Hui Zhang

Histidine triad nucleotide-binding protein 1 (HINT1), implicated in psychiatric disorders, is highly expressed in the nucleus accumbens (NAc). Although previous work has linked HINT1 to aggression and anxiety, its specific role and mechanism remain unclear. This study aimed to delineate HINT1 distribution in the NAc and its regulatory function in aggressive and anxiety-like behaviors. Using immunofluorescence, we mapped HINT1 expression in wild-type (WT) mouse NAc. Behavioral and molecular analyses were performed on Hint1-knockout (KO) and WT littermates. Adeno-associated virus (AAV) vectors were then used to knock down (KD) or overexpress (OE) Hint1 in the NAc of WT mice for further validation. HINT1 was expressed in medium spiny neurons (MSN), microglia, oligodendrocytes and cholinergic interneurons (ChINs) in the NAc. The Hint1-KO mice exhibited increased aggression, accompanied by elevated levels of dopamine D1 receptor (D₁R), CREB, ΔFOSB, and heightened p-PKA and p-CREB in the NAc. AAV-mediated KD of Hint1enhanced both aggressive and anxiety-like behaviors, whereas OE produced no significant behavioral changes. Molecular upregulation in KD mice mirrored KO alterations but was absent in OE mice. These findings indicate that NAc HINT1 inhibits aggression, likely via suppression of the D₁R-PKA-CREB-ΔFOSB pathway, although its role in anxiety-like behavior requires further investigation. Our findings indicate that HINT1 in the NAc inhibits aggressive behavior. Loss of Hint1 likely leads to enhanced aggression through aberrant activation of the D₁R-PKA-CREB-ΔFOSB pathway. The role of HINT1 in anxiety-like behavior and its underlying mechanisms warrants further investigation.

Introduction: Traditional Chinese medicine Gastrodia elata Blume (GEB) possesses properties that soothe the liver and dispel wind. Its constituents exhibit numerous pharmacological properties, including neuroprotective effects, analgesic properties for headache relief, memory enhancement, and others. Borneol enhances drug absorption by traversing the blood-brain barrier, thereby improving its bioavailability and therapeutic efficacy. The research aimed to design innovative drug molecules and contribute to the beneficial exploration of compound Chinese medicine modernization.Methods: This study employed the strategy of “compound Chinese medicine molecular chemistry” to integrate and fuse the effective substances of compound Chinese medicines. An excitotoxic injury model was established by exposing PC12 cells to glutamate. Cell viability was quantitatively evaluated utilizing a colorimetric assay with the CCK-8 reagent kit. Genecards, Disgenet, and OMIM databases were used to identify potential disease-related targets. Molecular docking methods were performed to predict the binding interactions between compounds and core targets.Results: We designed and synthesized compounds TB-1 to TB-16. Following the evaluation of their safety, TB-1, TB-2, TB-12, and TB-16 were selected for further investigation of their neuroprotective properties. The compound designed in this study exhibits a dose-dependent protective effect on glutamate-damaged PC12 cells. Further network pharmacology and molecular docking analyses indicate that TB-2 possesses a potential therapeutic effect against cerebral ischemia, and its possible targets were SRC, MAPK1 and KDR.Discussion: The results indicated that TB-2 displayed a significant neuroprotective effect against Glu-induced injury in PC12 cells, suggesting potential therapeutic implications for cerebral ischemia.

Objective: To evaluate the efficacy and safety of standardized dust mite allergen subcutaneous immunotherapy (SCIT) in children with allergic rhinitis (AR) during treatment. Methods: A total of 283 children with AR diagnosed with definite dust mite allergy and completed 2 to 3 years of SCIT who attended the Department of Otorhinolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, from August 2019 to October 2021 were included, including 205 males and 78 females, with a mean age of 10.8 years. The total nasal symptoms score (TNSS), symptom medication score (SMS), rhinoconjunctivitis quality of life questionnaire (RQLQ) and visual analogue scale (VAS) before and after 2 to 3 years' treatment were recorded, and the differences before and after treatment were compared. Adverse reactions during SCIT were recorded to evaluate its safety. SPSS 22.0 software was used for statistical analysis. Results: The overall effectiveness rate during SCIT in 283 children with AR was 89.4% (253/283). Compared with baseline, all symptom scores, medication scores and quality of life scores were significantly lower after 2 to 3 years of SCIT (all P<0.05). Further group comparisons showed positive efficacy in patients with different clinical characteristics, including age, gender, smoking status, family history of AR, symptom severity, mono-or poly-allergy, and second immunization, with no statistically significant differences between groups (all P>0.05). A total of 12 735 injections were administered during the SCIT, and a total of 213 (1.67%) injections of local adverse reactions occurred, mainly in the initial treatment phase, and the diameter of the local air mass was mostly 5 to 20 mm; 71 (0.56%) injections of systemic adverse reactions occurred, mainly in the initial treatment phase, and most of them were grade 1 reactions with no serious systemic adverse reaction such as shock. Conclusion: Standardized dust mite SCIT has a good safety profile and definite efficacy in treating AR children with different clinical characteristics. It can significantly improve all symptoms, reduce the use of symptomatic drugs and improve their quality of life.

Hyperprolactinemia is a common side effect of antipsychotic drugs. Although changes of antipsychotic drugs or reduction of their doses can solve this problem, a modification of the treatment regimen can lead to instability in patients. Herein, we followed up a patient with elevated prolactin caused by paliperidone and found that the prolactin level was decreased after the administration of a combination with a low-dose aripiprazole. In addition, we summarized and analyzed the findings from the case and the literature review conducted.

A 23-year-old female student presented with a five-year history of abnormal sleep in which she would sit up or stand up for brief periods in the early morning, talk loudly for a couple of minutes and then lie back down. When woken by family members she would remember vivid dreams and nightmares. In one episode she had a fall that resulted in a subdural hematoma. On presentation at the psychiatric hospital she had a normal mental status exam except for being mildly depressed and anxious about the chronic fatigue from poor sleep. Overnight polysomnography (PSG) showed multiple waking periods each night, poor sleep efficiency and a lack of normal muscle paralysis during REM sleep. The patient was diagnosed with REM Sleep Behavior Disorder and treated with 1 mg clonazepam nightly. Her sleep improved dramatically and remained better at a six-month follow-up, but repeat PSG exam found that the lack of muscle paralysis during REM sleep remained.

This article summarizes the clinical manifestations of one case of clozapine-associated neuroleptic malignant syndrome and discusses its diagnosis, predisposing factors and treatment based on a literature review. Early identification and treatment is critical to lower the mortality of clozapine-associated neuroleptic malignant syndrome.