Objective: To explore the molecular mechanism of miR-195-5p targeting FGF2 to inhibit the proliferation, apoptosis, invasion and migration of endometrial cancer HEC-1B cells. Methods: After culture and transfection, HEC-1B cells were divided into 4 groups: HEC-1B group, miR-195-5p mimic group, pLV-FGF2 group and miR-195-5p+FGF2 group. The expressions of miR-195-5p and mRNA levels of FGF2 were detected by qRT-PCR. The targeted relationship of miR-195-5p and FGF2 was verified by luciferase assay. The protein expression of FGF2 was examined by Western blotting; Proliferation of HEC-1B cells was measured by CCK-8; Apoptosis was tested by flow cytometry; HEC-1B cell invasion was detected by transwell, and migration was measured by scratch assay. Results: Compared with HEC-1B group, the expression of miR-195-5p in miR-195-5p mimic group was elevated while FGF2 mRNA level was declined (all P<0.01). Luciferase assay indicated that FGF2 was a target of miR-195-5p. Compared with HEC-1B group, the protein level of FGF2 in miR-195-5p mimic group was decreased, and the protein levels of FGF2 in pLV-FGF2 group were enhanced (P<0.01). The protein levels of FGF2 in miR-195-5p+FGF2 group were lower than that in pLV-FGF2 group (all P<0.01). The proliferation in miR-195-5p mimic group was lower than HEC-1B group (P<0.01), while the proliferation in pLV-FGF2 group was higher than that in HEC-1B group (all P<0.01). Compared with HEC-1B group, apoptosis in miR-195-5p mimic group was increased, and apoptosis in pLV-FGF2 group was decreased (P<0.01); moreover, apoptosis in miR-195-5p+FGF2 group was higher than that in pLV-FGF2 group (P<0.01). Compared with HEC-1B group, the number of invasive cells per field and the rate of wound healing in miR195-5p mimic group were decreased, while those in pLV-FGF2 group was enhanced (P<0.01); moreover, the number of invasive cells per field and the rate of wound healing in miR-195-5p+FGF2 group was lower than those in pLV-FGF2 group (all P<0.01). Conclusion: miR-195-5p inhibits proliferation, invasion and migration and promotes apoptosis of endometrial cancer HEC-1B cells by targeting FGF2, and could be used as a treatment target of endometrial cancer.

Objective: To investigate the effect of sulforaphane (SFN) on CD8+ T cells differentiation, phenotype and the secretion of intracellular cytokines, as well as to study the underlying molecular mechanism. Methods: In the in vitro culture experiment, the cells were categorized into control group, SNF 10 mmol/L group and SNF 20 mmol/L group according to the SNF concentration. The effect of SFN treatment on CD8+ T cells differentiation, phenotype and cytokine secretion were detected by flow cytometry, and the effect of mTOR siRNA on the expression of CD127 and LKRG1 in CD8+T cells was also detected by flow cytometry. Expression of Bcl-2 and Bcl-6 were analyzed by qRT-PCR. The effect of SFN on apoptosis of CD8+T cells was examined byAnnexin-V/PI staining. The protein expressions of p-mTOR, p-S6 and b-actin were detected by western blotting. Results: SFN significantly promoted the formation of memory precursor CD8+ T cells and decreased the expression level of PD-1 and Tim-3 in CD8+T cells(P<0.01); meanwhile, after the treatment of SFN, the expressions of anti-apoptosis genes Bcl-2 and Bcl-6 were significantly increased while the apoptosis of CD8+ T cells was significantly inhibited and the protein expressions of p-mTOR and p-S6 were also significantly inhibited(P<0.05 or P<0.01). Moreover, mTOR siRNA could significantly increasethe expression of CD127 and decrease the expression of LKRG1 (all P<0.01). Conclusion: Sulforaphone promotes the formation of memory precursor CD8+T cells possibly by inhibiting the p-mTOR signaling pathway, and this could obtain more T cells to provide new thoughts for clinical immunotherapy.

