目的 构建吉西他滨耐药乳腺癌细胞4T1耐药株并建立裸鼠乳腺癌肝转移模型。方法 采用低浓度加量持续诱导法,诱导吉西他滨耐药乳腺癌细胞4T1耐药株,命名为4T1/Gem;CCK-8法测定4T1与4T1/Gem细胞的增殖抑制率,计算耐药指数; Western blot法检测细胞P-gp蛋白表达;B超引导下注射4T1/Gem细胞悬液诱导裸鼠肝脏成瘤;HE染色观察肿瘤组织病理情况,免疫组化法检测瘤组织ER、PR、HER2、Ki-67和P-gp蛋白的表达。结果 经过14个月的诱导成功建立4T1/Gem细胞株,可在含40 μg/mL的Gem培养液中稳定生长。4T1/Gem细胞耐药指数为4T1细胞的788.547倍。与亲代相比,4T1/Gem处于G1期和G2期的细胞增加,S期细胞减少;上调P-gp蛋白的表达。4T1/Gem细胞成功建立裸鼠乳腺癌肝转移模型,瘤组织中ER、PR、HER2蛋白阴性表达,Ki-67阳性10％和P-gp蛋白阳性表达。结论 成功构建吉西他滨耐药乳腺癌细胞4T1耐药株并建立裸鼠乳腺癌肝转移模型,为开发治疗乳腺癌肝转移化疗耐药的药物提供实验基础。

Objective To construct a gemcitabine-resistant variant of the breast cancer cell line (4T1/Gem) and establish a nude mouse model of breast cancer with hepatic metastatic. Methods A gemcitabine-resistant variant of the breast cancer 4T1 cell line was induced by gradually increasing the concentration of gemcitabine; this variant is referred to in this study as 4T1/Gem. The proliferation suppression rates of 4T1 and 4T1/Gem cells were determined by using the CCK-8 essay to evaluate the drug resistance indices of the cell lines. Western blot analysis was used to detect P-gp protein expression. Under ultrasonography, a 4T1/Gem cell suspension was injected into nude mice to induce liver tumors. H&E staining was used to observe tumor pathology, and immunohistochemistry was used to detect the expression of ER, PR, HER-2, Ki-67, and P-gp. Results After 14 months of induction, a 4T1/Gem cell line is established successfully. The cell line can grow stably in culture liquid containing 40 μg/ml gemcitabine. The drug resistance index of 4T1/Gem is 788.547. Compared with the 4T1 cell line, the 4T1/Gem cell line can upregulate P-gp protein expression and successfully establish a nude mouse model of breast cancer with hepatic metastatic. ER, PR, and HER-2 proteins exhibit negative expression in the tumor tissue. The positive expression of P-gp and 10% of Ki-67 proteins is also observed. Conclusion This study successfully constructs a gemcitabine-resistant variant of the breast cancer cell line (4T1/Gem)and establishes a nude mouse model of breast cancer with hepatic metastatic, thereby providing an experimental basis for developing and treating a drug-resistant variant of breast cancer.

心肌梗死模型在心肌梗死病理发生机制、新药研发研究中占有重要地位。目前冠状动脉结扎法制作大鼠心肌梗死模型,模型稳定,操作简单,造价便宜,效果可靠,为最主要的心肌梗死造模方法,制作方法及具体操作中存在各自的优势和不足,影响着模型的进一步推广,有待继续进行改进和深入研究。

目的 通过建立大鼠泛耐药铜绿假单胞菌肺炎模型,对其进行联合用药,观察疗效,以便为治疗泛耐株引起的感染提供理论基础。方法 选择体外药敏实验中各药物组合同时有效的一株铜绿假单胞菌建立小鼠肺炎模型,于感染后6小时给药,对照组腹腔注射0.5 mL生理盐水,治疗组分别用头孢他啶+阿米卡星+环丙沙星以及头孢他啶+阿米卡星+环丙沙星+氨氯地平两组用药方案连续治疗三天后,根据肺组织匀浆细菌计数及病理结果评价疗效。结果 体内药敏试验显示用药组不管有无氨氯地平干预,对细菌的清除作用与对照组比较差异有统计学意义(P﹤0.05),而两用药组之间比较,差异无统计学意义。结论 对泛耐药铜绿假单胞菌感染后肺炎模型,联合应用体外单药药敏试验耐药的抗菌药后对细菌仍有一定的清除作用,但加入氨氯地平干预未显示有明显的治疗效应。

