Background/Objectives: ShenRongGuBenHuanShao Pill (SRGBHSP) is a traditional Chinese medicine (TCM) used for the treatment of erectile dysfunction (ED). However, its active constituents and pharmacological mechanisms remain unclear. This study characterized the flavonoid constituents of SRGBHSP and investigated its effects on HC-associated ED-related alterations and potential molecular mechanisms using an integrated multi-omics strategy. Methods: SRGBHSP constituents were characterized by UPLC-Q-TOF-MS/MS, and representative flavonoids were quantitatively analyzed by UPLC-MS/MS. Rats exposed to HC received SRGBHSP (1.08, 2.16, or 4.32 g/kg), Yougui Pill, or sildenafil concurrently with HC administration. Pharmacological effects were evaluated using APO-induced erectile responses, histopathology, sperm quality, reproductive hormones, oxidative stress indices, and serum NO/GC/cGMP-related parameters. Integrated 16S rRNA sequencing, untargeted metabolomics, transcriptomics, and DIA-based proteomics were combined with RT-qPCR and Western blotting to investigate potential regulatory mechanisms. Results: A total of 131 flavonoids were characterized in SRGBHSP, including flavones, isoflavones, flavonols, flavanones, chalcones, flavans, anthocyanidins, and aurones. Quantitative analysis identified baicalin as the predominant flavonoid constituent. APO-induced erection frequency decreased from 3.50 ± 1.29 in the control group to 0.50 ± 0.58 in the model group and increased to 4.50 ± 1.29 following high-dose SRGBHSP intervention. SRGBHSP also improved reproductive hormone homeostasis, sperm quality, and oxidative stress status in HC-treated rats. SRGBHSP increased serum NOS, NO, GC, and cGMP levels and increased the mRNA and total protein expression of PI3K, Akt, and mTOR in penile tissue. Integrated multi-omics analyses revealed coordinated alterations in gut microbiota, glycerophospholipid metabolism, and penile transcriptomic and proteomic profiles. Conclusions: SRGBHSP attenuated multiple ED-related alterations associated with HC exposure, accompanied by improvements in reproductive function, oxidative stress status, and serum NO/GC/cGMP-related parameters. Integrated multi-omics analyses together with expression-level validation revealed coordinated alterations in gut microbiota, glycerophospholipid metabolism, and PI3K/Akt/mTOR-related molecules following SRGBHSP intervention. These findings suggest the potential involvement of PI3K/Akt/mTOR-related signaling in the response to SRGBHSP, although its activation status and causal contribution remain to be established. Flavonoids may represent important bioactive constituents associated with the observed effects of SRGBHSP. Overall, this study provides an integrated pharmacological and multi-omics framework for understanding the effects of SRGBHSP on HC-associated ED-related alterations.

Background and Objectives: The transition from pediatric to adult endocrine care represents a vulnerable period for patients with congenital adrenal hyperplasia (CAH), given the risk of loss to follow-up and the evolving physiological and healthcare requirements associated with the transition to adulthood. This study aimed to compare structured and non-structured transition pathways in patients with CAH, focusing on the continuity of adult endocrine care and disease-specific hormonal, clinical, and treatment-related outcomes. Materials and Methods: This single-center, retrospective, observational study included patients with CAH who transitioned from pediatric to adult endocrine care and met predefined pediatric and adult follow-up eligibility criteria. Patients were classified according to whether the transition occurred through a structured multidisciplinary transition program or without participation in the structured program. Outcomes were evaluated during predefined observation periods before and after transfer and included continuity-of-care measures, 17-hydroxyprogesterone (17-OHP) and androstenedione concentrations, achievement of predefined hormonal targets, body mass index (BMI), glucocorticoid and mineralocorticoid treatment, and CAH-related clinical outcomes. Results: Among 67 patients assessed for eligibility, 29 were included: 20 in the structured transition group and 9 in the non-structured transition group. Overall, 62.1% of the study population was female. No significant between-group differences were observed in continuity-of-care measures, including the pediatric-to-adult care gap, first-year adult visit frequency, maximum visit-free interval, first-year loss to follow-up, or active adult endocrine follow-up at the study cutoff. Pre-transition and post-transfer 17-OHP and androstenedione concentrations and achievement of predefined hormonal targets did not differ significantly between groups. No significant longitudinal changes in hormonal outcomes, BMI, or body-surface-area-adjusted hydrocortisone-equivalent glucocorticoid doses were observed within either group. At the study cutoff, 85.0% of patients in the structured group and 77.8% in the non-structured group remained under active adult endocrine follow-up. Conclusions: In this small single-center cohort, no significant differences in the continuity of adult endocrine follow-up or disease-specific outcomes were observed between structured and non-structured transition pathways. Most patients remained engaged with adult endocrine care, and hormonal control showed no evident deterioration following transfer in either group. Given the small sample size and high overall retention, these findings should not be interpreted as evidence of equivalence between the two transition approaches.