[摘 要] 目的：探讨胶原三螺旋重复蛋白1（CTHRC1）在膀胱癌组织和细胞中的表达及其对膀胱癌5637细胞迁移和侵袭的影响及其机制。方法：利用TCGA和Arrayexpress数据库中膀胱癌基因表达数据，分析CTHRC1转录和翻译水平。收集2014年9月至2020年12月重庆医科大学附属第一医院手术切除的144例膀胱癌组织和25例全膀胱切除的癌旁组织标本，以及人膀胱癌细胞RT4、5637、T24、UMUC-3、TCCSUP和输尿管上皮永生化细胞SV-HUC-1。采用免疫组织化学染色法、qPCR法和WB法检测膀胱癌组织和细胞中CTHRC1的表达水平，通过Kaplan-Meier曲线分析CTHRC1表达对总生存期（OS）的影响。运用RNAi技术，敲降5637细胞CTHRC1表达后，通过细胞划痕实验和Transwell实验检测CTHRC1表达下调对5637细胞迁移和侵袭的影响。利用基因集富集分析（GSEA）预测CTHRC1相关的潜在信号通路，WB法检测敲降CTHRC1表达对FAK-ERK1/2通路相关蛋白表达的影响。结果：CTHRC1的转录和翻译水平在肌层浸润性膀胱癌（MIBC）组织和细胞中表达显著上调（均P<0.05），CTHRC1高表达组患者5年OS较低表达患者缩短（P<0.05）。干扰CTHRC1表达后，膀胱癌5637细胞迁移及侵袭能力均显著降低（均P<0.01）。GSEA预测显示，CTHRC1高表达组主要富集在黏着斑激酶（FAK）、肌动蛋白细胞骨架调节、FAK和ERK1/2信号通路。WB法实验结果表明，重组CTHRC1蛋白促进膀胱癌5637细胞FAK-ERK1/2信号通路活化（P<0.05或P<0.01）。结论：CTHRC1在MIBC中表达上调，且与膀胱癌患者不良预后密切相关；CTHRC1促进膀胱癌细胞迁移和侵袭，该过程可能与FAK-ERK1/2信号通路的激活有关。

Objective To explore the correlation between arterial total compliance indices, stroke volume/pulse pressure (SV/PP), SV adjusted by body surface area/PP (SV′/PP) and carotid-femoral pulse wave velocity (PWV), and investigate the value of SV/PP, SV′/PP in the evaluation of clinical arterial stiffness (AS). Methods Forty-five hospitalized patients with coronary heart disease (CHD) in Tangdu Hospital of Fourth Military Medical University from March to December 2016 were included in this study (CHD group). Forty-five healthy volunteers who took a health checkup in Tangdu Hospital at the same period were also included as healthy controls. SV was measured by echocardiography, and the PP was calculated through traditional blood pressure measurement. Body surface area was calculated by Du Bois formula. Carotid-femoral PWV was measured by Doppler ultrasonography. Unpaired t test was used to compare the AS indices between CHD group and healthy controls. Spearman correlation analysis was used to evaluate the correlation between SV/PP, SV′/PP and carotid-femoral PWV.Results SV/PP, SV′/PP were decreased [(1.23±0.26) ml/mmHg vs(1.37±0.27) ml/mmHg, (0.66±0.13) ml/m2?mmHg vs(0.74±0.15) ml/m2?mmHg, 1 mmHg=0.133 kPa], carotid-femoral PWV was increased [(9.49±2.05) m/s vs(8.16±1.07) m/s] in CHD patients when compared with control group with statistical significance (t=2.0971,P<0.05;t=2.1643,P<0.05;t=2.8321,P<0.01, respectively). Both SV/PP and SV′/PP in healthy controls and CHD group inversely correlated with the corresponding Carotid-femoral PWV (healthy controls:r=-0.64,-0.56, bothP<0.001; CHD group:r=-0.53, P=0.0002,r=0.61,P<0.001). While SV′/PP showed a stronger correlation with carotid-femoral PWV. Conclusions Arterial total compliance decreases and AS increases in CHD patients compared with healthy controls. SV/PP, derived from echocardiography and blood pressure measurement, correlates with carotid-femoral PWV, the″golden standard″ index of AS. After adjusted by body surface area, SV′/PP correlates more strongly with carotid-femoral PWV. SV/PP and SV′/PP are expected to provide a simple and convenient way for clinical noninvasive AS evaluation.

Objective To compare the diagnostic value of ultrasound,molybdenum target,magnetic resonance(MRI)and single examination for breast cancer.Methods From January 2017 to February 2018,100 patients with suspected breast cancer in Lishui Central Hospital were selected in the study.All patients were detected by ultrasound,mammography and MRI three ways for diagnosis.The results were verified with postoperative pathologic results as the standard.The diagnosis accuracy of three ways for breast cancer were analyzed.Results The detection accuracy of three ways joint detection in patients with breast cancer was the highest(91.00％),which was significantly higher than that of ultrasound(63.00％),mammography(72.00％)and MRI(72.00％)in single mode,the differences were statistically significant(χ2 =22.364,20.154,16.032,all P<0.05).Conclusion Ultrasonography,molybdenum target X ray and MRI have their respective advantages in the process of breast cancer differentiation and diagnosis,and the detection rate can be significantly improved if combined use.