目的 通过构建结构方程模型,分析某三级甲等综合医院腹股沟疝患者住院费用的影响因素,旨在为合理控制腹股沟疝单病种费用提供依据。方法 收集4 328份高州市人民医院2016—2022年主要诊断疾病名称为腹股沟疝且行腹股沟疝手术的患者的病历资料,预分析单个影响因素,采用AMOS28.0拟合构建模型。结果 结构方程模型拟合达到标准。性别、年龄、费别、住院次数、入院途径、伴随病、单双侧疝对总费用所产生的总效应数值分别为0.008、-0.044、0.062、0.014、-0.119、0.106、0.236;性别、年龄、费别、住院次数、入院途径、伴随病、单双侧疝通过住院时间间接对住院费用产生影响。结论 对住院费用产生的影响因素有性别、年龄、费别、住院次数、入院途径、伴随病、单双侧疝、住院时间,建议推行患者预住院模式及日间手术,在正式住院前完成相关检查,优化医疗服务流程,从而合理有效控制单病种住院费用。

Objective By utilizing a structural equation model, to analyze determinants that affect the hospitalization costs for individuals with inguinal hernia at a tertiary-level comprehensive medical center, offering insights for the potential management of costs associated with this specific ailment. Methods This study entailed the compilation of 4 328 patient files from individuals who received surgical treatment for inguinal hernia at a third-level general hospital over the period spanning 2016 to 2022. Preliminary analysis was conducted on isolated variables, followed by the development of a model using AMOS 28. 0 for fit assessment. Results The fitting of structural equation model reached the standard. The total effect values of gender, age, cost, number of hospitalizations, admission route, concomitant disease, unilateral and bilateral hernia on the total cost were 0. 008, -0. 044, 0. 062, 0. 014, -0. 119, 0. 106, 0. 236, respectively. Gender, age, cost, number of hospitalizations, admission route, concomitant disease, unilateral and bilateral hernia indirectly affected hospitalization expenses through hospitalization days. Conclusions Gender, age, cost, number of hospitalizations, of admission, concomitant diseases, unilateral and bilateral hernia, and length of hospital stay have an impact on hospitalization costs. It is suggested to implement the pre-hospitalization mode and day surgery, complete relevant examinations before formal hospitalization, and optimize the medical service process, so as to reasonably and effectively control the hospitalization cost of single disease.

目的 通过建立急性心力衰竭（AHF）患者服药依从性预测模型,提高AHF患者的服药依从性和临床管理效果。方法 纳入2021年1月—2023年12月在广州市番禺区何贤纪念医院住院治疗的580例AHF患者,通过收集患者的一般人口学资料、疾病相关资料及出院后6个月的服药依从性数据,应用Logistic回归模型分析患者服药依从性的影响因素,并基于影响因素建立预测模型。结果 患者服药依从性总体良好（75%）。依从性良好组与依从性差组的年龄、独居情况、合并基础病、服药种类、疾病了解评分、治疗信心评分和自我控制信心评分比较差异有统计学意义（P<0.05）。Logistic 回归分析显示危险因素包括年龄≥60岁（OR=1.774）、独居（OR=1.871）、合并基础病≥2种（OR=1.719）和服药种类≥7种（OR=1.456）。而疾病了解评分（OR=0.923）、治疗信心评分（OR=0.946）和自我控制信心评分（OR=0.901）是保护因素（P<0.05）。基于上述因素建立的预测模型,通过ROC曲线验证,曲线下面积为0.815（95%CI：0.780~0.850）,提示所构建的模型具有良好的区分度。对该模型的校准度进行评价,P=0.528,提示该预测模型拟合度良好。此外,该预测模型的一致性指数为0.738,说明模型的预测性能良好。绘制的决策曲线中,曲线位于极端线之上,当阈概率取值在9%~59%时,对应的净获益率为0~27%,提示建立的模型具有优秀的临床有效性。结论 AHF患者的服药依从性受到多种因素的影响,包括年龄、居住状态、合并基础病种类及服药种类等。

