American journal of translational research最新文献

Background: Degarelix is a long-acting gonadotropin-releasing hormone (GnRH) antagonist that suppresses gonadotropin and sex steroid secretion via competitive blockade of the GnRH receptor (GnRHR). Although its systemic endocrine effects have been clearly identified, its direct effects on non-pituitary-derived cells, as well as the roles of sex and context-dependent pharmacological properties, remain largely unexplored.

Methods: Degarelix was profiled in vitro (HEK293T, CHO-K1 cells) and in vivo (male and female New Zealand rabbits). Cell viability was measured using a cell counting kit-8 (CCK-8) assay. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E₂, in females), and testosterone (T, in males) were quantified by enzyme-linked immunosorbent assay (ELISA). Transcript levels were assessed by quantitative polymerase chain reaction (qPCR), and GnRHR protein abundance and localization were evaluated in hypothalamic-pituitary-gonadal (HPG) tissues using Western blot and immunohistochemistry (IHC).

Results: In vitro, degarelix exerted direct, time-dependent, and concentration-dependent effects on the viability of non-pituitary-derived cells (P < 0.05), with differential responses observed between HEK293T and CHO-K1 cell lines. In vivo, degarelix induced a biphasic, sex-dependent endocrine response, characterized by a transient elevation (days 1-7) followed by sustained suppression (days 10-28) of gonadotropins and sex steroids, without affecting body weight (P > 0.05). qPCR revealed tissue- and sex-specific transcriptional changes, including upregulation of pituitary follicle-stimulating hormone beta subunit (FSHβ) mRNA in male rabbits and downregulation of hypothalamic GnRHR mRNA in female rabbits. Notably, Western blot and IHC analyses indicated that these mRNA alterations were not accompanied by significant changes in GnRHR protein abundance or localization.

Conclusion: This study systematically demonstrates that degarelix exhibits concentration-dependent, sexually dimorphic, and tissue-specific effects in the regulation of reproductive endocrine functions, as well as direct actions on non-pituitary cells. Furthermore, its direct regulation of non-pituitary cells does not depend on changes in GnRHR protein abundance. These findings provide insight into the mechanisms underlying the antagonistic effects of GnRH and lay a theoretical foundation for the personalized application of degarelix in both experimental and clinical settings.

Objective: To identify key factors affecting sleep quality among Chinese college students.

Design: Systematic review and meta-analysis (PROSPERO: CRD42023486000) following the 2020 PRISMA guidelines.

Setting: Studies related to sleep quality among Chinese college students. Data sources and participants: CNKI, VIP, WanFang, PubMed, Embase, Web of Science, and Scopus were searched from inception to October 2025.

Results: Fifty-four studies (total N = 61,254) were included. Poor sleep quality was positively associated with mobile phone addiction (WMD = 1.85, 95% CI: 1.22-2.48, P < 0.001), presleep electronic device use (OR = 1.59, 95% CI: 1.34-1.89, P < 0.001; prediction interval [PI] 1.29-1.96; low heterogeneity, I² = 0.0%), poor dietary habits - fried foods (RR = 1.43, 95% CI: 1.20-1.71), barbecued foods (RR = 1.27, 95% CI: 1.02-1.60), sugar-sweetened beverages (RR = 1.38, 95% CI: 1.16-1.63), and fatty foods (RR = 1.70, 95% CI: 1.35-2.14; high heterogeneity across diet subgroups, I² = 73.5%), smoking (OR = 1.46, 95% CI: 1.23-1.74; PI 1.11-1.92; I² = 0.0%), and alcohol consumption (OR = 1.47, 95% CI: 1.32). No significant associations were detected for physical inactivity (RR = 0.89, 95% CI: 0.71-1.11, P = 0.301), depression (WMD = 3.61, 95% CI: -3.37-10.59, P = 0.310), or staying up late (RR = 1.28, 95% CI: 0.90-1.82, P = 0.175). Egger's tests suggested small-study effects for physical inactivity, stress, and anxiety/depression but not for the other factors. Trim-and-fill procedures, when applied, did not materially change effect estimates. Leave-one-out analyses identified single influential studies for physical inactivity and mobile phone addiction, yet conclusions remained unchanged after exclusion. The degree of evidence was generally low to moderate, with downgrades for study design (predominantly cross-sectional), heterogeneity, and potential publication bias.

