Purpose To investigate the correlation of Dock180 and miR-31 expression in breast cancer cells,and to observe the effect of miR-31 on the invasion of breast cancer cells by Dock180.Methods MiR-31 was transfected into breast cancer cells by liposome transfection technique.The actual binding site of miR-31 to the 3'-untranslated region of Dock180 was confirmed through luciferase assay.Western blot was performed to detect the expression of Dockl80 and other related proteins.Real-time PCR was used to measure the expression of Dock180.Matrigel invasion were performed to detect the invasion of breast cancer cell lines with miR-31 increased.Resuits The protein levels of Dock180 in breast cancer cell lines negatively correlated with miR-31 expression,and Dock180 was directly targeted by miR-31.Dock180 downregulation and miR-31 overexpression reduced breast cancer cells invasion.Conclusion Dock180 modulated by miR-31 plays an important function in breast cancer cell lines invasion.

Objective To observe the effects of Qingjiefang on insulin resistance and reduction of microalbuminuria in early diabetic nephropathy.Methods A total of 64 patients with early diabetic nephropathy were randomly recruited into a control group and a treatment group.The control group(32 cases)was treated with conventional western medicine,while the treatment group(32 cases)was treated with Qingjiefang based on the control group.The changes of the fasting plasma glucose(FPG),2hBG,glycosylated hemoglobin(HbAlC),fasting Insulin(FINS),24 hours urinary albumin excretion rate (UAER).body mass index(BMI)and insulin resistance(IR)were observed before and after the treatment.Results After the treatment,FINS,IR and UAER were decreased in the treatment group,the comparison with the control group showed significant difference (P<0.05).Conclusion Qingjiefang can effectively improve insulin resistance and prevent early diabetic nephropathy.

Objective To evaluate the impact of early enteral nutrition (EEN) compared with parenteral nutrition (PN) on patients after hepatectomy. Methods Seventy-eight patients undergoing liver resection were randomized prospectively into two groups: EEN group receiving early enteral nutrition (n=35) and PN group receiving parenteral nutrition (n=43). The patients in both groups received isocaloric and isonitrogenous nutritional formulas 24 h after operation and the formulas were stopped on postoperative day 7. The general conditions, liver function tests, clinical complications,and clinical nutritional variables at three time points that included preoperative phase, postoperative day 1 (POD 1) and postoperative day 8 (POD 8) were observed. Results No significant differences were found in length of hospital stay, liver function and clinical nutritional variables between the 2 groups. In the EEN group, the serum prealbumin level almost returned to the preoperative level on POD 8. The nutritional complication rate of the EEN group was increased significantly but it was milder than that of the PN group. The time of gut function recovery in the EEN group was shorter than that of the PN group. The costs of nutritional drugs showed a significant decrease in the EEN group.Conclusion Early enteral nutrition is safe, rational and effective in patients who have undergone hepatectomy. Early enteral nutrition is better than parenteral nutrition in promoting liver function recovery, liver protein synthesis, postoperative recovery of gut function and decreasing costs of nutritional drugs.

Background and purpose:Nir1 is a transmembrane receptor for chemokine (C-C motif) ligand 18. CCL18 speciifcally binds to Nir1 at the cellular membrane of breast cancer cells to exert its invasion and metastasis. However, the speciifc mechanism of Nir1 is not clear in glioma. This study probed the effect and mechanism of Nir1 in the invasion of glioma cells.Methods:Western blot was used to detect the expression of Nir1 in glioma cells. siRNA plasmid was used to transfect U251 cells. Western blot was used to analyze the expression of Nir1 and protein phosphorylation of Akt in the cells transfected by Nir1 plasmid.In vitro Matrigel invasion assay was used to detect the invasive ability in the cells that were transfected. F-actin polymerization assay was used to detect F-actin recognition ability in cells.Results:The expression of Nir1 was higher in all glioma cells. After transfection, the invasion of siNir1/U251 was obviously decreased than the SCR/U251, F-actin content was reduced compared to the control group. Akt phosphorylation experiment result showed that the protein phosphorylation of Akt was enhanced in control group cells CCL18 following stimulation. However, the existence of CCL18 would affect the phosphorylation of Akt in siNir1/U251.Conclusion:Nir1 is high expression in glioma cells, and Nir1 binding to chemokine CCL18 promotes glioma cells invasion and metastasis through regulation the phosphorylation of Akt and F-actin polymerization .