Objective To establish a predictive model for medication compliance among acute heart failure（AHF）patients in order to enhance their therapeutic compliance and optimize clinical outcomes. Methods A total of 580 AHF inpatients at He Xian Memorial Hospital in Panyu District, Guangzhou between January 2021 and December 2023 were enrolled. Demographic information, disease-specific data,as well as post-discharge medication compliance records within six-month were collected by investigators. Utilizing logistic regression analysis revealed several influential determinants affecting medication compliance which formed the basis for constructing our predictive model. Results Generally,patient compliance was good（75%）. The comparison between the good compliance group and the poor compliance group showed that there were significant differences in age, living alone,combined with underlying diseases, types of medication, disease understanding score, treatment confidence score and self-control confidence score（P<0. 05）. Logistic regression analysis showed that independent risk indicators including individuals aged ≥60 years（odds ratio[OR]=1. 774）, those living alone（OR=1. 871）, presence of two or more underlying diseases（OR=1. 719）, along with consumption of seven or more medications daily（OR=1. 456）. Conversely,disease awareness score（OR=0. 923）, treatment confidence score（OR=0. 946）, and self-control confidence score（OR=0. 901）were identified as independent protective factors. Validation using receiver operating characteristic curves demonstrated robust predictive performance with an area under curve value of 0. 815（95%CI：0. 780-0. 850）, affirming its efficacy. The calibration of the model was evaluated, with a P-value of 0. 528, indicating good fit of the predictive model. Additionally, the concordance index（C-index）of the model was 0. 738, suggesting its excellent predictive performance. The decision curve analysis revealed that the curve was above the extreme lines, with a net benefit rate ranging from 0 to 27% when the threshold probability falls between. Conclusions The medication compliance of AHF patients is influenced by various factors, including age, living arrangement, the number of underlying diseases, and the number of medications taken. Targeted interventions such as enhancing patient education, simplifying treatment regimens, and improving social support can effectively improve the medication compliance of AHF patients. The predictive model established in this study provides a scientific basis for clinicians to develop more precise and effective individualized intervention measures,thereby improving the prognosis and quality of life.

目的 建立大鼠急性心肌梗死缺血再灌注后无复流模型,并初步验证细胞焦亡在其中的发生情况。方法 选用20只标准成年雄性Sprague Dawley大鼠（体质量260~320 g）,随机分为对照组（n=5）和手术组（n=15）。对照组仅穿线冠状动脉,未行结扎;手术组结扎左前降支0.5 h后解除,进行再灌注4 h,以建立无复流模型。通过Evens blue和硫磺素S染色,评估心肌的正常供血区、再灌注区及无复流区,并对两组大鼠心肌组织进行病理分析。结果 对照组大鼠全部存活,未出现无复流现象,心肌组织中未见细胞焦亡。手术组存活13只,形成明确的正常供血区（n=13）、再灌注区（n=13）和无复流区（n=10）。在无复流区的心肌细胞中均观察到细胞焦亡（n=10）,而正常供血区未见（n=0）,再灌注区部分出现（n=4）,差异具有统计学意义（P<0.05）。结论 细胞焦亡现象主要存在于大鼠急性心肌梗死缺血再灌注后无复流区域中,细胞焦亡可能作为一种区域特异性程序性死亡方式,在心肌无复流的发生与发展中发挥重要作用。

