Background/Aims: Ubiquitination is widely involved in the progression of hepatocellular carcinoma (HCC) by regulating various cellular processes. However, systematic strategies for screening core ubiquitin-related genes, clarifying their functions and mechanisms, and ultimately developing potential therapeutics for patients with HCC are still lacking. Methods: Cox and LASSO regression analyses were performed to construct a ubiquitin-related gene prediction model for HCC. Loss- and gain-of-function studies, transcriptomic and metabolomics analysis were used to explore the function and mechanism of UBE2S on HCC cell glycolysis and growth. Results: Based on 1,423 ubiquitin-related genes, a four-gene signature was successfully constructed to evaluate the prognosis of patients with HCC. UBE2S was identified in this signature with the potential to predict the survival of patients with HCC. E2F2 transcriptionally upregulated UBE2S expression by directly binding to its promoter. UBE2S positively regulated glycolysis in a HIF-1α-dependent manner, thus promoting the proliferation of HCC cells. Mechanistically, UBE2S enhanced K11-linkage polyubiquitination at lysine residues 171 and 196 of VHL independent of E3 ligase, thereby indirectly stabilizing HIF-1α protein levels by mediating the degradation of VHL by the proteasome. In particular, the combination of cephalomannine, a small molecule compound that inhibits the expression of UBE2S, and PX-478, an inhibitor of HIF-1α, significantly improved the anti-tumor efficacy. Conclusions UBE2S is identified as a key biomarker in HCC among the thousands of ubiquitin-related genes and promotes glycolysis by E3 enzyme-independent ubiquitination, thus serving as a therapeutic target for the treatment of HCC.

Lacunar stroke (LS) is one of the subtypes of small cerebral vascular disease. Recent studies have shown that LS has a high risk of cognitive impairment, which imposes a heavy burden on patients, their families and society. However, at present, there is a lack of comprehensive discussion on the related factors, pathogenic mechanism, clinical features, prevention and treatment of cognitive impairment in LS patients. Therefore, this article reviews the relationship between LS and cognitive impairment, in order to provide clinical basis for early prevention and rehabilitation plan, and improve long-term follow-up awareness and comprehensive management ability of cognitive function in LS patients.

Buruli ulcer (BU), caused by

Objective:To investigate the correlation between item d560 of the International Classification of Functioning, Disability and Health (ICF) and the swallowing function of convalescing stroke patients.Methods:A total of 140 convalescent stroke survivors were evaluated for dysphagia using the ICF-d560 and the modified Watian drinking water test. Linear regression was used to analyze the influence of clinical factors when choosing a swallowing function assessment scale. Spearman correlation was computed to explore the correlation between ICF item d560 and the modified Watian drinking water test.Results:According to the ICF-d560 results, 10% of the patients had a mild disorder, with another 37.1% moderate, 29.3% severe and 23.6% completely dysphagic. The corresponding percentages according to the improved Watian drinking water test were 44.3% mild, 31.4% moderate and 24.3% severe. The total correlation coefficient between the two sets of results was 0.86, which was related to the stroke type, age, gender and stroke risk factors. The correlation coefficient of the cerebral infarction group was significantly higher than the cerebral hemorrhage group′s coefficient, and that of the women was slightly higher than that of the men. The strength of the correlation increased with age. The correlation coefficient was 0.84 among both diabetics and hypertension sufferers.Conclusions:Results from the ICF-d560 and the modified Wada drinking water test correlate well, which can provide a screening tool for swallowing function based on the ICF theoretical framework.

Objective To explore the relationship between ulcerative colitis (UC) susceptibility and tumor necrosis factor superfamily member (TNFSF) 15 gene polymorphisms and haplotypes in Han nationality in Zhejiang province of China. Methods A total of 408 UC patients and 574 healthy controls were recruited in this study. Three single nucleotide polymorphisms of TNFSF15 (rs3810936, rs4263839, rs4979462) were examined by improved multiple ligase detection reaction (iMLDR) technique. Analyses of linkage disequilibrium (LD) and haplotype were performed by Haploview 4.2 software in all study subjects. Results The variant allele A and genotype (GA+AA) of rs4263839 were less frequent in UC patients than in controls (45.34% vs. 50.17%, P=0.035; 68.38% vs. 76.66%, P=0.004). According to the severity and location of disease, UC patients were divided into different subgroups. After multiple comparison correction (α=0.012 5), the frequencies of variant allele A and genotype (GA+AA) of rs4263839 were lower in patients with severe UC than in the controls (37.69% vs. 50.17%, P=0.007;60.00% vs. 76.66%, P=0.004). Similar findings were also drawn for patients with extensive colitis in contrast with the controls (42.22% vs. 50.17%, P=0.009; 63.33% vs. 76.66%, P<0.001). Furthermore, the haplotype analysis indicated that three SNPs above were in a strong LD. The frequency of haplotype TAC was lower in UC patients than in the controls (40.83% vs. 46.04%, P=0.023). Also it was less prevalent in patients with severe UC and patients with extensive colitis when compared with controls respectively (33.38% vs. 46.04%, P=0.005;37.22% vs. 46.04%, P=0.003). Conclusions TNFSF15 (rs4263839) variation might not only reduce the risk of UC, but also affect the severity and lesion location of UC. The haplotype TAC formed by rs3810936, rs4263839 and rs4979462 might be related to a lower risk of UC, especially in patients with severe colitis or patients with extensive colitis.

