Effect of Using the Active Cycle of Breathing Technique Combined with Watson's Theory of Human Caring in Rapid Patient Rehabilitation Following Lung Cancer Surgery.

Background and Objective: We explored the effect of the Active Cycle of Breathing Technique (ACBT) on rapid patient rehabilitation following lung cancer (LC) surgery and the advantages of Watson's Theory of Human Caring. Method: A total of 64 patients with LC were chosen and randomly divided into 2 groups: the ACBT group and the routine care group. The ACBT group received Watson's Theory of Human Caring, and ACBT was adapted for respiratory training to promote airway secretions, excretions and pulmonary function (PF) recovery. After the intervention, PF, 6-Minute Walk Test (6MWT) distance, heart rate (HR), clinical treatment, quality of life (QoL), nursing satisfaction, negative emotions and postoperative complications were compared in the 2 groups. Results: The results showed that PF levels (peak expiratory flow [PEF], forced expiratory volume in 1 second/forced vital capacity ratio [FEV1/FVC], vital capacity [VC], partial pressure of oxygen dissolved in blood [PaO2], oxygenation index [OI] and oxygen saturation as measured by blood analysis [SaO2]) in the ACBT group were significantly higher than in the routine care group, while partial pressure of carbon monoxide (PaCO2) was significantly lower. In addition, after ACBT training, patient 6MWT distance increased, and the maximum HR, Borg fatigue score and Borg dyspnea score in the training group were lower than in the routine care group. In terms of clinical treatment, duration of drainage tube retention, total oxygen therapy, out of bed time, hospital stay and visual analog score (VAS) score in the ACBT group were all lower. At the same time, QoL and nursing satisfaction in patients in the ACBT group were higher, and anxiety and depression were significantly lower. Moreover, the incidence of postoperative complications was 6.25% in the ACBT group and 28.13% in the routine care group. Conclusion: ACBT combined with the Watson Theory of Human Caring can better restore LF in patients with LC following surgery, so as to promote rapid recovery and reduce postoperative complications. In addition, Watson's Theory of Human Caring is of great significance for improving the nurse-patient relationship and building a harmonious hospital.

The Role of Cholinesterase in Differential Diagnosis between Gastric Cancer and Benign Gastric Diseases.

BACKGROUND: Gastric cancer is the fifth most common malignancy worldwide. In early stages, no obvious symptoms are usually observed in gastric cancer patients, and it is especially hard to distinguish gastric cancer from benign gastric diseases, resulting in delayed diagnosis and poor prognosis. Common biomarkers of gastric cancer, such as CEA and CA19-9, are also elevated in benign diseases. There is an urgent need to develop a convenient and reliable biomarker for differentiating between gastric cancer and benign gastric diseases. METHODS: This study retrospectively analyzed the data of 126 patients, including 73 gastric cancer patients and 53 benign gastric disease patients. Patient characteristics collected for analysis included age, gender, laboratory data, and clinical staging. Unpaired t-test was used to check the difference of cholinesterase level between the gastric cancer group and the benign gastric disease group. Kruskal Wallis H test and Mann-Whitney U test were used to check the difference of cholinesterase level among different stage groups. Receiver operating characteristic (ROC) curve was used to assess whether cholinesterase level can be used as a biomarker for differentiating between gastric cancer and benign gastric diseases. RESULTS: Serum cholinesterase level was decreased significantly in the gastric cancer group in comparison to that of the benign gastric disease group (p < 0.001). In addition, cholinesterase level of stage IV patients was significantly lower than stage I patients. ROC curve analysis revealed that with a cutoff of 5,969.00 U/L, cholinesterase level showed an area under the curve of 0.819 (95% CI 0.732 - 0.905, p < 0.001) in differentiating between gastric cancer and benign gastric diseases. No significant difference in the levels of CEA and CA19-9 was observed between gastric cancer patients and benign gastric disease patients. CONCLUSIONS: This study indicated that serum cholinesterase level could be considered as a potential biomarker for differentiating between gastric cancer and benign gastric diseases.

The efficacy of enteral nutrition combined with accelerated rehabilitation in non-small cell lung cancer surgery: A randomized controlled trial protocol.

