Case Report: Chronic hepatitis E virus Infection in an individual without evidence for immune deficiency.

Chronic hepatitis E virus (HEV) infection occurs mainly in immunosuppressed populations. We describe an investigation of chronic HEV infection of genotype 3a in an individual without evidence for immune deficiency who presented hepatitis with significant HEV viremia and viral shedding. We monitored HEV RNA in plasma and stools, and assessed anti-HEV specific immune responses. The patient was without apparent immunodeficiency based on quantified results of white blood cell, lymphocyte, neutrophilic granulocyte, CD3+ T cell, CD4+ T cell, and CD8+ T cell counts and CD4/CD8 ratio, as well as total serum IgG, IgM, and IgA, which were in the normal range. Despite HEV specific cellular response and strong humoral immunity being observed, viral shedding persisted up to 109 IU/mL. After treatment with ribavirin combined with interferon, the indicators of liver function in the patient returned to normal, accompanied by complete suppression and clearance of HEV. These results indicate that HEV chronicity can also occur in individuals without evidence of immunodeficiency.

Potential of conserved antigenic sites in development of universal SARS-like coronavirus vaccines.

Given pandemic risks of zoonotic SARS-CoV-2 variants and other SARS-like coronaviruses in the future, it is valuable to perform studies on conserved antigenic sites to design universal SARS-like coronavirus vaccines. By using antibodies obtained from convalescent COVID-19 patients, we succeeded in functional comparison of conserved antigenic sites at multiple aspects with each other, and even with SARS-CoV-2 unique antigenic sites, which promotes the cognition of process of humoral immune response to the conserved antigenic sites. The conserved antigenic sites between SARS-CoV-2 and SARS-CoV can effectively induce affinity maturation of cross-binding antibodies, finally resulting in broadly neutralizing antibodies against multiple variants of concern, which provides an important basis for universal vaccine design, however they are subdominant, putatively due to their lower accessibility relative to SARS-CoV-2 unique antigenic sites. Furthermore, we preliminarily design RBDs to improve the immunogenicity of these conserved antigenic sites. Our study focusing on conserved antigenic sites provides insights for promoting the development of universal SARS-like coronavirus vaccines, thereby enhancing our pandemic preparedness.

Kinetics of severe acute respiratory syndrome coronavirus 2 infection antibody responses.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly throughout the world, causing severe morbidity and mortality. Since the first reports of Coronavirus disease 2019 (COVID-19) in late 2019, research on the characteristics of specific humoral immunity against SARS-CoV-2 in patients with COVID-19 has made great progress. However, our knowledge of persistent humoral immunity to SARS-CoV-2 infection is limited. The existence of protective immunity after infection will affect future transmission and disease severity. Therefore, it is important to gather knowledge about the kinetics of antibody responses. In this review, we summarize the information obtained so far on the characteristics and kinetics of the SARS-CoV-2 infection of specific humoral immune response, especially in neutralizing antibodies and their relationship with disease severity. In addition, with the emergence of variants of concern, we summarize the neutralizing effect of specific humoral immunity on variants of concern after the initial SARS-CoV-2 infection and vaccination.

Serum Metabolites Differentiate Amnestic Mild Cognitive Impairment From Healthy Controls and Predict Early Alzheimer's Disease via Untargeted Lipidomics Analysis.

Background and Aim: Alzheimer's disease (AD) is the most common type of dementia and presents with metabolic perturbations early in the disease process. In order to explore biomarkers useful in predicting early AD, we compared serum metabolites among patients suffering different stages of AD. Methods: We recruited 107 participants including 23 healthy controls (HC), 21 amnestic mild cognitive impairment (aMCI), 24 non-amnestic mild cognitive impairment (naMCI) and 39 AD patients. Via liquid chromatography-mass spectrometry based serum untargeted lipidomics analysis, we compared differences in serum lipid metabolites among these patient groups and further elucidated biomarkers that differentiate aMCI from HC. Results: There were significant differences of serum lipid metabolites among the groups, and 20 metabolites were obtained under negative ion mode from HC and aMCI comparison. Notably, 16:3 cholesteryl ester, ganglioside GM3 (d18:1/9z-18:1) and neuromedin B were associated with cognition and increased the predictive effect of aMCI to 0.98 as revealed by random forest classifier. The prediction model composed of MoCA score, 16:3 cholesteryl ester and ganglioside GM3 (d18:1/9z-18:1) had good predictive performance for aMCI. Glycerophospholipid metabolism was a pathway common among HC/aMCI and aMCI/AD groups. Conclusion: This study provides preliminary evidence highlighting that 16:3 cholesteryl ester were useful for AD disease monitoring while ganglioside GM3 (d18:1/9z-18:1) and neuromedin B discriminated aMCI from HC, which can probably be applied in clinic for early predicting of AD.

