OBJECTIVE:To explore the clinical efficacy and safety of nedaplatin combined with docetaxel in the treatment of advanced cervical cancer. METHODS:A total of 53 patients with advanced cervical cancer selected from our hospital during Apr. 2014-Apr. 2016 were divided into observation group(31 cases)and control group(22 cases)according to chemotherapy plan. Con-trol group was given Docetaxel injection 60 mg/m2,ivgtt,qw. Observation group was additionally given Nedaplatin for injection 35 mg/m2+0.9% Sodium chloride injection diluted into 500 mL,ivgtt (≥60 min),qw. A chemotherapy cycle lased for 21 d,and both groups received 2 cycles of chemotherapy. Clinical efficacies of 2 groups were evaluated 2 weeks after treatment,and the level of PCNA integal was detected before and 2 weeks after treatment. The occurrence of ADR was recorded. RESULTS:The total re-sponse rate of observation group (77.42%) was significantly higher than that of control group (63.64%),with statistical signifi-cance(P<0.05). Before treatment,there was no statistical significance in PCNA integval between 2 groups(P>0.05). After treat-ment,PCNA integval of 2 groups were decreased significantly,and the observation group was significantly lower than the control group,with statistical significance(P<0.05). ADR were concentrated in grade I,and there was no statistical significance in the in-cidence of ADR between 2 groups (P>0.05). CONCLUSIONS:Docetaxel combined with nedaplatin can significantly improve the clinical efficacy of patients with advanced cervical cancer,and does not increase the adverse reactions compared to docetaxel alone.

ObjectiveTo study the ability of response inhibition of depression.Methods30 depressed patients( depression group) and 30 healthy subjects (control group)were recruited in this study.The two groups were age,gender and education matched.All the subjects performed three visual Go/Nogo tasks using E-prime.The three Go/Nogo tasks were Happy Nogo Task(HNT),Normal Task (NT)and Sad Nogo Task (SNT).The two groups were instructed to press a button as quickly and correctly as possible when the Go trials were presented,but not to response when the Nogo trials were presented.In each task,the differences of accuracy (ACC) and response Time (RT) between the two groups were compared.Results ( 1 ) In HNT,during Go trials,ACC of depression group ( 0.85 ± 0.12 ) was higher than that of control group (0.75 ± 0.15 ) (P ＜ 0.05 ) ; during Nogo trials,ACC of depression group ( 0.91 ± 0.63 ) was lower than that of control group ( 0.95 ± 0.05 ) (P ＜ 0.05 ).(2) In NT,During Nogo trials,ACC of depression group(0.95 ± 0.04) was higher than that of control group (0.97 ± 0.03 ) (P ＜0.05 ).(3) There were no significant differences in RT between the two groups in any trails (P ＞ 0.05 ).ConclusionCompared with control group,depressed patients have a much higher recognize incline to the stimulus of sad emotion and a lower ability to complete normal response inhibition task.This is a new way to explain the depression pathogenesis mechanisms.

Objective To compare the expression of serum miR-100 in patients with esophageal cancer and healthy person ,and explore the value of miR-100 in diagnosis for esophageal cancer .Methods Real-time fluorescent quantitative polymerase chain reac-tion was used to detecting miR-100 in 40 esophageal cancer patients(study group) and 50 healthy person(control group) .Results The expression of miR-100 in the study group and control group were 6 .399 ± 3 .541 ,2 .625 ± 1 .515 respective ,the expression in the study group was significant higher than that of the control group(t= 9 .07 ,P< 0 .05) .The under area of receiver operating char-acteristic curve of miR-100 in diagnosis for esophageal cancer was 0 .832(95% confidence interval was 0 .731 - 0 .934) ,when the Cut off value was 5 .285 ,the sensitivity and specificity of miR-100 in diagnosis for esophageal cancer were 65% and 95% . Conclusion Serum miR-100 in esophageal cancer patients is higher than that in healthy person ,which might be a new molecular markers in diagnosis for esophageal caner .

