Cognitive impairment is associated with BDNF-TrkB signaling mediating synaptic damage and reduction of amino acid neurotransmitters in heart failure.

Heart failure (HF) is often accompanied by cognitive impairment (CI). Brain-derived neurotrophic factor (BDNF) deficiency is closely associated with CI. However, the role and mechanism of BDNF in HF with CI is still not fully understood. Here, the case-control study was designed including 25 HF without CI patients (HF-NCI) and 50 HF with CI patients (HF-CI) to investigate the predictive value of BDNF in HF-CI while animal and cell experiments were used for mechanism research. Results found that BDNF levels in serum neuronal-derived exosomes were downregulated in HF-CI patients. There was no significant difference in serum BDNF levels among the two groups. HF rats showed obvious impairment in learning and memory; also, they had reduced thickness and length of postsynaptic density (PSD) and increased synaptic cleft width. Expression of BDNF, TrkB, PSD95, and VGLUT1 was significantly decreased in HF rats brain. In addition, compared with sham rats, amino acids were significantly reduced with no changes in the acetylcholine and monoamine neurotransmitters. Further examination showed that the number of synaptic bifurcations and the expression of BDNF, TrkB, PSD95, and VGLUT1 were all decreased in the neurons that interfered with BDNF-siRNA compared with those in the negative control neurons. Together, our results demonstrated that neuronal-derived exosomal BDNF act as effective biomarkers for prediction of HF-CI. The decrease of BDNF in the brain triggers synaptic structural damage and a decline in amino acid neurotransmitters via the BDNF-TrkB-PSD95/VGLUT1 pathway. This discovery unveils a novel pathological mechanism underlying cognitive impairment following heart failure.

A blood-based multi-omic landscape for the molecular characterization of kidney stone disease.

Kidney stone disease (KSD, also named renal calculi, nephrolithiasis, or urolithiasis) is a common urological disease entailing the formation of minerals and salts that form inside the urinary tract, frequently caused by diabetes, high blood pressure, hypertension, and monogenetic components in most patients. 10% of adults worldwide are affected by KSD, which continues to be highly prevalent and with increasing incidence. For the identification of novel therapeutic targets in KSD, we adopted high-throughput sequencing and mass spectrometry (MS) techniques in this study and carried out an integrative analysis of exosome proteomic data and DNA methylation data from blood samples of normal and KSD individuals. Our research delineated the profiling of exosomal proteins and DNA methylation in both healthy individuals and those afflicted with KSD, finding that the overexpressed proteins and the demethylated genes in KSD samples are associated with immune responses. The consistency of the results in proteomics and epigenetics supports the feasibility of the comprehensive strategy. Our insights into the molecular landscape of KSD pave the way for a deeper understanding of its pathogenic mechanism, providing an opportunity for more precise diagnosis and targeted treatment strategies for KSD.

[Professor BAI Xing-hua's concept and experience in the diagnosis and treatment of gastroesophageal reflux disease].

In view of the five major misunderstandings in the clinical understanding of gastroesophageal reflux disease in traditional Chinese medicine, that is, wrong main symptoms, wrong position of the disease, wrong character of the disease, treating acid with acid, and attaching importance to drugs and neglecting acupuncture-moxibustion in treatment, Professor BAI Xing-hua has proposed the corresponding solving strategies, which includes grasping the main disease, carefully examining the disease position, distinguishing the character of disease, and no acid suppression for acid regurgitation. In addition, Professor BAI highly values the external treatment of traditional Chinese medicine. In particular, the acupuncture therapy of "Tongdu Jiangni (promote the circulation of the governor vessel and reduce the reversed qi)" based on many years of clinical experience provides new ideas and methods for the diagnosis and treatment of gastroesophageal reflux disease in traditional Chinese medicine.

[Clinical observation on gastroesophageal reflux asthma treated with tongdu jiangni needling technique].

OBJECTIVE: To compare the clinical effect on gastroesophageal reflux asthma between the tongdu jiangni needling technique of acupuncture (acupuncture for promoting the circulation of the governor vessel and reducing the reversed qi) and omeprazole enteric capsules (OME). METHODS: A total of 60 patients with gastroesophageal reflux asthma were randomized into an acupuncture group and a western medication group, 30 cases in each one. The basic treatment for anti-bronchial asthma was provided in both of the groups. Additionally, OME was prescribed for oral administration in the western medication group, twice a day, 20 mg each time, for 8 weeks. In the acupuncture group, the tongdu jiangni needling technique of acupuncture was added. The needles were inserted at the sites inferior to the spinous processes of T3 to T12. Acupuncture was given once in the morning on Tuesday, Thursday and Saturday respectively, totally for 8 weeks. Separately, before and after treatment, the score of reflux disease diagnostic questionnaire (RDQ), the score of asthma control test (ACT) and the tenderness threshold at the sites inferior to the spinous processes of T3 to T12 were observed and the clinical effect was evaluated in the two groups. RESULTS: ①The remarkably effective and curative rate was 46.7% (14/30) in the acupuncture group, higher than 3.3% (1/30) in the western medication group (P<0.01). The asthma control rate was 66.7% (20/30) in the acupuncture group, higher than 13.3% (4/30) in the western medication group (P<0.01). ②RDQ score after treatment was lower than that before treatment in either group (P<0.05). The decrease range of RDQ score in the acupuncture group was larger than that of the western medication group (P<0.05). After treatment, ACT score was increased as compared with that before treatment in either group (P<0.05) and the increase range of ACT score in the acupuncture group was larger than that of the western medication group (P<0.05). ③The tenderness thresholds at the sites inferior to the spinous processes of T3 to T8 and T10 to T12 were all increased after treatment as compared with those before treatment in the acupuncture group separately (P<0.05). In the western medication group, the thresholds were only increased at the sites inferior to the spinous processes of T6, T7 and T9 after treatment as compared with those before treatment separately (P<0.05). After treatment, the tenderness thresholds at T6 to T8 in the acupuncture group were all higher than the western medication group (P<0.05). CONCLUSION: The tongdu jiangni needling technique of acupuncture effectively relieves the symptoms of gastroesophageal reflux asthma and improves the quality of life in the patients and its effect is better than omeprazole enteric capsules.

