Search Results (10,802)

Purpose: Evaluation of predictors and outcomes in NSCLC patients treated with an immune checkpoint inhibitor (ICI) following a severe immune-related adverse event (irAE). Methods: We included all NSCLC patients receiving ≥ 1 ICI cycle and corticosteroids for CTCAE Grade ≥ 3 irAEs between 2017 and 2023 from three UK NHS teaching hospitals. Progression-free survival (PFS) and overall survival (OS) after the 1^st irAE, best overall response (BOR) to ICI, and predictors of clinical benefit were evaluated. Kaplan–Meier, Cox and logistic regression models, and Wilcoxon tests were used. Results: We screened 1658 NSCLC patients and identified 80 eligible subjects. The majority of patients had metastatic (n = 50, 63%) vs. localized (n = 30, 37%) NSCLC. Most patients developed a single ≥ Grade 3 irAE on 1^stline ICI (n = 71, 89%). Overall, 14 (18%) patients developed 2^nd irAEs, 7 after rechallenge with ICIs. In the complete cohort, median OS after 1^st irAE was 15.84 months (95% CI, 12.45–26.91). Lower neutrophil-to-lymphocyte ratio (NLR), patients receiving > 4 cycles of ICI or median duration of ICI of > 2.76 months before 1^st irAE were associated with improved OS (p < 0.05), the latter two with PFS (p < 0.05). Age, gender, stage, KRAS mutation, PD-L1 and ICI type were not associated with PFS or OS. Pneumonitis as 1^st irAE had the worst PFS and OS (p < 0.05). Median starting corticosteroid dose of ≤ 60 mg for 1^st irAE had an improved OS (p = 0.04). Post 1^st irAE response associated with better PFS and OS (p < 0.05). Number and duration of irAEs and additional immunosuppressive agents (14% of patients) were not associated with PFS or OS. Conclusions: In ≥ Grade 3 irAEs patients managed with corticosteroids, lower baseline NLR, longer ICI use, response to ICI after 1^st irAE, and a ≤ 60 mg corticosteroid dose had promising outcomes. Full article

Background/Objectives: Cholera remains a significant global health challenge. Shanchol (ShantaBiotech, India), one of the WHO prequalified Oral Cholera Vaccines (OCVs) available until recently, has been used to immunize people as a two-dose regimen (14 days apart, on day 0 and 14). However, growing evidence suggests that a single-dose strategy may mediate short-term protection, especially in those over 5 years of age. Hence, it is crucial to design a suitable and effective administration scheme for Shanchol, particularly in cholera-endemic regions. Methods: In this study, adult volunteers were vaccinated with either a single dose, a two-dose regimen with a 14-day interval, or a two-dose regiment with a 30-day interval. We studied the antigen-specific helper memory (CD4+CD45RO+) and cytotoxic memory (CD8+CD45RO+) T cells responses of vaccinees along with the specific mucosal immune responses to gut-homing ß7 lipopolysaccharides (LPSs). Results: By day 7 post-vaccination, Shanchol induced robust helper and cytotoxic memory T cell responses to V. cholerae membrane protein (AKI-MP) following a single dose of vaccination. In the two-dose groups, we observed a significant elevation of AKI-MP-specific responses after the 2nd dose. We found that circulatory gut homing (β7+) LPS-specific IgA responses of antibody-secreting cells (ASCs) peaked at D7 among all vaccine groups. Moreover, we observed that β7+ LPS-specific ASCs at D7 significantly correlated with the LPS-specific antibody titer in plasma. Conclusions: These findings suggest that a single dose of OCV in adults induces immune responses comparable to a two-dose regimen, suggesting a single-dose vaccination may be adequate to mediate protection against cholera in cholera endemic zones—especially in reactive campaigns. Full article