Objective To establish a rat model of myocardial no-reflow after acute myocardial infarction with ischemia-reperfusion injury and to preliminarily explore the occurrence of pyroptosis in the affected myocardium. Methods Twenty adult male Sprague-Dawley rats（260-320 g）were randomly divided into a control group（n=5）and a surgical group（n=15）. In the control group,the coronary artery was encircled with suture but not ligated. In the surgical group,the left anterior descending artery was ligated for 30 minutes, followed by 4 hours of reperfusion to induce the no-reflow model. Evans blue and thioflavin S staining were used to evaluate the normal perfusion area,reperfusion area,and no-reflow area of the myocardium. Histopathological analysis was conducted on myocardial tissues from both groups. Results All rats in the control group survived without evidence of no-reflow or pyroptosis in myocardial tissue. In the surgical group, 13 rats survived and showed distinct regions of normal perfusion, 13 with reperfusion, and 10 with no-reflow. Pyroptosis was observed in all no-reflow areas（n=10）, absent in the normal perfusion zones（n=0）, and partially present in the reperfusion zones（n=4）. The differences were statistically significant（P<0. 05）. Conclusions Pyroptosis predominantly occurs in the no-reflow zones following acute myocardial infarction and ischemia-reperfusion injury in rats. As a region-specific form of programmed cell death, pyroptosis may play an important role in the development of myocardial no-reflow.

       目的   构建并验证主动脉夹层B型（TBAD）患者急性期预后的列线图预测模型，帮助临床医生在急性期内更准确地评估TBAD患者的死亡风险，并制定更合适的治疗策略。方法   回顾性分析从重症监护医学信息数据库v2.2 中提取的399例 TBAD患者的人口学资料和临床资料，结局为TBAD患者急性期（≤14 d）内死亡。先采用最小绝对收缩选择算法回归筛选特征变量，再采用多因素分析确定独立预后因素，并据此构建预测模型。通过受试者工作特征曲线、校准曲线、决策曲线分析（DCA）评价列线图预测模型的性能和临床适用性。结果  APS Ⅲ评分、二氧化碳总量、红细胞分布宽度为TBAD患者14 d内死亡的独立预测因素。列线图预测模型在内部验证中的受试者工作特征曲线下面积为0.776（95% CI：0.691 ~ 0.860），Hosmer-Lemeshow 检验P=0.604，校准曲线和标准曲线高度重合，表明该模型具有良好的区分度和校准度。同时，DCA曲线显示，预测模型在大部分的阈值概率范围内提供了显著的净收益。结论   本研究基于APS Ⅲ评分、二氧化碳总量、红细胞分布宽度构建的列线图预测模型可以较准确地预测TBAD患者14 d内的死亡风险，有助于临床医生制定更合适的个体化治疗策略。

       Objective  To develop and verify a nomogram for predicting acute phase outcomes in patients with type B aortic dissection（TBAD），enabling clinicians to more precisely evaluate mortality  risk in TBAD patients during the acute stage and to devise better treatment plans．Methods  This retrospective study analyzed demographic and clinical data of 399 TBAD patients from the Medical Information Mart for Intensive Care IV v2.2，focusing on mortality within 14 days of the acute phase in TBAD patients．Initially，the Least Absolute Shrinkage and Selection Operator regression was employed for feature variable selection，and then multivariate analysis was used to identify independent prognostic factors for constructing the predictive model．The nomogram predictive model’s effectiveness and clinical applicability were assessed via the Receiver Operating Characteristic curve，calibration curve，and Decision Curve Analysis（DCA）．Results  Acute Physidogy Score Ⅲ score，total carbon dioxide，and red blood cell distribution width emerged as independent predictors of 14-day mortality in TBAD patients．The internal validation of the nomogram predictive model showed an area under the curve of 0.776（95%CI：0.691-0.860），with a Hosmer-Lemeshow test P-value of 0.604．The close alignment of the calibration and standard curves suggested the model’s strong discriminative power and calibration．Furthermore，the DCA curve  revealed that the predictive model offered substantial net benefits within a wide  range of threshold probabilities．Conclusions  This study's nomogram，developed using APS Ⅲ score，total carbon dioxide，and  red blood cell distribution width，accurately predicts the 14-day mortality risk in TBAD patients，assisting clinicians in creating better personalized treatment plans．

