Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

Objective To explore the impact of macrophage-to-myofibroblast transition(MMT)on pulmonary fibro-sis induced by acute lung injury by LPS.Methods Totally 21 male mice were randomly classified into 7 groups:control group,model group(LPS-PF)at different time points and intervention group of clodronate-liposomes(CL-LIP)treatement at different time points(n=3).Pulmonary fibrosis was identified by HE and Masson staining microscopy.The immuno-fluorescence technology was used for the evaluation of numbers of macrophage-to-myofi-broblast transition cells(MMT cell which co-expressed CD68 and α-SMA).Bone marrow-derived macrophages(BMDMs)were randomly classified into two group:control(Ctrl)group and TGF-β1-treated group induced by transforming growthfactor-β1.α-SMA,FN and Col1 were detected by RT-qPCR.The expression of α-SMA,Smad3 and p-Smad3 protein was evaluated by Western blot.Results At day 7,the Ashcroft score of lung tissue in LPS-PF mouse model was significantly increased when compared with the Ctrl group(P＜0.01);While the score signifi-cantly declined when the model was pretreated with CL-LIP(P＜0.05).As detected by immuno-fluorescence stai-ning,in CL-LIP group the number of CD68-positive cells co-labeled with α-SMA was obviously less then that of LPS-PF group of the corresponding time point(P＜0.01).When the BMDMs were stimulated by TGF-β1 at 24 h,48 h and 96 h respectively,a higher expression of α-SMA,FN,Col1,were found in TGF-β1-treated group than that in Ctrl group at the corresponding time point(P＜0.01).The expression of Smad3,p-Smad3 significantly higher in LPS-PF group(at both day 7 and day 10)and TGF-β1-treated group(at both 48 h and 96 h)as compared to cor-responding control group(P＜0.01).Conclusions MMT promotes pulmonary fibrosis induced by ALI via LPS.Smad3 is proved to be involved in the MMT process.

Objective To investigate carboxyl terminus of Hsc70-interacting protein(CHIP)and FAT a-typical cadherin 4(FAT4)expression in colorectal cancer(CRC)tissue and their clinical significance.Methods A total of 92 CRC patients treated in a hospital from May 2018 to May 2020 were selected as the study objects.The expressions of CHIP and FAT4 in CRC tissues and adjacent tissues were detected by im-munohistochemistry.Spearman rank correlation analysis showed the correlation between CHIP and FAT4 ex-pression in CRC tissues.Kaplan-Meier curve was used to analyze the relationship between CHIP and FAT4 expression and survival prognosis of CRC patients.Cox proportional risk model was used to analyze the prog-nostic factors of CRC patients.Results Compared with adjacent tissue,the positive rate of CHIP in CRC tis-sue was higher[65.22％(60/92)vs.10.87％(8/92)]and the positive rate of FAT4 was lower[28.26％(26/92)vs.89.13％(82/92)].The difference was statistically significant(X2=63.075,70.300,P＜0.001).There was a negative correlation between CHIP and FAT4 expression in CRC(r=-0.781,P＜0.001).The positive rates of CHIP and FAT4 were higher in CRC tissues with TNM stage Ⅰ to Ⅱ,high school differenti-ation and no lymph node metastasis,and the positive rates of CHIP and FAT4 were lower in CRC tissues with TNM stage Ⅲ,low differentiation and lymph node metastasis,and the difference was statistically significant(P＜0.05).The 3-year survival rates of CHIP positive and CHIP negative patients were 48.33％(29/60)and 78.13％(25/32),respectively,and the difference was statistically significant(Log-rank X2=6.709,P=0.010).The 3-year survival rates of FAT4-positive and FAT4-negative patients were 81.25％(13/16)and 53.95％(41/76),respectively,with statistical significance(Log-rank X2=5.124,P=0.032).TNM stage Ⅲ,low differentiation,lymph node metastasis and positive CHIP were risk factors for the prognosis of CRC pa-tients,while positive FAT4 was protective factor.Conclusion CHIP expression is increased and FAT4 ex-pression is decreased in CRC tissues.Both expressions are associated with poor clinicopathological features of CRC,which is helpful to evaluate the survival prognosis of CRC patients.