Porcine deltacoronavirus (PDCoV), an emerging enteropathogenic coronavirus, has inflicted substantial economic losses on the global swine industry. While the severity of infectious disease depends on the dynamic interplay between inoculum dose and host response, the molecular mechanism by which PDCoV dose modulates host immunity remains unclear. Hence, we systematically compared the transcriptomic changes in intestinal epithelial cells infected with different doses of PDCoV, and investigated the relationships between inoculum dose, host immune responses, and disease progression. PDCoV replication peaked at 24 h post-infection, and host responses showed a distinct dose-dependent pattern, with high-dose infection inducing more extensive transcriptional remodeling than low-dose infection. Both doses significantly activated the transcription of STAT1 and its downstream interferon-stimulated genes, while high-dose infection additionally triggered a cytokine storm characterized by excessive IL-6 and TNF-α expression. Functional validation demonstrated that STAT1 overexpression markedly inhibited PDCoV infection by enhancing ISRE promoter activity, and overexpression of its downstream ISG15 and MX2 also exerted independent and significant antiviral effects. These findings reveal the biphasic nature of PDCoV dose-dependent regulation of immunopathological mechanisms and identify STAT1 and specific ISGs (ISG15, MX2) as potent antiviral effectors, providing crucial insights into PDCoV pathogenicity and offering promising targets for developing immunomodulatory therapeutics or vaccines to control PDCoV outbreaks in swine. Full article

Non-small cell lung cancer (NSCLC) remains one of the leading causes of cancer-related mortality, with resistance to chemotherapy representing a major therapeutic challenge. In this study, we investigated the effects of conventional chemotherapeutics, Cisplatin and 5-fluorouracil (5-FU), in combination with small molecule inhibitors (SMIs) targeting the PI3K/AKT signaling pathway, on NSCLC cell viability. Two NSCLC cell lines, H460 (large cell lung carcinoma) and A549 (adenocarcinoma), both characterized by constitutive activation of PI3K/AKT signaling, were evaluated. A normal human lung fibroblast cell line, MRC-5, was used as a non-cancer control to assess selectivity and exclude cytotoxic effects. Dose–response analyses were performed to determine the optimal concentrations of Cisplatin, 5-FU, the AKT inhibitor MK2206, and the PI3K inhibitor BKM120, both as monotherapies and in combination treatments. We identified a synergistic combination of 5-FU and BKM120 that significantly reduced viability and induced apoptosis in NSCLC cells while sparing MRC-5 cells. Mechanistic studies revealed that apoptosis induction was mediated through the apoptotic pathway regulated by the Bcl-2 family and activation of caspase-3 and caspase-6. These findings highlight the therapeutic potential of combining PI3K/AKT inhibitors with conventional chemotherapy to overcome resistance mechanisms in NSCLC. Full article

Background: Although several epidemiological studies have suggested a potential association between infections and Parkinson’s disease (PD), relatively few have specifically examined the relationship between upper respiratory tract infections (URIs) and PD, apart from coronavirus disease 2019 (COVID-19). Objectives: We investigated whether a history of URI was associated with the diagnosis of PD among Korean individuals aged ≥40 years, using data from the Korean National Health Insurance Service–Health Screening Cohort. Methods: A total of 5844 patients newly diagnosed with PD were identified and matched with 23,376 control participants at a 1:4 ratio based on age, sex, income, and geographical region. Conditional logistic regression analyses were performed to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for PD, adjusting for potential confounders including smoking, alcohol consumption, body mass index, blood pressure, comorbidity scores, blood glucose, and serum cholesterol levels. Results: Overall, no significant association was found between a history of URI and PD when considering a two-year exposure window. However, in the one-year window analysis, individuals with a history of URI had a modestly reduced odds of PD (≥1, ≥2, or ≥3 episodes: (adjusted OR: 0.93, 95% CI: 0.88–0.97, aOR: 0.91, 95% CI: 0.87–0.96 and aOR: 0.92, 95% CI: 0.87–0.98, respectively). Subgroup analyses revealed that the inverse association was more pronounced among women, older adults (≥65 years), and those with higher comorbidity scores. No clear dose–response trend was observed across increasing frequencies of URI diagnoses. Conclusions: Our findings suggest that the apparent protective association between recent URI history and PD is unlikely to be causal and may instead reflect confounding by medication use or reverse causation related to the prodromal phase of PD. These results should therefore be interpreted with caution and regarded as hypothesis-generating. Further prospective studies incorporating detailed prescription data and long-term follow-up are warranted to clarify the role of infections and anti-inflammatory medications in the pathogenesis of PD. Full article

