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Background: Central fatigue (CF) is a subjective sense of tiredness associated with cognitive and memory disorders, accompanied by reduced physical endurance and negative emotions, such as anxiety and depression. Disease progression and prognosis with regards to CF have been unfavorable and possibly contribute to dementia, schizophrenia, and other diseases. Additionally, effective treatments for CF are lacking. KangPiLao decoction (KPLD) has been widely applied in clinical treatment and is composed of six Chinese herbal medicines, some of which have confirmed anti-fatigue effects. While glutamic acid (Glu) is the main excitatory transmitter in the central nervous system (CNS), gamma-aminobutyric acid (GABA) is the major inhibitory transmitter. Both are involved in emotional, cognitive, and memory functions. This research was designed to explore how KPLD regulates cognitive and emotional disorders in rats with CF and to identify the relationship between the regulatory effect and the GABA/Glu pathway.Methods: The compounds comprising KPLD were analyzed using high-performance liquid chromatography-mass spectrometry. Sixty Wistar rats were randomly divided into six groups. The modified multiple platform method was used to induce CF. Cognitive, emotional, and fatigue states were evaluated by performing behavioral tests (Morris water maze [MWM], open-field test [OFT], and grip strength test). Histomorphology, western blotting, immunohistochemistry, and RT-qPCR were performed to investigate protein and mRNA expression levels in the hippocampus and prefrontal cortexes involved in the GABA/Glu pathway.Results: Rats with CF exhibited impaired spatial cognition and increased negative emotions in the MWM and OFT. KPLD enabled the improvement of these symptoms, especially in the high-concentration group. Western blotting and RT-qPCR demonstrated that the expression of GABAARα1, GABAARγ2, GABABR1, and GAD67 in rats with CF was higher, whereas GAT-1 and NMDAR2B were lower in the hippocampus and prefrontal cortex. KPLD decreased the expression of GABAARα1, GABABR1, GABAARγ2, and GAD67 in the hippocampus and prefrontal cortex and enhanced the expression of NR2B in the prefrontal cortex.Conclusion: KPLD significantly improved cognitive and emotional disorders in rats with CF by regulating the GABA/Glu pathway. Overall, KPLD may be a promising candidate for developing a drug for treating CF.

Helicobacter pylori was classified by the World Health Organization as a class 1 carcinogen. The development of drug-resistant strains of this pathogen poses a serious threat to human health worldwide. The cell invasion of H. pylori activates xenophagy in gastric epithelial cells by mediating miR-30b/c, and the emergence of autophagosomes provides a niche that enables the survival of intracellular H. pylori and promotes its drug resistance. This study revealed that some clinical drug-resistant H. pylori strains present much stronger invasive ability than standard strains. Patchouli alcohol (PA), a tricyclic sesquiterpene from Pogostemon cablin (Blanco) Benth (Labiatae), showed reliable activity against intracellular H. pylori. The mechanisms appeared to involve the downregulation of miR-30c-3p/5p and miR-30b-5p, thereby upregulating xenophagy-related gene expression (ULK1, ATG5, ATG12, and ATG14) and enhancing xenophagy. PA also inhibited the nuclear transfection of miR-30b-5p induced by H. pylori, thereby enhancing transcription factor EB function and increasing lysosome activity. The finding of strongly invasive intracellular H. pylori has great implications for clinical treatment, and PA can act against invasive H. pylori based on the improvement of miR-30b/c mediated xenophagy. Taken together, the results demonstrate that PA have potential use as a candidate medication for intracellular drug-resistant H. pylori.

Introduction: existing research on children consists primarily of phase I/II clinical trials for VEGFR-TKI. System reports of safety on the use of VEGFR-TKI in pediatrics are lacking.Aim: to investigate the safety profiles of VEGFR-TKI in pediatrics via the FDA Adverse Event Reporting System (FAERS).Method: data regarding VEGFR-TKIs were extracted from the FAERS between 2004Q1 to 2022Q3 and categorized by the Medical Dictionary for Regulatory Activities (MedDRA). Population characteristics were analyzed, and reporting odds ratio (ROR) was performed to identify risk signals associated with VEGFR-TKI.Results: 53,921 cases containing 561 children were identified in the database from 18 May 2005, to 30 September 2022. Among those in the system organ class, skin, subcutaneous tissue disorders, and blood and lymphatic system disorders in pediatrics contributed to over 140 cases. Palmar-plantar eythrodysesthesia syndrome (PPES) in VEGFR-TKI presented the most significant 340.9 (95% 229.2–507.0). And pneumothorax also gave a high reporting odds ratio of 48.9 (95% 34.7–68.9). For a specific drug, musculoskeletal pain gave a ROR of 78.5 (95% 24.4–252.6) in cabozantinib and oesophagitis in lenvatinib with a ROR of 95.2 (95% 29.5–306.9). Additionally, hypothyroidism presented a high signal, especially sunitinib, with a ROR of 107.8 (95% 37.6–308.7).Conclusion: the present study explored the safety profile of VEGFR-TKI in pediatrics using the FAERS database. Multiple skin and subcutaneous tissue disorders, as well as blood and lymphatic system disorders, were common VEGFR-TKI-related AEs in system organ class. No serious hepatobiliary AEs were detected. For the specific AEs, PPES and pneumothorax were VEGFR-TKI-related AEs that presented significantly higher signals than those in the general population.