Hebei Mental Health Center

This paper presents a Multi-Load-Case topology optimization framework for aluminum alloy wheels to overcome the limitations of empirical rear-cavity lightweight designs. To balance structural integrity and mass reduction without altering the aerodynamic outboard styling, a region-constrained topology optimization was conducted. By employing a compromise programming method based on strain energy ratios, the weighting coefficients for bending fatigue and 13° impact load cases were scientifically calibrated. Furthermore, manufacturing constraints, including a 10 mm minimum member size and draw directions, were incorporated to ensure direct compatibility with conventional casting. The results demonstrate that the optimized depth-gradient cavities successfully reduced the peak von Mises stress for bending fatigue by 19.25% (from 133.9 to 108.13 MPa) and for the 13° impact by 14.57% (from 74.63 to 63.76 MPa), alongside a slight mass reduction of 0.53%. This approach offers a mathematically rigorous and industrially viable paradigm for the multi-objective lightweight design of high-performance automotive components.

Individual variations in depressive disorder (DD) treatment responses highlight the need for early efficacy prediction to optimize regimens. The niacin skin flushing response (NSFR) is a potential DD biomarker, and elevated inflammatory cytokines are linked to DD. This study explored the association between blunted NSFR and DD symptom severity, and evaluated the predictive value of NSFR and inflammatory cytokines for early antidepressant efficacy. Fifty DD patients were grouped as responders (≥ 50% Hamilton Depression Rating Scale reduction at week 2) or non-responders. Intergroup differences in NSFR index and inflammatory cytokines (Phospholipase A2 [PLA2], Cyclooxygenase-2 [COX-2]) were compared. Spearman’s correlation, binary logistic regression, and receiver operating characteristic (ROC) curves analyzed associations and predictive performance. (1) Baseline NSFR index was significantly negatively correlated with baseline HAMD score (r = -0.736, p < 0.001), indicating that the degree of NSFR attenuation reflects depression severity. (2) Both baseline NSFR index (AUC = 0.615) and COX-2 level (AUC = 0.725) independently predicted early treatment efficacy, with patients exhibiting lower baseline NSFR index or higher baseline COX-2 levels showing superior early efficacy. (3) The combined predictive model incorporating baseline NSFR index, COX-2, and PLA2 demonstrated optimal predictive performance (AUC = 0.786). This study confirms that greater NSFR attenuation is associated with more severe depressive symptoms. Baseline NSFR and COX-2 hold promise as potential predictive biomarkers. Furthermore, the combined model based on NSFR and inflammatory cytokines exhibits superior predictive value, providing a potential basis for optimizing individualized DD treatment strategies and exploring anti-inflammatory therapeutic targets. Assessed NSFR and inflammatory cytokines for predicting early antidepressant efficacy. Confirmed that blunted NSFR reflects the severity of depressive disorder. Demonstrated combined NSFR + COX-2 + PLA2 model has optimal predictive performance. Offer basis for optimizing individualized DD treatment.

BackgroundOptical genome mapping (OGM) is an emerging cytogenetic method for concurrently detecting structural variants (SVs) and copy number variants (CNVs). However, its clinical application in prenatal diagnosis remains underexplored.MethodsThis study retrospectively evaluated the clinical validity of OGM in prenatal diagnosis by comparing with two routine genetic testing methods: karyotyping and chromosomal microarray analysis (CMA). Both positive and negative cases detected by routine genetic methods were enrolled to evaluate the technical concordance of OGM and its capability to improve diagnostic rate in negative cases. The exclusion criteria were balanced centromeric translocations, mosaic cases with cellular fractions < 20%, and loss of heterozygosity (LOH) < 25 Mb. All samples subjected to OGM testing were anonymized and analyzed blindly. The results from OGM were compared with those from routine genetic testing, and statistical analyses were performed to assess technical concordance and diagnostic rate.ResultsOf 217 samples (166 positive samples and 51 negative samples for routine genetic testing), all were successfully tested with OGM, including 2 umbilical cord blood samples, 4 chorionic villi samples, and 211 cultured amniotic fluid samples. Of the 207 reportable chromosomal aberrations from 166 positive samples, the blinded concordance between OGM and CMA, karyotyping, and combination of karyotyping plus CMA was 97.81%, 96.36%, and 97.10%, respectively. OGM missed six aberrations initially, including one LOH, two marker chromosomes, and three microdeletions. However, after reanalysis, its concordance improved to 100% with CMA and 99.03% with karyotyping plus CMA. OGM also diagnosed one additional case of a 3-kb deletion in 51 negative samples, improving the diagnostic rate by 1.96%. Moreover, OGM reclassified the pathogenicity of two microdeletions from pathogenic to uncertain significance in 2 positive cases. Furthermore, OGM clarified the diagnosis suspected by routine genetic testing and improved diagnostic accuracy in some cases.ConclusionAs far as we know, this is the largest retrospective study on OGM in prenatal diagnosis, and it includes a broad range of sample types. The results showed that OGM exhibits high concordance among the tested methods and increases the diagnostic rate. Thus, OGM has the potential to become a first-line technique for prenatal diagnosis in the future.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12967-025-06901-9.

