Hepatocellular carcinoma (HCC) expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming. Aldolase A (ALDOA) plays a prominent role in glycolysis; however, little is known about its role in HCC development. In the present study, we aim to explore how ALDOA is involved in HCC proliferation. HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout, which is consistent with ALDOA overexpression encouraging HCC proliferation. Mechanistically, ALDOA knockout partially limits the glycolytic flux in HCC cells. Meanwhile, ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase; ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function. A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun, and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells. In HCC patients, the expression level of ALDOA was correlated with the phosphorylation level of c-Jun (Thr93) and poor prognosis. Remarkably, hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models, and the knockdown of A ldoa strikingly decreased HCC development in vivo. Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription, opening additional avenues for anti-cancer therapies.

Objective:To study the epidemiological and genetic characteristics of coxsackievirus B3 (CVB3) circulating in Guangdong Province from 2008 to 2021.Methods:This study collected the specimens of hand, foot, and mouth disease (HFMD) cases from 2008 to 2021 that were positive for other enteroviruses except for enterovirus 71 (EV71), coxsackievirus A16 (CVA16), and CVA6, as well as the specimens of herpangina and neonatal infection cases from 2020 to 2021. Enteroviruses in these specimens were detected and their types were identified. CVB3 strains were isolated and the entire VP1 sequences of CVB3 strains were amplified and sequenced. The genetic features of CVB3 strains were analyzed using DNAStar 7.1 and MEGA 6.06 software packages.Results:Among 3 484 HFMD cases positive for other enteroviruses from 2008 to 2021, CVB3-positive cases accounted for 1.6% (57/3 484); among 560 cases of herpangina from 2020 to 2021, CVB3-positive cases accounted for 2.1% (12/560); one neonatal infection case in 2021 was positive for CVB3. CVB3-positive cases accounted for 67.1% (47/70) in 2021 and 18.6% (13/70) in 2020, while there were less than five cases in other years. Forty-eight CVB3 strains were isolated and the entire VP1 sequences of 26 CVB3 strains were obtained. Phylogenetic analysis indicated that the CVB3 strains could be divided into eight genotypes (A-H) and the strains of genotypes A, D and E were prevalent in the Chinese mainland. The 26 CVB3 strains isolated in Guangdong Province shared 80.2%-100.0% nucleotide homology, and belonged to two genotypes of D and E, with genotype D prevalent from 2008 to 2017 and genotype E prevalent from 2020 to 2021.Conclusions:CVB3 is prevalent sporadically in Guangdong Province from 2008 to 2017, but the epidemic intensity increased during 2020 and 2021. CVB3 strains of genotypes D and E are prevalent in Guangdong Province during 2008 to 2021, with genotype E being the prevalent genotype during 2020 and 2021.

Objective:To investigate the etiological mechanism in single small subcortical infarction (SSSI) with different imaging features.Methods:The patients registered in a database of ischemic stroke in the Department of Neurology of the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2019 were analyzed. According to the lowest slice (LS) and the total number of involved slices (TNS) on diffusion-weighted imaging, the SSSI was divided into 3 types: proximal SSSI (pSSSI; LS≤2), distal and large SSSI (dl-SSSI; LS>2, TNS>2) and distal and small SSSI (ds-SSSI; LS>2, TNS≤2). The clinical and imaging features among 3 different lesion patterns were compared by using χ 2 test, Kruskal-Wallis H test and multiple Logistic regression analysis, etc. Results:In the 3 groups of ds-SSSI ( n=205), dl-SSSI ( n=157) and pSSSI ( n=166), the prevalences of parent artery disease (PAD)[10.7% (22/205) , 19.1% (30/157) , 42.8% (71/166), respectively, χ 2=54.89, P<0.001], coronary artery disease [8.3% (17/205), 14.0% (22/157), 16.9%(28/166), respectively, χ 2=6.44, P=0.040] and severe white matter hyperintensities (sWMHs)[58.0% (119/205), 43.3% (68/157), 41.0% (68/166), respectively, χ 2=12.94, P<0.001], the level of serum homocysteine (Hcy)[18.01 (13.54, 25.56), 16.03 (12.50, 21.09), 14.72 (11.12, 19.14) μmol/L, respectively, H=19.36, P<0.001], and the National Institutes of Health Stroke Scale (NIHSS) score[2(1, 3), 3(1, 4), 3(2, 6), respectively, H=39.53, P<0.001] showed statistically significant differences. Multiple Logistic regression analysis showed that compared with dl-SSSI patients, the lesion pattern of patients with higher proportion of PAD ( OR=3.12, 95% CI 1.86-5.24, P<0.001) was closer to pSSSI; the lesion pattern of patients with higher serum Hcy level ( OR=1.02, 95% CI 1.00-1.04, P=0.046) or higher proportion of sWMHs ( OR=1.79, 95% CI 1.12-2.86, P=0.015) was closer to ds-SSSI, and the lesion pattern of patients with higher proportion of PAD ( OR=0.50, 95% CI 0.27-0.93, P=0.029) or higher NIHSS score ( OR=0.84, 95% CI 0.77-0.92, P<0.001) was closer to dl-SSSI. Conclusions:The pathogenesis of ds-SSSI tends to be cerebral small vessel disease. The pathogenesis of pSSSI is related to atherosclerosis. The patients with dl-SSSI have the intermediate characteristics of pSSSI and ds-SSSI and may be unstable.

