Objective To explore the effect of toremifene on estrogen receptor （ER） expression and tumor micro-angiogenesis in rat Lewis lung carcinoma. Methods Cell suspension of rat Lewis lung carcinoma was implanted into 40 female Wistar rats subcutaneously. The rats were randomly divided into a control group，a estradiol group （0.006 mg/mL），a low dose toremifene group （0.25 mg/mL） and a high dose toremifene group （5 mg/mL）. Tumor size was measured every 3 days and the tumor growth curve was charted. On 15th day，the tumor weight and the growth inhibition rate were measured. Immunohistochemical method was used to detect the expressions of estrogen receptor α （ERα），estrogen receptor β （ERβ），vascular endothelial growth factor （VEGF），and platelet endothelial cell adhesion molecule-1 （PECAM-1）. Integral optical density （IOD） of ERα，ERβ and VEGF was calculated by image analysis software. Quantitative method of Weidner with PECAM-1 was employed for microvessel density （MVD） count. Results Tumor size of the four groups all presented a quadratic function growth trend with time （Plt;0.05）. Tumor growth speed was slower in toremifene groups of low and high doses than that in the control group and the estradiol group. The growth inhibition rate of the estradiol group，the low dose toremifene group and the high dose toremifene group was －15.1%，22.6%，and 45.1%，respectively. The expressions of ERα，VEGF，and MVD in the estradiol group were significantly higher than those in the control group，the low dose toremifene group and the high dose toremifene group （all Plt;0.05）. The expressions of ERα，VEGF，and MVD in the low dose toremifene group were significantly lower than those in control group，but higher than those in high dose toremifene group （all Plt;0.05）.The expression of ERα was positively related to VEGF （r=0.664，Plt;0.05） and MVD（r=0.593，Plt;0.05）. Conclusion Toremifene can inhibit tumor growth，which maybe involved in inhibiting ERα mediated VEGF expression.
Objective To study the method to inhibit perioperative internal mammary artery (IMA) spasm from the perspective of muscarinic receptor, and research the function of muscarinic cholinergic receptor subtypes of IMA. Methods IMA segments in vitro with intact endothelium were obtained from 30 patients who underwent coronary artery bypass grafting (CABG). According to muscarinic receptor antagonists of different concentrations， They were divided into control group (not using receptor antagonist), atropine group (nonselective M receptor antagonist), pirenzepine group (M1 receptor antagonist) and Methoctramine group(M2 receptor antagonist) by random number table. The effects of antagonists on vasodilatation were analyzed, Scott ratio was used to calculate affinity index (pD2) and Schild plot was used to count rivalry index (pA2). Results Acetylcholine (Ach)induced concentrationdependentrelaxation response of IMA segments with intact endothelium precontracted with potassium chloride (KCl). The pD2 was 6.92±0.05. The effects of atropine, pirenzepine and methoctramine on doseresponse curve induced by Ach with intact endothelium were all concentrationdependent. With the increase of the concentration of antagonists, the Achinduced doseresponse curves had a significant shift to right(Plt;0.05). Atropine, pirenzepine and Methoctramine competitively antagonized the reaction of vessel to Ach. The pA2 were 9.62±0.15,7.70±0.08 and 630±0.08, respectively. Conclusion The Achinduced relaxation response of IMA with intact endothelium is concentrationdependent. According to the affinity of different antagonist, IMA in Vitro Achinduced relaxation response is implemented by acting on nonneuronal muscarinic cholinergic M1 receptor subtype.
Objective To study the relationships between expressions of somatostatin receptor subtypes（SSTR1-SSTR5） and angiogenesis in colorectal cancer. Methods The expressions of SSTR1-SSTR5, VEGF, and CD34 in the paraffin sections of colorectal cancer tissues from 127 cases were detected by the standard streptavidin-peroxidase (SP) technique. CD34 was used as a marker to account microvessel density (MVD) in colorectal cancer tissues. The relationships between the expressions of SSTR1-SSTR5 and VEGF expression, or MVD were analyzed. Results The positive expression rate of SSTR1, SSTR2, SSTR3, SSTR4, and SSTR5 was 64.6% （82/127）, 36.2% （46/127）, 18.9% （24/127）, 18.9% （24/127）, and 38.6% （49/127） in colorectal cancer tissues, meanwhile, the positive expression rate of VEGF was 63.8% （81/127） and MVD was (34.67±16.62)/HP in colorectal cancer tissues. The positive expression rate of VEGF (47.8%， 22/46) and MVD 〔(29.00±15.32)/HP〕 in colorectal cancer tissues with SSTR2 positive expression were significantly lower than those in colorectal cancer tissues with SSTR2 negative expression 〔72.8%， 59/81； (37.90±16.56)/HP〕, Plt;0.05. There were no relationships between SSTR1, SSTR3, SSTR4, and SSTR5 expression and VEGF expression or MVD （Pgt;0.05）. Conclusion The positive expression of SSTR2 is related with angiogenesis in colorectal cancer tissues.