Conclusion: Multiple modifiable factors - including mobile phone addiction, presleep electronic device use, unhealthy diet, smoking and alcohol use, stress, anxiety, and academic stress - are associated with poor sleep quality among Chinese college students. Given the limited certainty and observed heterogeneity/publication bias, longitudinal studies are needed to strengthen causal inference; associations for physical inactivity, depression, and staying up late remain inconclusive.

Objective: To systematically evaluate the efficacy and safety of blood purification in the treatment of autoimmune encephalitis (AE).

Methods: Databases including PubMed, Embase, and Cochrane Library were systematically searched. Prospective and retrospective cohort studies were included. Data on patients' baseline characteristics, interventions, and outcomes were extracted. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of included studies. Meta-analysis was performed using RevMan 5.4 software.

Results: Fifteen studies (531 patients) were included; NOS scores of 7-9 indicated high quality. Efficacy analysis showed that in studies with control groups, blood purification significantly increased the likelihood of clinical improvement (Odds Ratio (OR)=5.61, 95% Confidence Interval (CI) [2.72, 11.56], P<0.00001). In studies without control groups, most efficacy indicators (e.g., clinical improvement, modified Rankin Scale (mRS) score improvement) showed statistical significance. Safety analysis revealed that the risk of therapeutic plasma exchange (TPE)-related adverse events was significantly increased (Risk Difference (RD)=0.46, 95% CI [0.40, 0.52], P<0.00001). The risks of complications and seizures were also elevated (RD=0.57 and 0.74, respectively, both P<0.05). The risk of total adverse reactions per cycle was increased (RD=0.09, 95% CI [0.04, 0.14], P=0.0004). The 1-year relapse risk was significantly increased (RD=0.07, 95% CI [0.02, 0.11], P=0.004), while there was no significant difference in mortality (P>0.05). Publication bias was assessed via funnel plots and Egger's test, with no evidence of bias, and sensitivity analysis results were stable.

Conclusion: Blood purification can significantly improve clinical outcomes in AE patients, but it is associated with higher risks of adverse events and relapse.

The transnasal route is a novel mode of drug delivery into the brain. It has several advantages of circumventing systemic first-pass metabolism that attenuates bioavailability and bypassing the blood brain barrier that excludes multiple categories of drugs or biologics. These include most compounds that have high molecular weight and low lipid solubility, bioactive neuropeptides, and monoclonal antibodies that have potential neurotherapeutic effects. In this review, we summarized how drugs and biologics can be delivered into the brain via (i) the olfactory/nasal lymphatic route, (ii) the epithelial or other supportive cells by receptor-mediated micropinocytosis for transcellular delivery, and (iii) transneuronal transport through the olfactory and trigeminal neurons. Dexamethasone and neuropeptide corticorelin acetate can be taken up by the lymphatic route, while larger molecular weight entities such as checkpoint inhibitors, bi-specific antibodies, and antibody-drug conjugates may require the slower transepithelial or transneuronal transport system. Tumor Treating Fields may increase the permeability of the tissue near the cribriform plate and therefore facilitate entry of these high-molecular-weight neurotherapeutics into the brain. For brain tumor patients, transnasal delivery holds promise for the delivery of drugs like dexamethasone, neuroactive peptide, and monoclonal antibodies for the treatment of malignancies in the brain while decreasing systemic toxicities.

