[摘 要] 目的：探究错配修复蛋白2（MSH2）在胃癌中表达和其与患者临床特征的关系及其对胃癌细胞恶性生物学行为的作用及机制。方法：收集2020年5月至2022年7月期间在邢台市人民医院收治的40例胃癌患者的癌组织和配对癌旁组织及患者的一般临床资料。常规培养正常人胃黏膜上皮细胞GES-1和胃癌细胞AGS、MKN45和BGC-823，用转染试剂分别将sh-NC、shMSH2-1和shMSH2-2慢病毒载体转染至AGS和MKN45细胞中，实验分为sh-NC、shMSH2-1和shMSH2-2组。CCK-8法、克隆形成实验、EdU染色、Transwell小室实验分别检测各组AGS和MKN45细胞的增殖、迁移和侵袭能力。构建裸鼠MKN45细胞移植瘤模型，观察敲减MSH2对移植瘤生长的影响。WB法检测各组细胞中及移植瘤组织中 MSH2、PI3K/AKT/mTOR通路、上皮间质转化相关蛋白的表达。结果：MSH2在胃癌组织和细胞中呈高表达且与淋巴结转移、T分期进展及组织学分化不良均有关联（均P < 0.001）；在AGS和MKN45细胞中成功地敲减了MSH2的表达（P < 0.001）；敲减 MSH2均能显著抑制AGS和MKN45细胞的活力、EdU染色阳性率、克隆形成能力、迁移及侵袭能力和移植瘤的生长（均P < 0.001）；均能显著抑制AGS和MKN45细胞和MKN45移植瘤组织中MSH2蛋白、PI3K/AKT/mTOR通路相关蛋白、N-cadherin蛋白的表达（均P < 0.001），促进E-cadherin蛋白的表达（P < 0.001）。结论：MSH2在胃癌组织和细胞中呈高表达且与淋巴结转移、T分期进展及组织学分化不良有关联，敲减MSH2表达通过抑制PI3K/AKT/mTOR通路调控AGS和MKN45细胞的恶性生物学行为，MSH2可能是胃癌治疗的潜在靶点。

Objective: To investigate the predictive value of EZH2 expression for malignant transformation in oral leukoplakia (OLK) and to provide a reference for clinical practice. Methods: This study was approved by the institutional ethics committee, and informed consent was obtained from all participants. A total of 114 patients diagnosed with OLK by pathological examination and treated at our hospital between November 2020 and July 2022 were initially enrolled. After excluding those with incomplete data or follow-up, 105 participants were included in the final analysis, comprising 14 in the high EZH2 expression group and 91 in the low EZH2 expression group. Histopathological examination of oral mucosa and immunohistochemical detection of EZH2 protein expression were performed. The follow-up period was 30 months; participants were followed until malignant transformation occurred or until the end of follow-up, at which point they were withdrawn from the study. The exposure factor was the level of EZH2 protein expression, and the outcome was the malignant transformation rate of OLK. Differences in EZH2 expression levels and transformation outcomes were analyzed. Results: There were no statistically significant differences between the high and low EZH2 expression groups in terms of age, sex, history of systemic disease, lifestyle habits, psychological status, diet, and sleep conditions (P > 0.05). Lesions in the high EZH2 expression group were mainly located on the ventral tongue, while in the low EZH2 expression group, they were more commonly found on the dorsal tongue and buccal mucosa. The malignant transformation rate was 28.6% (4/14) in the high expression group and 8.8% (8/91) in the low expression group; these differences were not statistically significant (P=0.053). In univariate Cox regression analysis, the risk of malignant transformation in the high EZH2 expression group was 3.647 times that of the low EZH2 expression group (HR = 3.647, 95% CI: 1.097-12.120, P<0.05). Kaplan-Meier survival analysis showed that over the 30-month follow-up period, the cancer-free survival rate in the high EZH2 expression group was 19.8% lower than in the low expression group, and the difference was statistically significant (P<0.05). In multivariate Cox regression analysis, only moderate and severe epithelial dysplasia were identified as independent risk factors for malignant transformation. The risk of malignant transformation in the moderate and severe dysplasia groups was 10.695 and 13.623 times higher, respectively, than in the mild dysplasia group (HR = 10.695, 95% CI: 2.270-50.396, P<0.05; HR=13.623, 95% CI: 1.918-96.774, P<0.05). EZH2 high expression was not an independent risk factor in the multivariate model (HR= 2.528, 95% CI: 0.752-8.500, P = 0.134). Conclusion High EZH2 protein expression is a risk factor for the malignant transformation of OLK but does not have independent predictive value.