Objective To investigate the expression of phosphate and tension homology deleted on chromsome ten (PTEN) and Basigin1, as well as their relationships with clinicopathological factors and molecular subtypes in invasive ductal carcinoma of breast. Methods The expressions of PTEN and Basigin1 protein were examined in 76 invasive ductal carcinoma of breast tissues by immunohistochemical method, and 20 breast benign hyperplasia tissues as control. These 76 patients underwent surgery in our hospital from Jan. 2014 to Dec. 2015. Results The high-expression rate of PTEN protein in invasive ductal carcinoma of breast tissues was lower than that in benign hyperplasia tissues [56.6% (43/76) vs. 85.0% (17/20), χ2=5.457, P=0.019], while the high-expression rate of Basigin1 protein was higher than that of the benign hyperplasia tissues [51.3% (39/76) vs 25.0% (5/20), χ2=4.417, P=0.036]. The high-expression of PTEN protein was positively correlated with WHO grade and lymph node metastasis status (P<0.05). The high-expression of Basigin1 protein was positively correlated with WHO grade, lymph node metastasis status, and TNM stage (P<0.05). In addition, the high-expression of PTEN protein was associated with molecular subtypes of breast cancer (P<0.001), and its high-expression rate was higher in Luminal A and Luminal B patients; the high-expression of Basigin1 protein was associated with molecular subtypes of breast cancer too (P<0.001), and the high-expression rate of Basigin1 protein was higher in Her-2 overexpression and basal-like subtypes of breast cancer patients. Spearman correlation analysis shown that expression of PTEN protein was negatively correlated with expression of Basigin1 protein (rs=–0.481, P<0.001). Conclusion PTEN and Basigin1 protein may have some mechanisms to promote the occurrence and development of breast cancer, which provide a new basis for targeted treatment of breast cancer.
ObjectiveTo isolate and culture cartilage derived stem cells from different subtypes of cartilages, and to identify their characteristics. MethodsCartilage derived stem cells were isolated from different subtypes of cartilages (auricle cartilage, articular cartilage, and intervertebral cartilage) by using adhesive method of fibronectin. The expressions of positive surface markers (CD29 and CD90) and negative surface markers (CD34 and CD45) in cartilage derived stem cells were detected via flow cytometry. The single cell colony-forming efficiency of cartilage derived stem cells was determined by clonal formation unit test; the multipotent differentiation capacity was identified by chondrogensis, osteogenesis, and adipogenesis induction. RT-PCR was used to test the expression of osteogenic, chondrogenic, and adipogenic genes; and bone marrow mesenchymal stem cells (BMSCs) served as control. ResultsThree cell populations were successfully isolated from different subtypes of cartilages, which could express CD29 and CD 90 highly, but did not express CD34 and CD45. After 2 weeks of culture, single cartilage derived stem cell could form single cell colony. In addition, cartilage derived stem cells had high chondrogenesis, osteogenesis, and adipogenesis potentials. After osteogenic induction, the expressions of collagen type Ⅰ and collagen type X in articular and intervertebral cartilage stem cells were significantly higher than those in BMSCs (P<0.05), while there was no significant difference between auricular cartilage stem cells and BMSCs (P>0.05). The expressions of Aggrecan and collagen type Ⅱ in cartilage derived stem cells after chondrogenic induction were significantly higher than those in BMSCs (P<0.05). While the ability of adipogenic differentiation was lower than that in BMSCs, but no significant difference was found (P>0.05). ConclusionCartilage derived stem cells in different subtypes of cartilages possess typical characteristics of stem cells.