As the most common cancer in men in the United States, risk factors for prostate cancer (PCa) need to be identified. Serum prostate specific antigen (PSA) levels are used for the screening of prostate cancer due to its association with the disease. Investigations have indicated that the risk of prostate cancer determined based on PSA can be further stratified on the basis of total PSA (tPSA) and f/t PSA. Further, the red blood cell distribution width-to-albumin ratio (RAR) has recently been identified as a novel biomarker for multiple inflammatory diseases. The relationship between RAR and PSA remains unclear. Here, we intended to study the association between RAR and PSA. National Health and Nutrition Examination Surveys (NHANES) represents a cross-sectional observational study within the United States. We obtained clinical data throughout the 2003 - 2010 NHANES study period. In 41,156 NHANES men, we selected 5,992 men aged 40 years or older. Missing data were imputed using multiple imputation. The association between RAR and PSA was assessed using multivariable adjusted linear regression analysis. Variance inflation factor (VIF) values were also calculated to exclude collinearity of independent variables. The association of the threshold effects was assessed using inflection points. The effect of RAR levels on PSA was significant in 5,992 subjects after adjusting the confounders (β = 1.13, 95% CI: 0.59-1.67). The notion of a threshold level was supported by the presence of inflection point at RAR = 3.762. The effect of a 1 unit increase in the RAR was a consistently increasing function of quartile of RAR. For instance, in the highest quartile of RAR, if RAR rises by 1 unit, PSA rises by 1.36 (β = 1.36, 95% CI: 0.90-1.83), suggesting a non-linearity of the two. For example, when RAR is below 3.762, higher RAR levels seem associated with higher PSA levels. This is important for understanding the factors that may play an important role in the occurrence and development of prostate cancer. Future studies must do assessments of prostate cancer incidence within the cohorts described.

Objective: To evaluate the effect of different initiation times of capecitabine metronomic chemotherapy on prognosis and safety in patients with early-stage triple-negative breast cancer (TNBC).

Methods: This retrospective study included 206 early-stage TNBC patients treated between March 2018 and January 2022. The patients were divided into early (≤ 4 weeks after surgery, n = 104) and delayed (> 4 weeks, n = 102) initiation groups. Clinical data, laboratory indicators (carcinoembryonic antigen [CEA], carbohydrate antigen 125 [CA125], neutrophil-to-lymphocyte ratio [NLR]), survival, and adverse reactions were compared between the two groups.

Results: The early initiation group showed significantly longer 3-year progression-free survival (PFS) (P < 0.05) but similar overall survival (OS) (P > 0.05). Reductions in CEA, CA125, and NLR were more prominent in the early initiation group (P < 0.05). Subgroup analysis indicated a PFS advantage for T2-stage patients. Adverse reactions, mainly hand-foot syndrome and bone marrow suppression, were comparable between groups, with most cases being grade 1-2.

Conclusion: Early initiation of capecitabine metronomic chemotherapy can improve the PFS in early-stage TNBC patients, especially for patients with T2 stage, with manageable safety.

Objective: To investigate the effects of oxytocin on cervical ripening and neonatal outcome in patients with late-pregnancy oligohydramnios (LPO).

Methods: The study retrospectively included 100 patients with LPO using propensity score matching (PSM). The patients were divided into two groups at a 1:1 ratio: the control group (amniotomy alone) and the observation group (amniotomy + oxytocin), with 50 cases in each group. General clinical data, blood and urine test results, imaging examination results, cervical assessment score (CAS), and neonatal Apgar scores were collected and compared between the two groups. Statistical analysis was performed using SPSS 26.0 software.

Result: Compared to the observation group, the control group had a lower induction success rate (84.0% vs. 76.0%, χ² = 10.0, P = 0.0015), a higher mean CAS (4.08 ± 0.87 vs. 4.76 ± 0.95, t = 2.761, P = 0.008), and a higher proportion of neonates with Apgar score < 9 (2.0% vs. 14.0%, χ² = 6.042, P = 0.017). Logistic regression analysis showed that serum ferritin level < 30 μg/L (OR = 4.25, 95% CI: 1.20-15.08, P = 0.025) and fetal chest-to-abdomen ratio (FAR) > 0.85 (OR = 5.95, 95% CI: 1.22-29.03, P = 0.028) were independent risk factors for inadequate cervical ripening.

Conclusion: Oxytocin is effective in inducing labor in patients with LPO. Its labor-inducing effect and effect on cervical ripening are influenced by maternal serum ferritin levels and fetal development indices.

Objective: To evaluate the clinical efficacy and lipid metabolism impact of intensified treatment with degludec-aspart dual insulin combined with semaglutide in patients with type 2 diabetes.

Methods: A systematic comparison and analysis were conducted on the changes in glycolipid metabolism-related indicators (including fasting blood glucose, glycated hemoglobin, fructosamine, and 2-hour postprandial blood glucose), blood glucose fluctuation indicators (specifically including standard deviation of blood glucose, postprandial blood glucose fluctuation amplitude, and 24-hour average blood glucose), insulin function status indicators (serum insulin level, fasting C-peptide (FCP), and 2-hour postprandial C-peptide (2hCP)), insulin resistance index, visceral fat index, and lipid index (including total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol) between the two groups of patients. Additionally, the adverse reactions and their incidence rates during the treatment period were statistically analyzed.

