Band 47, Heft 1

The increase in the formation of reactive oxygen and reactive nitrogen species of endogenous or exogenous origin causes oxidative stress due to pro-oxidant and antioxidant imbalance that causes cellular damage in metabolism. This can increase inflammation of cells, apoptosis and necrosis, damage to DNA base damage, DNA and protein cross-links, lipid membrane peroxidation, and mitochondrial dysfunction. Antioxidants can be described as a system that protects biomolecules and the organism against the harmful effects of free radicals, reduces or repairs the damage done by reactive oxygen species (ROS) to the target molecule, and this is called antioxidant defense. It is known that the mechanisms caused by the increase in ROS resulting from oxidative stress are positively related to the pathology of many diseases such as cancer, metabolic syndrome, atherosclerosis, malaria, Alzheimer’s disease, rheumatoid arthritis, neurodegenerative diseases and preeclampsia.

Objectives The shortage of grafts for liver transplantation requires risk stratification and adequate allocation rules. This study aims to improve the model of end-stage liver disease (MELD) score for 90-day mortality prediction with the help of different machine-learning algorithms. Methods We retrospectively analyzed the clinical and laboratory data of 654 patients who were recruited during the evaluation process for liver transplantation at University Hospital Leipzig. After comparing 13 different machine-learning algorithms in a nested cross-validation setting and selecting the best performing one, we built a new model to predict 90-day mortality in patients with end-stage liver disease. Results Penalized regression algorithms yielded the highest prediction performance in our machine-learning algorithm benchmark. In favor of a simpler model, we chose the least absolute shrinkage and selection operator (lasso) regression. Beside the classical MELD international normalized ratio (INR) and bilirubin, the lasso regression selected cystatin C over creatinine, as well as IL-6, total protein, and cholinesterase. The new model offers improved discrimination and calibration over MELD and MELD with sodium (MELD-Na), MELD 3.0, or the MELD-Plus7 risk score. Conclusions We provide a new machine-learning-based model of end-stage liver disease that incorporates synthesis and inflammatory markers and may improve the classical MELD score for 90-day survival prediction.

Objectives Concentrations of pyridoxal 5′-phosphate (PLP) in serum and whole blood are routinely measured. The suitability of these markers in capturing vitamin B6 insufficiency is not well studied. Methods In 212 subjects, concentrations of PLP and thiamine pyrophosphate (TPP) were simultaneously measured in EDTA-whole blood using Chromsystems ® (52052) method on HPLC devices. The whole blood PLP concentrations were compared to serum PLP concentrations measured using reagents from Immundiagnostik ® (KC 2100). The whole blood TPP concentrations measured with the Chromsystems ® (52052) were compared to those measured by the Chromsystems ® (35000) method. Concentrations of homocysteine (tHcy) and cystathionine (Cys) were measured and used to judge the PLP methods. Results Serum PLP concentrations were on average 41% lower than whole blood PLP [mean (SD)=55.4 (83.0) vs. 131 (217) nmol/L]. Serum and whole blood PLP showed a strong correlation [Pearson correlation coefficient=0.724, p<0.001, n=204]. Eighty-five samples showed discrepant results for PLP status (serum PLP ≤30 nmol/L, but whole blood PLP >51 nmol/L) while 102 samples showed coherent results (reference group). The discrepancy group showed higher odds ratio for elevated tHcy >12.0 μmol/L compared to the reference group [OR (95% confidence intervals, CI)=2.1 (1.2–4.0)]. The OR (95% CI) of elevated Cys >300 nmol/L was 1.9 (1.0–3.5) in the discrepancy group compared to the reference group. TPP concentrations were 6% lower when using the Chromsystems ® , 52052 compared to levels measured with Chromsystems ® , 35000. Conclusions Serum and whole blood PLP concentrations disagree in a substantial number of samples. Serum PLP was better in reflecting elevated tHcy and Cys compared to whole blood PLP. Whole blood PLP underestimates the prevalence of vitamin B6 insufficiency. Methods of measuring TPP concentrations in whole blood were exchangeable.

