Objective To investigate the effect and underlying mechanism of single,fractioned and continuous low dose rate radiation on CL187 colorectal cancer cell line.Methods CL187 cells were exposed to 6 MV X-rays at a high dose rate of 4 Gy/min and 125Ⅰ seed at a low dose rate of 2.77 cGy/h with three groups:single dose radiation group (SDR),fractioned dose radiation group (FDR) by 2 Gy/f,and continuous low dose rate radiation group (CLDR).The radiation doses were 0,2,4 and 8 Gy.Total cell number and cell viability were determined by trypan blue.Clone forming assay was used to evaluate the cell proliferation ability.The percentage of apoptosis cells was analyzed by flow cytometry.Western blot was used to detect the protein expression levels of PHLPP2,PTEN and Bax.Results Compared with SDR and FDR groups,the total cell number and survival fraction of CLDR group decreased.The relative biological effect (RBE) for 125Ⅰ seeds compared with 6 MV X-rays was 1.41.The percentage of apoptosis cells of CLDR group was significantly increased (t =-15.08,-11.99,P ＜ 0.05).The expression level of Bax increased in CLDR group,while no obvious changes were observed on PHLPP2 and PTEN among three groups.Conclusions The expression level of PHLPP2 increaseS in SDR,FDR and CLDR group,while it seems that it was not influenced by dose rate.The expression level of Bax increased in three groups,while more colorectal CL187 cells in CLDR group may be killed due to the increase of Bax expression.

Objective To investigate the combination effect of cetuximab and irradiation on colorectal carcinoma CL187 cell line and underlying molecular mechanism.Methods CL187 cells with or without cetuximab treatment were irradiated by 0,4 and 8 Gy X-rays,then cell death percentage was determined by MTT 24 and 48 h post-irradiation.Clone forming assay was used to evaluate the cell reproliferation ability.Cell cycle distribution,apoptosis,and necrosis were analyzed by flow cytometry.Western blot was used to detect the protein expressions of DNA-PKcs,Ku70 and Ku80.Results The cetuximab enhanced the percentage of radiation-induced cell death,while descreased the cloning formation capacity and increased radiosenvtivity (t =-6.14、-6.53,P ＜0.05).The SER of cetuximab on CL187 cell line approached to 1.38.In addition,cetuximab also increased radiation-induced G0/G1 phase arrest (t=-4.64,P＜0.05) and the percentage of apoptosis and necrosis (t=-9.16,P ＜0.05),but it descreased the expression levels of DNA-PKcs,Ku70 and Ku80 proteins.Conclusions The cetuximab treatment might enhance the inhibitory effect of irradiation on colorectal carcinoma CL187 cell line by influencing cell cycle distribution,cell apoptosis,and the expression of DNA repair proteins.

Objective Replacement of dexmedetomidine with propofol for maintaining the anes-thesia in elderly patients undergoing laparoscopic cholecystectomy.Methods Ninety patients,over 70 years old,undergoing laparoscopic cholecystectomy were randomly divided into 2 groups,propofol combined with remifentanil (group A),dexmedetomidine combined with remifentanil (group B),45 patients in each group.Group A was not treated with any preoperative medication,while group B was treated with loading dose of 0.5 μg/kg dexmedetomidine intravenously completed within 10 minutes. Induction methods were same in both groups,3 # or 4 # laryngeal mask were inserted after induction in both groups.Maintenance of anesthesia in group A treated with propofol 2.0-3.0 μg/ml + 4.5-5.5 ng/ml TCI;Maintenance of anesthesia in group B treated with dexmedetomidine 0.25 μg·kg-1·h-1 +remifentanil 4.5-5.5 ng/ml (TCI).HR,SBP,DBP,BIS were recorded at inserting the LMA (T1 ), beginning of the surgery (T2 ),dissociate the cholecyst (T3 ),withdrawal of the laparoscope (T4 ), extubate the LMA (T5 ).Postoperative recovery time,Steward awakening score and modified OAA/S score at extubation time were recorded.Results No significant difference was found between BIS val-ue of two groups at different time point.Compared with group A,HR at T1-T5 in group B were sig-nificantly lower,SBP,DBP were significantly decreased (P <0.05).There was no significant differ-ence between Steward awakening score and modified OAA/S score at recovery and extubation time in two groups.Conclusion Dexmedetomidine replacing propofol can be safely used in laparoscopic chole-cystectomy with less hemodynamic changes during maintenance of anesthesia in elderly patients.