Objectives: This study aims to evaluate the association between antibiotic prophylaxis (particularly cephalosporins) and clinical outcomes in elderly hip fracture patients. Methods: We analyzed 4044 elderly hip fracture patients (2008–2022) from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database using inverse probability treatment weighting (IPTW). Cox proportional hazards models assessed mortality risk, while logistic regression evaluated infection and Intensive Care Unit (ICU) admission risks. Dose–response and subgroup analyses were performed for significant findings. Results: In total, 166 patients received no antibiotics, 2589 received Cephalosporin monotherapy, 403 received non-cephalosporin therapy, and 886 received Cephalosporin combination therapy. After IPTW adjustment, monotherapy showed significantly lower mortality risk versus combination therapy at all timepoints (hazard ratio (HR) for 28-day mortality: 0.46, 95% confidence interval (95% CI): 0.28–0.75; HR for 90-day mortality: 0.60, 95% CI: 0.44–0.82; HR for 180-day mortality: 0.67, 95% CI: 0.51–0.87; HR for 1-year mortality: 0.71, 95% CI: 0.57–0.89). The SII cut-off values were 1310.1 for 28-day mortality, 2077.5 for both 90-day and 180-day mortality, 1742.2 for 1-year mortality, 2199.7 for ICU admission, and 1930.7 for infection. Subgroup analyses showed that males and internal fixation patients derived more benefits after cephalosporin monotherapy treatment at all time nodes. Patients with multiple injuries had a lower risk of 28-day mortality, while high-comorbidity patients (CCI ≥ 5) and those with osteoporosis exhibited particular advantages with cephalosporin monotherapy. Conclusions: Cephalosporin monotherapy appears non-inferior to combination therapy for elderly hip fracture patients, potentially reducing long-term mortality risk, especially in males, internal fixation cases, and patients with CCI ≥ 5 and osteoporosis. Full article

Background: Empagliflozin, a sodium–glucose cotransporter 2 (SGLT2) inhibitor, improves outcomes in heart failure (HF) patients, yet inter-individual variability in response remains unclear. Genetic variants in Brain-Derived Neurotrophic Factor BDNF (rs6265) and ATPase Sarcoplasmic/Endoplasmic Reticulum Ca²⁺ Transporting 2 ATP2A2 (rs1860561) may influence the treatment efficacy. Objective: To assess the association of BDNF and ATP2A2 polymorphisms with the response to low-dose empagliflozin (10 mg) in Pakistani patients with heart failure and a reduced ejection fraction (HFrEF). Methods: In this prospective study, 120 HF patients with an ejection fraction of 25–45% who had been on stable standard heart failure therapy for at least 3 months were initiated on 10 mg of empagliflozin. The brain natriuretic peptide (BNP) and LVEF left ventricular ejection fraction (LVEF) were assessed at 6 and 12 months. Genotyping for rs6265 and rs1860561 was performed via Sanger sequencing. A response was defined as a ≥5% EF increase or ≥20% BNP reduction. Associations were analyzed using chi-square and logistic regression. Results: Among 99 genotyped patients, BDNF T allele carriers (CT/TT) had a significantly lower EF (p = 0.028) and BNP (p < 0.001) response. The CC genotype was associated with improved outcomes (BNP OR: 7.70; EF OR: 5.97). For ATP2A2, the GG genotype showed a strong association with EF improvement (OR: 5.97; p = 0.001), with no BNP association. Variant allele frequencies were higher among Punjabis and Kashmiris than Pathans. Conclusions: BDNF rs6265 and ATP2A2 rs1860561 polymorphisms appear to influence the individual response to empagliflozin in HFrEF patients. These findings underscore the potential of pharmacogenetic profiling to guide personalized therapy and optimize treatment outcomes in heart failure. Full article

Spinal cord injury (SCI) results in significant motor, sensory, and autonomic dysfunction. The pathophysiology of SCI develops during the primary and secondary phases. Inflammation contributes to the secondary phase through the non-specific activation of the innate immune response. Glial scar formation (gliosis), a reactive cellular mechanism facilitated by astrocytes, also occurs during this phase. Synthetic steroids such as tibolone (Tib) have been proposed as a treatment for SCI since they exert neuroprotective effects in various models of central nervous system (CNS) injury. We studied the effect of Tib on locomotor functional recovery and the regulation of neuroinflammation and gliosis in an SCI model. We performed an SCI at the thoracic vertebrae nine in male Sprague Dawley rats. The animals received daily doses of Tib (1 or 2.5 mg per kg of body weight) administered orally. We quantified pro- and anti-inflammatory cytokine levels at the injury site and determined motor recovery using the Basso, Beattie, and Bresnahan (BBB) scale. Finally, we investigated the effect of Tib on the expression of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule 1 (Iba-1), two markers of gliosis, using an immunohistochemistry assay. Our findings showed that Tib regulated pro- and anti-inflammatory cytokine levels at 3 h and 3, 7, and 14 days post-SCI. Furthermore, Tib administered orally for 15 days reduced gliosis markers and favored tissue preservation and motor function recovery after SCI. Full article

