risk of recurrent ischemic stroke and also intracerebral hemorrhage. Furthermore, in patients with ≥5 cerebral microbleeds, these risks appeared to be time dependent. During the first year after index transient ischemic attack/ischemic stroke, the risk of a recurrent ischemic stroke exceeded that of an intracerebral hemorrhage. However, in years 1 to 5, the risk of intracerebral hemorrhage increased and matched that of ischemic stroke. Dr Saber suggests that evidence-based recommendations for the type and duration of antithrombotic therapy in patients with cerebral microbleeds should come from a study that also analyzes the risks in an untreated control group from the same population. We disagree that such a nonrandomized comparison would be helpful. Any control group of patients with transient ischemic attack/ischemic stroke in whom it was decided not to give antiplatelet treatment would be different to the treated group in many measured and unmeasured variables. Indeed, the strength of our study was that both cohorts had a policy of routine treatment, reducing any such selection biases. What is actually needed is a randomized controlled trial of antiplatelet treatment versus no treatment or withdrawal after an initial acute treatment period before definitive recommendations about use of antiplatelet agents in patients with transient ischemic attack/ischemic stroke with a high burden of cerebral microbleeds could be made.

Response by Lau and Rothwell to Letter Regarding Article, "Antiplatelet treatment after transient ischemic attack and ischemic stroke in patients with cerebral microbleeds in 2 large cohorts".

Peter M. Rothwell

Papers

Prognosis of Transient Ischemic Attack and Stroke

Re: Author response regarding the Letter to the Editor about the article 'Temporal trends in the accuracy of hospital diagnostic coding for identifying acute stroke: A population-based study'. European Stroke Journal 2019 Oct 14. DOI: 10.1177/2396987319881017.

Response by Lau and Rothwell to Letter Regarding Article, "Antiplatelet treatment after transient ischemic attack and ischemic stroke in patients with cerebral microbleeds in 2 large cohorts".

Asymptomatic carotid stenosis and stroke risk - Authors' reply.

Transient Ischemic Attack and Stroke: Carotid stenting and other interventions