The predictive value of plasma uridine for type 2 diabetes and its atherosclerotic complications.

Objective: Uridine might be a common link between pathological pathways in diabetes and cardiovascular diseases. This study aimed to investigate the predictive value of plasma uridine for type 2 diabetes (T2D) and T2D with atherosclerosis. Methods: Individuals with T2D and healthy controls (n = 218) were randomly enrolled in a cross-sectional study. Patients with T2D were divided into two groups based on carotid ultrasound: patients with carotid atherosclerosis (CA) (group DCA) and patients without CA (group D). Plasma uridine was determined using HPLC-MS/MS. Correlation and logistic regression analyses were used to analyze the results. Results: Fasting and postprandial uridine were significantly increased in patients with T2D compared with healthy individuals. Logistic regression suggested that fasting and postprandial uridine were independent risk factors for T2D. The receiver operating characteristic (ROC) curve showed that fasting uridine had a predictive value on T2D (95% CI, 0.686-0.863, sensitivity 74.3%, specificity 71.8%). Fasting uridine was positively correlated with LDL-c, FBG, and PBG and negatively correlated with fasting C-peptide (CP-0h) and HOMA-IS. The change in postprandial uridine from fasting baseline (Δuridine) was smaller in T2D patients with CA compared with those without (0.80 (0.04-2.46) vs 2.01 (0.49-3.15), P = 0.010). Δuridine was also associated with T2D with CA and negatively correlated with BMI, CP-0h, and HOMA-IR. Conclusion: Fasting uridine has potential as a predictor of diabetes. Δuridine is closely associated with carotid atherosclerosis in patients with T2D.

Analysis of Serum Anti-HBs Levels and HBsAg/HBeAg Markers in Children and Adolescents: A Cross-Sectional Study.

Hepatitis B virus (HBV) is a global public health concern, and China continues to face a high burden of HBV cases. Vaccination plays a critical role in controlling and eradicating HBV. However, studies have shown that some individuals may experience waning immunity over time, highlighting the importance of enhanced immunization strategies. This study aimed to investigate the relationship between age, gender, and anti-HBs antibody levels, as well as the prevalence of serum hepatitis B surface antigen (HBsAg)/HBV e antigen (HBeAg) positivity. This retrospective study included 43,609 pediatric patients who visited the outpatient department between January 2013 and December 2022. Serum biomarkers (HBsAg, anti-HBs, HBeAg, anti-HBe, and anti-HBc) were measured using Roche Cobas 8000. There is a significant difference in anti-HBs titer between genders and across different age groups (p < 0.05). The serological markers HBsAg/HBeAg exhibited the highest positivity rate in the age group of 15-18 years. The findings demonstrate a gradual decrease in anti-HBs levels following HBV vaccination. The prevalence of serum markers HBsAg/HBeAg is higher among adolescents aged 15-18 years, which should be a matter of concern and attention.

Turbulence of glutamine metabolism in pan-cancer prognosis and immune microenvironment.

Introduction: Glutamine is characterized as the nutrient required in tumor cells. The study based on glutamine metabolism aimed to develop a new predictive factor for pan-cancer prognostic and therapeutic analyses and to explore the mechanisms underlying the development of cancer. Methods: The RNA-sequence data retrieved from TCGA, ICGC, GEO, and CGGA databases were applied to train and further validate our signature. Single-cell RNA transcriptome data from GEO were used to investigate the correlation between glutamine metabolism and cell cycle progression. A series of bioinformatics and machine learning approaches were applied to accomplish the statistical analyses in this study. Results: As an individual risk factor, our signature could predict the overall survival (OS) and immunotherapy responses of patients in the pan-cancer analysis. The nomogram model combined several clinicopathological features, provided the GMscore, a readable measurement to clinically predict the probability of OS and improve the predictive capacity of GMscore. While analyzing the correlations between glutamine metabolism and malignant features of the tumor, we observed that the accumulation of TP53 inactivation might underlie glutamine metabolism with cell cycle progression in cancer. Supposedly, CAD and its upstream genes in glutamine metabolism would be potential targets in the therapy of patients with IDH-mutated glioma. Immune infiltration and sensitivity to anti-cancer drugs have been confirmed in the high-risk group. Discussion: In summary, glutamine metabolism is significant to the clinical outcomes of patients with pan-cancer and is tightly associated with several hallmarks of a malignant tumor.