Objective : To investigate the effect of laminarin(LAM) on nonproliferative diabetes retinopathy by high throughput sequencing(RNA-seq). Methods : The diabetes model was established by intraperitoneal injection of streptozotocin(STZ), and the effect of LAM on diabetic mice was observed.C57BL/6 mice were randomly divided into three groups: Control group, Model group, and LAM group, with 8 mice in each group. After 8 weeks of modeling, the LAM group received a 4-week intraperitoneal injection of LAM treatment. Changes in blood glucose and body weight of the three groups of mice were recorded, HE staining was performed to examine retinal lesions, and RNA-seq was used to identify differentially expressed genes(DEGs) in diabetic retinopathy(DR) under the action of STZ and LAM. Results : STZ successfully established the model of DR, and LAM reduced the blood sugar in diabetic mice to a certain extent and improved the pathological morphology of retinal structural looseness in diabetic mice. After RNA-seq analysis of DEGs, it was found that there were a total of 214 DEGs in the retina of the Model group mice compared to the Control group. Enrichment analysis revealed that DR could exacerbate the lesions through the PI3K Akt signaling pathway. There were a total of 42 DEGs in the retina of the Model group and LAM group mice, and enrichment showed that LAM improved the lesions through the neutrophil extracellular trap pathway. Early growth response factor 1(Egr1), FBJ osteosarcoma oncogene(Fos), nuclear receptor subfamily 4A member 1(Nr4a1), and salt-induced kinase 1(Sik1) were regulated by STZ, and LAM significantly regulated their expression, which might be closely related to LAM′s treatment of diabetic retinopathy. Conclusion DEGs can exacerbate the severity of diabetic retinopathyviathe PI3K-Akt signaling pathway. LAM can mitigate diabetic retinopathyviathe neutrophil extracellular trap pathway. Egr1, Fos, Nr4a1, and Sik1 are key genes involved in LAM treatment of STZ-induced DR.

ObjectiveTo investigate the relationship between the composition of traditional Chinese medicine (TCM) and depression/anxiety/sleep disturbances (D/A/S) in patients with chronic pain.MethodsThis cross-sectional study was conducted at 13 tertiary hospitals across China, enrolling patients who experienced chronic pain between November 2023 and May 2024. The Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Pittsburgh Sleep Quality Index, and TCM constitution categories were used to assess the patients. The association between the TCM constitution and the D/A/S ratio was analyzed using multivariable logistic regression.ResultsA total of 1107 patients (63.2% women) were analyzed. Compared with those with a balanced constitution, patients who had qi-deficiency and yin-deficiency were at a higher risk of depression. Qi-deficiency and yin-deficiency were associated with anxiety. Sleep disturbances were common in patients with qi-deficiency constitution (odds ratio [OR]: 2.32, 95% confidence interval [CI]: 1.42–3.81), yang-deficiency constitution (OR: 1.94, 95% CI: 1.26–2.98), yin-deficiency constitution (OR: 2.03, 95% CI: 1.24–3.32), blood stasis constitution (OR: 2.07, 95% CI: 1.01–4.22), and qi-stagnation constitution (OR: 2.66, 95% CI: 1.35–5.25).ConclusionIn patients with chronic pain, specific TCM constitutions may be associated with D/A/S. Further longitudinal studies are needed to clarify the potential causal relationships between TCM constitution types and these conditions.