Results: Before treatment, there was no significant difference in glycolipid metabolism indicators, blood glucose fluctuation, insulin function and resistance index, visceral fat index, or lipid indicators between the two groups (all P > 0.05). After treatment, these indicators in both groups improved compared to before treatment, and the observation group showed significantly better outcomes than the control group (all P < 0.05). Moreover, there was no =significant difference in the incidence of adverse reactions between groups (P=0.576).

Conclusion: Intensified treatment with degludec-aspart dual insulin combined with semaglutide could improve blood glucose control, enhance insulin function, stabilize lipid levels, and did not increase treatment-related adverse reactions.

Objective: To evaluate the efficacy and survival outcomes of bevacizumab combined with minocycline versus bevacizumab monotherapy in patients with glioblastoma (GBM).

Methods: We conducted a retrospective analysis of 132 GBM patients treated at multiple centers between January 2022 and December 2023. Patients were divided into a control group (bevacizumab monotherapy, n = 67) and an observation group (bevacizumab plus minocycline, n = 65). Short-term treatment response, serum biomarkers, immune function, inflammatory and angiogenic factors, quality of life, safety, and long-term survival were assessed.

Results: The observation group showed significantly higher objective response rate (53.85% vs. 29.85%) and disease control rate (78.46% vs. 61.19%), along with improved immune function, reduced inflammatory and angiogenic markers, and enhanced quality of life (all P < 0.05). Median progression-free survival (PFS) (8.5 vs. 6.7 months) and overall survival (OS) (10.6 vs. 8.9 months) were longer in the observation group. No significant difference in treatment-related adverse events was observed.

Conclusion: This retrospective analysis suggests that the combination of bevacizumab and minocycline is associated with promising efficacy in GBM patients, including improved objective response, survival, and quality of life, with a manageable safety profile. These findings support further evaluation in prospective randomized trials to confirm the therapeutic potential of this combination.

Objective: To systematically evaluate the multidimensional efficacy of entecavir in patients with Chronic Hepatitis B (CHB) complicated with metabolic-associated fatty liver disease (MAFLD), with a focus on virological response, liver function, and metabolic parameters.

Methods: A retrospective analysis was conducted on 285 patients with CHB and concurrent MAFLD who received entecavir treatment at Minzu Hospital of Guangxi Zhuang Autonomous Region between January 2022 and May 2024 (MAFLD with comorbidities group). During the same period, 310 CHB patients without MAFLD served as the viral-only group. Both groups were treated with entecavir. Baseline characteristics, treatment efficacy at week 35, virological response, liver function parameters, fibrosis progression, metabolic indicators, and safety profiles were compared between the two groups.

Results: Compared with the viral-only group, patients in the MAFLD with comorbidities group exhibited significantly higher body mass index (BMI), waist circumference (WC), homeostasis model assessment of insulin resistance (HOMA-IR), fasting insulin (FINS), and triglyceride (TG) levels, as well as lower high-density lipoprotein cholesterol (HDL-C) levels, alanine aminotransferase (ALT)/aspartate aminotransferase (AST) normalization rates, hepatitis B virus (HBV) deoxyribonucleic acid (DNA) negativity rates, and hepatitis B e-antigen (HBeAg) seroconversion rates (P < 0.05). AST and GGT levels were also significantly lower in the viral-only group than in the MAFLD with comorbidities group (P < 0.05). Post-treatment fibrosis staging was more advanced in the MAFLD with comorbidities group (P < 0.05). After treatment, patients with MAFLD maintained higher HOMA-IR and TG levels and lower HDL-C levels than those without MAFLD (P < 0.05). During follow-up, the overall incidence of adverse events was 2.11% in the MAFLD with comorbidities group and 1.94% in the viral-only group, with no statistically significant difference between the groups (P > 0.05).

Conclusion: Entecavir can effectively control viral replication in patients with CHB combined with MAFLD. However, the recovery of liver function, improvement of steatosis and improvement of metabolic indicators were all slightly inferior to those of the non-MAFLD population, suggesting that the coexistence of MAFLD may weaken the comprehensive benefits of antiviral treatment.