Objective To study the correlation between expression level of als3 gene and the in vivo biofilm formation of Candida albicans in mice.Methods The real-time polymerase chain reaction (PCR) assay was used to detect als3 gene expressions of the clinical Candida albicans isolates from February 2016 to August 2016 in Tianjing No.1 Central Hospital.According to the expression levels of als3 gene, Candida albicans isolates were divided into high and low-expression groups.Thirty C57 mice were randomly assigned to high-expression group (n=15), low-expression group (n=5) and blank group (n=5).Animal model of Candida albicans biofilm was established based on venous catheter and intraperitoneal injection of Candida albicans.Catheters were removed after two weeks;inverted microscope was used for the observation of Candida albicans biofilm formation and transmission electron microscope was used for the observation of its ultrastructure.After irrigating the catheter, the growth of Candida albicans was observed;real-time PCR was used to detect the expression levels of als3 gene 12, 24, and 48 h after the catheter being removed.In this study, t test was used for measurement data and chi-square test was used for rate comparisons.Results In high-expression group, 11 strains (11/15) formed biofilms.In als3 low-expression group, only one strain (1/10) formed biofilm.The difference between these two group was statistically significant (x2=9.64,P<0.05).In als3 high-expression group, two mice died and 8 strains (8/13) formed biofilms, while in low-expression group, there were only 2 strains (2/10) formed biofilms.The difference between these two group was statistically significant (x2=4.02,P<0.05).Thickened Candida albicans membranes and increased mitochondria in high-expression group were observed under transmission electron microscope.In als3 high-expression group, 9 of 13 catheter cultures were positive.However, in als3 low-expression group, 5 of 10 catheter cultures were positive.The difference between these two group was not statistically significant (x2=0.99, P>0.05).In the als3 high-expression group, the expression of als3 gene declined gradually during the biofilm formation.In the als3 low-expression group, the change of als3 gene expression was not obvious.The expressions of als3 gene over time between two groups were significantly different (t=8.7, 10.3 and 9.2, respectively, all P<0.05).Conclusion The high expression of als3 gene in Candida albicans facilitates the formation of biofilm in vivo.

Objective To study the effect of HCV receptors′sequence on virus entry based on the two-dimensional structure and via tandem expression of HCV receptors on mouse hepatocytes.Methods The construced recombinant expression vectors pCDH-hLDLR-hSR-BⅠ-hCD81-GFP, pCDH-hLDLR-hCD81-hSR-BⅠ and pCDH-hCLDN-1-hOCLN-DsRed were cotransfected into 293FT cells with package vectors.The collected recombinant lentivirus expressing hCLDN-1-hOCLN was concentrated and attacked mouse hepatocytes.The transgenic mouse hepatocytes with tandem overexpression of CLDN-1 and OCLN were established after G418-selection.The transduced cells LSCCO/Hepa1-6 and LCSCO/Hepa1-6 were sorted via flow cytometry and puro-G418-selection after recombinant lentivirus expressing hLDLR-hSR-BⅠ-hCD81 and hLDLR-hCD81-hSR-BⅠattacked Hepa1-6 respectively.The infectivity of transduced mouse hepatocytes LSCCO/Hepa1-6 and LCSCO/Hepa1-6 to HCV was analyzed via direct-infection of serum-derived virus.Furthermore, the effect of HCV receptors′sequence on virus entry was studied.Results Both LSCCO/Hepa1-6 and LCSCO/Hepa1-6 enhanced HCV-cell binding.The transduced mouse hepatocytes LSCCO/Hepa1-6 had more HCV endocytosis.Conclusion SR-BⅠhas priority over CD81 in HCV entry in the early stage.

Objective To explore humam cytomegalovirus(HCMV) encoded microRNAs during latent infection in order to help study HCMV virology and latent infection mechanisms.Methods A model of HCMV latent infection via THP-1 cells infected with HCMV was constructed.Deep-sequencing was performed using high-resolution Solexa sequencing platform.The secondary structure of the newly sequenced miRNA was predicted by RNAFold bioinformatics software. Results HCMV encoded various miRNAs during latent infection, including miR-US25-2-3p, miR-US25-2-5p, miR-UL112, miR-US25-1, miR-UL22A and PC-5p-148467 with a predicted length of 25 bp, named hcmv-miR-US33as-5p.Conclusion HCMV can express many types of miRNAs during latent infection.