       目的   本研究以脑卒中患者为研究对象，通过二代Illumina高通量测序平台对患者的粪便标本进行微生物群落多样性测序。选择物种丰度≥30%的24个门类（Phylum）作为肠道菌群的研究指标，进而研究肠道菌群与脑卒后抑郁（PSD）之间的相关关系。方法   以40位脑卒中患者的24个门类作为特征变量，抑郁组和对照组为二分类目标变量，建立以Logistic回归、随机森林、支持向量机和AdaBoost为基模型的Stacking分类模型。主成分分析方法作为该模型的特征选择方法选择恰当的主成分进行模型训练，通过二分类评价报告（precision、recall、f1-score）、ROC曲线和混淆矩阵等评价指标对其性能进行评价。结果   （1）通过差异性检验分析了两组（抑郁组和对照组）的基线一致（P＜0.05）；（2）从Stacking模型融合的角度定量分析了影响脑卒中后抑郁情绪的具体肠道菌群。研究结果可知，放线菌门、拟杆菌门、变形菌门和酸杆菌门在PSD患者中均增加（P＜0.001）；厚壁菌门，疣微菌门，绿弯菌门和软壁菌门在PSD患者中降低（P＜0.001）。结论   以上菌群是影响脑卒中后抑郁患者情绪的主要影响因素，因此，在临床上通过恰当干预肠道菌群的变化来调节脑卒中后抑郁患者的抑郁水平，这为脑卒中后抑郁情绪的诊断和治疗方案提供科学依据。

        Objective  In this study，patients with stroke were selected as the research object，and the microbial community diversity of patients’ stool samples was sequenced by the second-generation Illumina high-throughput sequencing platform．Twenty four phylum species with 30% species abundance were selected as indicators for the study of gut microbiota，and then the correlation between gut microbiota and post-stroke depression（PSD） was studied．Methods  Taking 24 categories of 40 stroke patients as characteristic variables，depression group and control group as dichotomous target variables，a stacking classification model based on Logistic regression，random forest，support vector machine and AdaBoost was established．As the feature selection method of the model，principal component analysis selects the appropriate principal components for model training，and evaluates its performance through dichotomous evaluation reports（precision，recall，f1 score），ROC curve and confusion matrix．Results  The baseline of the two groups（depression group and control group）was consistent（P＜0.05）through the difference test．From the perspective of stacking model fusion，the specific intestinal flora affecting post-stroke depression was quantitatively analyzed．The results showed that Actinobacteria，Bacteroidetes，Proteobacteria and Acidobacteria were significantly increased in PSD patients（P＜0.001），while Firmicutes，Verrucomicrobia，Chloroflexi and Tenericutes were significantly decreased in PSD patients（P＜0.001）．Conclusions  The above microbiota are the main factors affecting the mood of patients with post-stroke depression．Therefore，in clinical practice，we can adjust the depression level of patients with post-stroke depression by properly intervening the changes of intestinal microbiota，which provides a scientific basis for the diagnosis and treatment of PSD．

  目的   基于SEER数据库分析三阴性乳腺癌（TNBC）的预后，并建立Cox回归临床预测模型且进行内部验证。方法   使用SEER*Stat软件（8.4.2版）筛选2010—2015年诊断为TNBC的病例，进行单因素和Cox多因素回归以及向后逐步回归分析，明确与生存相关的独立危险因素，构建预测TNBC患者3年和5年癌症特异生存（CSS）率的Nomogram图，并用受试者工作特征曲线，Harrell’s一致性指数，临床预测模型校准曲线以及决策曲线对该模型进行评估及内部验证，以评估该模型的临床预测效能。结果   共筛选出符合纳入标准的TNBC患者5 564例，按照7∶3的比例随机拆分为训练集（n=3 894）和验证集（n=1 670）。通过单因素，多因素分析显示TNM分期、放射治疗、化学治疗以及手术和其他治疗的先后顺序是与TNBC患者CSS显著相关的独立危险因素（P＜0.05）。利用上述预后相关因素建立Nomogram图模型。训练集的C-index为0.731（95%CI：0.712~0.749），验证集的C-index为0.719（95%CI：0.688~0.749），训练集和验证集3年和5年生存ROC曲线的曲线下面积均＞0.7，区分度较好，且校准曲线拟合良好。结论  TNM分期、放射治疗、化学治疗以及手术和其他治疗的先后顺序是TNBC的独立预后因素，基于此建立的Nomogram图临床预测模型区分度、准确度以及临床适用性较好，能较好地预测TNBC患者的生存预后。

