The zinc finger protein A20 exists in many kinds of ceils in the body and plays multiple roles in physiological and pathological processes such as regulation of immune response,inflammatory diseases and cancers by inhibiting cell apoptosis induced by tumor necrosis factor (TNF) and restricting NFKB signaling pathway.Recently,the role of A20 in generation and development of tumors draws wide attention,hence,we summarized recent research progress of the relation between A20 and cancer in this review.

Objective To observe the level of autophagy induced by TRAIL in TT cell line and identify the role of autophagy in TRAIL-inducing apoptosis of TT cell line.Methods The growth inhibition of TT cells was measured by MTT assay.MDC staining was used to identify the happening of autophagy.Annexin V/PI double staining was used to analyze the apoptosis rate of TT cells by flowcytometry.The protein expression of caspase-8 and Beclin1 was detected by Western blot.Results ① The growth inhibition ratio of TT cells induced by TRAIL at the concentration of 250,500,1000 and 2000 ng/ml was (3.02 ± 1.82)％,(4.87 ± 1.45)％,(7.51 ± 1.57) ％,(12.76 ± 3.23) ％ respectively,which suggested significant resistance of TT cells to TRAIL.② MDC-labeled green light vesicles was significantly increased after the treatment of TRAIL for 48 h.③ The apoptosis rate of TT cells induced by TRAIL at the concentration of 500 ng/ml and 1000 ng/ml after the pretreat ment of 3-MA for 4 h was(17.83 ± 1.54) ％ and(27.81 ± 1.79) ％ respectively,which was significantly higher than the apoptosis rate induced by TRAIL(3.70 ± 0.34) ％,(6.55 ± 0.59) ％ alone and that induced by 3-MA(7.71 ± 0.64) ％ (t =3.282,P ＜ 0.05 ; t =7.830,P ＜ 0.01).④ The combination treatment of TRAIL and 3-MA increased the cleavage of caspase-8 and down-regulated the expression of Beclin 1.Conclusion Autophagy induced by TRAIL may contributes to the resistance of TT cells to TRAIL,which can be reversed by the inhibition of autophagy.

Objective To study the clinical characteristics and diagnosis of the solid-psendopapillary tumor of pancreas (SPT).Methods The clinical data of 40 SPT from January 1996 to January 2008 were retrospectively analyzed. The average age was (32.9 + 13.6 )years. The average clinical course was (8.6±0.1) months.Clinical symptoms usually included distensible pains and secret anguish in abdomen (60.0%).No jaundice appeared in any case.Results The surgical resection was favorable for the treatment of SPT,which had excellent prognosis.No tumor recurrence were found in those following-up patients. Grossly,the cut surface showed areas of solid and papillary tissue,cystic degeneration,hemorrhage,and necrosis.Pathological features included a combination of solid and cystic components with pseudopapillae formation and degenerative regions without glands.Conclusions SPT has its uniquely clinical and pathological characteristics.Its main diagnosed points are helpful for clinical doctors to make timely diagnosis and reduce the rate of misdiagnosis and mistreatment.

Objective To study the effect and related mechanism of celecoxib on tumor necrosis factorrelated apoptosis-inducing ligand(TRAIL) induced apoptosis of medullary thyroid cancer TT cell line.Methods MTT assay was used to measure the growth inhibition induced by TRAIL and celecoxib alone and their combination.TT cell cycle distribution was analyzed by flowcytometry.Hochest33258 staining and DNA ladder was used to detect the apoptosis of drug combination on TT cells.Western blot was used detect the protein change of cyclin A,Cdk2,caspase-8,c-FLIP,and RIP.Results ①MTT showed the growth inhibition ratio of TT cell intervened by the combination of TRAIL and celecoxib was 47.53％ ± 1.34％,which was much higher than that intervened by TRAIL(7.75 ％ ± 3.84％)and celecoxib alone.The differences had statistical significance (t test,F =5.234,P ＜0.01);②PI detection found the cells' number in G0/G1 phase in celecoxib group and combination group were increased compared to that in control group and TRAIL group(F =242.694,P ＜ 0.01);③Western blot indicated the expression of Cyclin A and Cdk2 were down regulated,there was no statistic significance;④ The apoptosis morph in nuclus was detected by Hochest33258 staining and showed the karyopycnosis and muclear fragmentation were increased in combination group with the apoptosis rate 24.23％ ± 2.91％,which was much higher than that in TRAIL(5.86％ ± 1.41％) and celecoxib(20％ ± 1.24％) (t test,F =1.824,P ＜0.01),the difference has statistic significance;⑤Western blot illustrated the active schizolysis of casplase-8 was higher and the expression of c-FLIP and RIP was down regulated in combination group.Conclusion celecoxib plays a positive effect on TRAIL-reduced apoptosis of medullary thyroid cancer TT cell line,which may due to the cell cycle arrest at G0/G1 phase,down-regulation of c-FLIP and RIP and subsequent activation of caspase-8.

