Heterologous Booster Immunization Based on Inactivated SARS-CoV-2 Vaccine Enhances Humoral Immunity and Promotes BCR Repertoire Development.

Recent studies have indicated that sequentially administering SARS-CoV-2 vaccines can result in increased antibody and cellular immune responses. In this study, we compared homologous and heterologous immunization strategies following two doses of inactivated vaccines in a mouse model. Our research demonstrates that heterologous sequential immunization resulted in more immune responses displayed in the lymph node germinal center, which induced a greater number of antibody-secreting cells (ASCs), resulting in enhanced humoral and cellular immune responses and increased cross-protection against five variant strains. In further single B-cell analysis, the above findings were supported by the presence of unique B-cell receptor (BCR) repertoires and diversity in CDR3 sequence profiles elicited by a heterologous booster immunization strategy.

Case Report: A case of PLA2G6 gene-related early-onset Parkinson's disease and review of literature.

Background: Early onset Parkinson's disease (EOPD) is a neurodegenerative disease associated with the action ofto genetic factors. A mutated phospholipase A2 type VI gene (PLA2G6) is considered to be one of pathogenic genes involved in EOPD development. Although EOPD caused by a mutated PLA2G6 has been recorded in major databases, not all mutant genotypes have been reported. Here, we report a case of PLA2G6-related EOPD caused by a novel compound heterozygous mutation. Case presentation: The case was an of 26-year-old young male with a 2-year course of disease. The onset of the disease was insidious and developed gradually. The patient presented with unsteady walking, bradykinesia, unresponsiveness, and decreased facial expression. Auxiliary examination showed a compound heterozygous mutation of the PLA2G6gene with c.991G > T and c.1427 + 1G > A. Mild atrophy of the cerebrum and cerebellum was detected on brain MRI. The patient was diagnosed with EOPD. We administered treatment with Madopar, which was effective. After a two-year disease course, we observed progression to stage 5 according to the Hoehn-Yahr Scale (without medicine in the off-stage). An MDS-UPDRS III score of 62 was obtained, with characteristics of severe disease and rapid progress. The diagnosis was an EOPD phenotype caused by a combination of mutations at the c.991G > T and c.1427 + 1G > A sites of the PLA2G6gene. Conclusion: After active treatment, the disease was set under control, with no significant progression during the three-month follow-up period. Dyskinesia did not recur after reducing the Madopar dose. The freezing sign was slightly decreased and the wearing-off was delayed to 2 h.

Platelet Parameters, C-Reactive Protein, and Depression: An Association Study.

OBJECTIVE: This study aims to investigate the correlation of platelet parameters and C-reactive protein (CRP) with depression. METHODS: The clinical data of 61 patients with depression and 30 healthy control subjects were collected to compare the platelet parameters, CRP levels, and Hamilton Depression Rating Scale (HAMD) scores of the two groups for correlation analysis. RESULTS: The results revealed that the body mass index (BMI) of patients with depression was lower (P < 0.05) than that of the healthy control subjects, and that this difference was more significant in women than in men. Patients with severe depression showed an increased mean platelet volume (MPV) (P < 0.05). In the patients with depression, MPV was positively correlated (P < 0.05) with HAMD scores for work and interest, gastrointestinal symptoms, hopelessness, the anxiety/somatization factor, and the hopelessness factor. Platelet count (PLT) was negatively correlated (P < 0.05) with HAMD scores for hypochondriasis, and plateletcrit (PCT) was negatively correlated (P < 0.05) with HAMD scores for middle insomnia and hypochondriasis. Platelet distribution width (PDW) was positively correlated (P < 0.05) with HAMD scores for gastrointestinal and systemic symptoms as well as hopelessness. Higher CRP levels (P < 0.05) were found in the patients with depression than in the healthy control subjects. Furthermore, in the patients with depression, CRP levels were positively correlated (P < 0.05) with HAMD scores for guilt and the cognitive impairment factor. CONCLUSION: Classical platelet parameters (PLT, MPV, PCT, PDW) and CRP were shown to be associated with specific depressive symptoms and cognitive impairment factors, including sleep, gastrointestinal symptoms, hypochondriasis, losing interest in work, and despair. These results suggest that both platelet parameters and CRP could be suitable biomarkers for predicting the occurrence and prognosis of depression, thus providing a new target for its treatment.

Herba Rhodiolae alleviates depression via the BDNF/TrkB-GSK-3ß signaling pathway.

