[摘 要] 甲状腺癌是内分泌系统中最为常见的恶性肿瘤，近年来其发病率呈现出显著的上升趋势。乙酰化修饰作为一种重要的蛋白质翻译后修饰，参与调控各个类型甲状腺癌相关基因的转录表达、细胞周期进程及侵袭能力。组蛋白去乙酰化酶（HDAC）抑制剂在甲状腺癌治疗中显示出潜在的应用前景。本文通过调研近年来相关文献，系统回顾了乙酰化修饰在参与甲状腺癌发生发展过程中的生物学功能及其调控机制，进一步探讨HDAC抑制剂在临床治疗中的应用前景，为甲状腺癌的靶向治疗提供坚实的理论依据和提出可行的治疗策略。

ObjectiveTo investigate the antitumor effect and mechanism of Guiqi Yiyuan ointment on Lewis lung cancer mice based on the extracellular regulatory protein kinase （ERK） signaling pathway. MethodsA Lewis lung cancer mouse model was established. Except for the blank group， the model mice were randomly divided into the model group， Guiqi Yiyuan ointment low， medium， and high dose groups， and the extracellular ERK1/2 inhibitor group， with 10 mice per group. The Guiqi Yiyuan ointment was administered by gavage at doses of 1.75， 3.5， 7.0 g·kg^-1·d^-1 for the low， medium， and high dose groups， respectively. The ERK1/2 inhibitor group was given the ERK1/2 inhibitor LY3214996 （100 mg·kg^-1·d^-1） by gavage. The treatment was administered for 14 consecutive days， after which samples were collected. Tumor histopathological changes were observed using hematoxylin-eosin （HE） staining. Transmission electron microscopy was used to observe ultrastructural changes in tumor cells. Immunofluorescence was performed to measure the phosphorylation of ERK1/2 （p-ERK1/2） and the expression of programmed cell death ligand-1 （PD-L1） in tumor tissues. Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression of p-ERK1/2， PD-L1， the autophagy marker Beclin-1， the autophagic protein p62， and the microtubule-associated protein light chains LC3Ⅰ and LC3Ⅱ at both the protein and gene levels. ResultsCompared with the model group， the average tumor weight was significantly reduced in the low and medium dose groups of Guiqi Yiyuan ointment （P<0.05）， and markedly reduced in the high dose and inhibitor groups （P<0.01）. Tumor cells in all treatment groups became progressively irregular， with ruptured nuclei and expanded areas of cell disintegration and necrosis. The number of organellar ablations in tumor tissues increased， and the number of autophagic vesicles also increased in all groups. The mean fluorescence intensity of p-ERK1/2 and PD-L1 was reduced in the low and medium dose groups of Guiqi Yiyuan ointment （P<0.05）， and significantly reduced in the high dose and inhibitor groups （P<0.01）. The mRNA expression of ERK1/2， PD-L1， Beclin-1， and p62 was reduced in the medium dose group （P<0.05）， while LC3Ⅰ/Ⅱ mRNA expression was elevated （P<0.05）. In the high dose and inhibitor groups， mRNA expression of ERK1/2， PD-L1， Beclin-1， and p62 was significantly reduced （P<0.01）， while LC3Ⅰ/Ⅱ mRNA expression was significantly increased （P<0.01）. Protein expression of p-ERK1/2， PD-L1， Beclin-1， and p62 was reduced in the medium dose group （P<0.05）， and LC3Ⅰ/Ⅱ protein expression was elevated （P<0.05）. In the high dose and inhibitor groups， protein expression of p-ERK1/2， PD-L1， Beclin-1， and p62 was significantly reduced （P<0.01）， while LC3Ⅰ/Ⅱ protein expression was significantly elevated （P<0.01）. ConclusionGuiqi Yiyuan ointment may inhibit the activation of the ERK signaling pathway， downregulate the expression of p-ERK1/2， promote autophagic flux in tumor cells， and regulate the expression of PD-L1， thereby exerting an inhibitory effect on tumor growth in Lewis lung cancer mice.