Objective To compare the extracellular space diffusion at different stages of rat C6-gliomas determined by MRI tracer method and analyze the influencing effect of extracellular matrix ( ECM) on the diffusion process.Methods Introducing adolinium-diethylene triaminepentaacetic acid ( Gd-DTPA) into extracellular space ( ECS) as a tracer.The diffusion parameters and half-life time were quantified according to mathematical model of diffusion.The main ECM components ( e.g. chordroitin sulfate proteoglycans ( CSPGs ) , collagen IV tenascin C ) were detected by immunohistochemical and immunoblot analysis.Results Gd-DTPA introduced into 20-day glioma in the rats diffused more slowly [(6.67 ±1.78) ×10 -5 mm2/s vs.(1.26 ±0.27) ×10-4 mm2/s; t =4.265; P<0.01)], deriving a larger tortuosity [(3.99 ±0.57) vs.(2.83 ±0.29);t=4.11;P<0.01)], localized within the tumor with a smaller clearance rate [(7.67 ±2.29) ×10 -5mm2/s)vs.(1.46 ±0.36) ×10 -4mm2/s);t=3.87;P<0.05), and a longer half-life time ((0.86 ±0.23 h)vs.(1.64 ±0.12 h);(t=5.91;p<0.01)] compared with 10-day gliomas in the rats.The increased levels of extracellular matrix of glioma were associated with different diffusion and clearance parameters of 20-day gliomas in the rats in comparision with those in the 10-day rat gliomas, in which the chordroitin sulfate proteoglycans[(0.48 ±0.07) vs.(0.32 ±0.09);t=4.663;P<0.01)], tenascin C [(0.29 ±0.04) vs.(0.58 ±0.11);t =6.50;P<0.01] and collagen IV [(0.24 ±0.07)vs.(0.33 ±0.06);t=3.81;P<0.05] were tested.Conclusions The ECS parameters are changed with the C6 glioma progression due to the increased ECM content.The results of our study may help us to better understanding the glioma micro-environment and provide beneficial references for the brain interstitial drug delivery to treat gliomas.

Objective To dynamic monitor and analyze the characteristic of polysomnography (PSG)and melatonin levels of delirium patients in intensive care unit (ICU). Methods A prospective observational study was performed from December 2013 to April 2014. The patients admitted to ICU of Affiliated Hospital of Binzhou Medical College for more than 72 hours were evaluated with confusion assessment method for the ICU (CAM-ICU),and were divided into delirium group and non-delirium group. Sleep patterns of all the patients underwent continuous PSG for up to 24 hours were evaluated. Melatonin levels were determined every 4 hours with enzyme linked immunosorbent assay (ELISA)duration sleep monitoring. Results Eighteen patients were enrolled,and 9 were delirium patients. All the patients had sleep disorders:a decrease in rapid eye movement (REM)sleep 〔(5.91±5.26)%〕,an increase in the sleep fragmentations 〔arousal index was (15.40 ±12.79)times/h〕,and the N3 sleep stage was on the lower limit of normal 〔(14.67 ±11.10)%〕. Compared with non-delirium group,the REM sleep was significantly decreased in delirium group〔(0.10±0.20)%vs.(8.83±3.81)%,t=4.782,P=0.001〕. Melatonin levels lost rhythm between day and night,and there was no difference in melatonin between delirium group and non-delirium group (time effect:F=1.370,P=0.287;between-group effect:F=1.646,P=0.250;interaction effect:F=1.558,P=0.247). The peak of melatonin levels of delirium group appeared on 06:00 〔(137.84±62.21)ng/L〕and 14:00 〔(148.24±58.8)ng/L〕, the minimum value on 22:00 〔(64.47 ±26.97) ng/L〕. But in non-delirium group,the peak of melatonin levels appeared on 02:00 〔(63.52 ±39.75)ng/L〕,the minimum value on 10:00 〔(44.87 ±11.19)ng/L〕. Conclusions ICU patients have sleep disorders,and the delirium patients have less REM stage. Normal rhythmic melatonin secretion changes of ICU patients were lost. The delirium peak of patients appears in the daytime.