OBJECTIVE: To investigate the effect of enteral nutrition combined with accelerated rehabilitation in treating the non-small cell lung cancer (NSCLC). METHODS: It is a randomized controlled experiment to be carried out from June 2021 to December 2021. It was permitted through the Ethics Committee of Cancer Hospital Affiliated to Shandong First Medical University (00923876). 100 patients are included in the study. The inclusion criteria contain: (1) patients with NSCLCs receiving surgery as the primary treatment; (2) over 18 years of age. The exclusion criteria are as follows: (1) age ≥65 years; (2) severe metabolic and systemic diseases, such as diabetes, hypertension, or severe liver and kidney dysfunction; (3) the body mass index <18.5 kg/m; (4) patients who have received preoperational radiotherapy or chemotherapy. Patients in the control group are provided routine nutrition, including preoperative nutritional risk screening and assessment and preoperative nutrition education and dietary guidance, while patients in the nutrition group are provided additional enteral nutrition preparations combined with accelerated rehabilitation as in the control group. The primary outcomes include the perioperative change of serum albumin, serum prealbumin, hemoglobin, and total lymphocyte counts. The second outcomes include length of hospitalization, quality of life, and risk of postoperative complications. RESULTS: shows the comparison of indicators after surgery between the 2 groups. CONCLUSION: Enteral nutrition combined with accelerated rehabilitation appears to be beneficial in decreasing the complications and improving postoperative recovery after NSCLC surgery.

TP53 R249S mutation detected in circulating tumour DNA is associated with Prognosis of hepatocellular carcinoma patients with or without hepatectomy.

BACKGROUND AND AIMS: Somatic mutation R249S in TP53 is highly common in hepatocellular carcinoma (HCC). We aim to investigate the effects of R249S in ctDNA on the prognosis of HCC. METHODS: We analysed three cohorts including 895 HCC patients. TP53 mutation spectrum was examined by direct sequencing of genomic DNA from tissue specimens in HCC patients with hepatectomy (Cohort 1, N = 260). R249S and other recurrent missense mutations were assessed for their biological functions and associations with overall survival (OS) and progression-free survival (PFS) of HCC patients in Cohort 1. R249S within circulating tumour DNA (ctDNA) was detected through droplet digital polymerase chain reaction (ddPCR) and its association with OS and PRS was analysed in HCC patients with (Cohort 2, N = 275) or without (Cohort 3, N = 360) hepatectomy. RESULTS: In Cohort 1, R249S occupied 60.28% of all TP53 mutations. Overexpression of R249S induced more serious malignant phenotypes than those of the other three identified TP53 recurrent missense mutations. Additionally, R249S, but not other missense mutations, was significantly associated with worse OS (P = .006) and PFS (P = .01) of HCC patients. Consistent with the results in Cohort 1, HCC patients in Cohorts 2 and 3 with R249S had worse OS (P = 8.291 × 10-7 and 2.608 × 10-7 in Cohorts 2 and 3, respectively) and PFS (P = 5.115 × 10-7 and 5.900 × 10-13 in Cohorts 2 and 3, respectively) compared to those without this mutation. CONCLUSIONS: TP53 R249S mutation in ctDNA may serve as a promising prognosis biomarker for HCC patients with or without hepatectomy.

Shape-Dependent Activity of Ceria for Hydrogen Electro-Oxidation in Reduced-Temperature Solid Oxide Fuel Cells.

Single crystalline ceria nanooctahedra, nanocubes, and nanorods are hydrothermally synthesized, colloidally impregnated into the porous La0.9Sr0.1Ga0.8Mg0.2O3-δ (LSGM) scaffolds, and electrochemically evaluated as the anode catalysts for reduced temperature solid oxide fuel cells (SOFCs). Well-defined surface terminations are confirmed by the high-resolution transmission electron microscopy--(111) for nanooctahedra, (100) for nanocubes, and both (110) and (100) for nanorods. Temperature-programmed reduction in H2 shows the highest reducibility for nanorods, followed sequentially by nanocubes and nanooctahedra. Measurements of the anode polarization resistances and the fuel cell power densities reveal different orders of activity of ceria nanocrystals at high and low temperatures for hydrogen electro-oxidation, i.e., nanorods > nanocubes > nanooctahedra at T ≤ 450 °C and nanooctahedra > nanorods > nanocubes at T ≥ 500 °C. Such shape-dependent activities of these ceria nanocrystals have been correlated to their difference in the local structure distortions and thus in the reducibility. These findings will open up a new strategy for design of advanced catalysts for reduced-temperature SOFCs by elaborately engineering the shape of nanocrystals and thus selectively exposing the crystal facets.