<b>Objectiveb> To investigate the influence of renal failure on the area under curve (AUC) and adverse reactions of docetaxel in breast cancer patients, and provide evidence for the dosage of docetaxel in renal failure patients. <b>Methodsb> A retrospective study was conducted on 24 patients with breast cancer who had undergone radical mastectomy and received AC-T adjuvant chemotherapy in our hospital from January 2019 to November 2021. According to renal function cases, the patients were divided into two groups: renal failure group (n=5) and normal renal function group (n=19). The clinical characteristics such as gender, age, body weight and body surface area of patients in two groups, docetaxel dose, blood concentration, area under the curve, liver and kidney function, white blood cell count and absolute value of neutrophil before chemotherapy were collected. Single factor linear regression was used to analyze the influencing factors of the AUC of docetaxel. Adverse reactions after chemotherapy with docetaxel including nausea and vomiting, bone marrow suppression, constipation and liver function injury were collected. CTCAE 4.0 evaluation standard was used to evaluate adverse reactions. <b>Resultsb> The clinical characteristics of creatinine [908.0 (819.0, 1018.0) μmol/L vs 54.8 (52.0, 65.0) μmol/L] and creatinine clearance rate [4.9 (4.3, 5.4) ml /min vs 86.3 (59.3, 92.5) ml/min] of the renal failure group and the normal renal function group have significant difference (P<0.001), while no significant difference (P>0.05) were found in the body surface area [1.4 (1.4, 1.5) m² vs 1. 6 (1.5, 1.6) m²], docetaxel dose [70.4 (69.4, 73.0) mg/m² vs 74.4 (72.3, 91.2) mg/m²], body weight [(51.4±3.8) kg vs (51.5±5.5) kg]. Liver function, white blood cells and neutrophils were within the normal range before chemotherapy with docetaxel. There was no significant difference in AUC value [(1.6±0.6) mg·h/L vs (1.8±0.8) mg·h/L] between the two groups after chemotherapy with docetaxel (P>0.05). Linear univariate regression analysis indicated that the blood concentration at the end of docetaxel infusion was significantly associated with AUC of docetaxel (P<0.001), while the body surface area, dose of docetaxel, body weight, liver and kidney function were not correlated with AUC of docetaxel (P>0.05). After chemotherapy with docetaxel, adverse reactions of patients in the two groups: nausea and vomiting (grade I incidence: 40% vs. 57.9%, grade II incidence: 60% vs. 42.1%), myelosuppression (grade I incidence: 60% vs. 84.2%, grade II incidence: 20% vs 15.8%) and constipation (all mild constipation) had no significant difference (P>0.05). <b>Conclusionb> Renal failure did not affect the exposure of docetaxel and the adverse reactions after chemotherapy with docetaxel in breast cancer patients.

Osteoarthritis is a common degenerative disease involving articular cartilage and surrounding structures, and there is no specific therapy so far. Physical therapy has its unique features in relieving osteoarthritis symptoms, correcting deformity and promoting functional recovery. This article mainly reviewed the clinical application of physical therapy in osteoarthritis, which includes kinesitherapy, ultra-sound therapy, extracorporeal shockwave therapy, electrotherapy, pulsed electromagnetic field and whole-body vibration.

[摘 要] 目的：采用生物信息学方法探索结肠癌组织中与焦亡相关的基因，并探讨其与预后的关系，为结肠癌患者提供新的治疗靶点。方法：分别从TCGA数据库、GEO数据库中下载结肠癌患者的基因表达、转录数据及临床数据。利用R软件提取出TCGA转录数据中细胞焦亡基因的表达量，并找到差异表达基因，构建差异表达基因的蛋白互作网络。采用单因素分析、聚类分析将基因进行分型，比较两种亚型之间生存差异，得到预后相关基因。然后通过Lasso回归分析、交叉验证及优化，得到基因系数（Coef系数），构建一种结肠癌预后的预测模型。根据该预测模型计算出TCGA样本的中位风险得分，将样本分为高、低风险组。以GEO样本作为验证组，分别对TCGA、GEO样本进行生存分析（Kaplan-Meier分析）、绘制ROC曲线、绘制风险曲线、PCA和t-SNE分析。结合模型中的风险评分，分别采用单因素及多因素分析来寻找结肠癌患者的独立预后因素。对高、低风险组进行GO和KEGG分析。最后行ssGSEA分析，对每个样本进行免疫细胞及免疫相关功能打分，得到高、低风险组之间免疫细胞及免疫细胞相关功能的差异。结果：共鉴定了52个焦亡基因在结肠癌及正常结肠组织中的表达，筛选出40个差异基因。通过Cox回归和Lasso回归分析，构建了一个基于15个基因的结肠癌预后风险预测模型，并将结肠癌患者分为高、低风险两组，两组之间生存有明显差异（P<0.001）。根据预测模型计算出TCGA样本的风险评分，并得到的中位风险评分，利用GEO数据库结肠癌患者进行验证，结果显示高低风险组之间生存率存在明显差异（P=0.013）。发现预测模型计算出的风险评分是预测结肠癌患者生存的独立预后因素。对差异基因进行GO富集分析、KEGG富集分析、ssGSEA分析结果显示，高风险组患者免疫细胞浸润明显减少。结论：通过生物学信息方法构建了一个基于15个基因的结肠癌患者预后风险预测模型，这些基因在结肠癌免疫中也发挥重要作用。