Objective To summarize and analyze the pathological characteristics of solid pseudopapillary tumor of pancreas (SPTs).Methods The clinical data of 51 cases of SPTs were retrospectively analyzed.The immunohistochemical localizations of different markers (HSE,SYN,CD_(56),CD_(10),Nestin,Vim,a1-ACT,EMA,AE1/AE3 and CK19) on 39 SPTs were studied.Results Pathological features included a combination of solid and cystic components with pseudopapillae formation and degenerative regions without glands.Among the 39 cases of SPTs,the expression rate of NSE was 97.4%,the expression rate of CD_(56),CD_(10) was 84.6%,the expression rate of Nestin and Vim was 64% and 87%,the expression rate of S100 was 79.5%,the expression rate of a1-ACT and a1-AT was 82.1% and 79.5%,while the expression rate of SYN was 12.8%;however there was low expression and weak positive reaction of EMA,AE1/AE3 and CK19.Conclusions The typical pathological characteristics of SPTs may result from gradual degenerative changes induced anoxemia in some SPT's areas.The heterogeneity of SPTs on different antibody markers showed that the SPTs may be originated from pancreatic embryonic stem cells,and result from immature differentiation of the pluripotential stem cells during pancreatic genesis.

Objective:To analyze the intellectual property risk of international cooperative scientific research involving human genetic resources, explore possible risk control measures regarding to intellectual property.Methods:By means of literature review, this paper analyzes the special attributes and strategic position of human genetic resources, reviews the policies and systems involving human genetic resources in international cooperative scientific research, identifies the intellectual property risk points, and puts forward suggestions on risk management and control from the perspective of intellectual property protection.Results:The management of human genetic resources in China is evolving quickly. However, there is still a lack of practical guidelines on intellectual property protection and development, more substantial engagement and contribution of Chinese investigators in the international collaborative research should be promoted, and the perception and awareness of the significance of human genetic resources should be enhanced.Conclusions:In the international cooperative scientific research involving human genetic resources, we should clarify the operating rules at the level of intellectual property protection, improve the substantive participation of Chinese investigators, enhance the strategic awareness and risk awareness of human genetic resources, and provide support at the level of executive management institutions.

Objective To investigate the expression of hypoxia-inducible factor-1α(HIF-1α),matrix metalloprotein-ase(MMP)-1 and MMP-2 in the serum of patients with diabetic retinopathy(DR),and to analyze their relationship with the stage of DR and angiogenesis.Methods A total of 280 patients with type 2 diabetes mellitus(T2DM)and no DR who were hospitalized in our hospital from December 2020 to December 2021 were selected as the T2DM group;276 DR patients who were hospitalized in the ophthalmology department of our hospital during the same period were selected as the DR group;another 282 healthy subjects who underwent physical examination in our hospital were selected as the normal group.There were no significant differences in gender and age distribution among the normal group,T2DM group and DR group(both P＞0.05).According to the results of fundus examination and fluorescein angiography,the patients in the DR group were divided into non-proliferative diabetic retinopathy(NPDR)group(129 patients)and proliferative diabetic reti-nopathy(PDR)group(147 patients).The fasting plasma glucose(FPG),glycosylated hemoglobin(HbA1c)and serum HIF-1 α,MMP-1,MMP-2 levels of subjects in the normal group,T2DM group and DR group,as well as NPDR group and PDR group were compared.The serum basic fibroblast growth factor(bFGF),angiopoietin-1(Ang-1)and vascular endo-thelial growth factor(VEGF)levels of subjects in the normal group,T2DM group and DR group,as well as NPDR group and PDR group were compared.Pearson correlation analysis was used to analyze the correlation between serum HIF-1α,MMP-1,MMP-2 and bFGF,Ang-1,VEGF levels in DR patients.Results The FPG,HbA1c and serum HIF-1α,MMP-1,MMP-2 levels of the T2DM group and DR group were higher than those of the normal group,and the differences were statis-tically significant(all P＜0.05).The serum HIF-1α,MMP-1 and MMP-2 levels of the DR group were significantly higher than those of the T2DM group(all P＜0.05);there were no significant differences in FPG and HbA1 c between the two groups(both P＞0.05).The serum HIF-1α,MMP-1 and MMP-2 levels of the PDR group were significantly higher than those of the NPDR group(all P＜0.05);there were no significant differences in FPG and HbA1c between the two groups(both P＞0.05).The serum bFGF,Ang-1 and VEGF levels of the T2DM group and DR group were higher than those of the normal group,and the differences were statistically significant(all P＜0.05).The serum bFGF,Ang-1 and VEGF levels of the DR group were significantly higher than those of the T2DM group(all P＜0.05).The serum bFGF,Ang-1 and VEGF levels of the PDR group were significantly higher than those of the NPDR group(all P＜0.05).Pearson correlation analysis showed that HIF-1α,MMP-1 and MMP-2 were positively correlated with bFGF,Ang-1 and VEGF levels in DR patients(all P＜0.05).Conclusion The serum HIF-1α,MMP-1 and MMP-2 levels of DR patients are abnormally elevated,and are closely related to the progression of DR and angiogenesis.These parameters can be used to predict the disease development trend and guide clinical intervention.