The key pathogenesis of coronary heart disease （CHD） is spleen deficiency and phlegm stasis， and dysfunctional high-density lipoprotein （dys-HDL） may be the biological basis for the occurrence of CHD due to spleen deficiency and phlegm stasis. Considering the biological properties and effects of high-density lipoprotein （HDL）， it is believed that the structure and components of HDL are abnormal in the state of spleen deficiency which led to dys-HDL； and dys-HDL contributes to the formation of atherosclerotic plaques through two major pathways， namely， mediating the dysfunction of endothelial cells and mediating the foaminess of macrophages and smooth muscle cells， thus triggering the development of CHD. It is also believed that dys-HDL is a microcosmic manifestation and a pathological product of spleen deficiency， and spleen deficiency makes foundation for the production of dys-HDL； dys-HDL is also an important biological basis for the phlegm-stasis interactions in CHD. The method of fortifying spleen， resolving phlegm， and dispelling stasis， is proposed as an important principle in the treatment of CHD by traditional Chinese medicine， which can achieve the therapeutic purpose by affecting the changes in the structure and components of dys-HDL， thus revealing the scientific connotation of this method， and providing ideas for the diagnosis and treatment of CHD by traditional Chinese medicine.

2-(4-Methylthiazol-5-yl) ethyl nitrate hydrochloride (W1302) is a nitro containing derivative of clomethiazole, which is a novel neuroprotective agent with both carbon monoxide (NO) donor and weak γ-aminobutyric acid type A (GABA_A) receptor allosteric regulatory excitatory effect. The current study used a rat model of transient middle cerebral arteryocclusion (tMCAO) brain injury to evaluate the therapeutic effect of W1302 on ischemic stroke and explore its potential mechanisms of action. This experiment has been reviewed and approved by the Laboratory Animal Management and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences (ethical review forms No. 620, 632, 5013). The results showed that gavage administration of 1, 3, and 10 mg·kg^-1 of W1302 can significantly reduce the volume of cerebral infarction in rats with ischemia for 2 h and reperfusion for 24 h, and the therapeutic effect was better than that of 200 mg·kg^-1 of DL-3n-butylphthalide. W1302 significantly increased NO levels in blood and brain tissue. It increased cerebral blood flow and brain adenosine triphosphate (ATP) content after reperfusion, as well as, inhibited the expressions of inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in brain tissue. The time window of W1302 was between 120-180 min after ischemia. These research results demonstrated that W1302 could increase NO release, dilate blood vessels, and increase cerebral blood flow, improve energy supply to brain tissue and increase ATP levels, and inhibit neuro-inflammation, which playing the protective roles in tMCAO stroke model rats. This provides theoretical support for the clinical application of W1302 in the treatment of ischemic stroke.

ObjectiveUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was used to identify the metabolites of harmine in rats， in order to explore the differences in distribution of metabolites in rats after single dose（40 mg·kg^-1） intragastric administration of harmine， as well to speculate the metabolic pathways. MethodSD rats were given a single dose of harmine by intragastric administration. Plasma， bile， urine and feces samples were collected after administration， and the samples were processed for determination by UPLC-Q-TOF-MS. The separation was performed on an ACQUITY UPLC™ HSS T3 columu（2.1 mm×100 mm， 1.8 μm） with acetonitrile（A）-0.1% formic acid aqueous solution（B） as mobile phase for gradient elution（0-2 min， 5%A； 2-9 min， 5%-35%A； 9-9.5 min， 35%-100%A； 9.5-12 min， 100%A； 12-12.5 min， 100%-5%A； 12.5-14 min， 5%A）， the mass spectra were obtained in positive ion mode with electrospray ionization（ESI）， the scanning range was m/z 50-1 200. The metabolites of harmine were identified based on the information of the obtained compounds and the literature data， and the metabolic pathways were hypothesized. ResultA total of 42 compounds（harmine and its metabolites） were identified in rats， including 27 in plasma， 17 in bile， 26 in urine and 13 in feces. The metabolic pathways involved in these 42 metabolites included monohydroxylation， dihydroxylation， demethylation， glucuronidation and sulfation. ConclusionHarmine can undergo phase Ⅰ and phase Ⅱ metabolic reactions in rats， and the prototype drug is metabolized rapidly in vivo， and the metabolites are mainly excreted by the kidneys， which can provide a reference basis for the pharmacodynamics and material basis of harmine.