Objective To explore the expression levels of microRNA(miR)-34a in hippocampus of temporal lobe epilepsy rats and the effect of miR-34a on its target signaling pathway Notch1.Methods Rats were divided randomly into experiment group (n=40) and control group (n=40) by adopting random number table method.The status epilepticus model and the temporal lobe epilepsy model were induced by using lithium-pilocarpine for experiment group.The control group rats received an injection of an equal amount of 9 g/L saline as instead of pilocarpine.Racine grading was performed at 24 hours,day 3,day 7,day 15,and 1 month after modeling to evaluate the behavior.Real-time fluorescent quantitative polymerase chain reaction was used to test the mRNA expressions of miR-34a and Notch1.Western blot was performed to explore the protein expression of Notch1.Results The expression levels of miR-34a at post-status epilepticus in 24 hours,day 3,day 7,day 15 were 2.55±0.29,2.11±0.17,1.68±0.49 and 1.84±0.42,respectively,which showed statistically significant difference compared with the control group (1.00±0.00) (t=-1.55,-1.11,-0.68,-0.84,all P<0.05).The expression levels of Notch1 mRNA at post-status epilepticus in 24 hours,day 3,day 7,day 15,1 month were 1.44±0.31,1.27±0.13,1.52±0.28,0.91±0.33,and 0.80±0.09 respectively.There were significant differences at 24 hours,day 7 in Notch1 mRNA expression (t=-0.44,-0.52,all P<0.05) compared with the control group(1.00±0.00).The expression level of Notch1 mRNA on day 15 was significantly lower than 24 hours and day 7 (t=-0.54,-0.62,all P<0.05),and the expression in 1 month was significantly lower than in 24 hours,or day 3 and day 7 (t=-0.64,-0.46,-0.72,all P<0.05).The expression levels of Notch1 protein at post-status epilepticus 24 hours,day 3,day 7,day 15,1 month were 0.78±0.09,0.57±0.13,0.55±0.16,0.42±0.13,and 0.33±0.09,respectively.There was significantly up-regulated at 24 hours of Notch1 protein expression compared with control group (0.51±0.15)(t=-0.20,P<0.05);and the expression level at day 15 were significantly lower than 24 hours (t=-0.26,P<0.05),while the expression in 1 month was significantly lower than in 24 hours and on day 3 (t=-0.36,-0.24,all P<0.05).Conclusion miR-34a is significantly up-regulated in the post-status epilepticus rat hippocampus,and it may contribute to temporal lobe epilepsy by activating Notch1 signaling pathway.

Objective To investigate the clinical effect of "pre-purse-string" suture on submucous gastric lesions of external growth type in endoscopic patients. Methods Clinical data of 27 patients with gastric lesions of external growth type admitted to the digestive endoscopy center of Renmin Hospital of Wuhan University from August 2016 to October 2016 for endoscopic submucosal dissection ( ESD ) were analyzed. Patients were randomly divided into two groups, the experiment group receiving the "pre-purse-string" suture, the control group receiving purse-string suture after ESD. Mean size of the lesions, procedure time, withdrawal time of gastric decompression, and hospitalization time were compared. Results In the 15 patients of the experiment group, there were 3 cases whose lesions were located in gastric antrum, 6 in gastric body and 6 in gastric fundus. In the 12 cases of the control group, 3 lesions were located in gastric antrum, 5 in gastric body and 4 in gastric fundus. All procedures were successfully completed in endoscopy. No obvious postoperative complications occurred. The mean size of lesions was 2. 5 cm × 3. 2 cm in the experiment group,and 2. 4 cm×3. 0 cm in the control group (P=0. 63). The operation time was 28. 0-43. 0 min (35. 8±6. 1 min) in the experiment group, and 45. 6-68. 8 min (48. 8±5. 3 min) in control group ( P<0. 01) . Conclusion "Pre-purse-string" technique is of clinical effect on gastric submucosal tumor of external growth.

BACKGROUND:Buccal Multiloop Removable Appliance can interceptively correct mutiple adolescent malocclusions. But the clinical problem of Buccal Multiloop fatigue fracture is not solved yet. How to prolong the fatigue fracture cycle is stil in the research stage. OBJECTIVE: To study the effect of different temperature of heat treatment on the Buccal Multiloop fatigue fracture cycle, thereby to select a relatively optimal method to enhance the fatigue fracture cycle. METHODS: Thirty-five left HL-2 Buccal Mltiloops were divided into seven groups according to different ways of heat treatment. Each group consisted of five samples. They were an untreated group, three pre-bending groups (320, 420, 520℃ heat treatment before bending) and three post-bending groups (320, 420, 520℃ heat treatment after bending). The dental stainless steel wires and Buccal Multiloop were respectively treated by low-temperature annealing. The data were recorded and evaluated after the samples tested by the 3D Simulating Movement of TMJ Testing Machine. The features of fatigue fracture were observed by scanning electron microscope. RESULTS AND CONCLUSION: The mean values of the Buccal Multiloop fatigue fracture cycle from largest to smalest were as folows: 520℃ pre-bending group > 420℃ pre-bending group > 320℃ pre-bending group > untreated group > 520℃ post-bending group > 320℃ post-bending group > 420℃ post-bending group. The fatigue fracture cycle of Buccal Multiloop made of the dental stainless steel wires after 520℃ annealing treatment was longer than others. By the observation of scanning electron microscope, the fracture crack extension area had the tendency to expand, transient interruption was delayed and the tissue structure became more uniform.