Neuroendocrine and circadian dysfunctions are thought to underlie bipolar disorder (BD) and could be implemented as markers of complex symptom conditions, including the presence of Post-Traumatic Stress Disorder (PTSD) comorbidity. The primary objective of this study was to investigate neuroendocrine profiles in different BD phenotypes through the measure of nocturnal urinary levels of Cortisol (stress-response factor) and 6-sulfatoxymelatonin (aMT6s; light/dark signal) in euthymic BD patients diagnosed with PTSD (PTSD group) or with major depressive episodes without trauma symptoms (DEP group). Both groups were compared against healthy controls (CTL). Nighttime urinary levels of aMT6s and Cortisol were analyzed by competitive ELISA, with ensuing values normalized for specific gravity. The Cortisol-to-aMT6s ratio (Cort/aMT6s) was calculated as an exploratory proxy for the homeostatic balance between HPA-mediated catabolic/coping activities and Melatonin-related reparative functions. Clinical severity and psychosocial activities were assessed by using mood HAM-D, YMRS, trauma IES-R and functioning WSAS scales. Results revealed distinct biological patterns: PTSD subjects showed increased nocturnal Cortisol compared to DEP and CTL groups, whereas DEP patients exhibited lower aMT6s levels and an elevated Cort/aMT6s ratio. Cortisol and aMT6s correlated positively in PTSD, while the ratio correlated positively with Cortisol solely in controls. Clinically, Cortisol correlated positively with IES-R and functional impairment (WSAS), whereas aMT6s correlated negatively with HAM-D and YMRS scores. Present findings suggest a possible neuroendocrine divergence in BD patients with depression versus PTSD: nocturnal Melatonin deficiency may be associated with depression, while HPA-axis hyperactivity and altered crosstalk between the two systems may characterize PTSD comorbidity, with the Cort/aMT6s ratio as a potential index of impaired daily functioning. These results could be promising for the use of biomarkers linked to allostatic and circadian responses within the BD spectrum.

Inflammation is a complex biological response involved in the pathophysiology of several chronic diseases. Although conventional anti-inflammatory therapies are effective, their prolonged use can be associated with relevant adverse effects. Although non-steroidal anti-inflammatory drugs and glucocorticoids are widely used, these agents cause gastrointestinal, renal, cardiovascular, hepatic and metabolic adverse effects. Essential oils (EO) exhibit relevant anti-inflammatory potential. However, their pharmaceutical application is limited by volatility, hydrophobicity, physicochemical instability and potentially low bioavailability. This review evaluated EO-loaded lipid nanocarriers for anti-inflammatory applications, with emphasis on physicochemical quality attributes, stability, safety and efficacy. Literature searches were carried out through PubMed/MEDLINE, PubMed Central, ScienceDirect, SciELO, Virtual Health Library, and Google Scholar websites, based on works published between 2021 and 2026. The investigated systems included liposomes, solid lipid nanoparticles, nanostructured lipid carriers and nanoemulsions. Different formulations were found regarding EO nature, nanocarrier type, administration route and biological models used, predominantly involving preclinical assays. Nanoencapsulation was frequently associated with suitable physicochemical properties and release profiles, but direct comparisons with the corresponding free EO and control nanocarriers were not consistently performed. Safety findings were mainly based on cytotoxicity, local tolerability and short-term assays, with limited repeated-dose and long-term toxicological data. Several formulations showed anti-inflammatory activity in acute, subacute, or chronic experimental models. In selected works using the same experimental conditions, some formulations produced responses of similar magnitude to hydrocortisone, diclofenac, or other anti-inflammatory drugs, but these results cannot be directly correlated with therapeutic equivalence. The reported mechanisms involved modulation of the NF-κB, MAPK and Keap1/Nrf2/HO-1 signaling pathways. Overall, lipid-based nanocarriers represent platforms for investigating the stability, delivery and biological performance of EO. However, further standardization and controlled assays are required to determine their therapeutic and translational potential.

