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Ethanol extracts frommerocallis citrina attenuate the decreases of brain-derived neurotrophic factor

Ethanol extracts from Hemerocallis citrina attenuate the decreases

of brain-derived neurotrophic factor,TrkB levels in rat induced by corticosterone administration

Li-Tao Yi a,n,Jing Li a,Huo-Chen Li b,Ying Zhou b,Bi-Fang Su a,Ke-Feng Yang b,

Meng Jiang b,Yan-Ting Zhang a

a Department of Chemical and Pharmaceutical Engineering,College of Chemical Engineering,Huaqiao University,Xiamen361021,Fujian province,PR China

b Department of Biotechnology and Bioengineering,College of Chemical Engineering,Huaqiao University,Xiamen361021,Fujian province,PR China

a r t i c l e i n f o

Article history:

Received5April2012

Received in revised form

27August2012

Accepted6September2012

Available online18September2012

Keywords:

Hemerocallis citrina

Antidepressant-like effect

Corticosterone

Brain-derived neurotrophic factor

TrkB

a b s t r a c t

Ethnopharmacological relevance:Hemerocallis citrina,a traditional herbal medicine,has been used for

the improvement of behavioral and emotional status in Eastern-Asia countries.

Aim of the study:Our previous studies have demonstrated that the ethanol extracts of H.citrina?owers

(HCE)reversed the behavioral alterations and monoamine neurotransmitter dysfunctions in stressed

mice.However,the relation of its antidepressant-like action with neurotrophic molecular expressions

remains unknown.

Materials and methods:To clarify this,we explored the effect of HCE(32.5,65,130mg/kg,p.o.)on the

behavior,brain-derived neurotrophic factor(BDNF)and its receptor(TrkB)in depression-like rats

induced by exogenous administration of the stress hormone corticosterone(40mg/kg,s.c.).

Results:It was observed that repeated administration of corticosterone induced an elevation on the

serum corticosterone levels,which caused the abnormalities observed in the sucrose preference test

and forced swimming test(FST).Administration of HCE(65and130mg/kg)reversed the changes above

and up-regulated the BDNF and TrkB receptor protein expressions in the brain region of frontal cortex

and hippocampus.

Conclusion:These?ndings con?rm that HCE produce an antidepressant-like effect in corticosterone-

induced depression-like model of rats and this effect is at least partly mediated by BDNF-TrkB signaling

in the frontal cortex and hippocampus.

1.Introduction

Hemerocallis citrina Baroni(Liliaceae)which is widely grown in

China,Japan and Korea has been used for food and medicinal

purposes for thousands of years.According to the phytochemical

and pharmacological studies,H.citrina mainly contains?avo-

noids,polyphenols and essential oils that contribute to the herb’s

biological effects,such as antibacterial(Zhan et al.,2005),anti-

oxidant(Lang and Luo,2007)and nitrite-eliminating(Fu et al.,

2009)activity.In addition,the effects of H.citrina such as

relieving gloom and improving sleeping were recorded in the

famous pharmaceutical text of‘‘Compendium of Materia Medica’’,

the most complete and comprehensive medical book ever written

in the history of traditional Chinese medicine.Clinically,H.citrina

has been widely used for the treatment of depressive disorders in

China(Chen et al.,2008).

In previous studies,we found that the ethanol extracts of

H.citrina(HCE)administration signi?cantly reduced the immo-

bility time in both the forced swimming test(FST)and tail

suspension test(TST)without accompanying changes in locomo-

tor activity in the open-?eld test(OFT)in mice(Gu et al.,2012).

Furthermore,we also demonstrated that HCE enhanced serotonin

(5-HT)and noradrenaline(NA)levels in the frontal cortex and

hippocampus as well as elevated dopamine(DA)levels in the

frontal cortex(Gu et al.,2012).However,until now,the neuro-

trophic molecular expression underlying the antidepressant-like

effect of HCE remains unclear.

Neurotrophic factors are critical regulators of the formation

and plasticity of neuronal networks(Lee and Kim,2010).Brain-

derived neurotrophic factor(BDNF),one of important neuro-

trophic factors,has also been implicated in the etiology of major

Contents lists available at SciVerse ScienceDirect

journal homepage:https://www.wendangku.net/doc/876566134.html,/locate/jep

Journal of Ethnopharmacology

https://www.wendangku.net/doc/876566134.html,/10.1016/j.jep.2012.09.016

Abbreviations:ANOVA,analysis of variance;BDNF,brain-derived neurotrophic

factor;DA,dopamine;FST,forced swimming test;GR,glucocorticoid receptor;

HCE,ethanol extracts of Hemerocallis citrina;NA,noradrenaline;OFT,open-?eld

test;5-HT,serotonin;TST,tail suspension test

n Corresponding author.Tel./fax:t865926162302.

E-mail addresses:litao.yi@https://www.wendangku.net/doc/876566134.html,,litaoyi@https://www.wendangku.net/doc/876566134.html,(L.-T.Yi).

Journal of Ethnopharmacology144(2012)328–334

depression and the mechanism of antidepressant treatment (Numakawa et al.,2010).Clinical study demonstrates that depres-sion is associated with reduced brain BDNF and its receptor (TrkB)levels and that the reductions can be restored up to the normal value by antidepressant treatment (Thompson et al.,2011).Animal studies have also demonstrated clear evidence that BDNF signaling through TrkB is involved in the mechanisms of action of antidepressant agents (Wang et al.,2010;Kutiyanawalla et al.,2011).BDNF and TrkB levels can therefore be useful markers for antidepressant-like response.

In the present study,we used a rat depression model by repeated corticosterone injections to investigate the antidepressant-like effect of HCE.Furthermore,the study explored whether the HCE could reverse the loss of BDNF and its receptor TrkB mRNA and protein levels in the rat brain regions of frontal cortex and hippocampus.

2.Materials and methods 2.1.Animals

Male Sprague-Dawley rats (220–250g)were purchased from Laboratory Animal Center,Fujian Medical University,Fujian Province,PR China.Animals were singly housed under a normal 12-h/12-h light/dark schedule with the lights on at 07:00a.m.and had free access to tap water and food pellets.Ambient tempera-ture and relative humidity were maintained at 22721C and at 5575%,and given a standard chow and water ad libitum for the duration of the study.The animals were allowed 1week to acclimatize themselves to the housing conditions before the beginning of the experiments.All procedures were performed in accordance with the published guidelines of the China Council on Animal Care (Regulations for the Administration of Affairs Con-cerning Experimental Animals,approved by the State Council on October 31,1988and promulgated by Decree No.2of the State Science and Technology Commission on November 14,1988).2.2.Chemicals and reagents

Corticosterone was purchased from TCI Development Co.,Ltd.(Tokyo,Japan).Fluoxetine hydrochloride was purchased from Changzhou Siyao Pharmaceuticals Co.,Ltd.(Changzhou,PR China).All primers used in this study were designed and synthe-sized by Sangon Biotech Co.Ltd.(Shanghai,PR China).The anti-BDNF and anti-TrkB antibody and the respective secondary antibody were purchased from Santa Cruz Biotechnology Inc.(Santa Cruz,USA).Trizol reagent was purchased from Invitrogen (Carlsbad,USA).Reverse transcriptase Moloney Murine Leukemia Virus (M-MLV)used for cDNA synthesis was from Promega Corporation (Madison,USA).All other reagents used in RT-PCR and western bolt were purchased from Sangon Biotech Co.Ltd.(Shanghai,PR China).2.3.Plant material and HPLC analysis

Flowers of H.citrina Baroni (Liliaceae)was purchased from Xiamen Wal-Mart and authenticated by Cheng-Fu Li,Department of Pharmacy,Xiamen Hospital of Traditional Chinese medicine (Voucher specimen number HU/CE-04281).

Since rutin is the main component of H.citrina (Yang et al.,2006),a ?ngerprint was analyzed in HPLC using rutin as an index.A Shimadzu Prominence LC-20A HPLC system equipped with an UV detector was used.Qualitative and quantitative analyses of rutin were performed using an Agilent C 18column (4.6mM ?250mM,5m m),and the column temperatures were kept at 251C.A linear gradient elution pro?le was used in our study [0–20min:methanol to 0.5%acetic acid water solution (v/v)ratio of 20/80

to 30/70;20–30min:30/70;30–70min:30/70to 80/20].Flow rates of elution in both cases were 1ml/min.The injection volume for the analyte was 10m l.The detection wavelength was set at 254nm for rutin.The raw material H.citrina was extracted with methanol at 251C for 30min.The content of the marker sub-stance rutin in H.citrina was calculated as 0.39%(Fig.1A and B).