Newly established LC-MS/MS method for measurement of plasma BH4 as a predictive biomarker for kidney injury in diabetes.

OBJECTIVE: The clinical research on BH4 is limited because of the difficulties on its measurement. In this study, we used our own established LC-MS/MS method to examine the plasma BH4 levels in diabetes to determine whether it could be used as a biomarker for the prediction of kidney injury in those patients. METHODS: Hospitalized diabetes patients in Renmin Hospital of Wuhan University from Jan to Aug 2021 were recruited. To assess the association between plasma BH4 with ACR or eGFR in diabetes, a total of 142 patients with type 2 diabetes (T2DM) were enrolled. They were divided into three groups by albuminuria levels: normoalbuminuria (n = 68), microalbuminuria (n = 48), and macroalbuminuria (n = 26) according to ACR; or into two groups by eGFR: eGFR≥90 or eGFR<90 ml/min for correlation and logistic regression analysis. Plasma BH4 level was measured by LC-MS/MS along with other biochemical indices. RESULTS: Plasma BH4 concentrations were decreased as ACR progressed. BH4 (r = -0.55, P < 0.001) and 2h C-Peptide (CP-2h) (r = -0.248, P = 0.003) levels were negatively correlated with ACR. Moreover, multivariable logistic regression analysis showed BH4 concentrations (B = -0.468, P < 0.001) and CP-2h (B = -0.257, P = 0.028) were independently associated with ACR progression. ROC curve showed that BH4 level has a predictive value on ACR (95%CI 0.686-0.841, sensitivity 69.1%, specificity 73%). Moreover, in diabetes patients with eGFR≥90 ml/min, plasma BH4 level (P = 0.008) is higher than those in diabetes with eGFR<90 ml/min and BH4 was remained independently associated with eGFR after multivariable logistic regression analysis (B = -0.193, P = 0.048). CONCLUSION: Our established LC-MS/MS method could be used on human plasma BH4 measurements and our data suggested that BH4 level can be used as a biomarker for kidney injury in diabetes indicated by its association with ACR progression and early renal function decline.

Analysis of Nucleic Acid and Antibody Detection Results for SARS-CoV-2 Infection.

BACKGROUND: Real-time polymerase chain reaction (RT-PCR) of virus nucleic acid test (NAT) has become the standard method to diagnose severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, there are still many limitations, especially the problem of the high false negative rate. Therefore, the aim of this study was to investigate the positive rate of SARS-CoV-2 NAT and evaluate the diagnostic performance of SARS-CoV-2 IgM and IgG antibody detection in novel coronavirus infection. METHODS: A total of 10309 suspected or high-risk cases of infection with SARS-CoV-2 in Wuhan Hubei, China, were tested for virus NAT by RT-PCR. Among those cases, 762 COVID-19 patients and 143 patients with non-COVID-19 who were tested for SARS-CoV-2 IgM and IgG during the NAT period were screened. The difference between the two test methods was analyzed using the chi-square test. RESULTS: The positive rate of 10309 cases was about 36% (95% CI: 33.39%-39.67%). SARS-CoV-2 was present in various types of specimens, and alveolar lavage fluid had the highest positive rate [52.38% (95% CI: 31.02-73.74)]. The clinical sensitivity of serum SARS-CoV-2 IgM and IgG was 77.17% (588/762) and 94.88% (723/762), respectively, and the clinical specificity was 93.71% (134/143) and 90.21% (129/143). The area under the curve (AUC) of SARS-CoV-2 IgG and combination of IgG with IgM were equally larger than IgM [0.973 (95% CI: 0.964-0.983) vs 0.930 (95% CI: 0.910-0.949)]. IgG antibody had the highest specificity [100.0% (95% CI: 100.00%-100.00%)] and sensitivity [94.0% (95% CI: 92.45%-95.55%)] when detected alone or in combination with IgM antibody. The total coincidence rate of SARS-CoV-2 antibodies detection and SARS-CoV-2 NAT for the diagnosis of SARS-CoV-2 infection was 92.04% (833/905). Among the 34 SARS-CoV-2 NAT-negative patients with clinical symptoms and CT imaging features, 29 (85.29%) patients were positive for SARS-CoV-2 IgM, and 31 (91.76%) were positive for IgG. CONCLUSION: SARS-CoV-2 NAT should be considered for many types of specimens, and the combined test of SARS-CoV-2 IgM and IgG can make up for the problem of missed NAT in COVID-19 patients.