Temporal Dynamic Changes of Intrinsic Brain Activity Associated with Cognitive Reserve in Prodromal Alzheimer's Disease.

BACKGROUND: Cognitive reserve (CR) is an important protective factor for Alzheimer's disease (AD), yet its mechanism has not been fully elucidated. OBJECTIVE: To explore the effect of CR on resting and dynamic brain intrinsic activity in patients with mild cognitive impairment (MCI). METHODS: 65 amyloid-ß PET-negative (Aß-) normal controls (NC) and 30 amyloid-ß PET-positive (Aß+) MCI patients underwent resting-state functional magnetic resonance imaging were included from Alzheimer's Disease Neuroimaging Initiative. According to the years of education, the subjects were divided into high education group and low education group. A two-way analysis of variance was employed for the fractional amplitude of low-frequency fluctuation (fALFF) and dynamic fALFF (dfALFF) comparisons among the four groups. Moreover, the interaction effect of neuroimaging×pathology on clinical cognitive function was tested with linear regression analysis. RESULTS: The value of fALFF in the left prefrontal lobe was increased in Aß+ MCI patients compared to Aß- NC. The significant interactive effect between disease state and education (binary factor) was observed in the right parahippocampal gyrus (PHG) for fALFF, the right PHG and the right inferior parietal lobule for dfALFF. While no significant results between education (continuous factor) and brain activity was found in voxel-by-voxel analysis. For MCI patients, a significant fluorodeoxyglucose hypometabolic convergence index×right PHG dfALFF interaction was found, indicating the maintenance of executive function at higher levels of dfALFF in the right PHG. CONCLUSION: High CR can alleviate the impairment of hypometabolism on executive function in MCI patients, which is partially achieved by regulating the dynamic brain activity in the right PHG.

Gut microbiota interacts with intrinsic brain activity of patients with amnestic mild cognitive impairment.

AIMS: To explore the potential relationships among gut microbiota (GM), local brain spontaneous activity, and neuropsychological characteristics in amnestic mild cognitive impairment (aMCI) patients. METHODS: Twenty aMCI and 22 healthy control (HC) subjects were recruited. The GM composition was determined by 16S ribosomal RNA gene sequencing. Resting-state functional magnetic resonance imaging scans were performed, and fractional amplitude of low-frequency fluctuations (fALFF) was calculated across different frequencies. The Spearman or Pearson correlation analysis was used to analyze the relationship between spontaneous brain activity and cognitive function, and GM composition. RESULTS: aMCI patients had altered GM state and local spontaneous brain activity as compared with HC subjects. Correlation analysis showed that aMCI and HC groups had different "GM-intrinsic brain activity interaction" patterns. In aMCI group, at the typical band (0.01-0.08 Hz), the relative abundance (RA) of Bacteroides from phylum to genus level was negatively correlated with fALFF value of cerebellar vermis IV-V, and the Ruminococcaceae RA was negatively correlated with fALFF values of left lenticular nucleus and pallidum. The Clostridiaceae RA and Blautia RA were positively correlated with the left cerebellum lobules IV-V at the slow-4 band (0.027-0.073 Hz). The Veillonellaceae RA was positively correlated with fALFF values of left precentral gyrus at the slow-5 band (0.073-0.08 Hz). Correlation analysis showed that Clostridium members (Lachnospiraceae and Blautia) were positively, while Veillonellaceae was negatively, correlated with cognition test. Bacteroides was positively correlated with attention and computation, and negatively correlated with the three-stage command score. CONCLUSIONS: aMCI patients have a specific GM-intrinsic brain activity-cognitive function interaction pattern.

Cilostazol plus clopidogrel in the prevention of in-stent stenosis after vertebral artery origin stenting in gout patients: three case reports.

It is unclear whether cilostazol instead of aspirin in combination with clopidogrel could prevent in-stent thrombosis in patients with a history of gout undergoing vertebral artery origin stenting. Three men (age range, 58-74 years) were diagnosed with acute ischaemic stroke or transient ischaemic attack. Vertebral artery origin stenosis was visible by computed tomographic angiography or digital subtraction angiography. Four bare metal stents were placed in the vertebral artery origin. The patients were administered 100 mg cilostazol orally twice a day and 75 mg clopidogrel orally once a day perioperatively and 100 mg cilostazol orally twice day was administered indefinitely after 3 months. No in-stent stenosis was observed in all of these patients during a follow-up period up to 19 months. Cilostazol plus clopidogrel has the potential to become an alternative to standard dual antiplatelet therapy in vertebral artery origin stenting. A high-quality clinical trial is needed to verify these preliminary findings.