2.4.Preparation of the ethanol extracts

Dried sample (500g)was cut into small pieces and extracted three times in a re?ux condenser for 4h with 3L of 75%ethanol by sonication at room temperature (25721C).The solutions were combined,?ltered,concentrated under reduced pressure and lyophilized into powders.The ?nal yield was 7.65%(w/w).

2.5.Drug treatments

Different groups of rats,7animals per group,were used for drug treatment and tests.Doses were calculated as mg/kg body weight.All the experimental animals including control and drug-treatment groups were simultaneously deprived food but not water 1h prior to drug administration.The aim of food with-drawn prior to drug administration was just to ensure the bioavailability of drug.In other time periods,all animals had free access to food.

The standard dose of HCE in rat (130mg/kg)was based on our previous mouse study (Gu et al.,2012)and calculated on the basis of body surface area ratio between rat and mouse.In addition,considering the long-term treatment used in the present study,the doses of 32.5,65,130mg/kg every 24h were selected.

The procedure and dose of corticosterone administration was performed as described in Mao et al.(2012).Corticosterone (40mg/kg),which was dissolved in a saline solution containing 0.1%dimethyl sulfoxide and 0.1%Tween-80,was administrated by subcutaneously (s.c.)in a volume of 5ml/kg once daily for 21days.HCE (32.5,65,130mg/kg)and the positive drug ?uoxetine (15mg/kg)were administered by oral (p.o.)gavage in a volume of 10ml/kg 30min prior to the corticosterone injection for 21days.

Fig.1.HPLC chromatograms of Hemerocallis citrina (A)and the standard com-pound of rutin (B).

L.-T.Yi et al./Journal of Ethnopharmacology 144(2012)328–334329

2.6.Sucrose preference test

The sucrose preference test was employed herein to evaluate anhedonia,one of the core symptoms of major depression in humans.The test was performed as described by Mao et al. (2012).Brie?y,the sucrose preference test was carried out24h after the last drug treatment.Before the test,the rats were trained to adapt to sucrose solution(1%,w/v)by placing two bottles of sucrose solution in each cage for24h;then one of the bottles was replaced with water for24h.After the adaptation procedure,the rats were deprived of water and food for24h.The sucrose preference test was conducted at10:00a.m.The rats were housed in individual cages and given free access to the two bottles containing100ml of sucrose solution(1%,w/v)and100ml of water,respectively.After60min,the volume(ml)of both the consumed sucrose solution and water were recorded,and sucrose preference was calculated as sucrose preference(%)?sucrose consumption(ml)/[sucrose consumption(ml)twater consump-tion(ml)]?100%.

2.7.Forced swimming test(FST)

The FST used was the same as described in detail elsewhere (Porsolt et al.,1978),with some modi?cation.Brie?y,the test was done by placing a rat in a glass cylinder(46cm in height,20cm in diameter)?lled with30cm high water(25721C).Water was replaced between every trial.Two swimming sessions were conducted:an initial15min pretest,followed by a5min test 24h later.A rat was considered immobile whenever it remained ?oating passively in the water and only making slight movements to keep its head above the water line.The test sessions were recorded by a video camera and scored by an observer blind to treatment.

2.8.Blood sampling and tissue extraction

Animals were killed by decapitation one day after FST.To avoid?uctuations on hormone levels due to circadian rhythm, animals were bled at12:00–13:00p.m.on the day of sacri?ce.The brain regions of frontal cortex and hippocampus were isolated immediately,and then stored atà801C for later analysis of BDNF and TrkB mRNA and protein levels.

2.9.Serum corticosterone assay

Blood was collected on ice and separated in a refrigerated centrifuge at41C(4000?g for10min).Serum was stored at–201C until assays were performed.Serum corticosterone levels were measured using a commercial kit(Enzo Life Sciences, Plymouth Meeting,USA)based on enzyme immunoassay (Crowther,1995).

2.10.RT-PCR

The procedure of RT-PCR was performed as described in detail elsewhere(Prediger,2001;Pan et al.,2010),with some modi?ca-tions.Total RNA was isolated from frontal cortex or hippocampus using Trizol reagent following the manufacturer’s instructions. The concentration and purity of RNA were measured by the optical density at260and280nm using spectrophotometer. Reverse transcription was performed with1m g RNA using M-MLV reverse transcriptase for cDNA synthesis.Ampli?cation of cDNA by PCR was performed in25m l reactions containing8m l cDNA,1m l forward and1m l reverse primers(10m m), 2.5m l PCR?10buffer containing MgCl2,0.5m l dNTP mixture(10mM), 0.5m l Taq polymerase(2.5U)and11.5m l sterile ddH2O.Primers used for BDNF was:50-TGTGACAGTATTAGCGAGTGGGT-30and 50-CGATTGGGTAGTTCGGCATT-30,that used for TrkB was 50-CTTATGCTTGCTGGTCTTGG-30and50-GGGTATTCTTGCTGCTC-TCA-30.In general,PCR was performed with a preheating cycle at941C for5min,denaturation,annealing and elongation were carried out at941C for30s,at501C for30s(BDNF)or591C for 60s(TrkB),and at681C for15s(BDNF)or721C for35s(TrkB), respectively.The reactions were repeated for40(BDNF)or38 (TrkB)cycles.The PCR products were resolved by a1.5%agarose gel electrophoresis and quanti?ed by the Bio-Rad ChemiDoc XRS Gel Documentation system and Bio-Rad Quantity One software (Hercules,USA).The results were normalized to the mRNA expression level of GAPDH in each sample.

2.11.Western blot

The procedure of western blot was performed as described in detail elsewhere(Blancher and Jones,2001;Chen et al.,2010), with some modi?cations.Brain samples were homogenized in a lysis buffer containing50mM Tris–HCl(pH7.4),1mM EDTA, 150mM NaCl,1%Triton X-100,1%sodium deoxycholate,0.1% SDS,1mM trichostatin A,phosphatase inhibitor cocktail.The homogenates were centrifuged at14000?g for20min at41C, and the supernatants were collected and stored atà201C until further use.The protein concentration was determined by a BCA assay.Total proteins were separated by SDS-PAGE and transferred to a PVDF membrane.Following blocking in3%BSA/TBST at room temperature for1h,the membranes were incubated with the appropriate primary antibodies at41C overnight(anti-BDNF: 1:500,anti-TrkB:1:1000).After being washed with TBST for three times,the membranes were incubated with an HRP-labeled secondary antibody(1:4000).The blots were washed again for three times by TBST buffer and the immunoreactive bands were detected by using the enhanced chemiluminescence method. Western blot bands were scanned and subsequently analyzed densitometrically with Bio-Rad Quantity One software(Hercules, USA).The results were normalized to the protein expression level of GAPDH in each sample.

2.12.Statistical analyses

All data were expressed as mean7S.E.M.To compare experi-mental and control groups,we used one-way ANOVA,followed by post-hoc Dunnett’s test.A value of P o0.05was considered statistically signi?cant for analysis.

3.Results

3.1.Effects of HCE on the sucrose preference

The effects of HCE on the sucrose preference in rats exposed to repeated corticosterone administration were given in Fig.2. Corticosterone administration induced a signi?cant decrease in the sucrose preference(P o0.05).65and130mg/kg HCE reversed the reduction to the baseline value(P o0.05,P o0.01,respec-tively).Fluoxetine,the positive drug,also increased the sucrose preference in the rat exposed to corticosterone(P o0.05).

3.2.Effects of HCE on the immobility time

Repeated corticosterone treatment(s.c.)caused a signi?cant elevation of immobility time in the rat FST compared with the controls(P o0.05).Long-term treatment with HCE(65and 130mg/kg)and?uoxetine(15mg/kg)for21days signi?cantly

L.-T.Yi et al./Journal of Ethnopharmacology144(2012)328–334 330

reduced the immobility time (P o 0.01,P o 0.01,P o 0.01,respec-tively)to baseline value (Fig.3).