Objective To determine the biological effectiveness of 125I radioactive seeds with continuous low dose rate radiation on the human esophageal cancer cell line KYSE150 in vitro and explore the underlying cellular mechanisms.Methods The cells were divided into three cell groups:control group,single dose radiation group (SDR) and 125I radioactive seeds with continuous low dose rate radiation group (125 I-CLDR).The KYSE150 cells were exposed to radiation of X-ray at a high dose rate of 1.052 Gy/min or 125I radioactive seeds at a low dose rate of 2.77 cGy/h.The responses of KYSE150 cells to two modes of irradiation were evaluated by the colony-forming assay,cell apoptosis as well as cell cycle analysis.Furthermore,the expression levels of γ-H2AX and Bax were detected by Western blot.Results KYSE150 cells were more radiosensitive to 125I-CLDR than SDR.The relative biological effectiveness (RBE) for 125I-CLDR related to SDR was 1.56.Compared with SDR,125I-CLDR yielded more proportions of the early and late apoptosis rate (t =4.07,11.08,P ＜0.05) as well as cells at G2/M phase (t =11.25,P ＜0.05).Moreover,γ-H2AX and Bax expression levels in 125I-CLDR significantly increased compared with SDR.Conclusions Compared with the high dose rate X-ray radiation,the continuous low dose rate radiation of 125I radioactive seeds had stronger inhibition effect on KYSE150 esophageal cancer cells by impairing clonogenic capacity,inducing apoptosis and G2/M cell cycle arrest,and increasing radiosensitivity.

Hyaluronic acid is a linear, high molecular weight glycosaminoglycan. It has the characteristics of good biocompatibility, hydrophilicity and antigenicity. In this paper, the application of hyaluronic acid in the fields of ophthalmology, surgery, arthritis, cosmetic surgery and trauma repair is reviewed as well as the potential application in the field of tissue engineering.
Humans ; Hyaluronic Acid ; therapeutic use ; Tissue Engineering ; Wound Healing

Objective:To explore the relationship between level of urinary iodine excretion (UIE) before 131I treatment and excellent response (ER) in low-to-intermediate risk differentiated thyroid carcinoma (DTC) patients. Methods:A retrospective analysis was performed with 432 DTC patients (124 males, 308 females, age: (42.1±11.0) years) who were treated with 131I for the first time after total thyroidectomy from June 2017 to October 2018 in Department of Nuclear Medicine, the Second Hospital of Shandong University. All patients were divided into 4 groups: G1, group 1, UIE<50 μg/L; G2, group 2, 50 μg/L≤UIE<100 μg/L; G3, group 3, 100 μg/L≤UIE<200 μg/L; G4, group 4, UIE≥200 μg/L. Patients were given 131I with a fixed dose (3 700 MBq). Response was evaluated 6 to 8 months after 131I treatment: ER, indeterminate response (IDR), biochemical incomplete response (BIR), and structural incomplete response (SIR). χ2 test and Kruskal-Wallis rank sum test were used to analyze the data. The adjusted standardized residual (residual) and Cramer′s V between G1-G4 and different treatment reactions were calculated to judge the difference among groups. IDR, BIR and SIR were classified into non-ER (NER) group, and binary logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed to find the influencing factors of treatment reactions. Results:There were 51.9%(41/79), 64.9%(98/151), 53.8%(63/117), 30.6%(26/85) patients achieved ER in G1-G4, and the proportion of G4 was significantly lower than that of G1-G3 ( χ2 values: 7.695-25.697, all P<0.05), and there was no significant difference among G1-G3 ( χ2 values: 0.072-3.667, all P>0.05). The UIE level of patients in ER, IDR, BIR, SIR group was 87.5(57.0, 129.0), 97.0(55.7, 211.5), 141.0(74.0, 231.0), 148.0(68.5, 221.0) μg/L( H=15.977, P=0.001), and there was significant difference between those of patients in ER and SIR groups ( χ2=8.729, P=0.019). There was a certain correlation between UIE levels and different treatment reactions (Cramer′s V=0.151, P=0.001). UIE (≥200 μg/L), gender and preablative stimulated thyroglobulin could be used as independent factors affecting ER ( Wald values: 4.029, 7.185, 56.301, all P<0.05). Conclusion:Among DTC patients with low-to-intermediate risk, 131I treatment does not affect ER when the UIE level is less than 200 μg/L, while 131I treatment should be performed carefully when the UIE level is more than 200 μg/L.