ObjectiveTo investigate the regulatory roles and changes of M3 receptor subtype in lipopolysaccharide (LPS)-preincubated rabbit pulmonary arteries, and assess the mechanism of altered vascular reactivity in septic shock. MethodsPulmonary arteries with intact endothelium were isolated from 26 male New ealand white rabbits weighing 2.0 to 2.5kg. he isolated pulmonary arteries were randomized into two grouops, including a normal group with normal saline and darifenacin adminstration, and an endotoxin group with LPS-preincubation and darifenacin adminstration.he response of arteries to phenylephrine (100μmol/L) and acetylcholine(ACH)(1μmol/L, 10μmol/L, 100μmol/L)were measured in normal and darifenacin-preincubated circumstances. ResultsThe percentages of ralaxation to ACH (1μmol/L, 10μmol/L, 100μmol/L) were (0.095±0.034)%, (0.150±0.036)%, and (0.445±0.090)% in the normal group, and (0.044±0.016)%, (0.093±0.029)%, (0.311±0.028)% in the endotoxin (LPS 4μg/mL, 4h) group. After pretreatment with M3 receptor antagonist darifenacin on different concentrations, the EC50 values responding to ACH (1μmol/L, 10μmol/L, 100μmol/L) were 1.483, 2.757, 2.958 in the normal group, and 6.015, 6.242, 6.411 in the endotoxin group. After pretreatment with M3 receptor antagonist darifenacin on different concentrations, the inherent activity of a value to ACH (1μmol/L, 10μmol/L, 100μmol/L) were 0.0146, 0.0323, 0.0825 in the normal group, and 0.0124, 0.0245, 0.0556 in the endotoxin group. ConclusionsLPS pre-incubation can reduce the relaxation response to ACH, and M3 receptor subtypes mediated this relaxation response. LPS also reduce the M3 receptor subtype intrinsic activity, which may be one of the mechanisms of decreased relaxation response to ACH in pulmonary arteris after LPS pretreatment, and also one of the mechanisms of pulmonary hypertension in septic shock.
ObjectiveTo investigate the correlation between histological subtypes of invasive lung adenocarcinoma and epithelial growth factor receptor (EGFR) gene mutation, and to provide a reference for clinical prediction of EGFR gene mutation status.MethodsFrom October 2017 to May 2019, 102 patients with invasive lung adenocarcinoma were collected, including 58 males and 44 females aged 62 (31-84) years. Invasive lung adenocarcinoma was classified into different histological subtypes. Scorpion probe amplification block mutation system (ARMS) real-time PCR was used to detect the mutation of EGFR gene in adenocarcinoma specimens, and the relationship between invasive lung adenocarcinoma subtypes and EGFR mutation status was analyzed.ResultsIn 102 patients with invasive lung adenocarcinoma, EGFR gene mutations were detected in 68 patients, and the mutation rate was 66.7% (68/102). The mutation sites were mainly concentrated in the exons 19 and 21; the mutation rate was higher in female patients (34/44, 77.3%) and non-smokers (34/58, 58.6%). EGFR mutation was mostly caused by acinar-like invasive lung adenocarcinoma, and was rare in solid-type lung adenocarcinoma. The EGFR gene mutation rates in different subtypes of adenocarcinoma were statistically different (P<0.05).ConclusionThe EGFR mutation status is related to gender, smoking status and histological subtype of invasive lung adenocarcinoma. EGFR mutation rates are higher in female, non-smoking and acinar-like invasive lung adenocarcinoma patients, and are lower in patients with solid type lung adenocarcinoma.
Objective To explore the relationship between the metastatic sites and prognosis in newly diagnosed stage Ⅳ breast cancer. Methods The data of newly diagnosed female patients with stage Ⅳ invasive breast cancer with complete follow-up data from SEER database from 2010 to 2015 were grouped according to different metastatic sites, and the differences of breast cancer-specific survival (BCSS) in different metastatic sites were analyzed by univariate and multivariate Cox. Kaplan-Meier method was used to draw the survival curve, and log-rank test was used to analyze the prognostic factors of BCSS in newly diagnosed stage ⅳ breast cancer. Results A total of 8 407 patients were included in the final analysis. Among them, 5 619 (66.84%) patients were confirmed with bone metastasis only, 1 483 (17.64%) patients with lung metastasis only, 1 096 (13.04%) patients with liver metastasis only, and 209 (2.49%) patients with brain metastasis only. The median follow-up time was 22 months, with 4 180 (49.72%) breast cancer-related deaths and a median BCSS of 39 months in those patients. The location of metastasis in newly diagnosed stage Ⅳ invasive breast cancer was significantly correlated with BCSS (χ2=151.07, P<0.001). Multivariate Cox model analysis showed that the BCSS was worse in patients with liver metastasis [HR=1.34, 95%CI (1.21, 1.49), P<0.001], lung metastasis [HR=1.09, 95%CI (1.04, 1.14), P<0.001] and brain metastases [HR=1.28, 95%CI (1.20, 1.36), P<0.001] than in patients with bone metastases. Further subgroup analysis showed that the BCSS of breast cancer patients with different molecular subtypes and different metastatic sites were also significantly different (P<0.05). Patients with brain and liver metastases in the HR+/HER2– subtype had worse BCSS than those with bone metastases (P<0.001). Patients with brain metastases in the HR+/HER2+ subtype had worse BCSS than those with bone metastases (P=0.001). In HR–/HER2+ subtype, the BCSS of patients with liver metastasis, lung metastasis and brain metastasis were worse than that of patients with bone metastasis (P<0.05). In HR–/HER2– subtype, the BCSS of patients with brain metastasis and liver metastasis were worse than that of patients with bone metastasis (P<0.05) . Conclusion The prognosis of newly diagnosed stage ⅳ breast cancer patients with different metastatic sites is different, and the prognosis of different molecular subtypes and different metastatic sites is also different.