BACKGROUND:Concerning the problem of the ruptured phenomenon in clinic work of HL-1 and HL-2 Buccal Multiloops removable appliance, we invented HL-3 Buccal Multiloops.
OBJECTIVE:Through the Buccal Multiloops Fatigue Testing Machine which can imitate oral movements, to compare the fatigue strength of the HL-2 and HL-3 Buccal Multiloops in the same condition.
METHODS:A pair of the HL-2 or HL-3 Buccal Multiloops with the completely symmetrical size, symmetrical height and symmetrical direction was fixed on the Buccal Multiloops Fatigue Testing Machine which could simulate oral movements, then keep the Buccal Multiloops Fatigue Testing Machine working until any Buccal Multiloops broke. The cyclic loading times of this pair Buccal Multiloops was recorded. Scanning electron microscope was used to observe the appearance of broken end of the Buccal Multiloops.
RESULTS AND CONCLUSION:The cyclic loading times of HL-3 Buccal Multiloops were more than HL-2 Buccal Multiloops (P < 0.01), suggesting that HL-3 Buccal Multiloops has stronger fatigue strength than HL-2 Buccal Multiloops. Scanning electron microscope observation showed that the fractures of HL-2 and HL-3 Buccal Multiloops al had the typical fatigue fracture morphology, indicating that the rupture of HL-2 and HL-3 Buccal Multiloops belongs to fatigue fracture. However, HL-3 Buccal Multiloops exhibited bigger crack compared with HL-2 Buccal Multiloops, the presence of running-in region, suggesting that HL-3 Buccal Multiloops reduced the probability of fatigue fracture and prolonged the time of fatigue fracture.

Objective To investigate expression of elastin,lysyl oxidase (LOX)and elafin in cardinal ligament of women with pelvic organ prolapse(POP) so as to determine their contributions to POP.Methods The cardinal ligament samples were obtained from 60 POP subjects and 60 non-POP control women undergoing hysterectomy.RT-PCR was used to verify the mRNA level of elastin,LOX and elafin.The protein concentration of the three genes was determined by western blotting technique,electrophoretic separation and quantification.Results The premenopansal and postmenopausal POP groups demonstrated significantly decreased expressions of elastin in cardinal ligament both in mRNA and protein levels than control group (mRNA 0.42±0.22,0.26±0.20 versus 0.79±0.30,0.63±0.23 ; protein 0.44±0.32,0.20±0.19 versus 0.89±0.27,0.78±0.25; P＜0.05).There was an identical tendency in the expression of LOX (mRNA 0.37±0.18,0.20±0.14 versus 0.65±0.22,0.53±0.20; protein 0.45±0.27,0.26±0.21 versus 0.85±0.39,0.69±0.31 ; P＜0.05).In POP group,the mRNA and protein levels of elastin and LOX in postmenopansal patients were significantly lower than premenopansal patients (P＜0.05).Inversely,POP group demonstrated an increased expression of elafin in cardinal ligament both in mRNA and protein levels than corresponding control group (mRNA 1.33±0.35,1.47±0.37 versus 0.62±0.25,0.55±0.24; protein 0.85±0.30,0.76±0.35 versus 0.21±0.15,0.29±0.22; P＜0.05). There was no significant difference in the expression of elafin between premenopansal and postmenopausal POP groups either in mRNA or protein levels(P＞0.05).There was a positive correlation between elastin and LOX both in mRNA and protein levels in POP group(r=0.9959,0.9708; P＜0.05),but there was no correlation between elastin and elafin(r=-0.0402,-0.0365;P＞0.05).Conclusions The results suggest that the decreased expression of elastin and LOX and the increased expression of elafin in the cardinal ligaments may contribute to POP.