Regulation of craving (ROC) by focusing on long-term negative consequences of drug use has been shown to successfully reduce subjective craving. This process is supported by the dorsolateral prefrontal cortex (dlPFC), which exerts control over reward and value signals in the ventral striatum (VS) and ventromedial prefrontal cortex (vmPFC). As stress impairs cognitive control and addiction is characterized by altered value computations manifesting in delay discounting, we examined how these factors interact with ROC and its neural correlates to better understand the use of ROC in high-risk situations. Sixty-eight male smokers underwent a delay discounting task and either a stress (socially evaluated cold pressor task) or a control condition. They subsequently completed a ROC task during fMRI while focusing on (1) long-term negative consequences (LATER) versus (2) short-term positive consequences (NOW). We found lower subjective craving ratings and attenuated neural responses in the VS (t = 4.33, p = 0.012) and vmPFC (t = 5.79, p < 0.001), as well as higher activation in the dlPFC (t = 4.09, p = 0.038) in the LATER compared to the NOW strategy. Although no neural or behavioural difference in ROC was observed between stress and control groups, both individual stress (cortisol) and delay discounting were positively related to vmPFC activity (NOW > LATER). We replicated previous results on ROC. Importantly, the association of vmPFC signals with stress response and delay discounting suggests that enhancing ROC success may involve reinforcing changes in self-referentiality of future thoughts to subjective value of drug use.

Paraneoplastic endocrine syndromes are well-recognised complications of lung malignancies, specifically small-cell lung cancer. The majority of patients with panhypopituitarism associated with lung cancer result from pituitary metastasis. In those with an enlarged pituitary stalk without obvious pituitary metastasis presenting with a combination of panhypopituitarism and arginine vasopressin deficiency (AVP-D), metastatic pituitary stalk infiltration should be considered rather than a paraneoplastic immune-mediated hypophysitis. We report a case of a 67-year-old gentleman with newly diagnosed lung adenocarcinoma, found to have panhypopituitarism before starting systemic anti-cancer treatment. Further hormonal tests revealed central hypothyroidism, hypogonadotropic hypogonadism and growth hormone deficiency. MRI of the pituitary demonstrated heterogeneous contrast enhancement without an obvious focal lesion. The pituitary stalk was slightly enlarged at the level of the optic chiasm, raising the possibility of hypophysitis. The patient was initiated on hydrocortisone and levothyroxine replacement therapy. Following hormone replacement, previously occult AVP-D became clinically apparent, manifesting as worsening dehydration, polyuria and polydipsia. The overnight water deprivation test confirmed AVP-D. The patient showed subsequent clinical improvement with desmopressin. Serum prolactin was mildly elevated, likely reflecting both pituitary stalk infiltration and concomitant metoclopramide therapy. This case discusses an exceptionally rare presentation of lung adenocarcinoma with isolated pituitary stalk infiltration, panhypopituitarism, and AVP-D before exposure to immune checkpoint inhibitors. Clinicians should be aware of this unusual manifestation, as prompt hormone replacement can significantly reduce morbidity and improve patient outcomes.

This case report describes a newborn diagnosed with very-early-onset autosomal dominant polycystic kidney disease (VEO-ADPKD) and congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. The patient presented with prenatally detected kidney cysts and exhibited clinical and laboratory features consistent with salt-wasting, including markedly elevated 17-hydroxyprogesterone levels, requiring treatment with hydrocortisone, fludrocortisone, and sodium chloride. Genetic analysis revealed a de novo truncating variant in PKD1 and two variants in CYP21A2. Hypertension developed at 3 years and 7 months despite unchanged steroid replacement doses, requiring antihypertensive treatment, and resolved after mineralocorticoid dose reduction. This case highlights the competing therapeutic demands of concurrent salt-wasting CAH and VEO-ADPKD, underscoring the importance of early genetic evaluation and integrated multidisciplinary surveillance.

