Objective:To investigate the protective effect of quercetin against 5-fluorouracil(5-FU)-induced damage in the human immortalized keratinocytes(HACAT),and to elucidate its possible mechanism.Methods:The HACAT cells were divided into control group(normal cultured cells),5-FU group(treated with 7.5 mg·L-1 5-FU for 24 h),and low,medium,and high doses of quercetin groups(HACAT cells treated with 25,50,and 75 μmol·L-1 quercetin combined with 7.5 mg·L-15-FU for 24 h).Cell counting kit-8(CCK-8)assay was used to detect the survival rates of HACAT cells treated with different doses(0,10,25,50,75 and 100 μmol·L-1)of quercetin in various groups.The fluorescent probe of reactive oxygen species(ROS)was used to detect ROS levels in the HACAT cells in various groups.Annexin Ⅴ-FITC/PI double staining was used to detect the apoptosis of HACAT cells in various groups.Western blotting method was used to detect the expression levels of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),Cleaved Caspase-3,cyclooxygenase-2(COX-2),interleukin-1 β(IL-1β),and interleukin-6(IL-6)in the HACAT cells in various groups.Results:The CCK-8 assay results showed that compared with 0 μmol·L-1 quercetin group,the survival rates of HACAT cells in 10,25,50 and 75 μmol·L-1quercetin groups showed no significant differences(P＞0.05),while the survival rates of HACAT cells in 100 μmol·L-1 quercetin group was significantly decreased(P＜0.05).Compared with 5-FU group,the survival rates of the HACAT cells in low,medium and high doses of quercetin group were significantly increased(P＜0.05).Compared with 5-FU group,the ROS levels in low,medium,and high doses of quercetin groups were significantly decreased(P＜0.05).Annexin Ⅴ-FITC/PI double staining assay showed that compared with 5-FU group,the apoptotic rates in low,medium and high doses of quercetin groups were significantly decreased(P＜0.05).The Western blotting results showed that compared with 5-FU group,the expression levels of Bcl-2 protein in medium and high doses of quercetin groups were significantly increased(P＜0.05),the expression levels of Bax and Cleaved Caspase-3 proteins in low,medium and high doses of quercetin groups were significantly decreased(P＜0.05),the expression levels of COX-2 protein in medium and high doses of quercetin groups were significantly decreased(P＜0.05),and the expression levels of IL-1β and IL-6 proteins in medium dose of quercetin group were significantly decreasd(P＜0.05).Conclusion:Quercetin has protective effect on 5-FU-induced damage in the HACAT cells,and its mechanism may be related to the reduction of the expression of ROS and inflammatory factor COX-2 which attenuate the apoptosis.

Objective To investigate cyclin D2(CCND2)expression in papillary thyroid carcinoma(PTC)and its association with the clinicopathological features.Methods The public databases TCGA,TIMER 2.0 and UALCAN were used to explore CCND2 expression level in PTC and adjacent tissues,and its diagnostic value for PTC was analyzed using ROC curves.GO enrichment analysis of CCND2-related differentially expressed genes(DEGs)in PTC was performed,and tumor immune infiltration of CCND2 in thyroid cancer was analyzed using TIMER database and CIBERSORT data source.RT-qPCR and Western blot were used to detect CCND2 expression in normal human thyroid cell line Nthy-ori-3-1 and human PTC cell lines TPC-1 and BCPAP.CCND2 expression was also detected in clinical specimens of PTC and adjacent tissues by immunohistochemistry,and its correlation with clinicopathological features of the patients were analyzed.Results Informatic analysis revealed significantly higher CCND2 mRNA expression in thyroid cancer than in the adjacent tissues(P<0.001)in close correlation with tumor stage,gender,age,pathological subtype,and lymph node involvement(P<0.05).ROC curve analysis showed that at the cutoff value of 4.983,the diagnostic sensitivity,specificity,and accuracy of CCND2 expression for PTC was 83.6%,94.9%,and 78.5%,respectively.CCND2 expression was positively correlated with B cells,CD4+T cells,and macrophages(P<0.001)and negatively with CD8+T cells(P<0.01),and also correlated with memory B-cell infiltration,CD4+T-cell memory activation,M2 macrophages,resting mast cells,and mast cell activation(P<0.05).RT-qPCR,Western blot and immunohistochemistry showed significantly higher CCND2 expression in the PTC cells than in Nthy-ori-3-1 cells(P<0.01)and also in clinical PTC tissues than in the adjacent tissues(P<0.05)in correlation with tumor size,lymph node metastasis and TNM stage(P<0.05).Conclusion CCND2 overexpression is closely correlated with tumor progression and immune cell infiltration in PTC patients..