    Objective  To analyze the prognosis of triple negative breast cancer（TNBC）based on the SEER database，and to establish a Cox regression clinical prediction model with internal validation．Methods  Cases diagnosed with TNBC from 2010 to 2015 were screened using SEER*Stat software（version 8.4.2），and univariate and Cox multifactorial  regression as well as backward stepwise regression analyses were performed to identify the independent risk factors associated with survival，and to construct a clinical prediction model for predicting the three- and five-year cancer specific survival（CSV）of TNBC patients．Survival（CSS）rates of TNBC patients at 3 and 5 years，and the model was evaluated and internally validated using the ROC curve，Harrell’s consistency index（C-index），clinical prediction model calibration curve，and decision-making curve（DCA curve）to assess the predictive efficacy of the model for clinical prediction．Results  A total of 5 564 TNBC patients meeting the inclusion criteria were screened and randomly split into a training set（n=3 894）and a validation set（n=1 670）according to a 7∶3 ratio．By univariate，multivariate analysis showed that T-stage，N-stage，M-stage，radiotherapy，chemotherapy，and the sequence of surgery and other treatments were independent risk factors significantly associated with CSS in TNBC patients．The above prognostic-related factors were utilized to build a Nomogram plot model．The C-index was 0.731（95%CI：0.712-0.749）for the training set and 0.719（95%CI：0.688-0.749）for the validation set，and the areas under the curves of the 3- and 5-year survival ROC curves of both the training and validation sets were ＞0.7，which was a good differentiation，and the calibration curves were well-fitted．Conclusions  T-stage，N-stage，M-stage，radiotherapy，chemotherapy，and the  sequence of  surgery and other treatments are independent prognostic factors for TNBC，and the Nomogram clinical prediction model based on this has good differentiation，accuracy，and clinical utility，and can better predict the survival prognosis of TNBC patients．

      目的   探讨导言-目标-前测-对照-后测-总结（BOPPPS）教学模式在基层护理培训中的应用效果。方法   采用类实验研究方法，将2021年5月—2021年12月参加培训的96名护士设为对照组，使用传统教学模式，将2022年1月—2022年12月参加培训的325名护士设为研究组，使用BOPPPS教学模式。对两组学员的教学效果通过理论、操作考核及问卷调查进行比较。结果   对照组学员理论知识、技能操作以及培训满意度均高于对照组，差异均有统计学意义（均P＜0.05）。结论  BOPPPS教学模式在基层护理实训课中具有重要意义，可提高学员理论和技能操作能力，提升学员满意度。

      Objective  To explore the application effect of BOPPPS teaching mode in nursing primary training．Methods  Adopting class experimental research method，96 nurses who participated in the training from May 2021 to December 2021 were the control group，using the traditional teaching method．The 325 nurses who participated in the training from January 2022 to December 2022 were set up as a study group using the BOPPPS teaching model．The teaching effectiveness of the two groups of nurses was compared through theoretical and operative examinations and questionnaires．Results  The theoretical knowledge，skill operation and training satisfaction of the trainees in the experimental group were higher than those in the control group，and the differences were statistically significant（P＜0.05）．Conclusions  BOPPPS teaching mode is of great significance in nursing primary practical training course，which can improve the theory and skill operation ability of trainees and enhance the satisfaction of trainees．