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) positively affect the initial control of non-small cell lung cancer (NSCLC). Rapidly acquired resistance to EGFR-TKIs is a major hurdle in successful treatment. However, the mechanisms that control the resistance of EGFR-TKIs remain largely unknown. RNA structures have widespread and crucial functions in many biological regulations; however, the functions of RNA structures in regulating cancer drug resistance remain unclear. Here, the psoralen analysis of RNA interactions and structures (PARIS) method is used to establish the higher-order RNA structure maps of EGFR-TKIs-resistant and -sensitive cells of NSCLC. Our results show that RNA structural regions are enriched in untranslated regions (UTRs) and correlate with translation efficiency (TE). Moreover, yrdC N⁶-threonylcarbamoyltransferase domain containing (YRDC) promotes resistance to EGFR-TKIs. RNA structure formation in YRDC 3' UTR suppresses embryonic lethal abnormal vision-like 1 (ELAVL1) binding, leading to EGFR-TKI sensitivity by impairing YRDC translation. A potential therapeutic strategy for cancer treatment is provided using antisense oligonucleotide (ASO) to perturb the interaction between RNA and protein. Our study reveals an unprecedented mechanism through which the RNA structure switch modulates EGFR-TKI resistance by controlling YRDC mRNA translation in an ELAVL1-dependent manner.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; ErbB Receptors/metabolism* ; GTP-Binding Proteins/therapeutic use* ; Lung Neoplasms/genetics* ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; RNA ; RNA-Binding Proteins/genetics* ; Tyrosine Kinase Inhibitors/therapeutic use*

Enzyme is an efficient and green biocatalyst, and widely used in many areas. Immobilized enzyme is superior to its free form in a variety of properties. Enzyme immobilization studies started in the 1970s in China. Till now, immobilized enzymes are widely applied in the fields of food, medical, energy, environmental management, among others. However, there are still some defects such as no universal method and the high cost. Therefore, based on the relatively mature traditional immobilization technologies, efforts have been made to innovate immobilization technologies. As a result, many new immobilization technologies focusing on new carriers and methods are continuously generated. Coupling with more than ten years' study on enzyme immobilization, we present here recent development and application of new immobilization technologies, as well as suggestions to future development of immobilization technology.

Objective: To investigate the causes of disease among patients with liver disease hospitalized in Department of Infectious Diseases in our hospital and the changes in such causes within the past 20 years. Methods: A retrospective analysis was performed for the clinical data of 7570 patients who were admitted to our hospital from January 1995 to December 2015. The chi-square test was used for the statistical analysis of constituent ratio. Results: Of all 7570 patients with liver disease, 4930 (65.13%) had viral hepatitis, 332 (4.39%) had immune disease, 215 (2.84%) had drug-induced liver injury, 192 (2.54%) had fatty liver disease, 88 (1.16%) had schistosome-induced liver disease, 160 (2.11%) had inherited metabolic diseases, and 20 (0.13%) had vascular disease; 689 (9.1%) still had no clear cause of disease at discharge. The proportion of patients with viral hepatitis was 77.61% in the first 10 years and 59.19% in the last 10 years (P < 0.01). As for liver disease caused by hepatotropic virus, there were significant increases in the proportion of patients with hepatitis C or hepatitis E from the first to the last 10 years (hepatitis C: 2.24% vs 15.56%, P < 0.01; hepatitis E: 18.61% vs 23.07%, P < 0.05), while there were significant reductions in the proportion of patients with hepatitis B (68.14% vs 60.01%, P < 0.05) or hepatitis A (10.7% vs 1.36%, P < 0.05). The proportion of patients with immune diseases was 0.82% in the first 10 years and 6.08% in the last 10 years (P < 0.01). There were also certain changes in the proportion of patients with liver disease caused by other reasons. Conclusion There is a large proportion of patients with viral hepatitis among patients with liver disease hospitalized in Department of Infectious Diseases in a large general hospital, especially hepatitis B and E caused by hepatotropic virus. There is a certain change in the epidemiology of liver disease within the past 20 years, with a reduction in the proportion of patients with viral hepatitis and an increase in the proportion of patients with non-infectious liver diseases. There is a large proportion of patients with unknown causes of liver disease.

