[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.

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.

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.

Objective To understand the status of behavioral intentions of defensive medical treatment in medical students,and explore the relationship between practice environment and behavioral intentions of defensive medical treatment.To provide reference for reducing the tendency of defensive medicine(DM)behavior of medical students and improving the negative effects of DM.Methods A web-based questionnaire survey was conducted among medi-cal students in four medical colleges in Heilongjiang Province.The structural equation modeling of the relationship be-tween practice environment and behavioral intentions of defensive medical treatment in medical students was con-structed by Amos 26.0 software.Results The mean score of medical students'behavioral intentions of positive and negarive defensive medical treatment was 44.49-6.90 and 20.06-6.83,respectively.The behavioral intention of posi-tively defensive medical treatment was positively associated(β=0.892,P＜0.05)with cognition of doctor-patient relationship.While the behavioral intention of negative defensive medical treatment was positively correlated(β=0.403,0.343,P＜0.05)with environment cognition,perception of risk and negatively correlated(β=-0.726,P＜0.05)with cognition of doctor-patient relationship.As an intermediary variable,the direct and indirect effects of cog-nition of doctor-patient relationship on negative defensive medical behavior tendency were-0.470 and 0.043,the difference was statistically significant(P＜0.05).Conclusion Improving cognition of medical students'doctor-pa-tient relationship is beneficial to understand defensive medical treatment for medical students.The negative defen-sive medical behavior tendency of medical students should be reduced by reducing their negative cognition of environ-ment or improving their cognition of doctor-patient relationship.

Objective:To analyze the characteristics of patients with chronic rhinosinusitis (CRS) in the South China region based on pathological tissue biomarkers for regional comparison.Methods:The study population consisted of CRS in-patients in the First Affiliated Hospital of Sun Yat-sen University from October 2019 to June 2022. Among all the 181 cases, 123 of them were male and 58 were female, with an average age of 40. Retrospectively collected clinical data included demographic information, preoperative symptom scores, preoperative endoscopic images, preoperative paranasal sinus computed tomography scanning images, and inflammatory serological features. In addition, 52 variables of pathological tissue biomarkers including cytokines, chemokines and remodeling factors were collected for analysis. Cluster analysis was performed on the integrated data of training set through centroid-based clustering algorithm, and the inflammatory characteristics, post-operation control status, and airway diseases comorbidity of each endotype were analyzed. R project (version 4.2.2) was used in statistical analysis.Results:Cluster analysis divided 181 patients with CRS into 4 endotypes. Cluster 1 ( n=101, 55.80%) showed a locally low inflammatory status. Cluster 2 ( n=23, 12.71%) showed a mixed type of inflammation with predominantly neutrophilic inflammation and tissue remodeling. Cluster 3 ( n=11, 6.08%) was characterized by type Ⅱ inflammation without tissue remodeling. Cluster 4 ( n=46, 25.41%) was mainly characterized by type Ⅱ inflammation with tissue remodeling, showing higher comorbidity rate of asthma and allergic rhinitis. This cluster presented more severe symptoms, significant olfactory dysfunction, extensive overall inflammation based on objective examination results, a notable increase in total eosinophil count and proportion in peripheral blood, and the highest uncontrolled rate observed one year post-surgery. In comparison to other regions, the endotype classification of CRS in Southern China was characterized by a predominant pattern of locally low inflammatory status, a moderate level of type Ⅱ inflammation with tissue remodeling, and a lesser presence of neutrophilic inflammation. Conclusion:CRS distribution in Southern China is mainly characterized by low inflammatory endotype and type Ⅱ inflammation with tissue remodeling. The latter shows more severe clinical manifestations and higher uncontrol rate after surgery.

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.

Background Due to the prominent particularity of medical work,nurses are prone to developing depression,which not only poses a considerable threat to the physical and mental health of nurses,but also affects the quality of nursing to some extent.Occupational stress is a known contributor to depression in nurses,whereas relatively little research has been done to investigate the underlying mediation path.Objective To explore the mediation effect of perceived organizational support and psychological capital on the relationship between occupational stress and depression among nurses,and to provide theoretical references for the prevention and treatment of occupational stress-induced depression in nurses.Methods From March to August 2019,a stratified random sampling method was utilized to select a sample size of 720 nurses in each department of a grade A tertiary hospital in Shandong Province.All subjects were assessed using Effort-Reward Imbalance Questionnaire(ERI),Perceived Organization Support Questionnaire(POS),Psychological Capital Questionnaire(PCQ)and Center for Epidemiologic Studies Depression Scale(CES-D).Pearson correlation was adopted to examine the correlation among above scales,and multilevel mediation analyses were conducted with model 6 in Process macro(version 3.3)for SPSS 26.0 using Bootstrap re-sampling method.Results A total of 658 nurses(91.39%)completed the effective questionnaire survey.ERI score was positively correlated with CES-D score(r=0.499,P<0.01),and negatively correlated with POS and PCQ scores(r=-0.318,-0.275,P<0.01).POS score was positively correlated with PCQ score(r=0.455,P<0.01),and negatively correlated with CES-D score(r=-0.401,P<0.01).PCQ score was negatively correlated with CES-D score(r=-0.567,P<0.01).The total effect value of occupational stress on depression was 0.466(95%CI:0.399～0.534).Perceived organizational support(indirect effect value of 0.027,95%CI:0.006～0.057)and psychological capital(indirect effect value of 0.059,95%CI:0.013～0.120),separately from each other,mediated the relationship between occupational stress and depression,and a chained mediation effect of perceived organizational support and psychological capital was also demonstrated(indirect effect value of 0.051,95%CI:0.031～0.082),accounting for 10.94%of the total effect.Conclusion Occupational stress is a influencing factor of nurses' depression,which can affect the occurrence of depression both directly and indirectly through either separate or chained mediation of perceived organizational support and psychological capital.