BACKGROUND: Depression is one of the most common psychiatric disorders worldwide. Many antidepressant drugs are only effective for specific patients and their long-term use can lead to treatment resistance. There is an ongoing need for more effective antidepressant treatments. METHODS: The rats were exposed to chronic unpredictable mild stress (CUMS) to induce depression model. The glutamate level in the hippocampus was determined by high performance liquid chromatography (HPLC). Protein levels in the tissues were measured using western blotting. The fluid consumption test was performed to evaluate potential anhedonia. Open field test was conducted to evaluate locomotor activity. Forced swimming test was used to evaluate susceptibility to negative mood. RESULTS: In the present study, the depressive-like behaviors induced by CUMS were alleviated in rats by treatments with Herba Rhodiolae (0.04 g/kg, 1 mL), venlafaxine (0.035 g/kg, 1 mL), and combination of Herba Rhodiolae and glycogen synthase kinase 3 beta (GSK-3ß) inhibitor (10 µM, 1 mL). Among these treatments, the combination of Herba Rhodiolae and GSK-3ß inhibitor was most effective. Abnormalities in the glutamate system and autophagy of the brain were decreased greatly in Herba Rhodiolae and GSK-3ß inhibitor-treated CUMS rats. Herba Rhodiolae was more effective in promoting the brain derived neurotrophic factor/tropomyosin receptor kinase B (BDNF/TrkB) signaling. The expression of GSK-3ß was remarkably suppressed by the GSK-3ß inhibitor. CONCLUSIONS: These findings indicated that the combined effects of Herba Rhodiolae and GSK-3ß inhibitor contributed to the activation of BDNF/TrkB-GSK-3ß signaling pathway.

Antidepressants effects of Rhodiola capsule combined with sertraline for major depressive disorder: A randomized double-blind placebo-controlled clinical trial.

BACKGROUND: We performed a proof of concept trial to evaluate relative safety and efficacy of Rhodiola Capsule for mild to moderate major depressive disorder(MDD). METHODS: It is a randomized double-blind placebo-controlled clinical trial which 100 patients were randomized to 12 weeks into three groups. One of which (group A: 33 patients) received one sertraline and two placebos(0.6 g/day) tablets daily, a second (group B: 33 patients) received one sertraline and two Rhodiola capsules (0.6 g/day) daily, and a third (group C: 34 patients) received one sertraline,one placebo tablet and one tablet of Rhodiola capsule (0.3 g/day)daily. Changes over time in Hamilton Depression Rating (HAM-D), Beck Depression Inventory (BDI), and Clinical Global Impression Change (CGI/C) scores were examined. Significant post-treatment improvements were observed for both groups (Rhodiola Capsule) in HAMD, BDI, and CGI scores. The decline in HAMD, BDI, and CGI scores was greater for group B versus group A and C.While the CGI (versus group A) were greater for group B and C. RESULTS: Statistically significant reductions were observed for HAM-D, BDI, and CGI scores for all treatment conditions with significant difference between groups. The decline in HAM-D, BDI, and CGI scores was greater for group B versus group C and A. CONCLUSIONS: It is concluded that the Rhodiola capsule shows anti-depressive potency in patients with depression disorder when administered in dosages of either 0.3 or 0.6 g/day over a 12-week period.Rhodiola capsule can improve the quality of life and clinical symptoms.The high doses of Rhodiola capsule are better than the lower doses.

Long non-coding RNA TCONS_00000200 as a non-invasive biomarker in patients with intracranial aneurysm.

We performed long non-coding RNA (lncRNA) microarray assay to identify lncRNAs with differential expression between patients with intracranial aneurysm (IA) and healthy control individuals to evaluate their potential use as biomarkers of IA. Arraystar Human lncRNA Microarray v3.0 was performed to identify differentially expressed lncRNAs and mRNAs in plasma samples (4 ml). lncRNAs with the most pronounced differential expression were used to select gene markers, and results were validated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Plasma levels of TCONS_00000200 (fold change: 2.28) and ENST00000511927 (fold change: 2.50) were significantly higher in IA patients than in healthy individuals (P<0.001), and plasma levels of ENST00000421997 (fold change: 0.45) and ENST00000538202 (fold change: 0.43) were significantly lower in IA patients than in healthy individuals (P<0.001). qRT-PCR confirmed the same trends of up- and down-regulation of these four lncRNAs. A receiver operating characteristic (ROC) curve for TCONS_00000200 showed that the area under the curve (AUC) was 0.963 (95% confidence interval, 0.919-1.000), optimal cut-off point was 0.0081, sensitivity was 90.0%, and specificity was 96.7%. These results indicate that the lncRNA TCONS_00000200 is differentially expressed in the plasma of IA patients and could serve as a biomarker of IA.