Background: Serum cystatin C is a promising biomarker for vascular risk, yet its nonlinear dose–response relationships and prognostic value in general populations remain unclear, particularly for stroke-specific outcomes. Methods: This study utilized data from the National Health and Nutrition Examination Survey (NHANES) conducted in 1999–2002 cycles. A total of 11,610 participants were included in the primary analysis examining the cross-sectional association between cystatin C and stroke morbidity, using multivariate logistic regression models and odds ratios (ORs). Analyses utilized complete-case data (n = 11,610 for morbidity; n = 11,598 for mortality). Subsequently, 11,598 adults were retained for mortality endpoint analyses, which focused on the longitudinal association between cystatin C and stroke mortality, using cause-specific weighted multivariable Cox models and ratios (HRs). Restricted cubic splines identified nonlinear thresholds, and piecewise regression quantified risk gradients. Models were adjusted for sociodemographic/clinical/behavioral confounders. Results: Serum cystatin C exhibited a nonlinear dose–response relationship with stroke morbidity (p for nonlinear < 0.001), with an inflection point at 1.24 mg/L; below this threshold, each 0.1 mg/L increase conferred 13.84-fold higher odds (95% CI: 7.11–27.03, p < 0.001). For mortality, nonlinear thresholds were identified at 1.24 mg/L for all-cause/cause-specific mortality (HR = 6.73–10.60 per 0.1 mg/L increase, p < 0.001) and 1.81 mg/L for stroke-specific mortality. Conversely, cerebrovascular mortality demonstrated a linear association (HR = 1.43 per 1 mg/L increase, p = 0.008), though cystatin C independently predicted risk (HR = 1.38/continuous, p = 0.034 in fully adjusted models). Conclusions: This study identifies serum cystatin C as an independent predictor after full adjustment of stroke morbidity and all-cause and cardio-cerebrovascular mortality. Consequently, cystatin C emerges as a dual-purpose biomarker for early vascular injury detection in subclinical populations and integrated mortality risk stratification. Future research should validate these thresholds in prospective neuroimaging-confirmed cohorts and investigate interventions targeting cystatin C pathways to optimize preventive strategies. Full article

Background: The perfusion of viscera, kidney, and spinal cord represents one of the main concerns during open repair (OR) of Thoraco-Abdominal Aortic Aneurisms (TAAAs). Passive shunting (PS) has been historically used for intraoperative distal aortic perfusion but has been progressively replaced almost entirely by partial left-sided heart or total cardiopulmonary bypass with extra-corporeal circulation (ECC). Despite several advantages of these methods, PS still has potential in mitigating some drawbacks of long extracorporeal circuits connected with centrifugal or roller pumps, such as the need for cardiac and great vessels cannulation, priming and large intravascular fluid volume shifts, high heparin dose, immunosuppressive effects, and systemic inflammatory response syndrome. Methods: This study prospectively analyzed data of a cohort of patients who underwent TAAA OR using a PS in a single institution. Outcomes of interest were mortality, rate of mesenteric, renal and spinal cord ischemia, cardiac complications, and intraoperative hemodynamic stability achieved in this setting. Our institutional bundle and a comprehensive literature review about the different configurations and applicability of PS for TAAA OR is also reported. The search was performed based on three databases (PubMed, EMBASE, and Cochrane Library) by two independent reviewers (LS and AA) from inception to 31 December 2023, and the reported clinical results (visceral, renal, and spinal cord complications and mortality) using PS during TAAAs OR were analyzed. Results: Between March 2021 and December 2023, 51 TAAA repairs were performed and eleven patients (n = 8, 73% male; mean age 67 years, range 63–79) were operated using a PS for a total of one (9%) type I, one (9%) type II, two (18%) type III, five (45%) type IV, and two (18%) type V TAAA. In our early experience, PS was indicated for limited staff resources during the COVID-19 pandemic to treat five non-deferable cases. The sixth and seventh patients were selected for PS as they already had a functioning axillo-bifemoral bypass that was used for this purpose. For the most recent cases, PS was chosen as the primary perfusion method according to a score based on clinical and anatomical factors with ECC as a bailout strategy. Selective renal perfusion with cold (4 °C) Custodiol solution was the method of choice for renal protection in all cases while antegrade perfusion of the coeliac trunk and the superior mesenteric artery was assured by PS through a loop graft (8–10mm) proximally anastomosed to the axillary artery (10 patients, 90.9%) or the descending thoracic aorta (one patient, 9%) and distally anastomosed to the infrarenal aorta (3), common iliac (3), or femoral vessels (5). In-hospital mortality was 9% as one patient died on the 10th postoperative day from mesenteric ischemia following hemodynamic instability; permanent spinal cord ischemia rate was 0% and the rate of AKI stage 3 was 9% (one patient). Bailout shifting to ECC was never required. No cardiac complications, nor a significant increase in serum CK-MB were reported in any patient. No prolonged severe intraoperative hypotension episodes (Mean Arterial Pressure < 50 mmHg) were assessed using the Software Acumen Analytics (Edwards LifeSciences, Irvine CA, USA). No peri-operative coagulopathy nor major bleeding was reported. Conclusions: Our experience showed satisfactory outcomes with the use of PS in specifically selected cases. Current data indicate that PS may represent an alternative to ECC techniques during TAAAs OR in high volume centers where assisted extracorporeal circulation could eventually be applied as a bailout strategy. However, due to the small sample size of this and previously published series, more data are needed to clearly define the potential role of such approach during TAAA OR. Full article