Objective:To investigate the value of multi-stage dynamic contrast enhanced MRI (DCE-MRI) histogram in predicting survival of patients undergoing surgical treatment of colorectal cancer (CRC).Methods:The retrospective cohort study was conducted. The clinico-pathological data of 81 patients with CRC who were admitted to the Jiuquan City People′s Hospital from January 2018 to February 2019 were collected. There were 47 males and 34 females, aged (62±6)years. All patients underwent routine MRI and DCE-MRI examination to extract relevant imaging parameters. Observation indicators: (1) treatment, imaging examination and follow-up; (2) imaging factors influencing postoperative disease-free survival of patients with CRC. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Univariate and multivariate analyses were conducted using the COX proportional risk model. Pearson correlation test was used to analyze and exclude factors with correlation in univariate analysis, and the multi-variate analysis was conducted on the rest of factors. The Kaplan-Meier method was used to calculate survival rates, and Log-Rank test was used for survival analysis. Results:(1) Treatment, imaging examination and follow-up. All 81 patients underwent preoperative MRI plain scan, enhanced imaging, and diffusion weighted imaging. After complete examination, all patients underwent radical resection of CRC and received postoperative chemotherapy using the FOLFOX regimen. All 81 patients were followed up for 42(range, 11-61)months after surgery. The 1-, 3-, 5-year overall survival rate of 81 patients after surgery was 98.8%, 96.3%, 93.8%, respectively. During the follow-up period, 56 of the 81 patients survived from disease-free and 25 patients had disease progressed. (2) Imaging factors influencing postoperative disease-free survival of patients with CRC. Results of multivariate analysis showed that the kurtosis value and skewness value of positive enhancement integral (PEI) were independent imaging factors influencing postoperative disease-free survival of patients of CRC ( odds ratio=1.840, 1.243, 95% confidence interval as 1.403-2.412, 1.020-1.516, P<0.05). Taking the median values of kurtosis value and skewness value of PEI as 4.864 and 5.042 for further analysis. The postoperative 5-year disease-free survival rate of patients with kurtosis value of PEI <4.864 and ≥4.864 was 89.7% and 10.3%, showing a significant difference between them ( χ2=31.265, P<0.05). The postoperative 5-year disease-free survival rate of patients with skewness value of PEI<5.042 and ≥5.042 was 63.4% and 36.6%, showing a significant difference between them ( χ2=8.164, P<0.05). Conclusions:The kurtosis value and skewness value of PEI in DCE-MRI are independent imaging factors influencing postoperative disease-free survival of patients of CRC. The DCE-MRI histogram can effectively evaluate the postoperative prognosis of patients of CRC.

OBJECTIVETo study the clinical significance of changes of serum myocardial enzymes in patients with acute carbon monoxide poisoning.

METHODSTo determine the dynamic changes of the activity of myocardial enzymes and ECG in 62 patients with acute CO poisoning.

RESULTSIn patients with acute CO poisoning 5 kinds of myocardial enzymes begin to increase within 24 hours, the activities of aspartate aminotransferase (AST), creatine phosphokinase (CPK), lactic dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (alpha-HBDH), CPK isoenzyme (CK-MB) were (20.2 +/- 12.3), (151.6 +/- 91.8), (146.8 +/- 50.4), (154.8 +/- 47.7), (13.8 +/- 8.1) U/L respectively, while those in control group were (12.1 +/- 6.7), (90.6 +/- 17.3), (118.7 +/- 13.5), (89.9 +/- 27.9), (5.9 +/- 3.3) U/L respectively. There was significant difference between two groups (P < 0.01); 3 d later, the activities of 5 enzymes were still increased [(21.3 +/- 12.3), (105.8 +/- 51.4), (144.8 +/- 51.4), (159.8 +/- 35.4), (16.2 +/- 9.1) U/L respectively]. 7 and 12 d later, the activities of alpha-HBDH and CK-MB were still higher than those of control (P < 0.01). LDH(1) and LDH(2) increased to peak value in 24 h after poisoning (35.3 +/- 5.8), (43.8 +/- 5.7) U/L vs (24.8 +/- 3.9), (36.9 +/- 4.3) U/L, P < 0.01. The abnormal rate of serum LDH(1) was 78.7%, LDH(2) 58.3%, LDH 45.2%, CK-MB 37.1%, alpha-HBDH 33.6% and the abnormal rate of ECG was less than 10%.

CONCLUSIONAcute carbon monoxide poisoning may cause myocardial injury. Determination of serum myocardial enzymes may contribute to showing myocardial injury, early diagnosis and treatment, results of treatment and prognosis.

Adult ; Carbon Monoxide Poisoning ; blood ; enzymology ; Creatine Kinase ; blood ; Creatine Kinase, MB Form ; Female ; Humans ; Hydroxybutyrate Dehydrogenase ; blood ; Isoenzymes ; blood ; L-Lactate Dehydrogenase ; blood ; Male ; Middle Aged ; Myocardium ; enzymology