Objective: To investigate the relationship of PD-L1 protein expression and gene amplification in gastric cancer and their correlation with clinicopathologic factors. Methods: The cohort included 247 gastric cancer specimens with follow-up data and clinicopathologic data obtained from Shanxi Cancer Hospital in 2011. PD-L1 expression was detected by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Results: PD-L1 protein was expressed in 25.9% (64/247) of the tumor cells and 26.7% (66/247) of the tumor infiltrating immune cells (IC). There was a correlation between the two (P<0.01). The expression of PD-L1 in tumor cells correlated with the degree of differentiation and tumor diameter(P<0.05). The PD-L1 expression in IC correlated with vascular tumor thrombi(P<0.05). The amplification rate of PD-L1 gene detected by FISH was 19.0% (47/247), and was associated with age, large/small curvature of the stomach, tumor location, tumor diameter, and lymph node metastasis(P<0.05). The positive coincidence rate of the two methods was 25.0% (16/64), negative coincidence rate was 83.0% (152/183), and total coincidence rate was 68.0% (168/247), suggesting that the coincidence of IHC and FISH was poor (P=0.157). There was a negative correlation between PD-L1 protein expression on tumor cells and prognosis in gastric cancer. There was no significant correlation between PD-L1 protein expression on IC and PD-L1 gene amplification with prognosis. Vascular tumor thrombi, tumor diameter, depth of invasion, and lymph node metastasis were all poor prognostic factors of gastric cancer(P<0.05). Multivariate Cox regression analysis showed that PD-L1 protein expression, depth of invasion and lymph node metastasis were all independent prognostic risk factors for gastric cancer. Conclusions Concordance between PD-L1 protein expression and gene amplification is poor. PD-L1 protein expression may signify poor prognosis. There is no significant correlation between PD-L1 gene amplification and prognosis of patients with gastric cancer.

The detection and molecular characterization of circulating tumor cells(CTCs) is one of the most important tool for liquid biopsy, which has the potential to enable non-invasive diagnostic tests for personalized medicine. Commercial platforms represented by CellSearch, the first FDA approved assay, have been considered to be valid for CTCs detection. However, special equipment and consumptive materials are required in the techniques listed above. Besides, most of them can not differentiate between apoptotic and viable cells, which indicates the portion of active and functional CTCs. Therefore, how to develop novel method for CTCs enrichment with metastatic potential has great significance in clinical routine. Telomerase-specific replication-selective oncolytic viruses expressing green fluorescent protein(GFP), including herpes simplex virus and adenovirus, allow the detection for human CTCs in the peripheral blood. After 24 h of transfection with recombinant virus, the tumor cells stably express GFP, and it could be used for CTCs counting by fluorescent microscopy or flow cytometry. Moreover, downstream analysis would be achieved by combination with PCR or DNA sequencing. Recombinant virus enables early detection of metastatic tumor cells, because the fluorescent signal is amplified only in viable, infected CTCs, by viral replication. This GFP-expressing virus-based method is remarkably sensitive, simple, and feasible, and it offers a new opportunity to detect and characterize CTCs in clinical routine.