Evaluation of Serum GDF15, AFP, and PIVKA-II as Diagnostic Markers for HBV-Associated Hepatocellular Carcinoma.

OBJECTIVE: To evaluate the potential diagnostic value of growth differentiation factor 15 (GDF15) alone and its combination with protein induced by vitamin K absence-II (PIVKA-II) and alpha-fetoprotein (AFP) for hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). METHODS: Serum levels of GDF15, PIVKA-II, and AFP were measured in 110 patients with HBV-associated HCC, 70 patients with HBV-related liver cirrhosis (LC), 70 patients with chronic hepatitis B (CHB), and 110 healthy patients. RESULTS: Serum GDF15 was positively related to the levels of PIVKA-II and AFP in patients with HCC (r = 0.352 and r = 0.378; all P <.0001). When the receiver operating characteristic (ROC) curve was plotted for patients with HCC vs all control patients, serum GDF15 had diagnostic parameters of an area under the curve (AUC) of 0.693, a sensitivity of 67.30%, and a specificity of 66.70%, which were lower than parameters for PIVKA-II and AFP (all P <.0001). When the ROC curve was plotted for patients with HCC vs patients with LC, the combination of GDF15 and PIVKA-II had the highest diagnostic accuracy of AUC and specificity as compared with other combinations (all P <.0001). CONCLUSION: We found that GDF15 is a potent serum marker for the detection of HBV-associated HCC and that PIVKA-II combined with GDF15 can improve diagnostic accuracy for HBV-associated HCC.

Analysis of adjunctive serological detection to nucleic acid test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection diagnosis.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused coronavirus disease 2019 (COVID-19) epidemic in China, December 2019. The clinical features and treatment of COVID-19 patients remain largely elusive. However, accurate detection is required for SARS-CoV-2 infection diagnosis. We aimed to evaluate the antibodies-based test and nucleic acid-based test for SARS-CoV-2-infected patients. METHODS: We retrospectively studied 133 patients diagnosed with SARS-CoV-2 and admitted to Renmin Hospital of Wuhan University, China, from January 23 to March 1, 2020. Demographic data, clinical records, laboratory tests, and outcomes were collected. Data were accessed by SARS-CoV-2 IgM-IgG antibody test and real-time reverse transcriptase PCR (RT-PCR) detection for SARS-CoV-2 nucleic acid in COVID-19 patients. RESULTS: Of 133 COVID-19 patients, there were 44 moderate cases, 52 severe cases, and 37 critical cases with no differences in gender and age among three subgroups. In RT-PCR detection, the positive rate was 65.9%, 71.2%, and 67.6% in moderate, severe, and critical cases, respectively. Whereas the positive rate of IgM/IgG antibody detection in patients was 79.5%/93.2%, 82.7%/100%, and 73.0%/97.3% in moderate, severe, and critical cases, respectively. Moreover, the IgM and IgG antibodies concentrations were also examined with no differences among three subgroups. CONCLUSION: The IgM-IgG antibody test exhibited a useful adjunct to RT-PCR detection, and improved the accuracy in COVID-19 diagnosis regardless of the severity of illness, which provides an effective complement to the false-negative results from a nucleic acid test for SARS-CoV-2 infection diagnosis after onsets.

Association of Apolipoprotein E Polymorphisms with White Matter Lesions and Brain Atrophy.