3.3.Effects of HCE on the serum corticosterone levels

Exposure to corticosterone resulted in a signi?cant increase in the serum corticosterone levels compared with the controls (P o 0.01).Long-term HCE (65and 130mg/kg)or ?uoxetine (15mg/kg)treatments normalized the increased levels of corti-costerone (P o 0.05,P o 0.01,P o 0.01,respectively)in the rat exposed to repeated corticosterone administration (Fig.4).3.4.Effects of HCE on the BDNF and TrkB receptor expression To investigate the effects of HCE on the mRNA expression of BDNF and TrkB,which are two molecules crucial for antidepressant-like behavior and neurogenesis,we conducted RT-PCR and western blot analyses after the corticosterone admin-istration for 21days.As can be seen in Fig.5and 6exogenous corticosterone reduced the BDNF but not TrkB mRNA levels in the frontal cortex and hippocampus (P o 0.01,P o 0.05,respectively).HCE (65and 130mg/kg)treatments reversed the changes in the frontal cortex (P o 0.01,P o 0.05,respectively)and hippocampus (P o 0.05,P o 0.001,respectively).

In addition,BDNF and TrkB protein levels in the frontal cortex (P o 0.05,P o 0.05,respectively)and hippocampus (P o 0.05,P o 0.05,respectively)were dramatically decreased by repeated corticosterone administration.HCE treatment (65,130mg/kg)alleviated the changes in the two brain regions.

4.Discussion

In general,the stress models of depression such as TST,FST and chronic mild stress are widely adopted by researchers to evaluate the antidepressant agents and their related mechanism (Willner,1997;Bai et al.,2001;Cryan et al.,2005).However,one of the biggest problems with experimenter-applied stress models is a lack of control over individual differences in responsivity to physical and psychological stressors (Sterner and Kalynchuk,2010).In such case,a more valid depression-like model needs to be established.

It is well-known that elevated levels of glucocorticoid have been implicated in depression (Zunszain et al.,2011).In general,glucocorticoid serves an adaptive function in protecting the organism against many defense reactions elicited by acute stress.Once released,glucocorticoids act on bodily tissues to limit non-essential functions and mobilize energy to deal with the stressor.Glucocorticoids also reach the brain where they exert an inhibi-tory in?uence to halt HPA axis activity through a negative feed-back inhibitory regulation (Sterner and Kalynchuk,2010).But if the prolonged stress exists,chronically elevated glucocorticoid levels will occur and impair the negative feedback inhibition,?nally lead to dysregulated emotional and physiological home-ostasis which is seen in the etiology of depression (Herman and Cullinan,1997).A number of experimental studies have also demonstrated the depression-like effects of the exogenous admin-istration of glucocorticoids.It has been observed,for instance,that corticosterone treatment (s.c.)induced depression-like behaviors in the FST and TST (Gourley et al.,2008;Lau et al.,2011).Long-term administration of corticosterone also resulted in depressed phenotype,reduced hippocampal cell proliferation and granule cell layer volume,as observed in patients suffering from depression (Murray et al.,2008).Thus,the ?ndings suggest that administra-tion of exogenous corticosterone is a useful method for studying the relationship between stress,behaviors,glucocorticoids,neuro-trophic factors and depression (Sterner and Kalynchuk,2010).

In our present study,repeated corticosterone treatment induced a reduction of sucrose preference and an increase of immobility time,which is in line with other ?ndings (Gourley et al.,2008;Mao et al.,2012).The sucrose preference,which re?ects a symptom anhedonia (inability to experience pleasure)existing in depressed patients,can be improved by antidepres-sants (Willner,1997).The present ?ndings revealed that repeated administration of HCE reversed the anhedonic-like behavior in corticosterone-induced rats.In the other behavioral test,the measurement index immobility time of the FST,which is

induced

Fig.3.Effects of HCE on the immobility time in the rat FST.#P o 0.05vs control with vehicle group.**P o 0.01vs corticosterone with vehicle

group.

Fig.4.Effects of HCE on the serum corticosterone levels (one day after FST)in the rats exposed to repeated corticosterone administration.##P o 0.01vs control with vehicle group.*P o 0.05and **P o 0.01vs corticosterone with vehicle

group.

Fig.2.Effects of HCE on the sucrose preference in the rats exposed to repeated corticosterone administration.#P o 0.05vs control with vehicle group.*P o 0.05and **P o 0.01vs corticosterone with vehicle group.

L.-T.Yi et al./Journal of Ethnopharmacology 144(2012)328–334331

by swimming stress,can be dramatically decreased by a broad spectrum of clinically effective antidepressants (Hasco¨et and Bourin,2009).Consistent with our previous study (Gu et al.,2012),HCE also reversed the elevation of immobility time induced by corticosterone treatment (s.c.)in the rat FST.Taken together,the results obtained from the behavioral studies again con?rmed that HCE treatment exerted an antidepressant-like effect in the rats treated by corticosterone (s.c.).

It was observed in our study that repeated corticosterone treatment (s.c.)caused an elevation of serum corticosterone levels in rats,which was consistent with the previous studies (Dwivedi et al.,2006;Johnson et al.,2006).This means that exogenous corticosterone results in an absolute increase in circulating serum corticosterone levels,an indicator of stress and depression in laboratory animals.Thus,the present study revealed that the behavioral consequences of repeated corticosterone administra-tion were accompanied by dysregulation of the HPA axis.

Glucocorticoid and glucocorticoid receptor (GR)has been considered to be especially important in relation to BDNF regula-tion (Numakawa et al.,2009).Stressors stimulate the activity of the HPA axis,and then glucocorticoids increase,which lead to the reduced expression of BDNF (Lee and Kim,2010).For example,previous study indicated drinking corticosterone decreased brain BDNF expression (Gourley et al.,2008).It was also observed that adrenalectomy resulted in an elevation in the levels of BDNF (Chao et al.,1998).Consistent with the studies,our study also found that administration of exogenous corticosterone reduced the BDNF mRNA and protein levels in the frontal cortex and hippocampus of rats.In addition,increases of BDNF in brain have been shown to attenuate depression-related behavior (Shirayama et al.,2002).Moreover,antidepressant increases BDNF-induced hippocampal neurogenesis via a GR-dependent mechanism (Anacker et al.,2011).Therefore,when we examined the effects of HCE on the corticosterone-mediated decrease in BDNF expres-sion,the results of long-term HCE treatment reversing the reduction suggested that the behavioral improvement in the model may be concurrent with increased BDNF levels.

Growing evidence suggests BDNF-TrkB signaling serves an important role in the regulation of many of the behavioral and molecular mechanism of antidepressant (Saarelainen et al.,2003).Either decreased BDNF availability or reduced levels of TrkB neurotrophin receptor could reduce BDNF signaling (Fahnestock et al.,2012).Short-or long-term treatments with antidepressants activate TrkB receptor in mouse brain (Rantam¨aki et al.,2007).Therefore,besides BDNF,we evaluated the effects of HCE on gene and protein expressions of TrkB receptor in the frontal cortex and hippocampus.The immunoblotting results showed that TrkB receptor proteins in frontal cortex and hippocampus were mark-edly decreased by repeated corticosterone administration and reversed by HCE treatment.However,there were no signi?cant changes in frontal cortex and hippocampal TrkB mRNA levels after long-term corticosterone or HCE treatment.The results

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Fig.5.Effects of HCE on the frontal cortex BDNF and TrkB receptor mRNA and protein expressions in the rats exposed to repeated corticosterone administration.#P o 0.05and ##P o 0.01vs control with vehicle group.*P o 0.05,**P o 0.01and ***P o 0.001vs corticosterone with vehicle group.

L.-T.Yi et al./Journal of Ethnopharmacology 144(2012)328–334

332

indicated that long-term corticosterone affected the rate of TrkB protein synthesis or degradation but not TrkB mRNA,which was partly consistent with the previous study by Kutiyanawalla et al.(2011).As a result,these data suggest HCE-induced antidepres-sant-like effect is likely through modulation of the BDNF-TrkB neurotrophic signaling pathway.However,the related mechan-ism involved in the regulation of TrkB mRNA and protein should be performed in further studies.

5.Conclusion

Taken together,the data from our study indicate that repeated corticosterone administration induces a decrease in BDNF and TrkB expressions as well as depression-related behaviors in rats.More-over,the behavioral changes attenuated by long-term HCE treat-ment are possibly mediated by increasing BDNF-TrkB signaling in the frontal cortex and hippocampus.Further studies will be neces-sary to improve our understanding of the correlation between HCE treatment and the BDNF induced hippocampal neurogenesis.