Increased perihematomal neuron autophagy and plasma thrombin-antithrombin levels in patients with intracerebral hemorrhage: An observational study.

Animal studies have demonstrated that autophagy was involved in neuronal damage after intracerebral hemorrhage (ICH). Several studies showed thrombin-antithrombin (TAT) plasma levels were elevated in patients with ICH. In this study, we aimed to evaluate if autophagy occurred in patients with ICH; and the relationship between the severity of brain injury and plasma TAT levels.A novel tissue harvesting device was used during hematoma removal surgery to collect loose fragments of tissue surrounding the affected brain area in 27 ICH patients with hematoma volumes of >30 mL in the basal ganglia. Control tissues were obtained from patients who underwent surgery for arteriovenous malformation (n = 25). Transmission electron microscopy (TEM) and immunohistochemistry for autophagy-related proteins were used to evaluate the ultrastructural and morphologic cellular characteristics; and the extent of autophagy in the recovered tissue specimens. Stroke severity was assessed by using the Glasgow Coma Scale (GCS) and the National Institutes of Health Stroke Scale (NIHSS). An enzyme-linked immunosorbent assay (ELISA) was used to measure plasma TAT levels.Transmission electron microscopy showed autophagosomes and autolysosomes exist in neurons surrounding the hematoma, but not in the control tissues. The number of cells containing autophagic vacuoles correlated with the severity of brain injury. Immunohistochemistry showed strong LC3, beclin 1, and cathepsin D staining in ICH tissue specimens. Plasma TAT levels correlated positively with autophagic cells and ICH severity (P < .01).Autophagy was induced in perihematomal neurons after ICH. Autophagy and plasma TAT levels correlated positively with severity of brain injury. These results suggest that autophagy and increased plasma TAT levels may contribute to the secondary damage in ICH patients.

A cross-sectional study to investigate the correlation between depression comorbid with anxiety and serum lipid levels.

BACKGROUND: Depression is a common psychological disorder that severely threatens human health. Its pathology remains unclear, but it has been suggested to be associated with abnormal blood lipid metabolism. OBJECTIVES: This study aimed to explore the changes in blood lipid levels in patients with depression accompanied or not by anxiety, and assess whether adjusting the clinical therapeutic strategy could be based on blood lipid test results, providing a novel insight into depression treatment. METHODS: This was a cross-sectional study. We assessed 60 outpatients and inpatients diagnosed with depression from January 2013 to January 2014 who met the Chinese Classification of Mental Disorders version 3 (CCMD-3) criteria, with Hamilton Rating Scale for Depression (HAMD-24) ≥20. They were grouped into depression with anxiety (n=29) and depression without anxiety (n=31) groups by the Hamilton Anxiety Scale (HAMA). RESULTS: TG levels were higher in the depression with anxiety group compared with patients without anxiety (P=0.045), which was confirmed by multifactorial analysis [P=0.017, OR=4.394, 95% CI (1.303-14.824)]. A negative correlation between anxiety score and HDL levels was observed in patients with depression (r=-0.340, P=0.046). Meanwhile, positive associations were obtained between retardation and LDL levels (r=0.307, P=0.017) as well as age at disease onset and total cholesterol levels (r=0.410, P=0.002). CONCLUSION: TG levels differ in patients with depression accompanied by anxiety compared with those without anxiety.

Ultrastructural Changes of Brain Tissues Surrounding Hematomas after Intracerebral Hemorrhage.

Our knowledge about pathophysiology of intracerebral hemorrhage (ICH) mainly originates from preclinical models of ICH. In this study, cerebral ultrastructure surrounding hematoma and its correlation with clinical severity were investigated in ICH patients. Thirty patients with basal ganglia hemorrhage and 6 control subjects were enrolled. Surgical evacuation was performed for patients with a blood loss >30 ml. Stroke severity was assessed using the Glasgow Coma Scale (GCS) and the National Institute of Health Stroke Scale (NIHSS). Transmission electron microscopy (TEM) was used to evaluate the ultrastructural characteristics of tissue specimens. Neural cells surrounding the hematomas showed evidence of cell swelling and necrosis. Decreased numbers of organelles and mitochondrial cristae were accompanied by cytoplasmic vacuolization, nuclear membrane invagination and breakdown, and intranuclear chromatic agglutination. These changes resulted in disintegration together with malacia, disappearance of the nucleus and nucleolus, and karyopyknosis. More serious ultrastructural damage was seen in patients with greater NIHSS scores, lower GCS scores, and greater bleeding volumes (p < 0.001). These findings suggest that neural cells undergo unfavorable ultrastructural changes that are responsible for dysfunction after ICH.