BACKGROUND: Fibroblast activation protein (FAP) is one of the surface markers of cancer-associated fibroblasts (CAFs) and is closely related to the malignant characterization of CAFs. SP13786 is a specific micromolecule inhibitor of FAP and this study is to investigate the effects and mechanism of SP13786 on the migration and invasion of A549 cells through regulating exosomes of CAFs. METHODS: CAFs and paracancerous fibroblasts (PTFs) were isolated and subcultured from freshly resected lung adenocarcinoma tissues and paracancerous normal tissues separately. MTT assay was used to detect the proliferation of CAFs incubated by different concentrations of SP13786; PTFs-exo, CAFs-exo and CAFs+SP13786-exo were extracted by polymer precipitation method. The A549 cells were divided into Ctrl group, PTFs group, CAFs group and SP13786 group and each group was incubated with DMEM, PTFs-exo, CAFs-exo and CAFs+SP13786-exo separately. Laser confocal microscope was used to observe the endocytoses of exosomes by A549 cells. The expression of alpha-smooth muscle actin (α-SMA) and FAP in PTFs and CAFs and the expression of E-cadherin, N-cadherin, Slug, Stat3 and P-Stat3 in A549 cells were detected by immunofluorescence, immunohistochemistry and Western blot. The migration and invasion ability of A549 cells were detected by cell scratch and transwell methods. RESULTS: α-SMA and FAP were expressed much higher in CAFs than that in PTFs which indicate that CAFs and PTFs were successfully obtained from lung adenocarcinoma and paracancerous tissues (P<0.05). MTT showed that the 50% inhibitory concentration (IC50) of SP13786 for CAFs was about 3.3 nmol/L. In addition, SP13786 can significantly decrease the expression of α-SMA and FAP in CAFs which means that targeted inhibition of FAP could reduce the malignant characteristics of CAFs (P<0.05). Laser confocal microscope found that exosomes from CAFs could be taken up by A549 cells and scratch and transwell tests showed that the endocytosed CAFs-exo could promote the migration and invasion of A549 cells (P<0.001), while FAP inhibitor SP13786 could inhibit the effects of CAFs-exo on A549 cells (P<0.05). Furthermore, Immunofluorescence and Western blot showed that CAFs-exo could promote EMT by decreasing E-cadherin expression and increasing N-cadherin, Slug expression in A549 cells while FAP inhibitor SP13786 could significantly supress CAFs-exo-induced epithelial-mesenchymal transition (EMT) of A549 cells (P<0.05). Moreover, the expression of P-Stat3 was obviously increased in A549 cells of CAFs group and significantly down-regulated in SP13786 group (P<0.05) whereas there was no significant difference in total Stat3 between CAFs and SP13786 groups (P>0.05). Finally, WP1066 (a specific inhibitor of Stat3) was used to comfirm whether SP13786 could influence EMT of A549 cells by inhibiting Stat3 phosphorylation via CAFs-Exo. The results showed that when the phosphorylation of Stat3 in CAFs group was inhibited by WP1066, SP13786 could not influence the P-Stat3 expression and EMT of A549 cells anymore (P>0.05). CONCLUSIONS As a specific micromolecule inhibitor of FAP, SP13786 indirectly inhibits the migration and invasion of A549 cells by affecting exosomes of CAFs. The possible mechanism is to inhibit the phosphorylation of Stat3 and thus affect the EMT of A549 cells.

Objective: To investigate the association between congenital hypothyroidism (CH) and the adverse outcomes during hospitalization in very low birth weight infants (VLBWI). Methods: This prospective, multicenter observational cohort study was conducted based on the data from the Sino-northern Neonatal Network (SNN). Data of 5 818 VLBWI with birth weight <1 500 g and gestational age between 24-<37 weeks that were admitted to the 37 neonatal intensive care units from January 1^st, 2019 to December 31^st, 2022 were collected and analyzed. Thyroid function was first screened at 7 to 10 days after birth, followed by weekly tests within the first 4 weeks, and retested at 36 weeks of corrected gestational age or before discharge. The VLBWI were assigned to the CH group or non-CH group. Chi-square test, Fisher exact probability method, Wilcoxon rank sum test, univariate and multivariate Logistic regression were used to analyze the relationship between CH and poor prognosis during hospitalization in VLBWI. Results: A total of 5 818 eligible VLBWI were enrolled, with 2 982 (51.3%) males and the gestational age of 30 (29, 31) weeks. The incidence of CH was 5.5% (319 VLBWI). Among the CH group, only 121 VLBWI (37.9%) were diagnosed at the first screening. Univariate Logistic regression analysis showed that CH was associated with increased incidence of extrauterine growth retardation (EUGR) (OR=1.31(1.04-1.64), P<0.05) and retinopathy of prematurity (ROP) of stage Ⅲ and above (OR=1.74(1.11-2.75), P<0.05). However, multivariate Logistic regression analysis showed no significant correlation between CH and EUGR, moderate to severe bronchopulmonary dysplasia, grade Ⅲ to Ⅳ intraventricular hemorrhage, neonatal necrotizing enterocolitis in stage Ⅱ or above, and ROP in stage Ⅲ or above (OR=1.04 (0.81-1.33), 0.79 (0.54-1.15), 1.15 (0.58-2.26), 1.43 (0.81-2.53), 1.12 (0.70-1.80), all P>0.05). Conclusion: There is no significant correlation between CH and in-hospital adverse outcomes, possibly due to timely diagnosis and active replacement therapy.
Infant ; Male ; Infant, Newborn ; Humans ; Female ; Prospective Studies ; Congenital Hypothyroidism/epidemiology* ; Risk Factors ; Infant, Very Low Birth Weight ; Birth Weight ; Gestational Age ; Retinopathy of Prematurity/epidemiology* ; Infant, Newborn, Diseases ; Hospitals

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone