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Tumor-associated macrophages (TAMs) play crucial roles in tumor progression and immune responses. However, mechanisms of driving TAMs to antitumor function remain unknown. Here, transcriptome profiling analysis of human oral cancer tissues indicated that regulator of G protein signaling 12 (RGS12) regulates pathologic processes and immune-related pathways. Mice with RGS12 knockout in macrophages displayed decreased M1 TAMs in oral cancer tissues, and extensive proliferation and invasion of oral cancer cells. RGS12 increased the M1 macrophages with features of increased ciliated cell number and cilia length. Mechanistically, RGS12 associates with and activates MYC binding protein 2 (MYCBP2) to degrade the cilia protein kinesin family member 2A (KIF2A) in TAMs. Our results demonstrate that RGS12 is an essential oral cancer biomarker and regulator for immunosuppressive TAMs activation.
Subject(s)
Mice , Humans , Animals , Tumor-Associated Macrophages/metabolism , Carcinoma, Squamous Cell , Squamous Cell Carcinoma of Head and Neck , Mouth Neoplasms , GTP-Binding Proteins/metabolism , Head and Neck Neoplasms , Ubiquitin-Protein Ligases/metabolism , Adaptor Proteins, Signal Transducing/metabolism , RGS Proteins/metabolism , Kinesins/metabolism , Repressor Proteins/metabolismABSTRACT
Objective@#To evaluate the influence of fracture resistance of endodontically treated teeth with different thickness of ferrule by mechanical fatigue test and static loading test, and so as to provide a reference for the clinical treatment planning.@*Methods@#Fifty bovine incisors were divided into 5 groups by random number table method (n=10). Group A was the control group in which the incisors were prepared without a ferrule design (0 mm). The other four groups (B, C, D, E) were experimental groups, and the thickness of the dentin ferrule prepared for specimens in each group was 0.5, 1.0, 1.5, and 2.0 mm. The height of ferrules in all the specimens was 2 mm. Cyclic fatigue loading (2.33 Hz, 50 N) was applied on each specimen until either the specimen was dislodged/fractured or the 300 000 cycles were finished. After fatigue loading, the mode of failure was observed. Those intact specimen after fatigue loading were tested under a gradually increasing force using a universal testing machine (0.05 mm/min) until fracture occurred. The forces required to fracture and failure model was recorded.@*Results@#The results of cyclic loading tests showed that: all specimens survived the 300 000 cycles of intermittent loading. The results of static loading tests showed that: the fracture force of A, B, C, D and E groups respectively were (226.4±67.7), (369.7±34.5), (400.7±48.2), (528.1±56.3), and (555.4±98.5) N (F=15.227, P=0.000). There was a significant difference in fracture resistance between group A and the other four groups, and between group B, C and group D, E (P<0.05). No statistical difference were found in fracture resistance among the other groups (P>0.05). There was strong correlation between the thickness of ferrule and the fracture force by Pearson correlation analysis (r=0.973, P=0.002).@*Conclusions@#Within the limitations of this study, the following conclusions can be drawn: The different thickness of ferrule can influence the fracture resistance of the teeth, and when the height of the ferrule is 2.0 mm, the fracture force increased significantly with an increasing ferrule thickness.
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Objective To evaluate the early diagnostic value of urinary insulin-like growth factor binding protein-7 (IGFBP-7) in sepsis-induced acute kidney injury (AKI),and to compare the effects of urinary IGFBP-7 to that of serum cystatin-C (sCys-C) and serum creatinine (sCr) on predicting the severity of sepsis-induced AKI patients.Methods A total of 105 patients with sepsis admitted to ICU in Tianjin First Hospital from September 2015 to August 2016 were divided into AKI group (n =48) and non-AKI group (n =57) according to the AKI diagnostic criteria.The samples of blood and urine of the patients were collected at 0,3,6,12,24 and 48 h,to measure the levels of urinary IGFBP-7,and serum Cys-C and sCr.Based on the receiver operating characteristic curve (ROC) and the area under the curve (AUC),the early diagnostic value of urinary IGFBP-7,and serum sCys-C and sCr in sepsis-induced AKI patients was determined.Results With the increase in length of ICU stay,the levels of urinary IGFBP-7,and serum sCys-C and sCr in AKI patients increased gradually.There was a significant difference between the two groups in the level of IGFBP-7 at 3 h [2.34 (2.03,4.19) ng/mL vs.1.79 (1.51,2.62) ng/mL,P ＜0.05].At 6 h,the difference in sCys-C between two groups was statistically significant [(1.63 ± 0.42)ng/mL vs.(1.20 ±0.46) ng/mL,P ＜ 0.05].At 12 h,the difference in sCr between two groups was statistically significant [80.5 (74.3,88.0) ng/mL vs.77.0 (67.0,84.0) ng/mL,P ＜ 0.05].The AUCs of urinary IGFBP-7 and sCys-C of sepsis-induced AKI patients were 0.881 (95％ CI:0.813-0.949) and 0.782 (95％ CI:0.692-0.872),which were superior to those in AUC of sCr 0.629 (95％CI:0.522-0.737).When the cutoff value of urinary IGFBP-7 was 1.82 ng/mL,the sensitivity was 93.8％ and the specificity was 77.2％.Conclusions Urine IGFBP-7 and sCys-C have higher predictive value in sepsis-induced AKI than sCr,whereas urine IGFBP-7 is more sensitive and specific than sCys-C,suggesting that IGFBP-7 may be used as sepsis signs of early diagnosis of AKI.
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Objective To evaluate the early diagnostic value of urinary insulin-like growth factor binding protein-7 (IGFBP-7) in sepsis-induced acute kidney injury (AKI),and to compare the effects of urinary IGFBP-7 to that of serum cystatin-C (sCys-C) and serum creatinine (sCr) on predicting the severity of sepsis-induced AKI patients.Methods A total of 105 patients with sepsis admitted to ICU in Tianjin First Hospital from September 2015 to August 2016 were divided into AKI group (n =48) and non-AKI group (n =57) according to the AKI diagnostic criteria.The samples of blood and urine of the patients were collected at 0,3,6,12,24 and 48 h,to measure the levels of urinary IGFBP-7,and serum Cys-C and sCr.Based on the receiver operating characteristic curve (ROC) and the area under the curve (AUC),the early diagnostic value of urinary IGFBP-7,and serum sCys-C and sCr in sepsis-induced AKI patients was determined.Results With the increase in length of ICU stay,the levels of urinary IGFBP-7,and serum sCys-C and sCr in AKI patients increased gradually.There was a significant difference between the two groups in the level of IGFBP-7 at 3 h [2.34 (2.03,4.19) ng/mL vs.1.79 (1.51,2.62) ng/mL,P ＜0.05].At 6 h,the difference in sCys-C between two groups was statistically significant [(1.63 ± 0.42)ng/mL vs.(1.20 ±0.46) ng/mL,P ＜ 0.05].At 12 h,the difference in sCr between two groups was statistically significant [80.5 (74.3,88.0) ng/mL vs.77.0 (67.0,84.0) ng/mL,P ＜ 0.05].The AUCs of urinary IGFBP-7 and sCys-C of sepsis-induced AKI patients were 0.881 (95％ CI:0.813-0.949) and 0.782 (95％ CI:0.692-0.872),which were superior to those in AUC of sCr 0.629 (95％CI:0.522-0.737).When the cutoff value of urinary IGFBP-7 was 1.82 ng/mL,the sensitivity was 93.8％ and the specificity was 77.2％.Conclusions Urine IGFBP-7 and sCys-C have higher predictive value in sepsis-induced AKI than sCr,whereas urine IGFBP-7 is more sensitive and specific than sCys-C,suggesting that IGFBP-7 may be used as sepsis signs of early diagnosis of AKI.
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Objective To study the changes of the symptoms and quality of life in the patients after the transvaginal tape-obtura-tor(TVT-O) operation .Methods To retrospectively analyze the clinical data of 96 female patients with stress urinary incontinence (SUI) in our hospital from February 2007 to April 2012 .48 cases of retropubic tension free vaginal tape(TVT) were taken as the control group and 48 cases of TVT-O as the experimental group .The intraoperative general condition and postoperative symptoms changes and life quality were analyzed and compared between the two groups .Results The operation time ,blood loss and hospital stay time in the experimental group were significantly less than those in the control group (t=17 .061 ,17 .026 ,15 .465 ,P>0 .05) , the difference of operative effects between the two groups was not statistically significant (χ2 =0 .711 ,P>0 .05) .After treatment , all the patients′scores of quality of life were significantly improved compared with that before treatment (29 .1 ± 9 .6 ,30 .3 ± 9 .8 vs . 70 .4 ± 10 .2 ,68 .5 ± 11 .4 ,P0 .05) ,af-ter treatment ,the symptom scores and urinal pad use of two groups were obviously improved compared with those before treatment (13 .9 ± 2 .8 ,14 .1 ± 2 .5 vs .5 .1 ± 1 .2 ,5 .4 ± 1 .7 89 .6% ,93 .8% vs .50 .0% ,58 .3% ,P0 .05) .Conclusion TVT-O can improve the symptoms and quality of life in the pa-tients with SUI .In the same time ,it has advantages of minimal invasion and low risk ,which is worth promoting ,but the surgeons need to accumulate more clinical experience .
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Objective To investigate the feasibility in screening of normal ovarian tissues by evaluating the expressions of tumor-associated genes in tissues adjacent to human epithelial ovarian cancer of orthotopic implantation in nude mice.Methods Human epithelial ovarian cancer cell lines OVCAR3 were grown in subcutaneous tissues,and the tumor tissues were orthotopic implanted.The expressions of CK-7,CA125,P53,survivin,MMP-2,and TIMP-2 were detected by immunohistochemical staining in proximal tissues,middle tissues,distal tissues adjacent to tumor,tumor tissues,and normal ovarian tissues of nude mice.Results 35 samples ovarian tissues with normal biopsy were gained from 40 cases of human epithelial ovarian cancers of orthotopic implantation model in nude mice.The expression rate of CK-7,CA125,P53,survivin,MMP-2,and TIMP-2 were 95.0％ (38/40),95.0％ (38/40),75.0％ (30/40),85.0％ (34/40),77.5％ (31/40),and 77.5％ (31/40) in tumor tissues,respectively; 71.4％ (25/35),68.6％(24/35),57.1％ (20/35),62.9％ (22/35),60.0％ (21/35),and 57.1％ (20/35) in proximal tissues adjacent to tumor,respectively; 34.3％ (12/35),31.4％ (11/35),31.4％ (11/35),31.4％ (11/35),34.3％ (12/35),and 31.4％ (11/35) in middle tissues adjacent to tumor,respectively; and 25.7％ (9/35),22.9％ (8/35),25.7％ (9/35),25.7％ (9/35),28.6％(10/35),and 31.4％ (11/35) in distal tissues adjacent to tumor,re respectively.The expressions of CK-7,CA125,P53,survivin,MMP-2,and TIMP-2 were all negative in 23 samples normal ovarian tissues adjacent to tumor.The expressions of CK-7,CA125,P53,survivin,MMP-2 and TIMP-2 in proximal tissues adjacent to tumor were lower than those in tumor tissues(P＜0.05),and higher than those in middle tissues and in distal tissues adjacent to tumor(P＜0.01).There were no expression difference between in middle tissues and in distal tissues (P＞0.05).The strong positive expressions of CK-7,CA125,and survivin were higher than those of P53,MMP-2,and TIMP-2 (P＜0.01).No significant difference was found in those expressions in the normal ovarian tissues adjacent to tumor gained from orthotopic implantation model with different severity.The expressions of CK-7,CA125,P53,survivin,MMP-2,and TIMP-2 were all negative in 20 normal ovarian tissues of nude mice.Conclusions The expression of CK-7,CA125,P53,survivin,MMP-2,and TIMP-2 showed decreasing trend to non-cancer direction.Negative expressions of these tumor-associated genes can be used as standard in screening of normal ovarian tissues adjacent to tumor.Relative safe normal ovarian tissues can be obtained from the tissues adjacent to tumor.
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Objevtive To investigate the safety of laparoscopic resection and ~(125)I seed implantation for recurrent gynecologic malignancies. Methods Laparoscopic surgery and ~(125)I seed implantation were used in five patients. All complications were recorded. Environmental radiation dose was detected at different distance from radioactive source and different time after operation with-γ-ray equipment. Results The procedure was safely achieved in all five patients. No serious complication was found. All patients experienced slight pain at the implant site and temporary vulva dropsy. With the increase of the distance from radioactive source and time passing, the radiation dose decreased quickly. The detected dose was close to a natural background radiation dose at the distance of 50cm from radioactive source and after 6 months. Conclusions Laparoscopic resection and ~(125)I seed implantation are safe to patient and environment.
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Objective To screen and identify the serum biomarker of anovulatory dysfunctional uterine bleeding (ADUB) , to determine the expression of biomarker protein in menses of ADUB pa-tients, and to investigate the relation between ADUB and the biomarker proteins. Methods Subjects included 128 ADUB patients and 93 age-matched controls( normal women ). Their serum and super-natant of mense were collected and stored for use at -80℃. The differential proteins in the serum of the 2 groups were detected by CM 10 and analyzed by Biomarker WizardTM3.2 software. Then, the differential proteins were identified by Trieine-SDS-PAGE gel separation, spectrometry identifica-tion, and immunoprecipitation. The expression of the protein identified above in the menses was test-ed by ELISA, RT-PCR, and Western blotting. SPSS 14.1 was applied for statistical analysis and chart drawing. Results Five differential protein peaks were screened and their peak values were 11.80, 13.59, 13.79, 13.85, and 14.20 km/z, respectively. The intensity of protein peak ( 11.80 km/z ) which was identified as serum amyploid protein A ( SAA ) of ADUB was significantly higher than that of the controls (P<0.05). While the intensity of protein peak (13.59 km/z) which was identified as vascular endothelial growth factor (VEGF) of ADUB was obviously lower than that of the controls (P<0.05). The intensity of protein peak 13.08, 13.85, and 14.20 was not different between the cases and controls. SAA expressed highly in the menses of ADUB but low in that of the controls. Conversely, VEGF expressed highly in the menses of the control but low in that of the ADUB. Conclusion Two biomarkers which might be related with ADUB have been correctly screened and identified as SAA and VEGF. It needs further study whether the increased expression of SAA and reduced expression of VEGF are the cause or result of ADUB.
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In order to investigate the effect of anti-hepato-cellular carcinoma of HSV-tk suicide gene system, we constructed the HSV - tk recombinant retroviral vector pLXT. SMMC - 7721 hepatocellular carconoma cells more transfected with pLXT by lipofectin were obtained by subsequent G418 screen. 3H-TdR incorparation assay showed that HSV - tk/ACV had strong cytotoxic effect on HSV - tk gene transfected tumor cells. Lipofectin pLXT complex was directly injected into murine H22 hepatoma tissue, followed by delivery of ACV prodrup, and it was found that the tumor growth masses more greatly reduced. Animals treated with Liptk + ACV and tk + ACV had an apparent reduction of tumor size as compared with the animals in other six groups ( P
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37 diabetic patients and 49 normal subjects were examined with Goldmann-Weekers dark adaptometer.The results showed that the absolute thresholds of dark adaptation in each group of diabetic patients were higher than those in normal controls. The more severe retinopathy was, the higher was the absolute threshold.The patients with more damaged visual acuity showed worse dark adaptation. However the dark adaptation in patients with good visual acuity was also abnormal.lt is suggested that dark adaptation is more sensitive than visual acuity in determining the visual function of diabetic patients.