Chronic insomnia disorder (CID) is characterized by dysregulation of the insula, a key hub integrating emotional, cognitive, and autonomic processes. This study investigated insular subregional functional connectivity (FC) abnormalities in CID, longitudinal FC modulation following treatment with Suanzaoren Decoction (SZRD) or estazolam, and the associated molecular signatures. We recruited 82 patients with CID and 80 healthy controls. Patients underwent clinical assessments and resting-state functional magnetic resonance imaging at baseline and after six weeks of treatment. Twelve insular subregions were defined as seeds for whole-brain FC analyses. Longitudinal treatment effects were examined using mixed-effects models. Spatial correlations between FC alterations and gene expression maps from the Allen Human Brain Atlas were analyzed. At baseline, CID patients exhibited increased FC between the hypergranular insula and the opercular part of the left inferior frontal gyrus (IFG). Following treatment, both the SZRD and estazolam groups showed enhanced FC between the left hypergranular insula and the bilateral anterior cingulate cortex, and between the right dorsal agranular insula and the right mid/posterior cingulate cortex. Estazolam treatment was further associated with decreased FC between the left dorsal agranular insula and the left cerebellar lobule VI, and increased FC with the bilateral precuneus. Gene enrichment analysis indicated that the identified genes were significantly involved in fatty acid transport, neuronal ensheathment, and early endosome localization. CID is characterized by aberrant insular-IFG connectivity. Both SZRD and estazolam effectively modulate the insular subregional FC, and functional alterations are linked to specific transcriptomic profiles.

Objectives: The aging population in China presents significant challenges related to polypharmacy and potentially inappropriate medication (PIM) use among older outpatients. This study aimed to evaluate the prevalence and risk factors of PIM use in older Chinese outpatients using the 2017 Chinese criteria, 2019 AGS/Beers criteria, and 2014 STOPP criteria, and to assess the concordance among these three criteria. Methods: A cross-sectional study was conducted using outpatient prescription data from 59 hospitals across six Chinese cities between January and December 2021. Prescriptions for patients aged ≥65 years were included. PIMs were identified using the three criteria. Concordance was evaluated using weighted kappa statistics. Multivariate logistic regression was used to identify factors associated with PIM use. Results: Among 131,894 prescriptions, PIM prevalence was 29.00%, 27.77%, and 19.85% according to the Chinese, Beers, and STOPP criteria, respectively. The most common PIM was estazolam. Concordance was moderate between the Chinese and Beers criteria (kappa = 0.58), STOPP criteria (kappa = 0.625), and good between Beers and STOPP criteria (kappa = 0.73). Factors associated with PIM use included age ≥80 years, polypharmacy, full self-payment, and diagnoses such as sleep disorders and arthritis. Conclusions: PIM use is prevalent among older outpatients in China, with varying rates across different criteria and regions. Interventions targeting high-risk groups and specific drug classes may improve medication safety in this population.

Insomnia is a prevalent sleep disorder associated with intestinal barrier dysfunction and immune dysregulation. Mongolian warm acupuncture (MWA) has shown therapeutic potential in insomnia; however, its effects on intestinal permeability and underlying mechanisms remain unclear. In this study, an insomnia rat model was established using chronic unpredictable mild stress combined with para-chlorophenylalanine (PCPA). To evaluate the therapeutic effects of MWA, comparative analysis was conducted among different groups, including Control, Model, MWA, Estazolam, and sham MWA groups. MWA group showed significantly improvement on sleep quality, cognitive performance, and anxiety-like behavior and alleviated colonic tissue damage. MWA treatment attenuated intestinal barrier dysfunction by modulating the expression of ZO-1, Occludin, and Claudin-4. In addition, MWA reduced inflammatory responses by decreasing TNF-α, IL-1β, and IL-6 levels while increasing IL-22 expression. Furthermore, MWA suppressed activation of the TLR4/MyD88/NF-κB signaling pathway. These findings suggest that MWA exerts protective effects against insomnia-associated intestinal barrier dysfunction and inflammation and may represent a promising non-pharmacological therapeutic strategy for insomnia.