Acknowledgment

The project was supported by the Natural Science Foundation of Fujian Province of China (No.2011J05081)and Huaqiao

University (No.09BS507).And we thank Dr.Di Geng and Mr.Hao Cheng for technical assistance in HPLC analysis of Hemerocallis citrina .References

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Fig.6.Effects of HCE on the hippocampal BDNF and TrkB receptor mRNA and protein expressions in the rats exposed to repeated corticosterone administration.#P o 0.05vs control with vehicle group.*P o 0.05,**P o 0.01and ***P o 0.001vs corticosterone with vehicle group.

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大苗老师执业医师笔记重点内容

精心整理慢支+肺气肿=COPD ?题目中慢支病人出现黄色脓性痰表示慢支急性发作。吸氧浓度（%）=21+4*氧流量（1）可同时用于两种疾病的药：氨茶碱（2）只能用于支气管哮喘的药：肾上腺素（或异丙肾） ADA(腺苷脱氨酶)：>45IU提示结核性胸膜炎．Rivalta试验：阳性--渗出液。胸膜间皮瘤---属于渗出的。气胸：肺萎陷<20%，无症状，伤后1-2周可自行吸收恢复，可观察保守治疗；肺萎陷>20%，行胸腔穿刺、闭式引流术。临床表现：急促，胸闷。

气体引流一般在前胸壁锁骨中线第2肋间隙；液体引流则在腋中线和腋后线6~8肋间隙；颈静脉怒张，皮下气肿-----就是张力性气胸纵膈肿瘤好发部位：歌诀：前面的机场(畸胎瘤)，后面的神经(神经源性肿瘤)，快看前上方有个胸(胸腺瘤) 胃溃疡（GU）好发于胃小弯，胃角；十二指肠溃疡（DU）好发于球前壁多见。粘膜皱襞向其集中------良性溃疡；粘膜皱襞中断或者断裂-----恶性溃疡；十二指肠（D U）的这种穿孔多发生于球部前壁。出血发生后部。

胃溃疡（GU）的穿孔发生于小弯促胃液素瘤：亦称Zollinger—Ellison（卓艾）综合征：溃疡最容易发生的部位：不典型部位（十二指肠降段、横段、甚或空肠近端）歌诀：横空下降胃大部切除术：①胃溃疡（GU）多选择胃十二指肠吻合术（毕I式） ②十二指肠溃疡(DU)首选胃空肠吻合术（毕II式）术。 1.U波：低钾 2.不规则龛影---恶变，胃癌。 3、长期腹泻---酸中毒肝脏的血液供应有：主要来自于门静脉占75%，肝动脉25%。

肝脏有两个管道系统：Glissom系统（格里森系统）和肝静脉系统。Glissom纤维鞘里包裹的管道有门静脉，肝动脉，肝胆管，这三者走形都是一致的。歌诀：母（M）鸡（J）感(G)动(D)郭(G)德(D)纲(G) 寒颤和高热＋肝区疼痛和肿大=肝脓肿肝癌：进行性肝肿大，这是个很特异性的表现（食管癌-进行性的吞咽困难；胆管癌 4.胆囊结石---梗阻---胆囊炎只要题目告诉你“进油腻食物后加重”就选胆囊结石和胆囊炎胆囊结石：无症状结石一般不需手术，有下列情况可考虑手术： 2类人群：（1）儿童胆囊结石（2）就医不方便的人群 2种质地：（1）胆囊壁增厚（2）胆囊钙化或瓷性胆囊

大苗笔记运动系统样本

第一节运动系统概述一、运动系统检查法物理学检查，是运动系统最重要和最基本检查办法二、肌力分级 0级肌肉完全瘫痪，触诊肌肉完全无收缩力 1级肌肉有积极收缩力，但不能带动关节活动【可见肌肉轻微收缩】 2级可以带动关节水平活动，但不能对抗地心引力【肢体能在床上平行移动】 3级能对抗地心引力做积极关节活动，但不能对抗阻力肢体可以克服地心吸取力，能抬离床面 4级能对抗较大阻力，但比正常者弱【肢体能做对抗外界阻力运动】 5级正常肌力【肌力正常，运动自如】伟大苗教师给咱们总结了“四个不”一不动、二不抗、三不阻、四不全一不动不能产生动作二不抗不能对抗地心引力三不阻不能对抗阻力四不全能抗阻力，但不全面第二节骨折概论 1、概论一、骨折定义与成因 1.定义：骨折是骨完整性或持续性中断。 2.成因（1）直接暴力：骨折发生在暴力直接作用部位，常伴有不同限度软组织损伤。（2）间接暴力：暴力通过传导、杠杆或旋转作用使远处发生骨折。（3）疲劳性骨折军人骨折和运动员骨折积累性劳损：长期、重复、轻微直接或间接暴力可集中在骨骼某一点上发生骨折，骨折无移

位，但愈合慢。好发部位：第2、3跖骨和腓骨中下1/3处。（4）骨骼疾病（也称病理性骨折）：有病骨骼（例如骨髓炎、骨肿瘤等）遭受轻微外力即发生断裂。二、分类 1.依照骨折与外界与否相通，骨折处皮肤与粘膜与否完整可分为：闭合性与开放性骨折。 2.依照骨折形态和限度分为（1）不完全骨折骨完整性或持续性发生某些中断，按其形态分为：裂缝骨折：只是有裂缝，没有完全裂开。多见于肩胛骨、颅骨。青枝骨折：骨质和骨膜某些断裂。见于小朋友。（2）完全骨折：骨完整性或持续性完全中断。按其骨折线方向和形态可分为：横形骨折、斜形骨折、螺旋形骨折、粉碎性骨折、嵌插性骨折、压缩性骨折、凹陷性骨折和骨骺分离。上面记不住不要紧，只要记住裂缝骨折和青枝骨折是不完全骨折外，其他类型全是完全骨折。 3.依照骨折稳定性分为（1）稳定性骨折：复位后经恰当外固定不易发生再移位者，如青枝骨折、裂缝骨折、嵌插性骨折、横形骨折、压缩骨折。（记忆：分值很差呀）（2）不稳定性骨折：复位后易于发生再移位者，如斜形骨折、螺旋形骨折、粉碎性骨折。 2、骨折临床体现及影像学检查一、全身体现可以有休克（骨盆骨折和股骨干骨折）和发热（考虑浮现感染）。二、局部体现（1）畸形：骨折段移位所致。（2）反常活动：无关节部位浮现活动。（3）骨擦音或骨擦感：骨折端互相摩擦导致。（4）疼痛与压痛。（5）局部肿胀与淤斑。

科学中国人(2014)年度人物获奖人公示

科学中国人(2014)年度人物获奖人公示 6月26日，由《科学中国人》杂志主办的“科学中国人（2014）年度人物颁奖典礼”在北京万寿宾馆举行。年度人物评选组委会面向全国，从基础研究、医药卫生、信息技术与电子、土木水利与建筑、机械运载、化工冶金材料、能源矿业、工程管理、农业、环境与轻纺十个领域评选出146位获奖者。终身成就奖曾庆存中国科学院大气物理研究所研究员/ 中国科学院院士杰出大学校长奖许智宏北京大学原校长/中国科学院院士杰出贡献奖丁晓青清华大学电子工程系教授基础研究领域陈翰馥中国科学院数学与系统科学研究院系统科学研究所研究员/中国科学院院士颜宁清华大学医学院教授王晗苏州大学生物钟研究中心教授

王学路华中农业大学生命科学技术学院院长黄来强清华大学深圳研究生院教授赖绍聪西北大学地质学系系主任师蕾暨南大学药学院研究员赵鹏江苏师范大学数学与统计学院副院长陈厚早中国医学科学院基础医学研究所副研究员李红深圳大学心理与社会学院院长于晓方吉林大学艾滋病与病毒研究所所长张学记北京科技大学化学与生物工程学院院长杨必成广东第二师范学院应用数学研究所所长尹大川西北工业大学生命科学学院副院长杨文力西北大学现代物理研究所教授钟涛复旦大学生命科学学院遗传工程国家重点实验室副主任医药卫生领域吴天一青海高原医学研究院研究员/中国工程院院士乔杰北京大学第三医院院长蔡志明深圳市第二人民医院院长萧伟江苏康缘药业股份有限公司董事长刘丽梅上海交通大学附属第六人民医院上海市糖尿病研