This study investigated physiological responses during professional competitions by measuring heart rate variability (HRV) and salivary α-amylase and cortisol in elite archers. Based on the vagal tank theory, we examined psychophysiological dynamics and assessed differences in HRV and salivary biomarkers between high- and low-scoring matches to evaluate their association with performance. Eight elite archers (four male, four female) participated, with data collected across 184 matches of the Chinese Enterprise Archery League. HRV was recorded pre- and during matches, and salivary α-amylase and cortisol were measured pre- and post-match. Heart rate significantly increased from 97.0 ± 11.5 bpm pre-match to 110.7 ± 15.3 bpm during matches, while RMSSD, an index of cardiac vagal control, remained stable. Heart rate, RMSSD, and high-frequency power were similar between high- and low-scoring matches. Post-match α-amylase concentrations were lower in high-scoring matches (51.37 ± 49.44 U/ml) than in low-scoring matches (71.00 ± 88.13 U/ml; p = 0.037), after controlling for pre-match values, whereas cortisol levels remained unchanged. These findings suggest that elite archers engage sympathetic arousal to mobilize cognitive and physiological resources while maintaining vagal regulation to preserve precision and composure. The observed autonomic profile aligns with the vagal tank theory, indicating that self-regulation capacity was maintained during competition. Lower post-match AA levels, an indicator of sympathetic-adrenal-medullary pathway activity, were associated with better performance, suggesting that effective anxiety management may enhance accuracy. Psychological skills training to manage competition-related stress may therefore improve performance in elite archery.

Transportation inevitable in modern beef industry disrupts physiological homeostasis and compromises cattle health. This study evaluated bovine appeasing pheromone (BAP) in alleviating transport-induced dysfunctions. Herein, 120 Simmental crossbred bulls (235 ± 5 kg) underwent a 1402-km transport trial with or without BAP treatment (5 mL topically). Data showed BAP decreased (p < 0.01) serum cortisol and haptoglobin levels on day 1 (D1) and D14 post-transport, with cortisol reduced by 32.99% and 47.09%, and haptoglobin by 51.67% and 53.48%, respectively. Concurrently, BAP lowered (p < 0.05) serum IL-1 (by 57.01%) and TNF-α (by 44.12%) on D1, reduced IL-1 (by 22.24%), IL-6 (by 15.18%), and TNF-α (by 23.29%) on D14, and increased (p < 0.01) IgG by 38.58% on D14. Consequently, BAP facilitated metabolic recovery, elevating (p < 0.01) serum glucose and insulin-like growth factor-1 from D14 to D35. Clinically, BAP reduced (p < 0.01) the incidence and duration of respiratory symptoms, increasing (p < 0.05) total feed intake. In summary, BAP protects beef cattle against transport stress-induced health impairment and growth decline by maintaining physiological homeostasis, offering a highly practical intervention to optimize animal welfare in the modern beef industry.

Objective. Adrenal insufficiency is predominantly managed by glucocorticoids, from which hydrocortisone is most frequently prescribed. However, limited data are available on prescription patterns among Indian healthcare professionals (HCPs). This study assessed the prescription practices of hydrocortisone among Indian HCPs and evaluated their awareness of tapering protocols and necessity for modified-release formulations of hydrocortisone. Methods. This online questionnaire-based survey involved 300 HCPs across India who prescribe oral hydrocortisone for various endocrinological and non-endocrinological indications. Google Forms were used and survey was carried out over a period of two months. Only fully accomplished responses were included in the analysis and the response rate was calculated. Results. The survey response rate was 84.27%. Among HCPs, 94.7% prescribed oral hydrocortisone with 47.5% using it often and 28.9% very often. Prescription frequency varied from 29.9% (prescribed once weekly) to 25.7% (two or more times weekly). Awareness of approved indications was high (96.8%). Tapering protocols were widely practiced (95.4%) often or very often by 82.7% HCPs. Hydrocortisone was mainly prescribed for primary adrenal insufficiency (77.5%), secondary adrenal insufficiency (63.0%), and congenital adrenal hyperplasia (55.6%). Frequent adverse events included hyperglycemia (43.3%) and weight gain (43.0%). Most HCPs (89.8%) felt need for sustained-release hydrocortisone, particularly for primary adrenal insufficiency (81.7%). Alternatives of hydrocortisone mainly included prednisolone (65.8%), prednisone (37.3%), and dexamethasone (21.8%). Conclusion. Indian HCPs frequently prescribe oral hydrocortisone and are well-versed in tapering protocols. However, frequent adverse events and unmet needs emphasize strong demand for modified-release formulations, particularly for management of adrenal insufficiency.