Myocardial infarction (MI) is one of the leading causes of death globally, and stress-aggravated cardiac injury exacerbates patient prognosis. The study aimed to clarify the role of notoginsenoside R1 (NR) in the myocardial infarction-induced differential gene 2 (CRIF1)/PINK1-Parkin complex by using a restrain stress-exacerbated MI rat model. Male Sprague Dawley rats were subjected to coronary artery ligation followed by treatment with NR (2.5, 5, or 10mg/kg, p.o.) for 10days post-surgery. NR significantly enhanced cardiac function (elevated LVEF (left ventricular ejection fraction), LVFS (left ventricular fractional shortening), LVEDD (left ventricular end diastolic diameter), LVESD (left ventricular end systolic diameter)) and attenuated serum markers of myocardial damage (LDH (lactate dehydrogenase), CK-MB (creatine kinase myocardial band), CPK (creatine phosphokinase), cTnT (cardiac troponin T), cTnI (cardiac Troponin I)). It brought the imbalanced electrolyte status back to equilibrium, increased antioxidants, and decreased inflammatory mediators and apoptotic markers. In addition, NR suppressed NF-κB (nuclear kappa B factor) and NOX (NADPH oxidase 1) isoforms but increased the expression of PINK1-Parkin-associated mitochondrial quality control genes and cardiac remodeling markers at mRNA levels. These results indicate that NR exerts cardioprotection by inhibiting oxidative stress, inflammation, and apoptosis via the coordinated regulation of NF-κB/NOX/PINK1-Parkin signaling. However, additional protein-level validation (Western blot) and pathway inhibition studies together with the mechanistic confirmation are warranted in order to promote a causal role and translational potential.

The concentration of antiseizure medications in vivo has a significant influence on therapeutic and adverse effects. To use antiseizure medications safely and rationally, it is crucial to establish a method of measuring their blood concentration, provide individualized medication guidance to patients, and avoid adverse effects through therapeutic drug monitoring. Therefore, we developed a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the rapid detection of antiseizure medication concentrations in blood and applied it to the monitoring of clinical antiseizure medication therapy. A Waters HPLC-ESI TQ-D with a Waters BEH C18 column (50 × 2.1 mm, 1.7 µm) was used; the blood samples were injected after protein precipitation in 50% methanol in water, and the analysis was conducted within 3.5 minutes. The ion source for mass spectrometry was an electrospray ionization source with the multiple ion reaction monitoring mode. An isotope standard was selected as the internal standard. The linearity of each epileptic drug was good in the studied concentration range (R2 > 0.9930), and the lower limit of quantification was 0.01-8.00 mcg/mL, with intraday and interday precision less than 15.00%. The recoveries of the method ranged from 91.86% to 113.97%, and the stability of the method was good and unaffected by matrix effects. The established LC-MS/MS method for the determination of antiseizure medication concentration was characterized by a simple operation procedure, short analysis time, high sensitivity, and good accuracy, providing a simple and reliable assay for the monitoring of antiseizure medication therapy.

BackgroundPrevious studies have yielded conflicting findings regarding the relationship between the use of sleep-related drugs (SRDU) and suicidal behaviors. This population-based study aimed to analyze the associations between SRDU and suicidal behaviors. Additionally, we examined the associations between SRDU and specific conditional suicidal behaviors, providing insights into the impact of SRDU on the progression of suicidal behaviors.MethodsThe study was conducted among community residents aged 18 and older using a cross-sectional design, analyzing 21,376 participants. Data on SRDU, suicidal ideation, plans, and attempts were collected. Participants were categorized into general individuals without suicidal behaviors (GNS), suicidal ideators without a plan or attempt (SINPA), suicidal ideators with a plan but no attempt (SIP), and individuals who attempted suicide (SA). Insomnia, sleep apnea, rapid eye movement sleep behavior disorder (RBD), and narcolepsy were assessed using the Athens Insomnia Scale, Berlin Questionnaire, Rapid Eye Movement Sleep Behavior Disorder Questionnaire, and Ullanlinna Narcolepsy Scale, respectively.ResultsAfter adjusting for sociodemographic variables, insomnia, sleep apnea, RBD, and narcolepsy, SRDU showed a positive association with suicidal ideation (OR = 3.02), plans (OR = 4.78), and attempts (OR = 6.40; all p < 0.001). Compared to GNS, and after controlling for the same variables, SRDU was associated with SINPA (OR = 2.46), SIP (OR = 5.11), and SA (OR = 6.93; all p < 0.001) respectively. However, no significant differences in SRDU were found between SINPA, SIP, and SA (all p > 0.05).ConclusionsThis population-based study confirms that SRDU is positively associated with suicidal ideation, plans, and attempts, even after accounting for the risk factors of insomnia, sleep apnea, RBD, and narcolepsy. Nonetheless, SRDU does not appear to influence the progression from suicidal ideation to attempt.