Bioinformatics study of cancer-related mutations within p53 phosphorylation site motifs.

p53 protein has about thirty phosphorylation sites located at the N- and C-termini and in the core domain. The phosphorylation sites are relatively less mutated than other residues in p53. To understand why and how p53 phosphorylation sites are rarely mutated in human cancer, using a bioinformatics approaches, we examined the phosphorylation site and its nearby flanking residues, focusing on the consensus phosphorylation motif pattern, amino-acid correlations within the phosphorylation motifs, the propensity of structural disorder of the phosphorylation motifs, and cancer mutations observed within the phosphorylation motifs. Many p53 phosphorylation sites are targets for several kinases. The phosphorylation sites match 17 consensus sequence motifs out of the 29 classified. In addition to proline, which is common in kinase specificity-determining sites, we found high propensity of acidic residues to be adjacent to phosphorylation sites. Analysis of human cancer mutations in the phosphorylation motifs revealed that motifs with adjacent acidic residues generally have fewer mutations, in contrast to phosphorylation sites near proline residues. p53 phosphorylation motifs are mostly disordered. However, human cancer mutations within phosphorylation motifs tend to decrease the disorder propensity. Our results suggest that combination of acidic residues Asp and Glu with phosphorylation sites provide charge redundancy which may safe guard against loss-of-function mutations, and that the natively disordered nature of p53 phosphorylation motifs may help reduce mutational damage. Our results further suggest that engineering acidic amino acids adjacent to potential phosphorylation sites could be a p53 gene therapy strategy.

Network effect of Wt-mutant p53 interactions and implications on p53 gene therapy.

Mutant p53 could have either a dominant negative effect or a gain of function to interfere with p53's ability to maintain genomic stability. In the present study, we screened for TP53 mutations in hepatocellular carcinoma (HCC) samples from 202 Chinese patients, followed by analysis of transcriptional and apoptotic activities of 21 p53 mutants with or without wild-type p53 present. We identified a new point mutation p.P72A, and a mutation (p.E294SfsX51) with a record long frameshift. We found TP53 mutations in HCC bear mutants without a dominant wild-type p53 inhibition on p21 transcription at a higher frequency. We found an anti-correlation for p53 WT/mutant heterotetramer to activate p21 and BAX transcription, i.e., at given p53 WT/mutant concentration, the fold increase p21 transcription is proportional to the fold of decreasing BAX transcription. Our kinetic model reproduced the trend in the experimental observation and confirmed that the p53 WT-dimer/mutant- heterotetramer is the major species to confer the differential activation of p21 and BAX transcription. p53 may have different binding modes on p21 and BAX, most likely resulting from the combinational effects of core domain binding and C-terminal mediation. Our study demonstrated that p53 mutants interfere with the ability of WT p53 to maintain genomic stability.

Carbonyl reductase 1 as a novel target of (-)-epigallocatechin gallate against hepatocellular carcinoma.

UNLABELLED: Human carbonyl reductase 1 (CBR1) converts the antitumor drug and anthracycline daunorubicin (DNR) into the alcohol metabolite daunorubicinol (DNROL) with significantly reduced antitumor activity and cardiotoxicity, and this limits the clinical use of DNR. Inhibition of CBR1 can thus increase the efficacy and decrease the toxicity of DNR. Here we report that (-)-epigallocatechin gallate (EGCG) from green tea is a promising inhibitor of CBR1. EGCG directly interacts with CBR1 and acts as a noncompetitive inhibitor with respect to the cofactor reduced nicotinamide adenine dinucleotide phosphate and the substrate isatin. The inhibition is dependent on the pH, and the gallate moiety of EGCG is required for activity. Molecular modeling has revealed that EGCG occupies the active site of CBR1. Furthermore, EGCG specifically enhanced the antitumor activity of DNR against hepatocellular carcinoma SMMC7721 cells expressing high levels of CBR1 and corresponding xenografts. We also demonstrated that EGCG could overcome the resistance to DNR by Hep3B cells stably expressing CBR1 but not by RNA interference of CBR1-HepG2 cells. The level of the metabolite DNROL was negatively correlated with that of EGCG in the cell extracts. Finally, EGCG decreased the cardiotoxicity of DNR in a human carcinoma xenograft model with both SMMC7721 and Hep3B cells in mice. CONCLUSION: These results strongly suggest that EGCG can inhibit CBR1 activity and enhance the effectiveness and decrease the cardiotoxicity of the anticancer drug DNR. These findings also indicate that a combination of EGCG and DNR might represent a novel approach for hepatocellular carcinoma therapy or chemoprevention.