究所副所长夏昭林复旦大学公共卫生学院职业卫生与毒理学教研室副主任静进中山大学公共卫生学院妇幼卫生系主任李先亮首都医科大学附属北京朝阳医院副主任医师李平亚吉林大学药学院国家发改委“人参创新药物开发国家地方联合工程研究中心主任陈国强中国医科大学航空总医院党委副书记孟元光中国人民解放军总医院妇产科主任陈卫红华中科技大学同济医学院劳动卫生与环境卫生学系系主任蒋忠民吉林大学大学中日联谊医院皮肤科副主任医师朱献军电子科技大学医学院研究员唐仕波中南大学爱尔眼科学院院长吴传斌中山大学药学院副院长魏启明重庆市科学技术研究院教授周永宁兰州大学第一医院副院长信息技术与电子领域郭华东中国科学院遥感与数字地球研究所所长/中国科

大苗呼吸系统笔记(最新完美打印版)

慢性支气管炎：病程发展(一个轴)：吸烟→慢支→COPD→肺动脉高压→肺心病 1、引起慢支的最主要原因是：吸烟；引起慢支发作的最主要原因是感染。 2、慢支感染最常见的致病菌：流感嗜血杆菌、肺炎球菌。（慢支感染球流感）。 3、慢支病人咳粘稠痰的原因是：杯状细胞增多。 4、慢支病人咳黄色浓痰的原因是：纤毛功能下降。 5、慢支的病人容易咳痰的病理基础是：粘液腺增生肥大。 6、慢支病理生理：早期主要为小气道功能异常，特点：一大一低即闭合容积大，肺动态顺应性降低。 7、慢支病人支气管病理变化：（整多花喂养）⑴支气管腺体的增生⑵粘液分泌增多⑶粘膜的鳞化上皮化生⑷支气管软骨发生萎缩⑸支气管炎症细胞的侵润。 8、慢支诊断：咳嗽咳痰伴喘息，每年发病持续3个月（3M三妹），连续两年以上。 COPD慢性阻塞性肺疾病 1、引起COPD最常见的原因是：慢支。 2、COPD发展到肺气肿的发病机制：宰相荣毅仁，狭窄、塌陷、融合、异常。 ⑴支气管管腔狭窄⑵支气管骨架塌陷⑶肺泡融合成肺大泡⑷α-抗胰蛋白酶异常。 3、COPD最大的气流特点：不完全可逆的气流受限。做题方法介绍：确诊：病理﹥活检﹥镜。 4、COPD发展到肺气肿的诊断依据：⑴桶状胸⑵双肺透亮度增加⑶RV/TLC（残气量/肺总量）﹥40﹪。RV/TLC不能诊断COPD。 5、COPD分型：：a型：气肿型（红喘型）杨大爷（老年人）爱（a）穿红（红喘）衣服，不穿紫衣服（无紫绀）。心功能正常（氧分压，二氧化碳分压正常）。 b型：支气管炎性（紫肿型） 6、COPD诊断：FEV1/FVC（一秒用力呼气容积/用力肺活量）﹤70﹪，正常FEV1/FVC为80﹪。COPD胸片无特异性。

李树云简介

画家潜力李树云，1957年生，安徽桐城人。现任中国美术家协会（ICAA），安徽省美术家协会，中国公共关系艺术委员会，全国文化艺术界联合研究会会员，当代书画艺术研究会会员，安徽省工笔画研究会理事，中国中外名人文化研究会艺委会一级书画师，终生荣誉会员。作品风格构图精严，层次丰富，画面呈现出源于传统而不同于传统的独特面貌。色调浓郁、厚重。笔墨线条劲健流畅，花瓣、鸟雀设色精严，花叶色彩丰富，浑然一体。意境恬淡宁静而又朴拙茂盛。装饰效果指数★★★★★ 收藏推荐指数★★★★★ 《篱落千秋》系80年代作品，参加安徽省工笔画研究会首届展。工笔画藏品属性作者姓名李树云具体尺寸45x68com 真伪状况真迹作者简介李树云：警督，男，1957年5月出生，笔名松涛，安徽桐城人。现任中国美术家协会（ICAA），安徽省美术家协会，中国公共关系艺术委员会全国文化艺术界联合研究会会员工，当代书画艺术研究会会员，东方文化联谊会美术部学术委员、《东方文化报》、《东方潮》、杂志社特约记者、《科学中国人中国专家人才库》、《东方之子》书画卷特邀编委，《世界名人录》担任中国国际交流出版社特约顾问编委，安徽省工笔画研究会理事，中国中外名人文化研究会艺委会一级书画师，终生荣誉会员。主要业绩：多年来潜心研究中国画，主要致力于工笔画创作，溶南北两派绘画专长，在继承传统的基础上有所创新，兼写意花鸟、人物、仕女、山水画，参加省市及全国海内外大展赛30余次，并多次获金、银、铜奖。作品《秋》荣获世界三等奖，并获得“世界铜奖艺术家”荣誉称号。1994年惠赐作品《为吴敬梓先生造像》在首届“大足石刻杯”海内外艺术大赛中获优秀奖，并被重庆大足艺术博物馆收藏。作品《洛神》入选《20 世纪国际美术精作博览》大型画册，同时被中外名人文化研究会收藏；《秋韵》入编《世界当代著名书画家真迹博览大典》；《情趣图》、《秋》入编导20世纪国际文化系列丛书《中国当代美术家作品通鉴》、《20世纪中国美术书法家作品拍卖库》，个人传略被收入《中国当代名人录》、《国际现代书画篆刻家大辞典》、《世界华人文学艺术界名人录》、《世界美术书法家世纪末成就大典》、《国际书画名家传略》并被授予“当代书画名人”称号。同时荣获“书画名人成就奖”。1998年8月参加中国首家“成功者研究会”第二届群英会，并荣获“成功者”奖章，在省市及全国报刊上发表作品30多幅。作品《寿带图》被国外友人收藏。1999年7月作品《春韵》入编《庆祝中华人民共和国建国五十周年书画集》，并被新风出版社收藏。1999年9月作品《鸣春》参加“庆祝建国五十周年暨迎接澳门回归全国诗人、书法家、画家作品大奖展览”中获佳作奖。2001年参加国际文化艺术交流与创作获金奖，同年参加公安部纪念党的八十周年京、津、皖、川、渝警察书画摄影展。2001年7月，经中华人民共和国文化部文化市场发展中心艺术品质部严格审核，创作的艺术品通过ISC2001艺术品价值标准评定：书法、国画作品为3000-5000/平方尺。油画、版画作品为20000-30000/平方尺，同年10月个人传略入编《国魂情系西部·爱心专家》大典。2002年作品《荷塘鸣翠》入编《世界美术大典》。

大苗笔记-内分泌(全)

总论重点：甲状腺疾病和糖尿病疾病下丘脑垂体（①神经垂体②腺垂体） ①甲状腺②肾上腺③性腺 1.人的最高司令部）下丘脑分泌→**释放激素（因子）、**抑制激素（因子），血管加压素（抗利尿激素）和催产素。 2.神经垂体（“仓库”储存下丘脑分泌的血管加压素、催产素）←垂体→（不干活就督促干活）腺垂体（分泌促***激素、泌乳素PRL和生长激素GH） 3.甲状腺(甲状腺激素)、肾上腺(肾上腺激素)、性腺(卵泡刺激素和黄体生成素) 负反馈→甲减：T3T4下降告诉“包工头”给他们反馈TSH增多（老板说了算所以TSH更精确）甲状腺滤泡上皮细胞----→T3T4 甲状腺滤泡旁细胞------→降钙素甲状旁腺-------------—>甲状旁腺激素（升钙降磷甲旁素，降钙降磷旁钙素） ①甲状腺→甲状腺素（甲状腺滤泡上皮细胞）→如果缺→甲减（呆小症） ②升钙降磷甲旁素（甲状旁腺激素(甲状腺旁腺分泌)→靶器官是骨、肾）， ③降钙降磷旁钙素（甲状腺滤泡旁细胞…C细胞’分泌） 4.诊断：内分泌系统检查：“功能检查是激素（最重要）(抽血也属于、但分段抽血除外)、定位检查是影像、定性是病理” 5.治疗： ①所有内分泌功能减退的疾病都选择激素的替代治疗（选择：生理需要量），但如果有发热、感染加重等存在---→激素加量到2-3倍 ②所有的垂体肿瘤都选择手术，只有“泌乳素瘤”除外！（闭经又泌乳→用溴隐亭或多巴胺受体激动剂）垂体腺瘤 1.最常见：泌乳素瘤PRL 2.根据大小分：①大腺瘤＞10mm，②微腺瘤＜10cm（最常见） 3.根据功能性分：①功能性腺瘤（激素分泌过多）②无功能性腺瘤（不分泌激素，只能分泌α亚单位）泌乳素瘤PRL 1.女人：闭经又泌乳，骨质疏松。治疗：多巴胺受体激动剂溴隐亭。男人：一般是大腺瘤，①压迫甲状腺、垂体窝②性功能障碍ED。治疗：手术。 2.功能检查：泌乳素PRL。定位检查：MRI。