Objective To investigate the effect of C225 on DNA repair and molecular pathways in CL187 colorectal cancer cells after irradiated by 125Ⅰ radioactive seeds.Methods In the experiment involved were four groups:control group,100 nmol/L C225 treatment group,125Ⅰ radioactive seeds continuous low-dose rate irradiation group and C225 combined with 125Ⅰ radioactive seeds continuous lowdose rate irradiation group.Cells were collected at 48 h after 4 Gy irradiation,and γH2AX foci/cell and γH2AX foci positive cells were counted with immunofluorescence.At the same time,DNA repair proteins were detected by Western blot.Cells were lyzed immediately after 4 Gy irradiation,and changs in EGFR downstream signaling molecules were detected by Western blot.Results Compared with 125Ⅰ seeds irradiated cells,cells treated with C225 and 125Ⅰ seeds irradiation showed more γH2AX foci per cell (t =8.0,P =0.05),and more γH2AX foci positive cells (t =6.8,P ＜ 0.05) and less expression of Ku70 (t =6.6,P ＜ 0.05) and DNA-PKcs (t =5.6,P ＜ 0.05).Combined with 125Ⅰ-CLDR irradiation,C225 reduced cellular EGFR level(t =4.9,P ＜0.05) and inhibited the activation of Akt(t =5.5,P ＜0.05).Conclusions In the condition of 125Ⅰ seeds irradiation,C225 reduced the expression of Ku70 and DNA-PKcs,inhibited the activation of Akt and attenuated the DNA damage repair capacity in CL187 colorectal cancer cells.

Objective To investigate the inhibition effect of continuous low dose rate radiation by 125Ⅰ radioactive seeds on Hep-2 cells and the corresponding mechanisms.Methods Hep-2 cells were divided into three groups,control group,single dose radiation group with high dose rate form X-rays (SDR) and continuous low dose rate radiation by 125Ⅰ seeds group (125Ⅰ-CLDR).After exposure to SDR and 125Ⅰ-CLDR,colony formation assay was used to determine the radiosensitivity and RBE,trypan blue exclusion assay was used to determine cell proliferation,and flow cytometry was used to detect cell apoptosis and cell cycle arrest.Results The radiosensitivity of Hep-2 cells to 125Ⅰ-CLDR was higher than that to SDR.The RBE of 125Ⅰ-CLDR versus SDR was approximately 1.61.The α/β ratio of 125Ⅰ-CLDR group was higher than that of SDR group.Both SDR and 125Ⅰ-CLDR inhibited cell proliferation (t =30.9,40.7,P＜0.05),in which 125Ⅰ-CLDR was stronger than SDR (t =9.8,P＜0.05).In addition,the incidences of apoptosis and G2/M arrest induced by125Ⅰ-CLDR were also stronger than those induced by SDR (t =5.8,19.8,P ＜ 0.05).Conclusions 125Ⅰ-CLDR generates more serious inhibition effects than SDR on reducing cellular DNA repair capacity,inducing cell apoptosis and G2/M arrest and inhibiting proliferation of Hep-2 cells.

[ABSTRACT]OBJECTIVETo study the mRNA expression of glucocorticoid receptor(GR) in peripheral blood mononuclear cells in patients with obstructive sleep apnea hypopnea syndrome(OSAHS) and its clinical significance. METHODSReal-time fluorescent quantitative PCR was used to detect GRα mRNA and GRβ mRNA exprssion in PBMC of 30 male patients with moderate to severe OSAHS and 27 healthy male subjects. The relationships between the expression of glucocorticoid receptor mRNA and the apnea hypopnea index, body mass index, neck circumference, waist circumference, the lowest oxygen saturation, the average oxygen saturation, the Epworth sleepiness scale(ESS) score, fasting blood glucose, heart rate and blood pressure were analyzed.RESULTSCompared with the control group, the expression level of GRα mRNA was lower in the OSAHS group(t=2.25,P<0.05) and the expression level of GRβmRNA had no difference between the two groups(t=1.43, P>0.05). We had not found the significant correlation between the expression of GRα mRNA and the clinical parameters above in OSAHS patients.CONCLUSIONThe expression of GRα mRNA in PBMC in moderate to severe OSAHS male patients have a downward trend compared with healthy group, but the mechanism remains unclear.

Objective To investigate the effect of cetuximab (C225) on the radiosensitivity of colorectal cancer cells CL187 and underlying mechanism.Methods Cell survival was detected by colony forming assay.The levels of apoptosis and cell cycle distribution were determined by flow cytometer.The mitotic ratio was measured by Wright' s-Giemsa mixed coloring method.The protein levels of Bax and Bcl2 were detected by Western blot.Results The sensitizing enhancement ratio of C225 was approximately 1.4.C225 treatment and 125I seed radiation induced G1 cell cycle arrest individually.C225 increased the radiation-induced apoptosis (t =6.6,P ＜ 0.05) and cellular Bax/Bcl-2 ratio (t =9.4,P ＜ 0.05),but did not increase radiation-induced G1 arrest.In addition,there was no difference in mitotic index among different groups.Conclusions C225 sensitizes CL187 to 125I seed irradiation,which might be related with increase of radiation-induced apoptosis.