西安医学高等专科学校

INTRODUCTION:The HSK16149-201/301 trial demonstrated short-term efficacy of the GABA analog crisugabalin for diabetic neuropathic pain. METHODS:In the current study, patients in both the crisugabalin and placebo control groups of the HSK16149-201/301 trial were invited to receive 80 mg/day crisugabalin for an additional 52 weeks. The primary end point was safety. The secondary end point was pain control as measured using the Short-Form McGill Pain Questionnaire (SF-MPQ). A total of 301 patients (mean age 59.7 years and males 58.1%) were enrolled. RESULTS:The rate of treatment-related adverse events (TRAEs) was 38.9% (117/301). The most frequent TRAEs were dizziness (27.2%), somnolence (8.3%), and peripheral edema (3.0%). The rate of Grade 3 or higher TRAEs was 1.7%. TRAEs led to dose reduction in 41 patients (13.6%), treatment interruption and discontinuation each in three patients (1.0%). At week 52, the mean difference in SF-MPQ pain rating index (PRI) and visual analog scale pain score from baseline was -2.5 (95% CI -2.9 to -2.0; paired t-test p < 0.0001) and -23.4 (95% CI -25.6 to -21.2; paired t-test p < 0.0001), respectively. The proportion of patients with SF-MPQ PPI score ≤ 1 increased by 19.0% over baseline (p < 0.0001). CONCLUSIONS:In summary, crisugabalin at 80 mg/day was well tolerated and demonstrated sustained analgesic activities. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT05890053.

Peripheral nerve injuries often lead to permanent functional deficits, and current surgical or grafting techniques offer only partial recovery. Conductive hydrogels have recently emerged as a versatile platform that integrates tissue-like softness with electrical conductivity to actively promote nerve regeneration. By providing both mechanical support and electroactive cues, these materials enhance axonal extension, Schwann cell function, and neuroimmune modulation. Advances in hydrogel design-such as self-healing networks, injectability, and controlled release-further expand their therapeutic potential. Incorporating conductive polymers, nanomaterials, or ion-based systems enables precise tuning of conductivity and biological interactions. Preclinical studies demonstrate accelerated nerve repair and functional restoration, highlighting conductive hydrogels as a promising interface between biology and bioelectronics. Nonetheless, critical challenges remain, including long-term biocompatibility, controlled degradation, and scalable manufacturing for clinical translation. This review summarizes current design strategies, mechanisms, critically identifies evidence-based design principles most relevant for near-term clinical translation, while distinguishing speculative bioelectronic concepts from validated strategies.

AIM: To investigate the levels of the triglyceride-glucose (TyG) index and sex hormone-binding globulin (SHBG) in patients with type 2 diabetes mellitus (T2DM) with diabetic retinopathy (DR), and to explore their correlations with biochemical parameters and the homeostasis model assessment of insulin resistance (HOMA-IR) in DR patients. METHODS: Patients with T2DM and healthy individuals were enrolled. Age and body mass index (BMI) of the participants were collected, TyG of the subjects was calculated using the formula, SHBG level of the subjects was detected, and blood biochemical indexes were measured at the same time. The changes of each index among the groups were statistically analyzed, and the relationship between TyG, SHBG, DR and each index was analyzed. RESULTS: A total of 150 patients with T2DM and 64 healthy individuals as normal controls (NC, 28 males and 36 females, mean age 54.49±10.10y) were enrolled following ophthalmic evaluation. Patients were categorized into non-DR group (42 males and 36 females, mean age 56.68±8.02y) and DR group (35 males and 37 females, mean age, 53.83±11.10y). TyG levels were significantly elevated in both non-DR (7.25±0.62) and DR groups (8.02±0.82) compared to controls (6.85±0.48), with the DR group demonstrating higher TyG values than the non-DR group (P<0.05). The level of SHBG (nmol/L) in DR group (25.05±14.06) was lower than that in control group (41.90±22.6) and non-DR group (36.27±20.00; P<0.05). TyG exhibited significant inverse correlations with SHBG (r=-0.455) and high density lipoprotein (HDL; r=-0.430) levels (P<0.05). It was positively correlated with BMI, fasting blood glucose (FBG), 2h postprandial blood glucose (PBG), fasting C-peptide (FCP), glycated hemoglobin A1c (HbA1c), HOMA-IR, total cholesterol (TC) and triglycerides (TG) (r=0.406, 0.768, 0.386, 0.393, 0.475, 0.250, 0.242, 0.888, respectively, P<0.05). SHBG was negatively correlated with BMI, FBG, FCP, HbA1c and TyG (r=-0.440, -0.304, -0.407, -0.209, -0.455, respectively, P<0.05), and positively correlated with age, TG and HDL (r=0.238, 0.034, 0.227, respectively, P<0.05). Further multiple regression analysis showed that SHBG was negatively correlated with TyG (P=0.006). CONCLUSION: Elevated TyG index, reduces SHBG levels, and their negative correlation in the DR group suggest potential roles of TyG and SHBG in the pathogenesis and progression of DR. Combined assessment of SHBG and TyG may provide valuable insights for DR prediction and diagnosis.