大苗循环系统笔记

第十二章心血管系统（50分）第一节心力衰竭一、基本知识（一）心力衰竭的基本病因及诱因 1、基本病因：记忆：前夫（前负荷），后夫（后负荷），不给力（心肌收缩力减弱）。（1）心肌收缩力减弱：冠心病最为常见（2）后负荷（压力负荷）增加：动脉压力增高。如高血压（体循环高血压）、主动脉瓣狭窄（左心室后负荷）、肺动脉瓣狭窄（右心室后负荷）和肺动脉高压。 ?记忆：后夫（后负荷）提刀（高血压）宰（狭窄）肥（肺动脉高压）羊记忆：落后了就有压力了，就是狭窄+压力增加。（3）前负荷（容量负荷）增加 1）心脏瓣膜关闭不全如二尖瓣关闭不全，主动脉瓣关闭不全 2）左，右心或者动静脉分流性先心病如间隔缺损，动脉导管未闭，动静脉瘘等。 3）伴有全身血容量增多或者循环血容量增多的疾病如慢性贫血，甲亢等。心脏的容量负荷也必然增加。 ?记忆：关（关闭不全）心（先心病）前（前负荷）夫评（贫血）价（甲亢） 2.诱因：感染、心律失常和治疗不当依次是心力衰竭最主要的诱因。呼吸道感染是心力衰竭最常见，最重要的诱因。 3、发病的基本机制：心室重构（二）心功能分级（难点） 1、Killip分级（用于急性心梗）：记忆：有急性心梗的就要快（K）抢救，为Killip。 Ⅰ级：无肺部啰音和第三心音； Ⅱ级：肺部啰音＜1/2肺野；有左心衰竭； Ⅲ级：肺部啰音>1/2（急性肺水肿）； Ⅳ级：心源性休克（血压小于90/60mmHg） Killip分级记忆：1无2啰半；3肿4休克；注意：心梗的临床表现：疼痛是心梗最早、最突出的症状。必须有这个症状。 2、用NYHA分级（用于心衰无心梗）：记忆：没有心梗或者不是急性的就是NO心梗，为NYHA。 Ⅰ级：患者有心脏病，但体力活动不受限制。一般体力活动不引起过度疲劳、心悸、气喘或心绞痛。【爬楼能爬顶楼】 Ⅱ级（心衰Ⅰ度）：患者有心脏病，以致体力活动轻度受限制。休息时无症状，一般体力活动（每天日常活动）引起过度疲劳、心悸、气喘或心绞痛。【爬楼梯到3楼】 Ⅲ级（心衰Ⅱ度）：患者有心脏病，以致体力活动明显受限制。休息时无症状，但小于一般体力活动，或从事一般家务活动即可引起过度疲劳、心悸、气喘或心绞痛。【爬楼梯到2楼】 Ⅳ级（心衰Ⅲ度）：患者有心脏病，休息时也有心功能不全或心绞痛症状，进行任何体力活动均使不适增加。【在底楼喘气】 NYHA分级记忆：1无2轻3明显；4级不动也困难（不能平卧）二、慢性心力衰竭（一）临床表现 1、左心衰：●左心衰=高血压+劳力性呼吸困难（常考点）症状：主要为●肺淤血+心排出量下降的表现。临床表现：3大临床表现 1)●呼吸困难：劳力性呼吸困难→夜间阵发性呼吸困难（心源性哮喘）→端坐呼吸→急性肺水肿（咳粉红色泡沫痰）。 I●劳力性呼吸困难可为首发症状（最早出现）。 II随着病情的发展演化成夜间阵发性呼吸困难（心源性哮喘）。 2)咳嗽可粉红色泡沫痰（或者白色泡沫痰） 3)两肺底湿啰音和喘鸣音：I两肺底常可闻及湿啰音（中小水泡音）和喘鸣音；心脏听诊可闻及II肺动脉第二心音（P2）亢进； III舒张期S3奔马律（心衰特有体征之一）注：心源性哮喘（也叫夜间阵发性呼吸困难）有高血压史，禁用肾上腺素；支气管哮喘无高血压史，禁用吗啡（抑制呼吸）；氨茶碱两者都可用。左心衰的病人一般有高血压病史，因为有体循环高压。●高血压引起的急性左心衰首选硝普钠（考点）2、右心衰：最常见的疾病是●三尖瓣关闭不全

大苗老师执业医师笔记重点内容

慢支+肺气肿=COPD ?题目中慢支病人出现黄色脓性痰表示慢支急性发作。吸氧浓度（%）=21+4*氧流量（1）可同时用于两种疾病的药：氨茶碱（2）只能用于支气管哮喘的药：肾上腺素（或异丙肾）（3）只能用于心源性哮喘的药：吗啡（抑制呼吸，降低心肌耗氧量）进行性呼吸困难就是ARDS（呼吸窘迫综合症），氧疗不管用，只能用PEEP（呼吸末正压通气） PaO2<60mmHg，伴或不伴PaCO2>50mmHg（只要PaO2<60mmHg 可以诊断为呼衰）吸入氧浓度=21+4*氧流量胸水：有积液不一定有体征，胸水<300ml可无症状；300~500ml为少量积液，出现症状；>500ml，出现呼吸困难，出现症状少量（300~500ml）见肋膈角变钝；小于300x线不可见。大量（>500ml）积液见弧形上缘的积液影（呈“抛物线”）；纵膈推向键侧。包裹性积液呈“D”字型。不随体位改变而变动。。LDH（乳酸脱氢酶）：>500IU提示恶性胸液。 ADA(腺苷脱氨酶)：>45IU提示结核性胸膜炎．Rivalta试验：阳性--渗出液。胸膜间皮瘤---属于渗出的。

气胸：肺萎陷<20%，无症状，伤后1-2周可自行吸收恢复，可观察保守治疗；肺萎陷>20%，行胸腔穿刺、闭式引流术。临床表现：急促，胸闷。气体引流一般在前胸壁锁骨中线第2肋间隙；液体引流则在腋中线和腋后线6~8肋间隙；颈静脉怒张，皮下气肿-----就是张力性气胸纵膈肿瘤好发部位：歌诀：前面的机场(畸胎瘤)，后面的神经(神经源性肿瘤)，快看前上方有个胸(胸腺瘤)大的。胃周围淋巴依据主要引流方向分为4群： ①胃小弯上部淋巴液引流到腹腔淋巴结群； ②胃小弯下部淋巴液引流到幽门上淋巴结群； ③胃大弯右侧淋巴液引流到幽门下淋巴结群； ④胃大弯上部淋巴液引流到胰脾淋巴结群。歌诀：小弯上腹腔，大弯上胰腺。小弯下幽门上，大弯幽门下溃疡： Curing—“r”像高的火苗，是烧伤引起的。 Cushing—脑肿瘤，脑外伤引起的。十二指肠悬韧带（treitz）是空肠起始部的标志。长25cm。 A型胃炎发，胃酸贫血差。

大苗笔记-病理(全)

病理学第一节细胞、组织的适应、损伤和修复细胞受到外界刺激做出应答反应①适应②损伤一、适应性改变 1、萎缩：细胞体积缩小“脂褐素” ①生理性---成人胸腺萎缩，更年期性腺萎缩，老年各器官萎缩 ②病理性 2、肥大：体积大 ①代偿性肥大 ②内分泌性肥大：雌激素---导管 3、增生：数量多心肌、骨骼肌只有肥大，没有增生。 4、化生：一种成熟—变为-另一种成熟。适应性改变最常见的是化生，占70%。 ①鳞状上皮化生：主要发生在支气管、宫颈、膀胱 ②肠上皮化生：慢性萎缩性胃炎 ③结缔组织化生：骨化性肌炎二、损伤（一）可逆性损伤变性：出现异常物质或正常物质异常增多。 1、细胞水肿（又叫水变性，最常见变性）：ATP生成减少，钠水潴留，形成水肿。电镜可以看到肿胀的线粒体和内质网，常见于病毒性肝炎（又叫气球样变----里面是水）