Objective:To evaluate whether index of microcirculatory resistance(IMR)is associated with left ventricular(LV)remodeling in acute anterior ST elevation myocardial infarction(STEMI)pa-tients undergoing primary percutaneous coronary intervention(PPCI).Methods:This was a single-center retrospective cohort study.The patients with first anterior STEMI who received PPCI from January 2014 to August 2017 in Peking University Third Hospital was enrolled.After PPCI,IMR was measured immediately by using pressure/temperature guidewire.The success rate of IMR measurement was 100％.Also we collected some related clinical data from the medical records and laboratory results.Infarct size[assessed as creatine kinase(CK)peak],echocardiography at baseline and 1 year follow-up were as-sessed.LV adverse remodeling(LVAR)was defined as ≥20％increase in LV end-diastolic volume(LVEDV).Results:A total of forty-three patients were enrolled,with an average age of(58.7±12.4)years.The patients were divided into two groups as IMR ≤25 and IMR＞25 by normal values recommen-ded by previous literature.Compared with IMR ≤25 group,IMR＞25 group had a higher percentage of initial thrombolysis in myocardial infraction(TIMI)grade 0(95.7％vs.65.0％,P=0.029),higher serum CK peak value[4 090(383,15 833)vs.1 580(396,5 583),P=0.004].The IMR＞25 group suffered higher rates of ventricular aneurysm(30.4％vs.5.0％,P=0.021).There was no difference in LVEDV[(111.0±18.8)mL vs.(115.0±23.6)mL,P=0.503]between the two groups 1 day after MI,but after 1 year,LVEDV in IMR＞25 group was significantly higher than in IMR≤25 group[(141.5± 33.7)mLvs.(115.9±27.9)mL,P=0.018].The incidence of LVAR was more significant in IMR＞25 group(47.4％vs.11.8％,P=0.024).Binary Logistics regression showed that IMR[B=0.079,exp(B)(95％CI)=1.082(1.018-1.149),P=0.011]and serum triglyceride level[B=1.610,exp(B)(95％CI)=5.005(1.380-18.152),P=0.014]were the predictors of LVAR 1 year after MI.IMR had a good predictive value for LVAR 1 year after MI[area under the curve(AUC)=0.749,P=0.019],IMR＞29 was a good cutoff value with sensitivity 81.8％and specificity 68.0％.Conclusion:Our study elaborates that immediate measurement of IMR after PPCI in patients with STEMI can reflect the microvas-cular function.And IMR could be used as a quantitative biomarker to predict LVAR after STEMI.

Superior vena cava syndrome(SVCS)is a group of clinical syndromes caused by obstruction of the superior vena cava and its major branches from various causes.Pulmonary artery stenosis(PS)is a complication of lung cancer or mediastinal tumours.SVCS combined with PS due to pulmonary metastases from bladder cancer is extremely rare and has not been reported in the literature.Here we reported an old male patient with pulmonary metastases from bladder cancer presenting with swelling of the head,neck and both upper limbs.SVCS combined with PS was clarified by pulmonary artery computed tomography angiography(CTA)and digital subtraction angiography(DSA).Endovascular stenting was used to treat SVCS.Angiography also showed that PS had not caused pulmonary hypertension and did not need to be treated.The swelling of the patient's head,neck and upper limbs was gradually reduced after the procedure.

