Although the development of COVID-19 vaccines has been a remarkable success, the heterogeneous individual antibody generation and decline over time are unknown and still hard to predict. In this study, blood samples were collected from 163 participants who next received two doses of an inactivated COVID-19 vaccine (CoronaVac®) at a 28-day interval. Using TMT-based proteomics, we identified 1,715 serum and 7,342 peripheral blood mononuclear cells (PBMCs) proteins. We proposed two sets of potential biomarkers (seven from serum, five from PBMCs) at baseline using machine learning, and predicted the individual seropositivity 57 days after vaccination (AUC = 0.87). Based on the four PBMC's potential biomarkers, we predicted the antibody persistence until 180 days after vaccination (AUC = 0.79). Our data highlighted characteristic hematological host responses, including altered lymphocyte migration regulation, neutrophil degranulation, and humoral immune response. This study proposed potential blood-derived protein biomarkers before vaccination for predicting heterogeneous antibody generation and decline after COVID-19 vaccination, shedding light on immunization mechanisms and individual booster shot planning.
Humans ; COVID-19 Vaccines ; Leukocytes, Mononuclear ; Proteomics ; COVID-19/prevention & control* ; Vaccination ; Antibodies ; Antibodies, Viral ; Antibodies, Neutralizing

Objective : To investigate the awareness of nutritional health knowledge regular unpaid blood donors in Zhoushan City, Zhejiang Province, so as to provide insights into nutrition and health education among unpaid blood donors. Methods: The regular unpaid blood donors were sampled using a convenient sampling method from Zhoushan Central Blood Station from January 1, 2021 to June 30, 2022. The nutritional health knowledge was investigated using the Chinese Nutrition Health Knowledge Questionnaire for Adults compiled by Chinese Center for Disease Control and Prevention, and the awareness and source of nutritional health knowledge was descriptively analyzed. Results: Totally 526 questionnaires were allocated, and 502 valid questionnaires were recovered, with an effective recovery rate of 95.44%. The respondents included 240 men (47.81%) and 262 women (52.19%), and included 343 individuals at ages of 18 to 44 years (68.33%), and 159 individuals at ages of 45 years and older (31.67%). The overall awareness of nutritional health knowledge was 14.54% among regular unpaid blood donors in Zhoushan City, and a higher awareness was seen among female regular unpaid blood donors (17.56%) than among males (11.25%) (P<0.05), while the awareness of nutritional health knowledge was significantly higher among respondents at ages of 18 to 44 years than among those at ages of 45 years and older (16.91% vs. 9.43%, P<0.05). The awareness of nutritional health knowledge was significantly higher among respondents with an educational level of junior college and above than among those with an educational level of high school/technical secondary school/technical school (17.24% vs. 12.22%, P<0.05), and the awareness was significantly higher among respondents with healthcare-related occupations than among those with other occupations (16.44% vs. 14.22%, P<0.05). Wechat, Weibo, Tik Tok and Kuaishou were main routes to obtain nutritional health knowledge (83.86%). Conclusions The awareness of nutritional health knowledge is low among regular unpaid blood donors in Zhoushan City. Men, middle-aged and elderly residents and residents with a low educational level are targets that should be given a high priority for nutritional health education, and new media may be fully utilized for nutritional health education.

Chronic hepatitis B (CHB) virus infection is an important threat to global health despite the administration of vaccines and the use of antiviral treatments. In recent years, as the prevalence of obesity and metabolic syndrome has increased, non-alcoholic fatty liver disease (NAFLD) in patients with CHB has become more common. Both diseases can lead to liver fibrosis and even hepatocellular carcinoma, but the risk of dual etiology, outcome, and CHB combined with NAFLD is not fully elucidated. In this review, we assess the overlapping prevalence of NAFLD and CHB, summarize recent studies of clinical and basic research related to potential interactions, and evaluate the progressive changes of treatments for CHB patients with NAFLD. This review increases the understanding of the relationship and mechanisms of interaction between steatosis and hepatitis B virus infection, and it provides new strategies for the future clinical management and treatment of CHB combined with NAFLD.