2、脂肪变性（脂肪沉积）：脂滴可被苏丹Ⅲ染成橘红色脂肪沉积在肝—脂肪肝；脂肪沉积在心脏----黄色斑纹—虎斑心，电镜可以看到大小不等的空泡 3、玻璃样变性（透明变性）蛋白质聚集分为：(1)结缔组织玻璃样变：----纤维 (2)血管壁玻璃样变：-----见于高血压，发生在细动脉 (3)细胞内玻璃样变：XXX小滴、小体。病理性钙化：除了骨骼、牙齿以外，有了钙化，就叫…… (二)不可逆性损伤——细胞死亡 1．细胞核的变化-----细胞坏死的主要形态学标志核固缩，核碎裂，核溶解坏死的4大类型： (1)凝固性坏死（最常见），多见于心、肝、脾、肾等实质器官和干酪性坏死（结核） (2)液化性坏死：脑（乙脑）和胰腺（急性胰腺炎） (3)纤维素样坏死：和变态反应、免疫反应有关， (4)坏疽：坏死+腐败菌感染 ①干性坏疽：见于四肢末端 ②湿性坏疽：与外界相通的内脏，如肺、肠、子宫、阑尾、胆囊 ③气性坏疽：深达肌肉的开放，厌氧菌感染。-捻发感。细胞坏死的结局：

大苗课堂笔记呼吸系统

大苗课堂笔记：备注本笔记纯属个人手记，请到大苗官方购买正版。慢性支气管炎（45分）2分病程发展（一个轴）：吸烟-慢支-COPD-肺动脉高压-肺心病 1弓I起慢支最常见的原因（或高危因素）是：吸烟。 2、慢支病人咳粘液痰的原因是：杯状细胞增多。 3、慢支病人咳黄色脓痰的原因是：纤毛功能下降。 4、慢支急性发作的最主要原因是：感染。是所有呼吸系统疾病急性发作的原因。 5、慢支感染最常见的致病菌：肺炎球菌、流感嗜血杆菌。（慢支感染球流感）。 6、慢支病理改变：1）早期主要为小气道功能异常，特点：一大一低一增加，即闭合容积大，肺动态顺应性降低，肺的静态顺应性增加。 2）中后期大气道功能异常，表现1:肺通气功能障碍2：FEV1和最大通气量下降。 7、慢支诊断标准：咳痰喘，每年发病持续3个月（三妹3M）,连续两年以上。 8辅助检查：慢支、肺气肿.、COPD、支气管哮喘、ARDS首选肺功能。9?治疗：慢支发作首选抗感染，痰多不易咳出可用祛痰剂，如氨溴索。但绝对禁用中枢镇静剂如可待因，因为会加重呼吸道阻塞，导致病情恶化。 10补充知识点：1）慢支早期X线无特异表现。 2）与慢支发病有关最常见的病毒是鼻病毒、流感病

毒、腺病毒、呼吸道合胞病毒。 3）小气道指内径v 2mm的气道。 4）潮气量VT ,平静呼吸每次吸入或呼出气量，成人约 500ml。5）肺活量VC深吸气末再做呼气所能呼出的最大气量。 6）残气量RV深呼气末肺内剩余的气量。 7）功能残气量FRC平静呼气末肺内剩留的气量。 8）肺总量TLC深吸气后肺内所含的气量。 9）用力肺活量FVC深吸气后以最大的力量所呼出的气量。 10）阻塞性通气障碍先表现为FEV1/FVC下降。 11）肺气肿时TLC增加。 COPD慢性阻塞性肺疾病3分 1、引起COPD最常见的原因是：慢支。慢支+肺气肿=COPD 2、COPD的病理改变：狭窄（慢支使细支气管管腔狭窄）、塌陷（慢性炎症破坏小气管软骨发生塌陷，肺泡弹性回缩力下降）、融合（反复肺部感染的慢性炎症导致肺泡融合成肺大泡，其炎症感染主要来自于中性粒细胞的活化聚集）、异常（a l-抗胰蛋白酶异常）。宰相荣毅仁，先天性a1-抗胰蛋白酶缺乏是欧洲人的发病原因，不是我国的发病原因。最重要的病理改变是肺泡融合成肺大泡。 3、临床表现：1）气短是COPD的标志性症状，看到直接诊断COPD。

2018年大苗笔记-妇儿

妇科第1节：女性生殖系统解剖外生殖器外阴的范围和组成外生殖器指生殖器官的外露部分，称为外阴，前为耻骨联合，后为会阴。 1.阴阜位于外阴最前面，上面有阴毛，呈倒三角形生长 2.大阴唇为两股内侧一对纵行隆起的皮肤皱襞，自阴阜向后延伸至会阴。皮下为疏松结缔组织和脂肪组织，含丰富血管、淋巴管和神经，外伤后易形成血肿。（只要说外阴受伤疼痛肿胀，那就是大阴唇血肿） 3.小阴唇 4.阴蒂 5.阴道前庭又称巴多林腺，腺管细长（1～2mm），向内侧开口予阴道前庭后方小阴唇与处女膜之间的沟内。如果发炎等原因引起腺管口闭塞，形成前庭大腺囊肿或前庭大腺脓肿。内生殖器及其功能女性内生殖器位于真骨盆内，包括阴道、子宫、输卵管和卵巢。输卵管和卵巢可以并称为子宫附件。一、阴道 1.它的黏膜层由复层鳞状上皮 2.阴道的下端开口于阴道前庭后部。 3.上端包绕宫颈阴道部，形成阴道穹隆，分前、后、左、右4部分，阴道后壁短（7～9cm），后壁长（10～12cm），所以后穹隆最深，卧位时是人体最低点，常用来穿刺。二、子宫 1.子宫的形状像一个倒置的梨形，重50克；长7-8mm；宽4-5mm；容量5毫升；上部较宽为宫体，顶部为宫底，宫底两边为子宫角，下部为宫颈。 2.宫体与宫颈之间形成最狭窄的部分称子宫峡部，它连接宫体与宫颈，它既不属于宫体也不属于宫颈，没怀孕时长约1cm，怀孕时长约7-9cm。 3.子宫峡部有上下两个口，上口窄，为解剖学内口。下口宽，为组织学内口（子宫内膜与宫颈黏膜的交界处）。 4.宫体与宫颈的比例：女童为1：2，成年妇女为2：1，老年妇女为1：1。 1.组织结构子宫内膜属于柱状上皮分为两部份（1）上2/3为功能层，每月定期脱落，形成月经（2）下1/3为基低层，作用就是形成功能层。 2.子宫韧带（1）圆韧带起源于两侧子宫角，往前下终止于大阴唇的前端，它维持子宫前倾位置。

大苗笔记---消化系统(全)

第一节食管、胃、十二指肠疾病 1、胃食管反流病（反流性食管炎） 1、发病机制：①一过性食管下端括约肌松弛，最为主要。②食管酸廓清能力下降。③胃排空延迟。④食管粘膜屏障破坏。此病与幽门螺杆菌毫无关系。 2、临床表现：典型表现烧心反酸或称胸骨后灼烧感，非典型症状为胸痛，食管外症状为咽炎、声嘶、咳嗽、吸入性肺炎。反酸出现在餐后1小时。攻击因子是胃酸和胃蛋白酶。胃酸、胃蛋白酶破坏碳酸氢盐屏障（胆汁反流的攻击因子是非结合胆盐和胰酶） 3、实验室检查：确诊选胃镜活检，主要看食管黏膜的损害程度并分级。本病是否有胃酸反流：24小时PH值监测。 4、两大并发症：①食管下段鳞状上皮被柱状上皮替代：Barrettle食管，属癌前病变应定期随访检查而不是手术。②食管狭窄。③食管溃疡。④食管腺癌 5、首选治疗抑酸：奥美拉唑（或称洛赛克、PPI），避免食用浓茶、咖啡、高脂肪食物。 2、食管癌 1、好发部位：胸中段。（颈段：咽——食管入口、胸上段：食管入口——主动脉弓、胸中段：主动脉弓——肺下静脉、胸下段：肺下静脉——贲门） 2、病理分型：髓质型（最常见），缩窄型（最容易发生梗阻），蕈伞型，溃疡型最容易发生食管气管瘘（一厚、一窄、一突出、一凹陷）。食管最常见鳞癌，最容易出现淋巴转移。 3、临床表现：①早期：早期最典型的症状，进食哽噎感。典型X线：局限性管壁僵硬②中晚期：进行性吞咽困难。典型X线：充盈缺损、狭窄梗阻。确诊中晚期的食管癌。 ①如癌肿侵犯喉返神经——声音嘶哑；中晚期的食管癌，侵犯喉反。 ②压迫颈交感神经——Horner综合征（单侧瞳孔缩小、眼睑下垂及眼球内陷）； ③侵入气管、支气管——吞咽水或食物时剧烈呛咳 4、实验室检查：确诊食管镜活检。筛查：食管拉网脱落细胞学检查。 5、鉴别诊断：①贲门失弛缓征：x线：成鸟嘴状（乙状结肠扭转也会出现此征）、漏斗状。 ②食管静脉曲张：X线：串珠样、虫蚀样、蚯蚓样。③食管憩室：吞咽时有咕噜咕噜声。④胃底静脉曲张：X线：菊花样。④食管平滑肌瘤：是食管肿瘤中最常见的良性肿瘤。x线：半月状切迹，绝对禁忌黏膜活检。 6、治疗：①首选手术：胸下段选弓上吻合术，余下的选颈部吻合术；②年龄70以上或身体不耐受手术者首选放疗。放疗时白细胞小于3、血小板低于80，暂停放疗。严重饮食困难先胃造瘘。 3、胃基础知识 1、胃部淋巴引流： ①胃小弯上部淋巴液引流到腹腔淋巴群------小沈阳很肤浅。 ②胃小弯下部淋巴液引流到幽门上淋巴群-----小侠女很友善。 ③胃大弯右侧淋巴液引流到幽门下淋巴群-----罗大佑是游侠。 ④胃大弯上淋巴液引流到胰脾淋巴群----骑着一匹马来到达上海。 2、区分幽门和十二指肠的解剖标志是幽门前静脉。 4、急性胃炎