[摘 要] 目的：探究连翘苷（Phi）通过调控Hippo/YAP信号通路对结肠癌LS180细胞增殖、迁移和侵袭的影响。方法：用不同浓度（0、5、10、20、40、80 µmol/L）的Phi处理人结肠癌LS180细胞，MTT法检测24、48 和72 h时的细胞活力。将LS180细胞分为对照组、Phi-L（5 µmol/L Phi）组、Phi-M（10 µmol/L Phi）组、Phi-H（20 µmol/L Phi）组、Phi-H+YAP抑制剂维替泊芬（VP）组（20 µmol/L Phi+5 µmol/L VP），各组均处理24 h。EdU法检测Phi对各组细胞增殖的影响，划痕愈合实验、Transwell小室法分别检测Phi对细胞迁移和侵袭的影响，免疫荧光法和WB法检测Phi对细胞Ki-67表达率和LATS1、YAP和p-YAP、MMP-2、MMP-9、E-cadherin、N-cadherin表达的影响。构建LS180细胞移植瘤裸鼠模型，观察Phi对移植瘤体积和质量的影响，免疫荧光法和WB法检测移植瘤组织中Ki-67表达率和LATS1、YAP和p-YAP蛋白的表达水平。结果：与对照组比较，Phi-L、Phi-M和Phi-H组LS180细胞EdU阳性率、划痕愈合率、侵袭细胞数、Ki-67阳性率、MMP-2、MMP-9、N-cadherin表达均显著降低（均P<0.05），E-cadherin、LATS1和p-YAP/YAP表达均显著升高（均P<0.05）；同时使用VP则部分逆转了Phi对LS180细胞增殖、迁移与侵袭的抑制作用（均P<0.05）。Phi显著抑制裸鼠移植瘤生长，与对照组比较，Phi组裸鼠移植瘤体积、质量和Ki-67阳性率均显著降低（均P<0.05），LATS1和p-YAP/YAP水平均显著升高（均P<0.05）。结论：Phi可能通过激活Hippo/YAP信号通路抑制结肠癌LS180细胞的恶性生物学行为。

Abstract As a rapid analytical method for both the types and activities of γ radionuclides, the γ-ray spectrometry method is widely used in the measurement of γ radionuclides in environmental and biological samples. The Gamma-ray Spectrometry Method for the Determination of Radionuclides in Environmental and Biological Samples (GB/T 16145—2022）was implemented  on  July  1,  2023,  replacing  the Determination of Radionuclides in Soil by Gamma Spectrometry (GB/T 11743—2013), Determination of Radionuclides in Water by Gamma Spectrometry (GB/T 16140—2018), Gamma Spectrometry Method of Analyzing Radionuclides in Biological Samples (GB/T 16145—2020), and Determination of Radionuclides in Air by Gamma Spectrometry (WS/T 184—2017). The background of the revised standard, the content and basis of the main revisions, and some issues that need to be discussed are briefly explained in this paper, in order to provide a useful reference for the detection of radioactivity in soil, water, biological, and air samples, as well as samples of similar matrices.

[摘 要] 目的：探讨低剂量辐射（LDR）与人端粒酶逆转录酶C末端多肽27（hTERTC27）过表达联合治疗对肺癌A549细胞增殖和凋亡的影响，同时观察LDR与常规放疗（CONV-RT）结合的体内抑瘤效应。方法：将pEgr-hTERTC27质粒转染人非小细胞肺癌A549及小鼠LLC肺癌（LLC）细胞，用G418筛选建立稳定表达C27的A549-C27细胞和LLC-C27细胞。细胞实验分为6组，分别是CONV-RT（A549-Con）、低剂量照射（A549-Low）、C27（A549-C27）、常规剂量联合C27（A549-C27-Con）、低剂量照射联合C27（A549-C27-Low）和对照（A549-Mock）组，其中Low组的辐照剂量仅为Con组的36%。MTT法检测各组细胞增殖活性，流式细胞术检测各组细胞凋亡率。通过皮下种植建立LLC肺癌移植瘤小鼠模型，动物实验分组同细胞实验；记录各组小鼠肿瘤生长情况，并检测各组肿瘤体积和质量，H-E染色观察各组移植瘤组织邻近肌肉浸润情况。结果：与A549-Mock比较，A549-Con和A549-Low组细胞增殖活性均显著降低（均P < 0.01）；而且A549-C27-Con和A549-C27-Low组细胞增殖活性显著低于A549-C27组（均P < 0.01）。与A549-Mock组比较，A549-Con组和A549-Low组细胞凋亡率均显著升高（均P < 0.01）；A549-C27、A549-C27-Con和A549-C27-Low组细胞凋亡率无显著差异（P > 0.05）。与未经照射治疗的荷瘤小鼠相比较，CONV-RT及LDR + CONV-RT均可使荷瘤小鼠肿瘤质量显著降低（均P < 0.01）。此外，LDR + CONV-RT + C27组肿瘤质量显著减小，局部浸润减少（均P < 0.01）。结论：LDR与CONV-RT相结合能够在降低辐射总剂量的同时达到与CONV-RT单独使用相似的非小细胞肺癌肿瘤抑制效果。而且，LDR与C27多肽有协同抗肿瘤作用，两者同时使用能够使移植瘤局部浸润减少。