[摘 要] 目的：探讨甲基转移酶样因子3（METTL3）在食管鳞状细胞癌（ESCC）组织和细胞中的表达水平及其对ESCC细胞糖酵解和增殖能力的影响和潜在的分子机制。方法：基于TCGA数据库分析METTL3在ESCC细胞中的表达及可能的富集通路。收集2021年1月至2021年6月间在北川医学院附属医院外科手术切除的34例ESCC组织及相应癌旁组织，采用免疫组化法验证ESCC组织中METTL3的表达。采用CCK-8法和平板克隆形成实验检测干扰METTL3后ESCC细胞增殖能力的变化，利用比色法检测干扰METTL3后ESCC细胞总RNA中m6A的表达水平，采用甲基化RNA免疫沉淀定量PCR（MeRIP-qPCR）检测METTL3对葡萄糖转运蛋白4（GLUT4）基因mRNA的m6A修饰水平的影响，采用WB和qPCR等技术探索METTL3参与ESCC细胞糖酵解的生物学机制。结果：METTL3在ESCC组织以及细胞中均呈高表达（均P<0.001）。干扰METTL3表达后，ESCC细胞的增殖能力明显减弱、细胞内总RNA的m6A修饰水平显著降低（均P<0.001）。此外，干扰METTL3可显著抑制KYSE150和TE-1细胞中GLUT4基因mRNA的m6A修饰水平（均P<0.01），并通过下调GLUT4的表达抑制葡萄糖的摄取以及乳酸的释放（均P<0.01），最终下调mTORC1通路活性并抑制ESCC细胞的增殖；在干扰METTL3的ESCC细胞同时联合运用mTORC1通路抑制剂显示有协同的抗癌作用。结论：METTL3介导的m6A修饰通过调控GLUT4-mTORC1信号轴影响ESCC细胞的糖酵解及增殖。

[Abstract] Objective: To explore the relationship between cerebral endothelial cell adhesion molecule (CERCAM) and prognosis of colon cancer patients, so as to establish a nomogram with good prognostic value by using Cox model and verify its diagnostic value. Methods: The expression profile of CERCAM in colon cancer tissues and normal tissues as well as clinicopathologic data of colon cancer patients were downloaded from TCGA and GTEx databases. At the same time, colon cancer and paracancerous tissue samples collected from 4 colon cancer patients admitted to Nanjing First Hospital from Feburary 2013 to June 2019 were used for verification. Firstly, differential analysis, pathway enrichment analysis, and survival analysis were performed to investigate the tissue localization, functional and prognostic value of CERCAM expression. In addition, Cox regression analyses was conducted to screen the risk factors for the prognosis of colon cancer. A nomogram was established based on CERCAM and various risk factors, and was verified and evaluated by concordance indices, calibration curves, and time-dependent receiver operating characteristic (ROC) curves. In addition, the survival curves were plotted according to risk stratification. Results: The expression of CERCAM in colon cancer tissues was significantly lower than that in normal tissues (P<0.001). The overall survival (P=0.032) and survival status (P=0.002) of colon cancer patients with high CERCAM expression level was significantly inferior to those with low CERCAM expression level. CERCAM was correlated with the activation of proteoglycans in cancer and PI3K-Akt signaling pathway. Cox analysis showed that CERCAM expression level (HR=2.22, P=0.015), T stage (HR=5.65, P=0.015), M stage (HR=2.62, P=0.022) were independent risk factors for prognosis of colon cancer, while vascular infiltration (HR=2.30, P=0.089) was a risk factor as well. Based on the above factors, a nomogram was established. The concordance indices suggested good discrimination of the nomogram, and the training set was consistent with the test set. The calibration curves and ROC curves also indicated good predictive ability of the nomogram. Survival curves plotted according to risk stratification suggested that the high-risk group had lower survival rates (P<0.000 1). Conclusion: High level CERCAM expression is correlated with the poor prognosis of colon cancer patients, which is possibly associated with proteoglycans in cancer and PI3K-Akt signal pathway. The nomogram established based on CERCAM is superior to the traditional prediction model, which has certain clinical value in predicting survival prognosis of colon cancer patients. This practical model is helpful for the risk stratification and the optimization of treatment plan.