大苗笔记内分泌全

大苗笔记内分泌全 Company number：【0089WT-8898YT-W8CCB-BUUT-202108】

①所有内分泌功能减退的疾病都选择激素的替代治疗（选择：生理需要量），但如果有发热、感染加重等存在---→激素加量到2-3倍 ②所有的垂体肿瘤都选择手术，只有“泌乳素瘤”除外！（闭经又泌乳→用溴隐亭或多巴胺受体激动剂）垂体腺瘤 1.最常见：泌乳素瘤PRL 2.根据大小分：①大腺瘤＞10mm，②微腺瘤＜10cm（最常见） 3.根据功能性分：①功能性腺瘤（激素分泌过多）②无功能性腺瘤（不分泌激素，只能分泌α亚单位）泌乳素瘤PRL 1.女人：闭经又泌乳，骨质疏松。治疗：多巴胺受体激动剂溴隐亭。男人：一般是大腺瘤，①压迫甲状腺、垂体窝②性功能障碍ED。治疗：手术。2.功能检查：泌乳素PRL。定位检查：MRI。生长激素分泌腺瘤GH 1.临床表现青春期前分泌多--→巨人症（容易诱发糖尿病）成人期分泌多----→肢端肥大症分泌严重不足----→侏儒症 2.实验室检查：最可靠指标：GH和IGF-1。 GH兴奋试验：阳性提示生长激素不足，提示侏儒症。

专家共识及指南

Objectives This study sought to investigate the outcomes following cardioversion or catheter ablation in patients with atrial ?brillation(AF)treated with warfarin or rivaroxaban. Background There are limited data on outcomes following cardioversion or catheter ablation in AF patients treated with fac-tor Xa inhibitors. Methods We compared the incidence of electrical cardioversion(ECV),pharmacologic cardioversion(PCV),or AF ablation and subsequent outcomes in patients in a post hoc analysis of the ROCKET AF(Ef?cacy and Safety Study of Ri- varoxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation)trial. Results Over a median follow-up of2.1years,143patients underwent ECV,142underwent PCV,and79underwent catheter ablation.The overall incidence of ECV,PCV,or AF ablation was1.45per100patient-years(n?321; 1.44[n?161]in the warfarin arm,1.46[n?160]in the rivaroxaban arm).The crude rates of stroke and death increased in the?rst30days after cardioversion or ablation.After adjustment for baseline differences, the long-term incidence of stroke or systemic embolism(hazard ratio[HR]:1.38;95%con?dence interval[CI]: 0.61to3.11),cardiovascular death(HR:1.57;95%CI:0.69to3.55),and death from all causes(HR:1.75;95% CI:0.90to3.42)were not different before and after cardioversion or AF ablation.Hospitalization increased after cardioversion or AF ablation(HR:2.01;95%CI:1.51to2.68),but there was no evidence of a differential effect by randomized treatment(p value for interaction?0.58).The incidence of stroke or systemic embolism(1.88% vs.1.86%)and death(1.88%vs.3.73%)were similar in the rivaroxaban-treated and warfarin-treated groups. Conclusions Despite an increase in hospitalization,there were no differences in long-term stroke rates or survival following cardioversion or AF ablation.Outcomes were similar in patients treated with rivaroxaban or warfarin.(An Ef?cacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation[ROCKET AF];NCT00403767)(J Am Coll Cardiol2013;61:1998–2006)?2013by the American College of Cardiology Foundation From the*Duke Clinical Research Institute,Duke University Medical Center, Durham,North Carolina;?The Cardiovascular Institute,Mount Sinai Medical Center,New York,New York;?Clinical Epidemiology Unit,General Medicine Division,Massachusetts General Hospital,and Harvard Medical School,Boston, Massachusetts;§Department of Neurology,Royal Perth Hospital,Perth,Australia;?Ruprecht-Karls University,Heidelberg,Germany;?Johnson&Johnson Pharmaceu-tical Research and Development,Raritan,New Jersey;#University of Edinburgh,and Royal In?rmary of Edinburgh,Edinburgh,United Kingdom;**Duke Translational Medicine Institute,Duke University Medical Center,Durham,North Carolina;and the??Department of Cardiovascular Medicine,Hospital of the University of Münster,Münster,Germany.The ROCKET AF trial was sponsored by Johnson& Johnson Pharmaceutical Research and Development and Bayer HealthCare AG.Dr. Piccini has received research grants from Johnson&Johnson and is a consultant/ advisory board member for Medtronic,Forest Laboratories,Sano?Aventis,and Journal of the American College of Cardiology Vol.61,No.19,2013?2013by the American College of Cardiology Foundation ISSN0735-1097/$36.00 Published by Elsevier Inc.https://www.wendangku.net/doc/876566134.html,/10.1016/j.jacc.2013.02.025

大苗老师血液系统笔记教学

血液系统贫血成人标准：男性：<120；女性：<110；孕妇：<100 贫血分度：轻度：>90；中度：60~90；重度：30~60；极重度：<30 形态学分类：MCV（红细胞平均体积）：正常：80~100 MCHC（红细胞平均血红蛋白浓度）：正常：32~35 坐小（小细胞贫血）的喜洋洋（海洋贫血）地铁（缺铁贫学）正（正细胞）在（再生功能障碍）急性失血（急性失血）病因分类： A.红细胞生成减少：1.骨髓造血功能衰竭—→再生功能障碍 2.原料的缺乏导致的合成障碍：1.）缺铁性贫血—→缺铁 2.）海洋贫血—→珠蛋白 3.）巨幼贫血—→叶酸、B12 B.红细胞破坏过多：1.内源性：1.）XX球型，椭圆形增多症 2.）海洋贫血—→珠蛋白守到破坏 2.外源性：自身免疫性溶血性贫血 C.失血性贫血造血干细胞：a.红细胞：原始红细胞—→早、中、晚幼红细胞——网织红细胞—→红细胞 b.粒细胞 c.巨核细胞缺铁性贫血自然界Fe来源：a.动物食品：Fe2+；b.植物食品：Fe3+ Fe主要来源：衰老的红细胞人体吸收：Fe2+；人体转运：Fe3+ 好搭档：Fe+Vc；吸收部位：十二指肠和空肠上段转运载体：转铁蛋白（转铁蛋白下降，转铁蛋白饱和度升高）正常人：a.1分子转铁蛋白转运2分子Fe3+ b.转铁饱和度：33% 缺铁贫：（只有Fe3+才能转运和转铁蛋白结合）铜蓝↑ 食物—→吸收Fe2+ （十二指肠和空肠上段）—→运输Fe3+ +转铁蛋白—→a.红细胞（2500mg）蛋白 b.单核巨噬细胞系统（300~1000mg）最先缺乏、最敏感→储存形式：铁蛋白、含铁血黄素 c.肌红蛋白（40mg）

大苗笔记,消化系统

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