ObjectiveTo investigate the effect of breast conservation therapy (BCT) and mastectomy (Mast) on the prognosis of early luminal breast cancer (ELBC).MethodsBy retrieving the PubMed, Embase, Web of Science, CNKI, Wanfang data, and VIP databases, the meta-analysis was performed on the documents that met the inclusion criteria. The Review Manager 5.3 and Stata 12.0 were used for statistical analysis.ResultsA total of 25 articles were included, involving 13 032 patients with ELBC, of which 8 419 underwent the BCT and 4 613 underwent the Mast. The results of meta-analysis showed that there was no significant difference in the postoperative local regional relapse (LRR) between the BCT and the Mast in the treatment of all patients with ELBC [OR=0.84, 95% CI (0.43, 1.64), P=0.61]. For treating with BCT, the local relapse (LR), distant metastasis rate (DMR), disease-free survival (DFS), and overall survival (OS) in the patients with luminal A ELBC were better than those in the patients with luminal B ELBC (P<0.05); Using the same method, the DMR and DFS in the patients with luminal A/B ELBC were better than those in the patients with luminal-HER2 ELBC (P<0.05). For treating with Mast, the LRR, LR, DMR, and OS in the patients with luminal A ELBC were better than those in the patients with luminal B ELBC (P<0.05); Using the same method, the LRR in the patients with luminal A/B ELBC was better than that in the patients with luminal-HER2 ELBC (P<0.05).ConclusionsFor patients with ELBC, similar LRR can be obtained by BCT and Mast treatment. Regardless of the surgical strategy, patients with luminal A ELBC are more likely to obtain relatively ideal clinical prognosis. Luminal-HER2 ELBC has the worst prognosis after BCT treatment.
Objective To explore the white matter microstructural abnormalities in patients with different subtypes of attention-deficit/hyperactivity disorder (ADHD) and establish a diagnostic classification model. Methods Patients with ADHD admitted to West China Hospital of Sichuan University between January 2019 and September 2021 and healthy controls recruited through advertisement were prospectively selected. All participants underwent diffusion tensor imaging scanning. The whole brain voxel-based analysis was used to compare the diffusion parameter maps of fractional anisotropy (FA) among patients with combined subtype of ADHD (ADHD-C), patients with inattentive subtype of ADHD (ADHD-I) and healthy controls. The support vector machine classifier and feature selection method were used to construct the individual ADHD diagnostic classification model and efficiency was evaluated between each two groups of the ADHD patients and healthy controls. Results A total of 26 ADHD-C patients, 24 ADHD-I patients and 26 healthy controls were included. The three groups showed significant differences in FA values in the bilateral sagittal stratum of temporal lobe (ADHD-C<ADHD-I<healthy controls) and the isthmus of corpus callosum (ADHD-C>ADHD-I>healthy controls) (P<0.005). The direct comparison between the two subtypes of ADHD showed that ADHD-C had higher FA than ADHD-I in the right middle frontal gyrus. The classification model differentiating ADHD-C and ADHD-I showed the highest efficiency, with a total accuracy of 76.0%, sensitivity of 88.5%, and specificity of 70.8%. Conclusions There is both commonality and heterogeneity in white matter microstructural alterations in the two subtypes of patients with ADHD. The white matter damage of the sagittal stratum of temporal lobe and the corpus callosum may be the intrinsic pathophysiological basis of ADHD, while the anomalies of frontal brain region may be the differential point between different subtypes of patients.