Enlarged perivascular spaces（EPVSs）are one of the imaging biomarkers of cerebral small vessel disease（CSVD），and associated with other pathological changes of CSVD，worse cognitive function，and aging. This review describes the imaging characteristics and visual rating of EPVSs using magnetic resonance imaging and summarizes the research progress of EPVSs in Alzheimer disease in recent years in order to promote the understanding of this field.
Alzheimer Disease

Objective: To explore sex differences in 3D T1texture features in the progression of Alzheimer&#39;s disease (AD) and to predict the diagnosis of AD patients of different sex． Methods: Seventy-seven AD patients (34 males and 42 females) ，74 amnestic mild cognitive impairment ( aMCI) patients ( 35 males and 39 females) and 75 healthy controls (HC) (35 males and 40 females) were recruited and high-resolution 3-dimensional T1 structural images were collected． Brain regions closely related to AD brain damage were selected as regions of interest ( ROIs) ，texture feature extraction and feature screening were performed．Analyses were performed by sex，and the support vector machine (SVM) was used for classification and prediction. Results : In the AD vs HC，AD vs aMCI and aMCI VS HC groups by different sex，we obtained some brain regions with relatively high recognition index in different subgroups，and found that there were significant differences between female patients and male patients with high recognition index，and the recognition index of female patients ( area under the curve，accuracy，sensitivity and specificity were generally higher than that of male． Conclusion There are significant sex differences in texture features in AD process，and the classification and prediction ability of texture features in female patients is better， suggesting the importance of sex differences in AD research．This study provides some reliable biomarkers for early sex-specific identification of AD，which may be helpful for the early diagnosis and treatment of AD in the future.

Objective : To analyze the expression and immune infiltration levels of the BMP7 gene ( BMP7) in e- sophageal squamous cell carcinoma(ESCC) ． Methods : Initially，in 274 cases of ESCC and 242 cases of normal tissues，the level of BMP7 was verified by immunohistochemistry ，and the relationship between the expression difference and the survival cycle and clinical pathological characteristics of patients with ESCC was explored，and BMP7 overexpression plasmid transfection of ESCC cells was established，and the effect of BMP7 on the biological behavior of ESCC cells was examined by CCK-8，Clone，and Transwell. Results : BMP7 expression in normal e- sophageal tissues was higher than that of ESCC(P＜0. 001) ，the expression level of BMP7 was correlated with the degree of differentiation of patients(P = 0. 006) and TNM staging(P ＜0. 001) ，and the survival of patients with high expression of BMP7 exceeded that of patients with low BMP7 (P = 0. 041) ，and the experiments of CCK-8 and Clone showed that the proliferation effect of cells in the overexpressed BMP7 group was lower than that of the control group．Transwell experiments confirmed that the cell invasion migration capacity of the overexpressed BMP7 group was less than that of the control one．The immune infiltration results showed that BMP7 was positively correlated with macrophages(P = 0. 008) and negatively correlated with γ-δT cells(P = 0. 028) ． Conclusion BMP7 is low in ESCC and associated with poor prognosis and immune infiltration levels in patients.