Melatonin is a hormone synthesized by the pineal gland from tryptophan as a precursor and serotonin as an intermediate. It is secreted during the night and displays a peak around 3 a.m., depending on the individual chronotype. This rhythm is generated by an endogenous biological clock located in the suprachiasmatic nuclei (SCN) of the hypothalamus and entrained to the light/dark cycle (circadian rhythm). The roles of melatonin are numerous, but this hormone is described as a messenger of nighttime to the body, a modulator of circadian rhythmicity in mammals (including humans), and a regulator of seasonal rhythms in photoperiodic animals. Melatonin, as a hormone message controlled by the central circadian clock, distributes temporal cues to the complex network of peripheral circadian clocks found in a multitude of target structures. This message favors the adaptation of the entire organism to the photoperiod. In this way, melatonin plays the role of an endogenous synchronizer capable of reinforcing the circadian rhythms, stabilizing them and maintaining their phase relationships (internal synchronization), which contributes to a physiological coherence. In fact, melatonin is not the sleep hormone, but it reinforces the contrast between day/night and activity/sleep. Further, exogenous administration of melatonin favors sleep onset (soporific effect) and influences the endogenous melatonin rhythm (advancing or delaying it according to the time of administration; a so-called chronobiotic activity) via the circadian clock. This chronobiotic activity is the pharmacological basis for the treatment of dysrhythmia (jet lag syndrome, delayed-sleep phase syndrome, non-24 circadian sleep disorder in blind people, etc.).

Determining fatal insulin overdose remains a major challenge in forensic practice due to the absence of characteristic histopathological findings and technical limitations in postmortem insulin detection. This report presented a complex case of a 69-year-old diabetic female involved in a suicide pact with her son, who was subjected to estazolam ingestion, excessive insulin injection, and a sharp-force incised wound of the left wrist with transection of the radial artery. She survived for more than 48 h after drug administration before ultimately succumbing to fatal sharp-force trauma inflicted by her son. Immunohistochemical staining confirmed insulin deposition at injection sites, and radioimmunoassay revealed markedly elevated insulin levels accompanied by a suppressed C-peptide concentration-findings consistent with exogenous insulin administration. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) detected estazolam at a concentration of 18.2 ng/mL in blood. Forensic evidence confirmed the son's direct involvement at the scene. Based on the totality of the evidence, it was definitively concluded that the injuries were homicidal. This study offered valuable insights for the forensic identification and investigation of complex insulin-related fatalities.

BACKGROUND: Endocrine disturbances after organophosphate exposure are rarely emphasized in routine psychiatric care. In older inpatients, severe hyponatremia is often attributed to antidepressant-induced SIADH, which may delay recognition of relative hypocortisolemia. We report a hypothesis-generating case supporting a multifactorial ‘second-hit’ model. CASE PRESENTATION: A 67-year-old woman with long-standing major depressive disorder attempted suicide after an argument with family members by ingesting a suspected dimethoate emulsion (half a bottle found at the scene), approximately 20 estazolam tablets, and a small amount of detergent. She was transferred to a psychiatric ward for presumed depressive exacerbation. On day 1, serum sodium was 141.0 mmol/L (reference 137.0-147.0) but 8 AM cortisol was low at 112.4 nmol/L (reference 166-507). Influenza B was confirmed on day 2. After venlafaxine XR was initiated (75 mg/day) and up-titrated to 150 mg/day on day 4 because of apparent non-response, sodium progressively declined to 125.0 mmol/L on day 7, continued to fall to 120.2 mmol/L on day 8 and reached a nadir of 119.4 mmol/L on day 9, and remained low on day 10 (123.9 mmol/L) despite supplementation and fluid restriction. Repeat 8 AM cortisol was 122.0 nmol/L with an inappropriately normal ACTH of 24.4 pg/mL (reference 7.2-63.3) given systemic inflammation. Brain CT, adrenal ultrasound, and thyroid function were unremarkable. Urine sodium/osmolality and plasma osmolality were not measured. Oral prednisone acetate 5 mg twice daily was started on day 11 while venlafaxine was continued. Sodium rose to 130.0 mmol/L on day 12 and normalized by day 16 (141.0 mmol/L), accompanied by rapid improvement in appetite, spontaneous speech, and psychomotor activity. CONCLUSIONS: Causality cannot be definitively established. However, this case highlights that medically stressed psychiatric inpatients may develop refractory hyponatremia from interacting factors (infection, SNRI up-titration, and relative HPA-axis insufficiency). Early-morning cortisol assessment should be considered when hyponatremia co-occurs with apparent antidepressant non-response, particularly in older, low-BMI patients.