Objectives Lung cancer is a common malignant tumour of the lung and the leading cause of cancer mortality worldwide. Non-small cell lung cancer (NSCLC) accounts for 80–85% of lung cancers, and 40% of NSCLCs have spread beyond the lungs by the time they are diagnosed. The long noncoding RNA (lncRNA) prostate androgen-regulated transcript 1 (PART-1) has been reported to promote the development of several cancers. Methods In the current study, we investigated the role of PART-1 in the proliferation, invasion, and migration of NSCLC. Results The expression levels of the PART-1 gene were higher in NSCLC cell lines, including A549, H1229, H1650, H1975, and PC9, than in human bronchial epithelia (HBE) cell lines. Knocking down PART-1 inhibited the proliferation, invasion, and migration of A549 cells and decreased tumour proliferation in nude mice. We confirmed that PART-1 targeted miR-204-3p directly and that miR-204-3p targeted insulin-like growth factor binding protein 2 (IGFBP-2) directly. Furthermore, we discovered that PART-1 impacts NSCLC progression by regulating the miR-204-3p-targeted IGFBP-2 pathway. Conclusions The lncRNA PART-1 might be a target for treating NSCLC and an early marker in the diagnosis of early lung cancer.

Objectives Administration of the third dose of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine was initiated on December 1, 2021, in Japan. However, data on the long-term effects of this third vaccination remain scarce. Here, we examined the levels of SARS-CoV-2 antibodies in those who received the Pfizer BioNTech (BNT162b2) vaccine, 6 months after the third vaccination. Methods Samples from 40 healthy volunteers were used to measure SARS-CoV-2 antibodies with chemiluminescent assays against the receptor-binding domain (RBD) of the virus. Results At 445 days after the first dose of BNT162b2, which is 180 days after the third vaccination, the mean anti-RBD IgG level was 159.4 AU/mL (SD 100.1 AU/mL), which was significantly higher than 144 days after the second vaccination, while mean anti-RBD IgM was baseline level (0.4 C.O.I.). The decline in IgG, 180 days after the third vaccination, was 74.1% (SD 16.1%), which was significantly lower than the 88.6% (SD 4.4%) decline observed 144 days after the second vaccination. Furthermore, we revealed that the reduction in IgG from 14 to 180 days after the third vaccination showed a significant inverse correlation with age, and the higher antibody response in younger participants at 14 days after the third vaccination disappeared at longer time points. Conclusions The long-term durability of the IgG titer was significantly higher following the third vaccination compared with the second vaccination, and the reduction in IgG titer after the third vaccination inversely correlated with age.

Objectives This study aimed to describe the pathogen spectrum of bacteria and viruses of RTIs in hospitalized children during the Coronavirus disease 2019 (COVID-19) epidemic in Shenzhen. Methods From October 2020 to October 2021, the results of pathogenic tests causing RTIs were retrospectively analyzed in hospitalized children in Shenzhen Luohu Hospital Group. Results 829 sputum samples for bacterial isolation and 1,037 nasopharyngeal swabs for virus detection in total. The positive detection rate (PDR) of bacteria was 42.1%. Staphylococcus aureus (18.8%) was the predominant bacteria detected in positive cases, with Moraxella catarrhalis (10.9%), Streptococcus pneumoniae (9.5%) following. The PDR of the virus was 65.6%. The viruses ranking first to third were Human Rhinovirus (HRV), Respiratory syncytial virus (RSV), and Human Parainfluenza (HPIV), with rates of 28.0, 18.1, and 13.5%, respectively. Children under 3 years were the most susceptible population to RTIs. The pathogens of S. aureus , M. catarrhalis , S. pneumoniae , HRV, and HPIV were more prevalent in autumn. Meanwhile, RSV had a high rate of infection in summer and autumn. S. aureus and HRV had higher co-infection rates. Conclusions Our findings demonstrate the pathogen spectrum of 1,046 hospitalized children with RTIs in Shenzhen, China, during the COVID-19 outbreak.