BACKGROUND:Preoperative anxiety is a prevalent concern among preschool pediatric patients. Esketamine, an S-enantiomer of ketamine, has emerged as a potential option for pediatric premedication. This study aimed to determine the 95% effective dose (ED95) of oral or intranasal esketamine for alleviating preoperative anxiety in this age group. METHODS:Children patients aged between 1 to 6 years old who were undergoing elective surgery under general anesthesia were recruited in the study. The initial patient received a single dose of esketamine orally (2.5 mg/kg) or intranasally (1 mg/kg), which was adjusted for subsequent patients using the Dixon up-and-down method, where the dose of esketamine administered orally or intranasally to each patient depended on the sedation success of the previous patient. Doses were increased or decreased by increments of 0.5 mg/kg (oral) or 0.05 mg/kg (intranasal). An effective response was defined as having a modified Ramsay sedation score ≥3a, separation anxiety score ≤2, and mask acceptance score ≤2 during inhalational anesthesia induction. RESULTS:A total of 62 children in the oral group and 66 children in the intranasal group were included in the final analysis. The ED95 for a single dose of oral or intranasal esketamine to alleviate preoperative separation anxiety in children was 8.2125 mg/kg (95% confidence interval [CI]: 7.4250-8.4597) and 2.1770 mg/kg (95% CI: 2.0952-2.1958), respectively. After surgery, the median of consciousness recovery time in esketamine oral and intranasal group was 30.00 (13.00-41.25) and 31.00 (20.00-45.00) min, respectively. Nausea, vomiting, increased secretions, and emergence delirium were the major adverse events that occurred following esketamine administration. CONCLUSION:This study demonstrates the efficacy of single-dose esketamine regimens, administered orally (ED95: 8.2125 mg/kg; 95% CI: 7.4250-8.4597 mg/kg) and intranasally (ED95: 2.1770 mg/kg; 95% CI: 2.0952-2.1958 mg/kg), in mitigating preoperative anxiety within a pediatric population. These findings highlight the safety and efficacy of esketamine for this patient group.

BACKGROUND:Thyroid cancer (TC), the most common endocrine malignancy, is closely linked to aging. In this study, we estimated DNA methylation (DNAm) age in TC tissues versus adjacent non-cancerous thyroid tissues using TCGA and GSE97466 datasets. METHODS:We employed multi-tissue DNAm age estimators, specifically Horvath's clock and the Bayesian Neural Network (BNN) clock, to quantify epigenetic aging in TC and adjacent normal tissues from the TCGA and GSE97466 cohorts. We further integrated genomic, transcriptomic, and mutational analyses, including assessments of senescence-associated secretory phenotype (SASP), immune cell infiltration, and thyroid differentiation, to elucidate the associations between DNAm age acceleration and various cancer-related features. RESULTS:Our results revealed marked DNAm age acceleration in TC tissues relative to controls, with both models yielding significantly higher DNAm age estimates in tumors. Although DNAm age correlated strongly with chronological age in control tissues (R ≈ 0.94), this association was notably diminished in TC tissues (R ≈ 0.62). Moreover, TC tissues with accelerated DNAm age exhibited higher telomerase-associated gene expression score, heightened SASP signaling, and distinct immune profiles characterized by elevated M2 macrophages and reduced activated NK cells. Genomic analysis further showed a higher prevalence of BRAF mutations and lower thyroid differentiation scores (TDS) in the accelerated subgroup. No significant associations were detected between DNAm age and clinicopathological parameters or overall survival. CONCLUSIONS:Our findings provide valuable insights into the complex interplay between epigenetic regulation, immune dysfunction, and genomic instability in thyroid cancer, highlighting promising avenues for future research and therapeutic intervention.