p53 Promotes proteasome-dependent degradation of oncogenic protein HBx by transcription of MDM2.

Hepatitis B virus X protein (HBx) is closely involved in the development of hepatocellular carcinoma (HCC). Tumor suppressor p53 was reported to induce HBx degradation and repress its oncogenic function recently, but the molecular mechanism is unknown. In this study, we attempted to identify the underlying mechanism. We found that overexpression of p53 protein reduces the level of HBx protein and shortens its half-life, however, in MDM2 knock out cells, p53 has no effects on degradation of HBx, meanwhile, overexpression of MDM2 in absence of p53 can accelerate turnover of HBx protein. These indicate that p53-mediated HBx degradation is MDM2-dependent. MDM2 interacts with HBx in vitro and in vivo but does not promote its ubiquitination. In consistent with the results above, HCC tissue samples with wild-type p53 hardly detect HBx protein, whereas, HBx always accumulate in the tissues with mutant p53. Our data provide a possible mechanism on how p53 regulate HBx stability and also a new clue for the study of p53 mutation and HCC development.

Poly[[µ-1,4-bis-(imidazol-1-ylmeth-yl)benzene]bis-(µ(4)-cyclo-hexane-1,4-dicarboxyl-ato)dinickel(II)].

The structure of the polymeric title compound, [Ni(2)(C(8)H(10)O(4))(2)(C(14)H(14)N(4))](n), features a five-coordinate Ni(II) centre defined by four carboxyl-ate O atoms from two different cyclo-hexane-1,4-dicarboxyl-ate (chdc) ligands and an N atom from one end of a 1,4-bis-(imidazol-1-ylmeth-yl)benzene (1,4-bix) mol-ecule. The NO(4) coordination geometry is distorted square-pyramidal with the N atom in the apical position. Each end of the chdc ligand links pairs of Ni(II) atoms into a paddle-wheel assembly, i.e. Ni(2)(O(2)CR')(4). These are connected into rows owing to the bridging nature of the chdc ligands, and the rows are connected into a two-dimensional grid via the 1,4-bix ligands. The 1,4-bix ligand, which is disposed about a centre of inversion, is disorderd. Two positions of equal occupancy were discerned for the -H(2)C(C(6)H(4))CH(2)- residue.

Decreased expression of the human carbonyl reductase 2 gene HCR2 in hepatocellular carcinoma.

Altered gene expression was associated with the induction and maintenance of hepatocellular carcinoma (HCC). To determine the significance of HCR2 in HCC, here we compare the expression levels of HCR2 in carcinoma and in paired non-carcinoma tissues using semiquantitative reverse-transcription polymerase chain reaction (RT-PCR), Western blot analysis, and immunohistochemical staining. The expression ratio (ER) of HCR2 between the tumor and paired tumor-free tissues was calculated for each case and the data was clinicopathologically analyzed. The expression of HCR2 mRNA was found to be significantly decreased in HCC tissues compared with paired normal tissues (P < 0.001). HCR2 was downregulated in 58% (n = 22) of 38 HCC patients. The ER of HCR2 was higher in Edmondson's grade I/II carcinomas than that in Edmondson's grade III/IV carcinomas (P < 0.05). Western blot analysis showed HCR2 to be notably depressed in carcinoma tissues in 3 out of 4 HCC patients. Immunohistochemical staining indicated most HCR2 protein accumulated in non-carcinoma cells. These results suggested that altered HCR2 expression might play roles in the carcinogenesis and progression of HCC, and it could be a clinical marker for prognosis, and a molecular target for screening potential anti-HCC drugs.