Objective: To investigate the exposure to television advertising of sugar sweetened beverages and the use of persuasive marketing techniques among children and adolescents in Beijing, so as to provide evidence for reduing childrens intake of sugar sweetened beverages. Methods: From October 19, 2020 to November 16, 2021, 32 days were randomly selected. The top four popular channels of children and adolescents aged 3-18 years were defined. Each channel was monitored from 6:00:00 to 23:59:59 for each date. A total of 2 304 h was recorded. Advertisements involving sugar sweetened beverages broadcast before, during or after the program were included. The frequency and the use of persuasive marketing techniques were analyzed. Results: A total of 1 237 advertisements for sugar sweetened beverages were included, of which 50.93% were dairy beverages, 28.38% were teabased beverages, and 19.48% were vegetable protein beverages. The average frequency of sugar sweetened beverages advertisements on every channel was (0.62±1.29)piece/h. The frequency of sugar sweetened beverages advertisements on every local channel [(1.04±1.35)piece/h] and childrens channel [(1.11±1.61)piece/h] was separately higher than every national channel [(0.48±1.24)piece/h] and general channel [(0.12±0.48)piece/h] (t=-14.05, 31.64, P<0.01). There were seasonal differences in television advertising of sugar sweetened beverages, and were more frequent during lunch and dinner times. The most frequently used persuasive marketing techniques were "images of children" (74.54%), "nutritional message" (61.76%), "product composition details" (58.61%), "nutrition claim" (57.24%), and "nutrition function claim or other function claim" (53.11%). Conclusions Children and adolescents are often exposed to television advertisement of sugar sweetened beverages on childrens channels and during meal times. There is an urgent need to formulate relevant policies to regulate the marketing of sugar sweetened beverages advertisement and reduce children and adolescents intake.

Alcoholic liver disease is liver disease caused by heavy and/or chronic alcohol consumption.Bile acids are synthesized in the liver and regulate the body through liver-intestinal circulation.Many studies have shown that bile acid is closely related to alcoholic liver disease.Alcohol intake can cause liver damage by affecting bile acid synthesis,hepato-enteric circulation and intestinal flora.This article summarizes the mechanism of action of bile acids in alcoholic liver disease and the current research status of improving alcoholic liver disease based on bile acid regulation,in order to provide new ideas for future research on the prevention and treatment of alcoholic liver disease.

Objective To establish a recurrence risk prediction model for meningioma based on HOXA9 DNA methylation.Methods Meningioma-related datasets were downloaded from GEO database for screening homeobox genes(HOXs)with prognostic values using differential methylation and ROC curve analysis and Cox regression analysis.The differentially methylated CpG sites with high predictive efficacy were selected to establish the risk prediction model using Lasso-Cox regression analysis,based on which the patients were divided into high-and low-risk groups by the cutoff value.The methylation levels of CpG sites were verified at the cell and tissue levels using methylation-specific PCR(MS-PCR).Clinical meningioma tissue samples were used to validate the predictive efficacy of the model.Results HOXA9 methylation level was significantly up-regulated in meningiomas(P<0.001)and showed a high diagnostic efficiency(AUC=0.884)as an independent risk factor for overall survival(P<0.01)positively correlated with the degree of malignancy and poor prognosis of meningioma(P<0.05).Risk stratification by HOXA9 methylation was more accurate than WHO grading for predicting recurrence and patient survival time.The AUCs of the sites cg03217995 and cg21001184 were both above 0.8 for meningioma diagnosis and above 0.6 for predicting recurrence.The patients'clinical characteristics differed significantly between the high-and low-risk groups(P<0.001),and the prediction score of the model was an independent prognostic factor for meningioma(P<0.05).MS-PCR results showed that the methylation levels of the two sites increased significantly in meningioma cells.In clinical samples,the combined model showed a high prediction efficiency(AUC=0.857),and the predicted risk of progression was highly consistent with the patients'actual condition.Conclusion High HOXA9 methylation level is a predictor for poor prognosis of meningiomas,and the combined prediction model based on its CpG sites provides a new approach to early screening of meningioma patients at risk of progression.