Bin Zhang, Na Li, Fang Liu, Guorui Wang, Quanwei Chen, Yiming Sun, Ni Yang, Hao Zhang, Jianjun Han
Despite being a globally prevalent chronic liver disease, MASLD currently lacks any approved pharmacotherapy. MET and ATO individually confer benefits against MASLD, but their combined therapeutic effects have seldom been investigated. The current work aimed to verify the therapeutic benefits of their combined intervention on MASH. A MASH-like mouse model was established via HFD feeding combined with CCl 4 injection, alongside an FFA-induced HepG2 steatosis model. Serum biochemical markers and inflammatory cytokines were measured, and lipid deposition was assessed by Oil Red O staining. Western blotting was performed to evaluate the expression of lipid metabolism-related proteins and AMPK/NF-κB signaling pathway components. Additionally, Compound C, a pharmacological inhibitor of AMPK, was used to verify the underlying molecular mechanism. Co-treatment with MET and ATO markedly alleviated FFA-induced lipid accumulation and TG/TC levels in HepG2 cells. Combination therapy in HFD/CCl 4 -induced MASH-like mice reduced body/liver weights, fasting glucose and HOMA-IR. Mechanistically, it downregulated lipogenic proteins SREBP-1 and HMGCR while upregulating fatty acid oxidation regulators CPT1A and PPARα. Additionally, it suppressed IL-6, TNF-α and IL-1β secretion via inhibiting NF-κB phosphorylation, thereby mitigating hepatic and cellular inflammation. Moreover, the combination enhanced AMPK phosphorylation, while the AMPK inhibitor Compound C largely abolished these protective effects. These observations indicate that the combined MET and ATO treatment exerts lipid-lowering and anti-inflammatory effects possibly via the AMPK/NF-κB signaling axis.
To investigate the short-term impact of unilateral salpingectomy on ovarian reserve and to evaluate its comprehensive value regarding long-term reproductive outcomes in women of reproductive age. In this prospective cohort study, 96 reproductive-aged women diagnosed with ectopic pregnancy (EP) were enrolled. Base on the surgical and therapeutic regimens, participants were allocated into a study group (undergoing laparoscopic unilateral salpingectomy, n = 48) and a control group (preservation of the fallopian tube, including either laparoscopic salpingostomy or systemic methotrexate [MTX] therapy, n = 48). Biochemical markers of ovarian reserve (anti-Müllerian hormone [AMH], serum follicle-stimulating hormone [FSH], etc.) and morphological parameters (ovarian volume and antral follicle count [AFC]) were dynamically monitored and compared between the two groups at baseline and at 1, 3, and 6 months postoperatively. All participants were followed up for 24 months to compare spontaneous ovulation rates, spontaneous pregnancy rates, and the incidence of recurrent EP. The study group exhibited transient fluctuations in biochemical markers indicative of diminished ovarian reserve in the early postoperative period (1 month), which normalized by 6 months postoperatively. Regarding morphological compensation, the contralateral ovarian volume and AFC in the study group increased significantly at 1–3 months postoperatively compared with the control group ( P < 0.05); however, these parameters converged between the two groups by 6 months ( P >0.05). Over the 24-month follow-up, there were no statistically significant differences in spontaneous ovulation or spontaneous pregnancy rates between the groups ( P >0.05). Notably, the recurrence rate of EP in the study group was 2.08% (1/48), significantly lower than the 16.67% (8/48) observed in the control group ( P < 0.05). Unilateral salpingectomy induces a transient early decline in ovarian reserve, counterbalanced by a distinct short-term compensatory response in the contralateral ovary. Crucially, this procedure does not compromise long-term natural conception potential while significantly mitigating the risk of recurrent EP. For patients with normal ovarian reserve and a healthy contralateral tube, unilateral salpingectomy represents a safe, effective, and optimal treatment strategy for maximizing protection against recurrent EP.
Obstructive sleep apnea (OSA) affects up to 80% of patients at diagnosis of acromegaly and often persists despite treatment. Currently, patients at risk for OSA are recommended to be identified to offer polygraphy evaluation. To study the prevalence and risk factors for OSA in patients with acromegaly. Prospective, single-center study; polygraphy was performed on 36 patients with acromegaly (age 54.1 ± 12.9 years). OSA was found in 17 patients (47.2%), mostly mild (64.7%). Patients with OSA were older both at diagnosis (p = 0.02) and at polygraphy (p = 0.008), had a longer diagnostic delay (p = 0.003) and higher BMI (p = 0.03). Patients with uncontrolled acromegaly exhibited a significantly higher number of apneas (p=0.02) and obstructive apneas (p=0.04) and had significantly lower minimum oxygen saturations (p=0.02) and a higher percentage of time spent with oxygen saturation <90% (p=0.03) as compared to those with full disease control. Diagnostic delay was the best predictor of apnea-ipopnea index (AHI, p=0.04) and oxygen desaturation index (ODI, p=0.04) scores, independently on BMI. Insulin resistance (p = 0.05), glucose profile impairment (p = 0.05) and STOP-Bang score (p=0.001), but not Epworth Sleepiness Scale score (p = 0.96), were significantly higher in patients with OSA as compared to those without. Diagnostic delay and patients’ age, rather than disease status, appear to predict the development of OSA and influence its severity. These findings reinforce the importance of early identification of patients at higher risk for OSA.
Baoyi Liao, Yongzhe Gu, Nuo Ma, Aiping Jin, Shengqi Yao
While intracranial atherosclerosis (ICAS) and insulin resistance (IR) often co-occur in ischemic stroke, their combined prognostic impact is unclear; we hypothesized their synergy predisposes to worse short-term outcomes. We conducted a retrospective analysis of 712 consecutive patients with acute ischemic stroke. The primary outcome was poor functional status, defined as modified Rankin Scale score > 2 at 90 days. Participants were categorized according to TyG index (as a surrogate for IR) and ICAS status. Subsequent stratification based on ICAS severity (none, moderate, severe) and number of affected vessels (none, single, multiple) enabled dose-response evaluation. Subgroup analyses and interaction analyses were further performed to assess the robustness of the associations and explore potential interactive effects between TyG index and ICAS. Exploratory mediation analysis quantified the proportion of ICAS’s total statistical effect on functional outcomes that could be explained via the TyG index. Univariate analysis demonstrated that both elevated TyG index (OR 1.34, 95% CI 1.01-1.79) and presence of ICAS (OR 1.74, 95% CI 1.19-2.56) were associated with poor outcomes. Although the combination of high TyG index and ICAS showed a non-significant trend (OR = 1.77, 95% CI: 0.98–3.17, p = 0.057), high TyG index significantly increased poor outcome risk in patients with severe ICAS (OR = 2.15, 95% CI: 1.13–4.09) or multiple ICAS lesions (OR = 2.11, 95% CI: 1.11–4.02). The exploratory mediation analysis showed that the mediated proportion of the TyG index in the association between ICAS and poor post-stroke functional outcome was approximately 9.0% (95% CI: −0.8% to 68.2%), and this mediated effect was not statistically significant. The combined assessment of the TyG index and ICAS burden shows promise for identifying stroke patients at high risk of poor prognosis.