OBJECTIVE: Apolipoprotein E (ApoE) is mainly synthesized in the liver. So far, it is unknown the relationship among APOE gene polymorphisms and WML, brain atrophy. Therefore, the aim of the study was to assess the associations of APOE gene polymorphisms in patients with WML and brain atrophy. METHODS: A total of 58 patients with WML, 128 patients with brain atrophy, 112 patients with co-occurrence of WML and brain atrophy and 95 healthy elderly volunteers were recruited from Renmin Hospital of WuHan University. RESULTS: Allele E3 was the most common allele. The alleles E2 had significantly higher levels of ApoB and lower age in WML group. The alleles E2 was associated with the lower level of ApoB, LDL-Ch, TCh, and sdLDL in co-occurrence group. The E3/E3 genotype has higher level of sdLDL, but lower age and female frequency in WML. The E3/E4 genotype had higher level of TG, but lower age in WML. Gender, Age, E2, Hyperhomocysteinemia and UA were also significantly associated with disease progression. CONCLUSION: This study found that clinical data, lipids and metabolic complications were closely related to ApoE genotypes and alleles, and also disease progression and type.

Influenza A virus inhibits influenza virus replication by inducing IL-37.

BACKGROUNDS: The influenza virus is one of the major pathogens that seriously affect human health. It can cause a strong immune response and trigger a series of complications. Interleukin 37 (IL-37) is a newly discovered cytokine that plays an important regulatory role in infection and immunity. To date, there have been few studies on the correlation between influenza virus infection and IL-37. METHODS: Serum levels of IL-37 in 115 patients with influenza A virus (IAV) infection and 102 healthy subjects were measured by an enzyme-linked immunosorbent assay (ELISA). Real-time quantitative PCR (RT-qPCR) was used to detect differences in IL-37 expression in peripheral blood mononuclear cells (PBMCs) between IAV patients and healthy subjects. IL-37 expression was measured in A549 cells and PBMCs infected with IAV H3N2 using ELISA and RT-qPCR. After the H3N2-infected A549 cells were treated with human IL-37, the concentration of viral RNA was determined using RT-qPCR, and the titer of influenza virus was determined by a hemagglutination test. RESULTS: The IL-37 levels in the sera and PBMCs of patients infected with IAV were higher than those of healthy subjects. The expression of IL-37 mRNA and protein in IAV-infected A549 cells and PBMCs was upregulated, and IL-37 protein was able to inhibit the replication of IAV RNA. CONCLUSION: IAV-induced IL-37 expression inhibits IAV replication.

Age and gender distribution of Hepatitis C virus prevalence and genotypes of individuals of physical examination in WuHan, Central China.