Objective To explore the effect of the clinical case oriented management model on nurses comprehensive ability, psychological and critical mind. Methods In 2014 on the implementation ofroutine clinical case management modelas the control group, collected 97 cases of clinical cases. In 2015 on the implementation ofthe clinical case oriented management modelas the observation group, collected 110 cases of clinical cases. Compared two methods of management to improve the nurse management theoretical knowledge, clinical practice ability and deal with the size of the case skills help. When/after clinical special case found the influence for nurses, including psychology, work in the nursing work will, enthusiasm, independent ability to deal with related cases and the nurse critical thinking ability, etc. Results The proportion of the nurses thought that it was helpful to improve the management of theoretical knowledge, clinical practice ability and deal with the size of the case skills and the case analysis of satisfaction were 98.79%(244/247), 99.19%(245/247), 98.79%(244/247), 99.60%(246/247) in the observation group, and 88.57%(217/245), 87.35%(214/245), 87.76%(215/245), 90.61%(222/245) in the control group. The differences were statistically significant (χ2=21.390-27.571, P < 0.01). The proportion of the nurse considered that special case on the psychological effects of nursing work, engaged in the willingness and enthusiasm were the main factor were 15.79%(39/247), 13.77%(34/247), 11.34%(28/247) in the observation group, and 31.84%(78/245), 31.02%(76/245), 30.61%(75/245) in the control group. The differences were statistically significant (χ2=17.475, 21.097, 27.611, P < 0.01). After special case, the percentage of nurses to independently handle the case, help others, loss rates were 97.57%(241/247), 2.02% (5/247), 0.40% (1/247) in the observation group, and 85.71% (210/245), 12.24% (30/245), 2.04% (5/245) in the control group. The proportion of nurses to independently handle the case in the observation group was higher than that in the control group, but the ratio of nurses to help others, loss rates in the observation group were lower than those in the control group, the differences were statistically significant (χ2=22.647, P<0.01).Critical thinking score, the observation group of nurses in the search for truth, open mind, analytical ability, system organization, judging thinking self-confidence, curiosity, cognitive maturity, such as total score were respectively (43.24±4.01), (43.03±4.12), (47.66±4.23), (44.21± 3.92), (44.00 ± 4.97), (52.13 ± 4.44), (48.23 ± 4.85), (319 ± 14.57) points. The control group nurses were respectively (39.00±3.56), (38.90±3.28), (43.65±2.47), (40.55±1.99), (39.00±3.40), (47.87±4.01), (41.89± 5.11), (292.23 ± 6.02) points. The differences were statistically significant(t =12.15-24.19, P < 0.01). Conclusions The clinical case oriented management model can improve nurses comprehensive ability, reduce the adverse impact of the special case for nurses, improve the clinical nurses' critical thinking ability, to ensure patient safety.

Objective To explore the effect of competency based education (CBE) in the nursing training of GNS (gerontological nurse specialist).Method The CBE was used in the nursing training of GNS and the differences in knowledge and nursing skills,ability in nursing training,and aiblity in organization and scienticific research.Result After the training,the GSN was above 80 in knowledge and skills,ability in nursing training,ability in organization and scientific research and self-assessment better than that before training (P＜0.05).Conclusion The CBE for the nursing training can upgrade the abilities in the GSN in the aspects of knowledge and skills,nursing training,organization and scientific research so that they become more competent in the gerontological nursing.

Objective To explore the training model of nurse specialists in geriatric and study its practical effect. Methods Forty-two nurse specialist participating in the training courses in geriatrics were enrolled in the study. The training was divided into 2 stages: the first one was for 1 month theoretical study together with 2 months clinical practice; the second was for 9 months clinical research on a specific topic. The examinations were done both at the two stages. They were interviewed on their views on theoretical study and internship at the end of first stage. Results The degree of satisfaction with the theoretical course was 91.6%, and the satisfaction degree of internship was 92.9%. The average scores at the end of the final examination and graduation examination were more than 85 points. Toally they were funded with 4 muncipal scientific research programs and 3 municipal patents, and published 9 academic papers. Conclusions The standardized training model is accessible for the nursing because of the training content and form. This model is feasible and effective, and it is worth applying and popularizing in the training of nurse specialist in the future.

Objective To study the effect of new barrel theory in improving evaluation of hospitalized patients. Methods Eight hundred hospitalized patients from September 2012 to August 2013 were randomized equally into the control group and the observation group.The last one or two items affecting patient satisfaction from the control group were used as objectives to be improved.Causal effect analysis was done pertinent to the items and the worksheet was bettered and improved and then enforced.The two groups were compared after intervention with new barrel theory in terms of satisfaction of patients during admission and discharge. Result The satisfaction of patients in the observation group during admission and discharge was significantly better than that in the control group(P<0.05).Conclusion The new barrel theory used to detect the flaws in nursing service and improve the workflow can improve assessment from the patients so that the management quality can be enhanced.