Aggregation of Vascular Risk Factors Modulates the Amplitude of Low-Frequency Fluctuation in Mild Cognitive Impairment Patients.

Background: Several vascular risk factors, including hypertension, diabetes, body mass index, and smoking status are found to be associated with cognitive decline and the risk of Alzheimer's disease (AD). We aimed to investigate whether an aggregation of vascular risk factors modulates the amplitude of low-frequency fluctuation (ALFF) in patients with mild cognitive impairment (MCI). Methods: Forty-three MCI patients and twenty-nine healthy controls (HCs) underwent resting-state functional MRI scans, and spontaneous brain activity was measured by the ALFF technique. The vascular risk profile was represented with the Framingham Heart Study general cardiovascular disease (FHS-CVD) risk score, and each group was further divided into high and low risk subgroups. Two-way ANOVA was performed to explore the main effects of diagnosis and vascular risk and their interaction on ALFF. Results: The main effect of diagnosis on ALFF was found in left middle temporal gyrus (LMTG) and left superior parietal gyrus (LSPG), and the main effect of risk on ALFF was detected in left fusiform gyrus (LFFG), left precuneus (LPCUN), and left cerebellum posterior lobe (LCPL). Patients with MCI exhibited increased ALFF in the LMTG and LSPG than HCs, and participants with high vascular risk showed increased ALFF in the LFFG and LCPL, while decreased ALFF in the LPCUN. An interaction between diagnosis (MCI vs. HC) and FHS-CVD risk (high vs. low) regarding ALFF was observed in the left hippocampus (LHIP). HCs with high vascular risk showed significantly increased ALFF in the LHIP than those with low vascular risk, while MCI patients with high vascular risk showed decreased ALFF in the LHIP than HCs with high vascular risk. Interestingly, the mean ALFF of LHIP positively correlated with word recall test in HCs with high vascular risk (rho = 0.630, P = 0.016), while negatively correlated with the same test in MCI patients with high vascular risk (rho = -0.607, P = 0.001). Conclusions: This study provides preliminary evidence highlighting that the aggregation of vascular risk factors modulates the spontaneous brain activity in MCI patients, and this may serve as a potential imaging mechanism underlying vascular contribution to AD.

Depression Affects Intrinsic Brain Activity in Patients With Mild Cognitive Impairment.

Numerous observational studies have shown that depressive symptoms are common in individuals with mild cognitive impairment (MCI) who have a higher rate of progress to dementia. However, it is still uncertain whether there are any differences between MCI patients with and without depression symptom in their brain function activities. Here we have identified the brain function activity differences in two groups of MCI patients (with depression or without depression) using the resting state MRI (rsfMRI) measurements. 76 right-handed MCI subjects have been recruited in this study, including 27 MCI patients with depression symptom (MCID), 49 MCI patients without depression symptom (MCIND). Analyses based on 7 rsfMRI measurements, including four static measurements (ALFF, fALFF, PerAF, and ReHo) and three dynamic measurements (dALFF, dfALFF, and dReHo) have been used to explore the temporal variability of intrinsic brain activity. No significant differences in ALFF and dALFF between the two group were found. In the MCID group, fALFF decreased in temporal gyrus, frontal gyrus, inferior occipital gyrus, middle frontal gyrus and cerebellum, but increased in cuneus, calcarine, lingual; while PerAF increased in left parahippocampus. The differences of ReHo in the two groups was only found in cerebellum. Compared to MCIND group, dfALFF in MCID decreased in cuneus, occipital gyrus and calcarine, while dReHo in MCID increased in bilateral temporal gyrus, frontal gyrus, superior parietal gyrus, inferior parietal gyrus and precuneus. Our results may provide a better understanding in the relationship between the depressive symptoms and memory deficits.

A model to predict the onset of non-alcoholic fatty liver disease within 2 years in elderly adults.

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic hepatitis, which leads to cirrhosis and hepatocellular carcinoma. However, it is difficult to identify subjects at high risk for NAFLD onset. This study aims to construct a model to predict the onset of NAFLD within 2 years in elderly adults. METHODS: This study included and followed 3378 initial NAFLD-free subjects aged 60 years or over for 2 years, which were randomly divided into a training set and a validation set. NAFLD was diagnosed on ultrasound. Clinical and laboratory data were recorded at baseline. A model was constructed in the training set to predict the onset of NAFLD and validated in the validation set. RESULTS: Body mass index, hemoglobin, fasting blood glucose, and triglycerides were identified as predictors for the onset of NAFLD. A risk score (R) was calculated by them. It classified the subjects into low-risk group (R ≤ -2.88), moderate-risk group (-2.88 < R ≤ -1.26), and high-risk group (R > -1.26). In the training set, 4.68% of the participants in the low-risk group, 11.59% of the participants in the moderate-risk group, and 31.02% of the participants in the high-risk group developed NAFLD. In the validation set, 5.84% of the participants in the low-risk group, 10.57% of the participants in the moderate-risk group, and 29.44% of the participants in the high-risk group developed NAFLD. CONCLUSIONS: This study developed a model to predict the onset of NAFLD in elderly adults, which might provide indications for intervention to these subjects.