This study aimed to evaluate the effects of phytase enzyme supplementation on the thermoregulatory responses of Japanese quails (Coturnix japonica) exposed to different thermal environments. A total of 720 one-day-old laying quails were assigned to a completely randomized design with five dietary treatments (0, 500, 1000, 1500, and 3000 FTU of phytase) and three thermal conditions: thermal comfort (24 °C) and heat stress environments (30 °C and 36 °C). Each treatment had six replicates with eight quails per experimental unit. Data were collected during the early laying phase, peak egg production, and the final laying phase. Measurements included rectal and surface temperatures (assessed via thermographic imaging), allowing the calculation of core-to-surface and surface-to-environment thermal gradients. Quails exposed to severe heat stress (36 °C) showed increased heat dissipation via convection (p = 0.001) and radiation (p = 0.029) when supplemented with phytase doses above 1500 FTU/kg. Additionally, high-dose phytase supplementation reduced the cloacal temperature and optimized thermal gradients, indicating a potential protective effect of exogenous phytase in alleviating heat stress. Overall, these findings highlight phytase supplementation as a promising nutritional strategy to enhance heat tolerance, mitigate thermal stress, and improve the welfare and physiological resilience of quails throughout the production cycle. Full article

Thiamine is a vitamin essential for the function of central metabolic enzymes, of which pyruvate dehydrogenase (PDH) possesses one of the broadest regulations. Diurnal effects of thiamine supplementation on energy metabolism have previously been shown for the rat brain. Here, we report data on the diurnal changes and the effects of thiamine administration to rats on the function of thiamine-dependent enzymes in the cerebral cortex, heart, and liver. The most pronounced diurnal differences were found at the level of cerebral PDH activity. Analysis of PDH phosphorylation in five rat tissues revealed diurnal and thiamine-dependent differences in the cerebral cortex and heart. The expression of tissue-specific PDH kinases PDK3 and PDK4 showed a daytime-dependent response to thiamine administration in the cerebral cortex and heart, respectively. In addition, cardiac PDK4 expression was doubled in the evening, compared to morning. Furthermore, cerebral cortex demonstrated tissue-specific diurnal changes in thiamine diphosphate (ThDP) and monophosphate levels. Elevation of blood, cardiac, and cerebral ThDP was more effective upon the evening thiamine administration. Importantly, only ThDP was elevated in the rat cerebral cortex exclusively after evening thiamine supplementation. Coenzyme role of ThDP and/or other thiamine functions in nerve tissue reduced the existing daytime changes in animal behavior and ECG parameters. The reported data on diurnal regulation of central energy metabolism as well as the diurnal difference in thiamine accumulation in the cerebral cortex, heart, and other tissues are of clinical importance, as high doses of thiamine are used for the treatment of acute thiamine deficiencies and many other mostly neurological diseases in patients. Full article