Effects of norfloxacin and butylated hydroxyanisole on the freshwater microalga Scenedesmus obliquus.

The toxic effects of norfloxacin (NOR) and butylated hydroxyanisole (BHA) on the microalga Scenedesmus obliquus were assessed in terms of growth rate, concentration of chlorophyll a, activities of 7-ethoxyresorufin-o-dealkylases (EROD), glutathione s-transferase (GST), catalase (CAT) and total malondialdehyde content (MDA). The 96 h EC(50) was 38.49 and 11.12 mg/l for NOR and BHA, respectively. Growth of S. obliquus was affected slightly under low concentrations of BHA (<4 mg/l) and NOR (<15 mg/l) over the 96 h exposure period. With the increasing concentrations of these two compounds, growth of S. oblique decreased significantly. Growth inhibition was 82.4% at 60.0 mg/l for NOR and 60.6% at 16.0 mg/l for BHA after 96 h. A similar trend was also observed for chlorophyll alpha. NOR and BHA affected Phase I and Phase II enzyme activities differently. Upon exposure to NOR, EROD was induced at concentration <15.0 mg/l and depressed at concentrations >30 mg/l significantly. CAT and GST exhibited similar trends during the exposure period. Compared to controls, MDA content only showed high induction at high concentrations of NOR (>30 mg/l). However, EROD activity did not display any change compared to control responses during BHA exposure, whereas GST showed significant induction for all concentrations over the exposure period. CAT activity showed induction at low concentration and depression at high concentration. MDA content increased with the rise of BHA during the exposure period. These types of assays, revealing toxic effects of NOR and BHA to phototrophs, could be employed to assess the potential risks of these xenobiotics to aquatic ecological systems.

Characterization of the T-cell receptor repertoire by deep T cell receptor sequencing in tissues from patients with prostate cancer.

Prostate cancer (PC) is the most prevalent urological cancer in men. T cells serve a central role in the cancer's immunological microenvironment. In the present study, we applied multiplex PCR and Illumina next-generation sequencing to study the clonal diversity of the T-cell receptor (TCR) repertoire in cancer tissues and paracancer tissues from patients with PC. It was found that the TCR repertoire in the PC samples had a notably more skewed clonotype composition, with a greater number of highly expanded clones (HECs) compared with the prostate paracancer samples. The amino acid sequences ATSRVAGETQY (1.008 vs. 0.002%), ATSRTGRWETQY (3.985 vs. 0.007%), ATSDSSDYEQY (12.464 vs. 0.027%), ATSDFRGQPQETQY (2.205 vs. 0.06%), ASSQQDEAF (1.109 vs. 0.002%) and ARPTRTEETQY (1.263 vs. 0.002%) were found to vary markedly between cancer and paracancer tissues, respectively. In conclusion, the present study identified PC-specific HECs, which are critical to improving understanding of the TCR repertoire in PC. This may accelerate the screening process for potential new autoantigens and provide information for generating more effective T cell-targeted diagnostic and therapeutic strategies.

Association of the characteristics of B- and T-cell repertoires with papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Complementarity-determining region 3 (CDR3) of B-cell receptors (BCRs) and T-cell receptors are the major site of antigen recognition, which determines a unique clone type, and are considered to be the representative of the disease. In the present study, high-throughput sequencing was used to analyze the association of characteristics of the BCR immunoglobulin heavy chain (IGH) and the T-cell receptor ß chain (TRB) CDR3 genes in PTC and corresponding pericarcinous tissues from patients. A difference of CDR3 length distributions of total IGH CDR3 sequences between the two groups was revealed. IGHV3-11/IGHJ6, TRBV2/TRBJ1-2 and TRBV2/TRBJ1-1 may be biomarkers for the development of PTC. Furthermore, it was revealed that the extent of the common clonotype expressions at the amino acid level was slightly higher compared with the nucleotide level. The Shannon entropy demonstrated a diversity reduction in PTC compared with the pericarcinous group, and the highly expended clone (HEC) expression of PTC was higher compared with that of the corresponding pericarcinous group. Additionally, the highest clone frequency percentage of IGH and TRB was at 0.1-1.0% degree of expansion, as HEC expression was higher in PTC compared with the matched group. There was no shared clone of HECs in the two groups either at the amino acid level or at the nucleotide expression level. The differential expression of CDR3 sequences of PTC have been identified in the present study. Further research is required for assessing the immune repertoire size, diversity, cloning tracking and finding public clones of T-cell and B-cell populations in the development of PTC.