Metal composition of layered double hydroxides (LDHs) regulating ClO(-)4 adsorption to calcined LDHs via the memory effect and hydrogen bonding.

A series of calcined carbonate layered double hydroxides (CLDHs) with various metal compositions and different M(2+)/M(3+) ratios were prepared as adsorbents for perchlorate. Adsorption isotherms fit Langmuir model well, and the adsorption amount followed the order of MgAl-CLDHs ≥ MgFe-CLDHs >> ZnAl-CLDHs. The isotherms of MgAl-CLDHs and MgFe-CLDHs displayed a two-step shape at low and high concentration ranges and increased with an increase in the M(2+)/M(3+) ratio from 2 to 4. The two-step isotherm was not observed for ZnAl-CLDHs, and the adsorption was minimally affected by the M(2+)/M(3+) ratio. The LDHs, CLDHs and the reconstructed samples were characterized by X-ray diffraction, SEM, FT-IR and Raman spectra to delineate the analysis of perchlorate adsorption mechanisms. The perchlorate adsorption of MgAl-CLDHs and MgFe-CLDHs was dominated by the structural memory effect and the hydrogen bonds between the free hydroxyl groups on the reconstructed-LDHs and the oxygen atoms of the perchlorates. For ZnAl-CLDHs, the perchlorate adsorption was controlled by the structural memory effect only, as the hydroxyl groups on the hydroxide layers preferred to form strong hydrogen bonds with carbonate over perchlorate, which locked the intercalated perchlorate into a more confined nano-interlayer. Several distinct binding mechanisms of perchlorate by CLDHs with unique M(2+) ions were proposed.

Aromatic and hydrophobic surfaces of wood-derived biochar enhance perchlorate adsorption via hydrogen bonding to oxygen-containing organic groups.

The pH-dependent adsorption of perchlorate (ClO4(-)) by wood-derived biochars produced at 200-700 °C (referred as FB200-FB700) was investigated to probe the anion retention mechanisms of biochars and to identify the interactions of water and biochar. ClO4(-) adsorption was controlled by the surface polarities and structural compositions of the organic components of biochars, rather than their inorganic mineral components. FB500-FB700 biochars with low polarity and high aromaticity displayed a superior ClO4(-) adsorption capacity, but which was affected by solution pH. Besides electrostatic interaction, hydrogen bonding to oxygen-containing groups on biochars was proposed the dominant force for perchlorate adsorption, which led to the maximum adsorption occurring near pHIEP, where surface charge equals zero. The dissociation of these surface oxygen-containing groups was monitored by zeta potential curves, which indicated that the H-bonds donors on biochar surface for ClO4(-) binding were changed from -COOH (ClO4(-)···HOOC-) and -OH (ClO4(-)···HO-) to -OH alone with an increase in pH. The H-bond force was strengthened by the condensed aromatic surfaces, since high temperature biochars provided a hydrophobic microenvironment to accommodate weakly hydrated perchlorate and facilitated the H-bonds for ClO4(-) binding to functional groups by the large π subunit of their aromatic substrate. Lastly, the batch and column tests of ClO4(-) adsorption showed that biochars like FB700 are effective adsorbents for anion pollutant removal via H-bonding interaction.

[Oxidative stress in patients with chronic hepatitis B].

BACKGROUND: To study oxidative stress in patients with chronic hepatitis B. METHODS: Malondialdehyde (MDA), total anti-oxidative ability and ascorbic acid were measured as markers of oxidative stress in 30 patients with chronic hepatitis B, besides HBV DNA and ALT. RESULTS: MDA was significantly higher in patients with hepatitis B than the controls (P less than 0.05). Ascorbic acid was significantly higher in patients with normal ALT than the controls (P less than 0.01). MDA was significantly higher in patients with increased ALT than the controls and in patients with normal ALT. MDA was significantly positively correlated with ALT (r=0.61), and ascorbic acid was significantly negatively correlated with ALT (r=-0.64) in patients with hepatitis B. No significant relationship was found between HBV DNA and other indices of oxidative stress. No significant difference in total anti-oxidative ability was found among all groups. CONCLUSION: There was a disturbance between oxidative stress and anti-oxidative ability in patients with chronic hepatitis B. In patients with increased ALT, oxidative stress became high. In patients with normal ALT, oxidative stress level was low. The indices of oxidative stress should be detected in patients with hepatitis B, in addition to HBV markers.