Background & Aims The development of COVID-19 vaccines has progressed with encouraging safety and efficacy data. Concerns have been raised about SARS-CoV-2 vaccine responses in the large population of patients with non-alcoholic fatty liver disease (NAFLD). The study aimed to explore the safety and immunogenicity of COVID-19 vaccination in NAFLD. Methods This multicenter study included patients with NAFLD without a history of SARS-CoV-2 infection. All patients were vaccinated with 2 doses of inactivated vaccine against SARS-CoV-2. The primary safety outcome was the incidence of adverse reactions within 7 days after each injection and overall incidence of adverse reactions within 28 days, and the primary immunogenicity outcome was neutralizing antibody response at least 14 days after the whole-course vaccination. Results A total of 381 patients with pre-existing NAFLD were included from 11 designated centers in China. The median age was 39.0 years (IQR 33.0–48.0 years) and 179 (47.0%) were male. The median BMI was 26.1 kg/m 2 (IQR 23.8–28.1 kg/m 2 ). The number of adverse reactions within 7 days after each injection and adverse reactions within 28 days totaled 95 (24.9%) and 112 (29.4%), respectively. The most common adverse reactions were injection site pain in 70 (18.4%), followed by muscle pain in 21 (5.5%), and headache in 20 (5.2%). All adverse reactions were mild and self-limiting, and no grade 3 adverse reactions were recorded. Notably, neutralizing antibodies against SARS-CoV-2 were detected in 364 (95.5%) patients with NAFLD. The median neutralizing antibody titer was 32 (IQR 8-64), and the neutralizing antibody titers were maintained. Conclusions The inactivated COVID-19 vaccine appears to be safe with good immunogenicity in patients with NAFLD. Lay summary The development of vaccines against coronavirus disease 2019 (COVID-19) has progressed rapidly, with encouraging safety and efficacy data. This study now shows that the inactivated COVID-19 vaccine appears to be safe with good immunogenicity in the large population of patients with non-alcoholic fatty liver disease.
Background The long-held notion that, without urinary tract or circulatory infection, bladder urine and blood are sterile biofluids has been disproven. There have been no previous reports on the kidney pelvis urinary microbiome after bladder disinfection in kidney stone patients. This study aimed to determine whether a kidney pelvis urinary microbiome is present after eliminating the influence of the bladder urinary microbiome, whether the microbiome composition is different in patients with stone kidney pelvis (SKP) and non-stone kidney pelvis (NSKP), and the correlation between SKP and patient clinical characteristics. Results Comparisons of bacterial diversity and community structure exhibited that urine in bladder was similar to SKP and NSKP. However, the comparisons showed that urine samples were different from blood. The most common operational taxonomic units were shared by all three types of urine samples. Corynebacterium was significantly higher in SKP compared to NSKP. Several bacteria were associated with patient characteristics, including Lactobacillus, which was positively correlated with fasting blood glucose, and Prevotella was negatively correlated with BMI. Lactobacillus was significantly higher in SKP compared to blood but not in NSKP compared to blood. Conclusions The composition of the kidney pelvis urinary microbiome after disinfection of the bladder and its similarity to the bladder microbiome indicate that bladder urine can be used to replace kidney pelvis urine in microbiome research. Additionally, the comparison of SKP and NSKP and clinical associations suggest that the occurrence of kidney stones is responsible for the SKP urinary microbiome.
The focus of this study was to detect novel sera biomarkers for smear-positive and smear-negative pulmonary tuberculosis and to establish respective diagnostic models using the surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF MS) technique. A total of 155 sera samples from smear-positive pulmonary tuberculosis (SPPTB) and smear-negative pulmonary tuberculosis (SNPTB) patients and non-tuberculosis (non-TB) controls were analyzed with SELDI-TOF MS. The study was divided into a preliminary training set and a blinded testing set. A classification tree of spectra derived from 31 SPPTB patients, 22 SNPTB patients, and 42 non-TB controls were used to develop an optimal classification tree that discriminated them respectively in the training set. Then, the validity of the classification tree was challenged with another independent blinded testing set, which included 20 SPPTB patients, 14 SNPTB patients, and 26 non-TB controls. SNPTB patients and non-TB controls also were analyzed alone using the same method. The optimal decision tree model with a panel of nine biomarkers with mass:charge ratios (m/z) of 4821.45, 3443.22, 9284.93, 4473.86, 4702.84, 3443.22, 5343.26, 3398.27, and 3193.61 determined in the training set could detect 93.55%, 95.46%, and 88.09% accuracy for classifying SPPTB patients, SNPTB patients, and non-TB controls specimens, respectively. Validation of an independent, blinded testing set gave an accuracy of 80.77% for controls, 75.00% for SPPTB, and 71.43% for SNPTB samples using the same classification tree. With the peaks displaying differences between SNPTB patients and non-TB controls, a simplified dendrogram (m/z 4821.45, 4792.74) demonstrated classification efficacy of 85.94% (sensitivity 86.36% and specificity 85.71%) for distinguishing SNPTB patients from non-TB controls. The independent blinded testing set containing 14 SNPTB patients and 26 non-TB controls gained an accuracy of 81.59% (sensitivity 78.57% and specificity 84.62%) for diagnosing SNPTB. Special proteins/peptides may change in SPPTB and SNPTB patients and those changes may be used to distinguish them with the proper discriminant analytical method and to pursue and identify some involved proteins underlying the biological process of tuberculosis.
Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling has a protective effect on normal cells. A number of previous studies demonstrated that Keap1/Nrf2 signaling is associated with drug resistance in numerous tumors. The aim of the present study was to investigate the roles of Keap1 in renal cell carcinoma (RCC) and its effect on sensitivity to chemotherapy. Reverse transcription-quantitative polymerase chain reaction was used to detect the mRNA expression of Keap1 in 45 cases of RCC tumors and adjacent normal tissues. A total of five randomly selected patients with RCC, five RCC cell lines and normal renal tubular cells were examined to detect the protein and mRNA expressions of Keap1. The 5-year survival rate was analyzed by Kaplan-Meier analysis. The cell viability was assessed by a Cell Counting kit-8 assay. The cell apoptosis and reactive oxygen species (ROS) were determined by flow cytometry. The expressions of associated proteins were determined by western blot analysis. It was identified that in RCC tissues and RCC cell lines, the expression of Keap1 was downregulated, which was considered to be associated with poor prognosis. In total, 1 µ M Axitinib significantly decreased cell viability, promoted ROS release and induced cell apoptosis in ACHN cells. Silencing Keap1 was able to reverse the inhibitory effect of Axitinib and enhance the protein expressions of Nrf2, NAD(P)H dehydrogenase [quinone] 1 and heme oxygenase 1. However, silencing Nrf2 increased the cell sensitivity to Axitinib. Under Axitinib condition, overexpressing Nrf2 was able to increase cell viability; however, overexpressing Keap1 resulted in an opposite effect. Keap1 serves as a tumor suppressor; its low expression was associated with poor prognosis and a decreased sensitivity of RCC cells to Axitinib. A possible mechanism underlying Axitinib resistance may involve Nrf2 overexpression.
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