Objective:To investigate the relationship between serum vascular endothelial growth factor (VEGF), peripheral blood microRNA-126 (miR-126) and the number and distribution of cerebral microbleeds (CMBs).Methods:Consecutive patients with non-acute ischemic cerebrovascular disease admitted to the Department of Neurology, the First Affiliated Hospital of Baotou Medical College from June 2019 to June 2020 were enrolled. The clinical data were collected, 3.0 T MRI examination was performed, and susceptibility-weighted imaging was used to detect CMBs. The serum VEGF concentration was detected by enzyme-linked immunosorbent assay, and miR-126 was detected by fluorescence quantitative polymerase chain reaction. Multivariate logistic regression analysis was used to determine the independent influencing factors of CMBs. Multiple linear regression analysis was used to determine the correlation between serum VEGF concentration, miR-126 in peripheral blood and the number of CBMs. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of serum VEGF concentration and relative expression of miR-126 in peripheral blood for CMBs. Results:A total of 193 patients with non-acute ischemic cerebrovascular disease were enrolled, including 110 patients (57.0%) in the non-CMBs group, 20 (10.4%) in the strictly lobar CMBs group and 63 patients (32.6%) in non-strictly lobar CMBs group. The comparison among the three groups showed that age might be a risk factor for strictly lobar CMBs, while higher VEGF, higher cystatin C level, lower relative expression of miR-126 in peripheral blood, hypertension and previous stroke or transient ischemic attack might be the risk factors for non-strictly lobar CMBs. Multivariate logistic regression analysis showed that higher serum VEGF concentration was an independent risk factor for non-strictly lobar CMBs (odds ratio 1.186, 95% confidence interval 1.035-1.358; P=0.014), while the higher relative expression of miR-126 was an independent protective factor for non-strictly lobar CMBs (odds ratio 0.154, 95% confidence interval 0-0.269; P=0.026). Multiple linear regression analysis showed that higher serum VEGF concentration ( r=0.848, P<0.001) and the lower relative expression of miR-126 ( r=-0.043, P=0.035) significantly increased the number of CMBs. ROC curve analysis showed that the area under the curve of serum VEGF for predicting non-strictly lobar CMBs was 0.803 (95% confidence interval 0.741-0.865), the optimal cut-off value was 120.55 ng/L, the sensitivity was 70.7%, and the specificity was 75.5%. Conclusions:In patients with non-acute ischemic cerebrovascular disease, there is a significant correlation between serum VEGF concentration and the relative expression of miR-126 in peripheral blood and the number and distribution of CMBs. Serum VEGF can be used as a biomarker for predicting the presence of non-strictly lobar CMBs.

Objective:To screen for the mutation types of the FOXL2 in 4 families with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES), and explore their genotype-phenotype correlations.Methods:To retrospectively analyze the result of FOXL2 gene detection by fluorescence quantification PCR, Sanger sequencing and multiplex ligation-dependent probe amplification(MLPA) in probands and families of BPES from January 2018 to January 2021, obtain mutation sites of pathogenic genes.Results:4 BPES families (8 cases) including 4 males and 4 females, with age ranged form 4 to 52 years (mean 24). The proband of family 1 has fragment deletion of Chr3∶138, 944, 224-138, 947, 137 region of FOXL2 gene. Proband of family 2 has heterozygosity deletion upstream of the 5’end of FOXL2 gene. There are missense mutations of c. 241 T>C(p.Y81 H)in proband and affected mother of family 3. There are c. 672_701dup(p.A224_A234dup) in-frame duplication mutations in proband and affected mother of family 4.Conclusions:Identification of causative mutations in the BPES patients has provided a basis for genetic counseling and reproductive guidance. The fragment deletion of Chr3∶138, 944, 224-138, 947, 137 region of FOXL2 gene and heterozygosity deletion upstream of the 5’end of FOXL2 gene are all new mutations that have not been reported. The novel mutations have enriched the mutation spectrum of the FOXL2 gene.

Metabolic-associated fatty liver disease (MAFLD) is currently the most common chronic liver disease in the world, which may eventually progress to cirrhosis, hepatocellular carcinoma and liver failure. Fatty liver disease was once considered to be the most common cause of cryptogenic cirrhosis. Recently, a new definition of MAFLD suggests that MAFLD-related liver cirrhosis is no longer a kind of cryptogenic cirrhosis, and it belong to two different concepts and may have different liver and extrahepatic adverse outcomes. In this paper, the definition, epidemiology, diagnosis, treatment and other aspects of MALFD-related liver cirrhosis and cryptogenic liver cirrhosis are described in order to facilitate clinical practice, improve the efficiency of clinical research, and benefit clinicians and patients.

Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in the world. Liver cirrhosis, liver cancer and a variety of extrahepatic chronic diseases are important risk factors for NAFLD. Currently, there is still a lack of effective therapeutic drugs. Liver inflammation is a key driving factor for the progression of NAFLD, so regulating liver inflammation may provide a potential means to delay and reverse the progression of nonalcoholic steatohepatitis (NASH). Studies have found that the gut-liver-immune axis plays an important role in the progression of NASH. Gut microbiota can use its metabolites to induce glycolipid toxicity, oxidative stress and intestinal barrier damage, while bacterial components such as lipopolysaccharides, peptidoglycans, bacterial DNA and extracellular vesicles can translocate into the liver through the damaged intestinal barrier, causing excessive activation of immune cells, thus aggravating liver inflammation and promoting the progress of NASH. This paper focuses on the gut-liver-immune axis to analyze the gut microbiota mediated liver immunity and its mechanism in the occurrence and development of NASH, so as to lay a theoretical foundation for the research and development of new therapeutic strategies for NASH.

Objective:To screen for the mutation types of the FOXL2 in 4 families with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES), and explore their genotype-phenotype correlations.Methods:To retrospectively analyze the result of FOXL2 gene detection by fluorescence quantification PCR, Sanger sequencing and multiplex ligation-dependent probe amplification(MLPA) in probands and families of BPES from January 2018 to January 2021, obtain mutation sites of pathogenic genes.Results:4 BPES families (8 cases) including 4 males and 4 females, with age ranged form 4 to 52 years (mean 24). The proband of family 1 has fragment deletion of Chr3∶138, 944, 224-138, 947, 137 region of FOXL2 gene. Proband of family 2 has heterozygosity deletion upstream of the 5’end of FOXL2 gene. There are missense mutations of c. 241 T>C(p.Y81 H)in proband and affected mother of family 3. There are c. 672_701dup(p.A224_A234dup) in-frame duplication mutations in proband and affected mother of family 4.Conclusions:Identification of causative mutations in the BPES patients has provided a basis for genetic counseling and reproductive guidance. The fragment deletion of Chr3∶138, 944, 224-138, 947, 137 region of FOXL2 gene and heterozygosity deletion upstream of the 5’end of FOXL2 gene are all new mutations that have not been reported. The novel mutations have enriched the mutation spectrum of the FOXL2 gene.

Objective:To investigate the safety and efficacy of anlotinib in treatment of advanced malignant tumors.Methods:The clinical data of 65 patients with advanced malignant tumors after the failure of the second-line treatment in Shanxi Bethune Hospital from July 2018 to July 2019 were retrospectively analyzed, including 32 cases of non-small cell lung cancer, 12 cases of small cell lung cancer, 15 cases of ovarian cancer, and 6 cases of peritoneal cancer. The objective total remission rate (ORR), disease control rate (DCR), progression-free survival (PFS) time, and the related adverse events were also analyzed.Results:ORR in non-small cell lung cancer group was 43.7% (14/32), DCR was 68.8% (22/32); ORR in small cell lung cancer group was 8.3% (1/12), and DCR was 25.0% (3/12). ORR in ovarian cancer group was 33.3% (5/15), DCR was 73.3% (11/15). In peritoneal carcinoma group, ORR was 0 (0/6) and DCR was 33.3% (2/6). The median PFS time was 8.0 months (95% CI 6.2-9.8 months) in the non-small cell lung cancer group, 3.0 months (95% CI 1.9-4.1 months) in the small cell lung cancer group, 5.0 months (95% CI 3.1-6.9 months) in the ovarian cancer group, and 2.0 months (95% CI 0.0-5.6 months) in the peritoneal cancer group. Hypertension was the most common non-hematology-related adverse event, and there were 6 cases (9.2%) of grade Ⅰ-Ⅱ adverse event and 1 case (1.5%) of grade Ⅲ-Ⅳ adverse event. Among the hematology-related adverse events, thrombocytopenia was the most common, and there were 8 cases (12.3%) of grade Ⅰ-Ⅱ adverse event and 1 case (1.5%) of grade Ⅲ-Ⅳ adverse event. All patients could tolerate the adverse reactions. Conclusion:Anlotinib is one of the options for the treatment of advanced malignant tumors, with mild drug-related adverse reactions and definite efficacy.

Current studies have confirmed that liver diseases are closely related to intestinal microorganisms; however, those studies have mainly concentrated on bacteria. Although the proportion of intestinal microorganisms accounted for by colonizing fungi is very small, these fungi do have a significant effect on the homeostasis of the intestinal microecosystem. In this paper, the characteristics of intestinal fungi in patients with chronic liver diseases such as alcoholic liver disease, nonalcoholic fatty liver disease and cirrhosis are summarized, and the effects of intestinal fungi and their metabolites are analyzed and discussed. It is important to realize that not only bacteria but also intestinal fungi play important roles in liver diseases.