OBJECTIVE:To explore the effects of early treatment with mouse nerve growth factor on the wound healing in aged patients with electric burn. METHODS:78 elderly patients with electric burn were divided into control group and observation group by random number table method,with 39 cases in each group. Control group was given routine method for electric burn, and observation group was additionally given Mouse nerve growth factor for injection 30 μg dissolved in 2 ml 0.9% Sodium chlo-ride injection within 24 h,im,qd,on the basis of control group. Treatment course of 2 groups lasted for 2 weeks. Clinical effica-cies of 2 groups were compared as well as VAS score before treatment,3,5,7 days after treatment. The survival rate of skin flaps and the rate of wound healing 3,5,7 days after treatment,the recovery of wound scar,the value of wound blood perfusion,the time of complete wound healing and the occurrence of ADR were also compared. RESULTS:The total effective rate of observation group(94.9%)was significantly higher than that of control group(66.7%),with statistical significance(P<0.05). 3,5,7 days after treatment,VAS score of observation group was significantly lower than that of control group,and the survival rate of skin flaps and the rate of wound healing were significantly higher than those of control group,with statistical significance(P<0.05). Af-ter treatment,VSS score of observation group was significantly lower than that of control group,while the value of wound blood perfusion was significantly higher than that of control group;the time of complete wound healing was significantly lower than that of control group,with statistical significance (P<0.05). No obvious ADR was found in 2 groups. CONCLUSIONS:Early treat-ment with mouse nerve growth factor for elderly patients with electric burns can effectively lower the VAS and VSS score,improve the survival rate of skin flaps and the rate of wound healing,increase the value of wound blood perfusion and shorten the time of complete wound healing with good clinical efficacy and safety.

Objective To investigate the correlation of the 24?hour ambulatory systolic blood pressure (SBP) and carotid intima?media thickness(CIMT) in the elderly. Methods A total of 2 464 who were more than or equal to 60 years old participants were selected with random sampling in accordance with the inclusion criteria from the retired workers in Tangshan Kailuan Company. Dynamic blood pressure monitoring, neck vascular ultrasound and other examination were performed for the participants. . Multivariable linear regression analysis was used to analyze correlation between the SBP of 24?hour, daytime and nightime with CIMT, respectively. Results ( 1) The observation population was divided into three groups according to the tertiles of SBP of 24?hour, daytime and nightime, respectively. With the levels of different SBPs inceasing, CIMT values thickened markedly ( P<0. 01 ) . ( 2 ) Multivariable linear regression analysis showed that after adjusting for confounding factors,the SBP of 24?hour,daytime and nightime associated with CIMT positively and linearly(P<0. 05),and regression coefficient(95%CI) were 0. 022(0. 009-0. 035), 0. 021(0. 008-0. 035), 0. 019 ( 0. 006-0. 032) respectively. In addition,clinic SBP step into the multivariable linear regression,and regression coefficient ( 95%CI ) were 0. 016 ( 0. 003-0. 029 ) , 0. 016 ( 0. 003-0. 030 ) , 0. 019 ( 0. 007-0. 032 ) , respectively. Conclusion The effect of increased 24?hour ambulatory SBP on CIMT was greater than the clinic SBP. Active monitoring of 24 h ambulatory blood pressure and maintaining a low level of blood pressure is essential for preventing and delaying atherosclerosis.

Objective To explore the relationship between different blood glucose levels and new carotid artery plaques.Methods A total of 5 440 participants met the inclusion criteria were selected stratified randomly from the 101,510 serving and retired workers of Tangshan Kailuan Company who participated the health examination from 2006 to 2007.The follow-up health examination were respectively preformed from 2010 to 2011 and from 2012 to 2013 which included carotid ultrasound for these 5 440 participants.The 5 440 participants were divided into three groups (ideal blood glucose group,impaired fasting glucose group and diabetic group) according to their fasting glucose levels in 2010-2011 examination.Multivariate Logistic regression analysis was used to analyze the risk factors of new carotid artery plaques.Results Among 5 440 subjects,participants whose FPG,ultrasound data incomplete and ultrasound detection of carotid plaques during the 2010-2011 health examination were excluded,then 3 084 participants were included in this study,among them,175 participants who did not participate the 2012-2013 health examination and 561 participants whose carotid plaque ultrasound data incomplete were excluded.Thus,a total of 2 348 participants were included in the present analysis.The total detection of new carotid artery plaque rate was 15.0％ (352/2 348) after 2 years of follow-up.The detection of new carotid artery plaque rate in normal glucose group(n =1724),impaired fasting glucose group(n=464) and diabetic group(n=160) were 14.2％(245/1 724),14.9％(69/464) and 23.8％(38/160),respectively.The diabetic group was higher than that of the ideal blood glucose group and the impaired fasting glucose group,the difference was statistically significant(P＜0.05).Impaired fasting glucose group and diabetic group had an increased risk of new carotid artery plaque compared with those in ideal glucose group(OR =0.924,95％CI 0.691-1.235 and OR =1.733,95％CI 1.107-2.713,respectively),the difference was statistically significant(P＜0.05).After adjusted for the other risk factors,with the risk-adjusted ratio (OR =1.117,95％CI 0.824-1.513 and OR =1.393,95％CI 0.872-2.226).Conclusion The detection of new carotid artery plaque increase in the diabetic group.However,after adjustment for other risk factors associate with emerging danger of new carotid artery plaque is no significant difference.This requires more long-term follow-up study of a large sample to be further confirmed.