Approximately 170 million people in the world are infected with Hepatitis C virus (HCV). There are no published population based studies about the prevalence of HCV genotypes and the associations of genotype and Infection frequency with gender and age in WuHan. We aimed to investigate the distribution of HCV prevalence and genotypes among different gender and age patients with chronic HCV infection in WuHan from 2011 to 2015. A total of 2685 anti-HCV positive serum samples from individuals of physical examinationwere recruited from the Renmin Hospital of WuHan University, Hubei Province in China from January 2011 to December 2015. From these 2685 anti-HCV positive serum samples, 496 samples were with a positive PCR for HCV RNA. The number of HCV infection showed an increase with year, but the annual infection rate has remained similar (χ(2) = 2.94, P = 0.568). 2685 cases were infected with HCV from 2011 to 2015 in WuHan city of China. Blood transfusion (18.14 %) was the main routs of transmission, followed by Surgery (8.94 %). The highest prevalence of HCV infection was at the age group 50-59 (25.85 % of 2685) and the lowest prevalence was 0-9 (0.93 % of 2685). HCV genotype 1 was the most prevalent (73.39 %), followed by genotypes 2 (17.14 %), 3 (5.25 %) and 6 (3.22 %). Genotype 4 and 5 was not detected in these patients. The most prevalent subtype was subtype 1b (71.98 %), followed by genotypes 2a (17.14 %). Five patients had mixed infection across the HCV subtypes. Among all genotypes, genotype 1 was highest in both male (73.27 %) and female (73.47 %) patients, followed by genotype 2. Genotype 1 (male: 29.84 % of 496, vs female: 43.55 % of 496, χ(2) = 20.07, P < 0.0001), genotype 2 (male: 6.25 % of 496, vs female: 10.89 % of 496, χ(2) = 6.81, P = 0.009), and 6 (male: 1.41 % of 496, vs female: 1.81 % of 496, χ(2) = 0.626, P = 0.401) were more common in female patients than males, while no significant gender differences were observed for genotype 6. Among age group 50-59 years Genotype 1 was most common in male patients (29.05 % of 148) followed in 20-29 years (23.65 % of 148), genotype 2 in the age group 60-69 (12 cases of 31) and genotype 3 in the age group 50-59 (4 cases of 13) and genotype 6 was most frequent in the age group 30-39 (4 cases of 7). The frequency of HCV prevalence was significantly higher in female patients compared to males before ages 60, while the opposite result was observed after 60 years. The most common HCV genotype in WuHan was subtype 1b followed by 2a and more common among women than males patients. Further studies are needed to collect a large number of samples to estimate the different epidemiology of the HCV genotypes, because the sample size of non-genotype 1b and 2a is not large enough and other factors like disease history/monthly income/etc. are not included in our study.

Value of HLA-DR genotype in systemic lupus erythematosus and lupus nephritis: a meta-analysis.

AIM: Human leukocyte antigen (HLA)-DRB1 allele polymorphisms have been reported to be associated with systemic lupus erythematosus (SLE) susceptibility, but the results of these previous studies have been inconsistent. The purpose of the present study was to systematically summarize and explore whether specific HLA-DRB1 alleles confer susceptibility or resistance to SLE and lupus nephritis. METHODS: This review was guided by the preferred reporting items for systematic reviews and meta-analyses (PRISMA) approach. A comprehensive search was made for articles from PubMed, Medline, Elsevier Science, Springer Link and Cochrane Library database. A total of 25 case-control studies on the relationship between gene polymorphism of HLA-DRB l and SLE were performed and data were analyzed and processed using Review Manager 5.2 and Stata 11.0. RESULTS: At the allelic level, HLA-DR4, DR11 and DR14 were identified as protective factors for SLE (0.79 [0.69,0.91], P < 0.001; 0.72 [0.60, 0.85], P < 0.0001; 0.47 [0.59, 0.95], P < 0.05, respectively). HLA-DR3, DR9, DR15 were potent risk factors for SLE (1.88 [1.58, 2.23], P < 0.001; 1.24 [1.07, 1.45], P < 0.05; 1.25 [1.10, 1.43], P < 0.001, respectively). However, HLA-DR8 was not statistically significant between the SLE group and control group (OR, 1.11 [0.96, 1.30], P > 0.05). DR4 and 11 (OR, 0.55 [0.39, 0.79], P < 0.01; 0.60 [0.37, 0.96], P < 0.05, respectively) conferred a significant protective effect for lupus nephritis. DR3 and DR15 (OR, 2.00 [1.49, 2.70], P < 0.05; 1.60 [1.21, 2.12], P < 0.001, respectively) were at a high risk of developing lupus nephritis. HLA-DR8, DR9 and DR14 (OR, 1.47 [0.9, 2.33], P > 0.05; 0.90 [0.64, 1.27], P > 0.05; 0.61 [0.36, 1.03], P > 0.05, respectively) were not statistically significant between the lupus nephritis and control groups. CONCLUSIONS: The HLA-DR4, DR11, DR14 alleles might be protective factors for SLE and HLA-DR3, DR9, DR15 were potent risk factors. In addition, HLA-DR4 and DR11 alleles might be protective factors for lupus nephritis and DR3 and DR15 suggest a risk role. These results proved that HLA-DR3, DR15, DR4 and DR11 might be identified as predictors for lupus nephritis and SLE.