Introduction: Adequate maternal vitamin D status during pregnancy is essential for fetal skeletal development and neonatal vitamin D reserves. Evidence from Central and Eastern Europe on maternal deficiency, its determinants, and supplementation effectiveness in late pregnancy is limited. This study assessed the impact of 2000 IU/day and 4000 IU/day maternal vitamin D supplementation during the third trimester, compared to no supplementation, on maternal and neonatal 25-hydroxyvitamin D [25(OH)₂D] levels at birth, and explored sociodemographic, obstetric, dietary, and lifestyle factors affecting vitamin D status. Methods: In a cross-sectional study at Târgu Mureș County Clinical Hospital, Romania, 322 term mother–newborn pairs (37–41 weeks) from January 2021 to July 2023 were evaluated. The maternal and umbilical cord 25(OH)₂D was measured via electrochemiluminescence immunoassay. Data on socioeconomic status, parity, sun exposure, diet, and supplementation were collected through questionnaires and records. Statistical analysis included chi-square, linear regression, and multivariate modeling. Results: Vitamin D insufficiency and deficiency affected 32.3% and 18.9% of mothers, respectively. Supplementation was the strongest predictor of sufficiency (p < 0.01), showing a dose–response effect (r = 0.84, p < 0.01). Maternal and neonatal 25(OH)₂D levels were strongly correlated (r = 0.99, p < 0.01). Although several factors correlated with deficiency in univariate analyses, only supplementation remained significant in multivariate models. No link was found between 25(OH)₂D status and neonatal anthropometrics or early complications. Conclusions: A high prevalence of vitamin D deficiency has been documented among pregnant women in Romania. High-dose supplementation during late pregnancy is critical to ensure sufficient maternal and neonatal vitamin D, highlighting the need for standardized antenatal supplementation protocols, especially in disadvantaged groups. Full article

Objective: This study aims to evaluate free vancomycin concentrations in tissues of septic patients that received empirical doses. Methods: A PBPK model was built in PK-Sim to simulate vancomycin concentrations in healthy volunteers and septic patients. Literature data were used to validate the model. A strain of MRSA (methicillin-resistant Staphylococcus aureus) was evaluated through time-kill curves. Based on the information obtained from the time-kill study, a PD model, including adaptive resistance, was developed using NONMEM. The PBPK and PD models were combined to evaluate the vancomycin effect in plasma and tissues against MRSA. Results: A PBPK model was successfully built for both healthy volunteers and septic patients. The tissue concentrations were found to be significantly lower than plasma concentrations. The studied strain of MRSA was found to have an MIC of 2 µg/mL, and the PD model described the EC50 as 1.05 µg/mL. The PBPK and PD models were successfully combined, and septic patients infected with MRSA strains with MIC of 2 µg/mL had effective treatment response. However, septic patients infected with MRSA strains with MICs of 4 µg/mL and 8 µg/mL did not have adequate response to vancomycin treatment. Conclusions: In septic patients, response was limited against resistant MRSA strains. These findings should be considered hypothesis-generating and interpreted with caution, underscoring the need for individualized approaches and rigorous monitoring. Full article

Background/Objectives: As a non-medicinal part resource of Ziziphus jujuba, this study focuses on the total flavonoids from Ziziphus jujuba mesocarp (TFZJM), aiming to optimize the extraction process and explore its sedative and hypnotic effects. Methods: The extraction process of TFZJM was optimized by using single-factor experiments and the Box-Behnken response surface design method. The material basis of TFZJM was analyzed using Ultra-Performance Liquid Chromatography-Quadrupole-Time of Flight-Mass Spectrometry (UPLC-Q-TOF-MS). The mouse insomnia model was induced by intraperitoneal injection of PCPA, and the effects of TFZJM on this model and its potential mechanism were evaluated using multiple methods, such as sleep enhancement induced by pentobarbital sodium, HE staining of tissue sections, ELISA, RT-PCR, WB, and serum metabolomics. Results: The results showed that by optimizing the extraction conditions, a solid-liquid ratio (SLR) of 1:25 g·mL⁻¹, ethanol concentration of 60%, extraction time of 60 min, and extraction rate of 1.98% were achieved. The common chemical basis of the 10 flavonoid components was identified using UPLC-Q-TOF-MS analysis. Compared with the model group, the high-dose TFZJM (TFZJM-H) group had the most significant effect, followed by the medium-dose (TFZJM-M) and low-dose (TFZJM-L) groups. Conclusions: Metabolomic analysis revealed that TFZJM regulates pathways related to the metabolism of phenylalanine, tyrosine, cytochrome P450, and alanine. This lays the foundation for further exploration of the active substances and mechanisms of action of TFZJM in sedation and hypnosis. Full article