Objective To study the effects of efflux pump inhibitors(CCCP and PAβN)on carbapenems in Pseudomonas aernginosa(P.aeruginosa)clinical isolates and investigate the association between the resistance to imipenem or meropenem and expression levels of efflux pumps of P.aeruginosa.Methods MICs of imipenem or meropenem combined with efflux pump inhibitors including carbonyl cyanide m-chlorophenylhydrazone(CCCP,107 strains)and Phe-Arg-β-naphthylamide(PAβN,71 strains)against imipenem-resistant strains were determined by agar dilution method,and changes of MICs were observed.For 32 strains with different resistant phenotypes to imipenem and meropenem,the mRNA expression levels of three efflux pump genes(mexA,mexD and mexF)were quantified by real time fluorescent quantitative PCR.Results The resistance rate of imipenem and meropenem didn't prove any significant difference in the presence of efflux pump inhibitors.The X2 value of imipenem combined with CCCP and PAβN were 0.338 and 0.086,respectively(P＞0.05),while that of meropenem combined with CCCP and PAβN were 1.065 and 1.458(P＞0.05).No significant in MICs of carbapenems were seen in over half of P. aeruginesa isolates. MICs of carbapenems was significantly downregulated for 4-fold or above in eight isolates. Overexpression of efflux pumps genes were present in 24 of 27 carbapenem-resistant isolates(88. 9% ). Efflux pumps genes including MexAB-OprM, MexCD-OprJ and MexEF-OprN were all overexpressed in 13 isolates,constituting 54. 2% of all carbapenem-resistant isolates. There were 3 isolates in which beth MexAB-OprM and MexCD-OprJ showed overexpression,constituting 12. 5%. Also,MexAB-OprM and MexEF-OprN overexpressed in 3 isolates. There were 2 isolates (8.3%) showing MexEF-OprN overexpression and MexAB-OprM alone. MexCD-OprJ didn't showed overexpression alone. Furthermore,the expression levels of efflux pumps genes mexA,mexD and mexF in isolates susceptible to both in imipenem and meropenem were 0. 48±0. 48,0. 48±0. 53 and 0. 30±0. 41,respectively,which were much lower than that in carbapenem-resistant ones (P＜0. 05 ). MexA gene was expressed at a higher level in meropenemresistant isolates than meropenem-susceptible ones (P＜0. 05 ). Conclusions When the concentration of CCCP and PAβN were 5 μg/ml and 20 μg/ml respectively,the efforts on the carhapenems resistance of P.aeruginosa were small Overexpression of MexAB-OprM might play an important role in meropenemresistance in P. aerugines. Overexpression of MexCD-OprJ and MexEF-OprN was associated with imipenemresistance. However,the relationship between them and meropenem-resistance need to be explored in the future.

Objective To evaluate the antidepressant action of melatonin in stress model of depres-sion and the effects of the melatonin on depressive-like behavior.Methods Forty male Wistar rats were ran-domly divided into four groups(n=10):controls group(CON),chronic unpredictable mild stress group (CUS),chronic unpredictable mild stress group + melatonin group(CUS+MT)and chronic unpredictable mild stress group +ketamine group(CUS+KET).The rats in CUS group,CUS+MT group and CUS+KET group were given different stress stimulation for 42 days to establish the chronic mild unpredictable stress ani-mal model.Sucrose preference experiments was used to detect the depression model and the level of depres-sion was tested by forced swim test.The influence of Short-term low doses of melatonin on the level of BDNF and GluR1 in the prefrontal cortex,was detected by immunohistochemistry(IHC)on 58 day after the start of the experiment.Results (1)The CUS showed depressant-like behavior,and the percent sucrose uptake scores and the cumulative immobility time of the CUS group were decreased significantly(P<0.05).(2)After injection melatonin 14 d,the cumulative immobility time of CUS+MT group((60.70±18.56)s)and CUS+KET group((56.43±20.46)s)were decreased significantly in comparison to the CUS group(146.34±34.10) s).It was observed a highly significant(P<0.05)decrease of and up-regulation of the BDNF cells in CUS+MT group((1 328.99±282.46)/mm2)and CUS+KET group((1 224.76±116.53)/mm2)in comparison to the CUS group,the number of BDNF cells in CUS+MT group was increased significantly in comparison to the CUS+KET group;(3)After administration drug 14 days,the number of GluR1 cells of CUS+KET((807.82± 153.25)/mm2)but not CUS+MT((632 ± 156.34)mm2)significantly increased compared with CUS ((807.82±193.25)/mm2).Conclusion The results indicate that the melatonin induce an antidepressant-like action like ketamine.The antidepressant effects of melatonin may be related with the level of BNDF.

Objective To explore the effect of expressive writing intervention on social support,resilience and school maladjustment in university freshman.Methods Selecting the freshmen volunteer of 600 university freshmen of Shandong,through the scale before the test recovery and comprehensive scoring chosen the part of low grade college students as the intervention object and were divided into writing expression(n=60) person and control group(n=60).The intervention group received a positive subject writing expression and the control group in the normal writing.Before and after the intervention tested the social support rating scale,the resilience scale for Chinese adolescents and the the student adaptation to college questionnaire were tested to evaluate the effect of active writing expression intervention.Results (1)After intervention,the intervention group and the control group had significant differences among the scales,objective support (t =-2.36,P＜0.05),learning adaptation(t=-1.98,P＜0.05) and subjective support (t=-2.56,P＜0.05),target focus(t=-2.66,P＜0.01),emotional control(t=-2.81,P＜0.01),family support (t=-3.46,P＜0.01),adaptation (t=-2.73,P＜0.01),support utilization (t=-5.91,P＜0.01) and social support score (t =-4.04,P＜ 0.01),positive cognition (t=-2.73,P＜0.01),interpersonal assistance (t=-3.13,P＜0.01),resilience score (t=-7.40,P＜0.01),life adaptation (t=-3.83,P＜ 0.01),emotional state (t =-3.39,P＜ 0.01),and school adaptation score (t=-3.46,P＜0.01).(2)There was no significant difference in objective support between the control group before intervention and after intervention.In addition,the remaining dimensions such as subjective support (20.72±2.46,22.96±2.81,t=4.54,P＜0.01),support utilization (7.49± 1.40,9.86± 1.90,t =7.56,P＜0.01) and social support score (36.79±4.24,41.89±5.18,t=5.76,P＜0.01) were significantly increased.The intervention group had significant difference among target focus (15.98±2.86,17.89±3.35,t=3.28,P＜0.01),emotional control (14.98±2.77,15.70±2.71,t=3.35,P＜0.01),positive cognition (14.61 ± 2.04,16.26±3.09,t=3.36,P＜0.01),interpersonal assistance (15.30±2.44,17.49±2.73,t=4.52,P＜0.01),resilience score(77.65±6.01,88.25±5.74,t=9.63,P＜0.01) and family support(16.77±2.28,19.58± 2.44,t =6.35,P＜ 0.01).In the intervention group of school adaptation scale,life adaptation (40.44± 6.36,45.12± 7.21,t=3.68,P＜0.01),emotional state (34.04±6.99,38.84±5.95,t=3.95,P＜0.01) and school adaptation score (145.21 ±22.86,160.51±21.78,t=3.66,P＜0.01),interpersonal assistance (32.30±5.34,35.23±5.18,t=2.98,P＜0.01),learning adaptation (38.44±7.06,41.32± 5.92,t=2.36,P＜0.05) were significantly increased.Conclusion Written expression intervention has a positive effect on improving the low level of social support,the poor resilience and freshman's adaptation to college.

To retrospectively analyze the efficacy and safety of modified cell infusion method in reducing the incidence of febrile non?hemolytic transfusion reaction (FNHTR). Methods A total of 69 patients were enrolled in the clinical trial of CD19 chimeric antigen receptor T (CAR?T) cell treatment from February 2017 to October 2018. Study group received the modified cell infusion method, that 1×106 CAR?T cells were re?suspended in 2 mg human serum albumin with total volume of 20 ml and injected intravenously. The control group was intravenously administrated with CAR?T cell in 100 ml normal saline. The incidence of FNHTR, cytokine releasing syndrome (CRS) grade, cytokine level and efficacy were compared. Results (1)The incidence of FNHTR in the study group was 21.1%, significantly lower than that in the control group (71%)(P=0.000). (2)There was no statistical difference in cell proliferation between the study group and the control group on day 4, 7, 14 and 21 after CAR?T cell infusion (P=10.223, 3.254, 5.551, 7.605). (3)There was no statistical difference in CRS grading between the study group and the control group (P=0.767). There was no statistical difference in the levels of interleukin 2 receptor (IL?2R), IL?6, tumor necrosis factor (TNF)?α between the two groups. (4)The C?reaction protein (CRP) level of the study group was lower than that of the control group on day 4 and 7 (P=0.026, 0.007). (5)There was no statistical difference of response rates in acute lymphocytic leukemia (ALL) and non?Hodgkin lymphoma (NHL) patients between the two groups (PALL=0.842; PNHL=0.866). Conclusion The modified cell infusion method in CD19 CAR?T cell treatment reduces the incidence of treatment?related FNHTR. It does not affect the proliferation of CAR?T cells in vivo, the grading of CRS and the response rates.