Background::Few evidence is available in the early prediction models of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer’s disease (AD). This study aimed to develop and validate a novel genetic-clinical-radiological nomogram for evaluating BPSD in patients with AD and explore its underlying nutritional mechanism.Methods::This retrospective study included 165 patients with AD from the Chinese Imaging, Biomarkers, and Lifestyle (CIBL) cohort between June 1, 2021, and March 31, 2022. Data on demographics, neuropsychological assessments, single-nucleotide polymorphisms of AD risk genes, and regional brain volumes were collected. A multivariate logistic regression model identified BPSD-associated factors, for subsequently constructing a diagnostic nomogram. This nomogram was internally validated through 1000-bootstrap resampling and externally validated using a time-series split based on the CIBL cohort data between June 1, 2022, and February 1, 2023. Area under receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to assess the discrimination, calibration, and clinical applicability of the nomogram.Results::Factors independently associated with BPSD were: CETP rs1800775 (odds ratio [OR] = 4.137, 95% confidence interval [CI]: 1.276-13.415, P = 0.018), decreased Mini Nutritional Assessment score (OR = 0.187, 95% CI: 0.086-0.405, P <0.001), increased caregiver burden inventory score (OR = 8.993, 95% CI: 3.830-21.119, P <0.001), and decreased brain stem volume (OR = 0.006, 95% CI: 0.001-0.191, P = 0.004). These variables were incorporated into the nomogram. The area under the ROC curve was 0.925 (95% CI: 0.884-0.967, P <0.001) in the internal validation and 0.791 (95% CI: 0.686-0.895, P <0.001) in the external validation. The calibration plots showed favorable consistency between the prediction of nomogram and actual observations, and the DCA showed that the model was clinically useful in both validations. Conclusion::A novel nomogram was established and validated based on lipid metabolism-related genes, nutritional status, and brain stem volumes, which may allow patients with AD to benefit from early triage and more intensive monitoring of BPSD.Registration::Chictr.org.cn, ChiCTR2100049131.

Objective To investigate cyclin D2(CCND2)expression in papillary thyroid carcinoma(PTC)and its association with the clinicopathological features.Methods The public databases TCGA,TIMER 2.0 and UALCAN were used to explore CCND2 expression level in PTC and adjacent tissues,and its diagnostic value for PTC was analyzed using ROC curves.GO enrichment analysis of CCND2-related differentially expressed genes(DEGs)in PTC was performed,and tumor immune infiltration of CCND2 in thyroid cancer was analyzed using TIMER database and CIBERSORT data source.RT-qPCR and Western blot were used to detect CCND2 expression in normal human thyroid cell line Nthy-ori-3-1 and human PTC cell lines TPC-1 and BCPAP.CCND2 expression was also detected in clinical specimens of PTC and adjacent tissues by immunohistochemistry,and its correlation with clinicopathological features of the patients were analyzed.Results Informatic analysis revealed significantly higher CCND2 mRNA expression in thyroid cancer than in the adjacent tissues(P<0.001)in close correlation with tumor stage,gender,age,pathological subtype,and lymph node involvement(P<0.05).ROC curve analysis showed that at the cutoff value of 4.983,the diagnostic sensitivity,specificity,and accuracy of CCND2 expression for PTC was 83.6%,94.9%,and 78.5%,respectively.CCND2 expression was positively correlated with B cells,CD4+T cells,and macrophages(P<0.001)and negatively with CD8+T cells(P<0.01),and also correlated with memory B-cell infiltration,CD4+T-cell memory activation,M2 macrophages,resting mast cells,and mast cell activation(P<0.05).RT-qPCR,Western blot and immunohistochemistry showed significantly higher CCND2 expression in the PTC cells than in Nthy-ori-3-1 cells(P<0.01)and also in clinical PTC tissues than in the adjacent tissues(P<0.05)in correlation with tumor size,lymph node metastasis and TNM stage(P<0.05).Conclusion CCND2 overexpression is closely correlated with tumor progression and immune cell infiltration in PTC patients..

Objective To evaluate the value of SOX1 and PAX1 gene methylation detection in the sec-ondary triage of high-grade cervical lesions.Methods Exfoliated cervical cells were collected from 122 patients tested positive for human papilloma virus(HPV)and subjected to thin-prep cytologic test(TCT)and SOX1/PAX1 gene methylation tests.Results The HPV test combined with TCT showed the sensitivity of 95.24％and the specificity of 23.75％for detecting cervical intraepithelial neoplasia(CIN)grade 2 and above(CIN2+).After the addition of the SOX1/PAX1 gene methylation detection in secondary triage,the sensitivity for detecting CIN2+was 83.33％,which had no statistically significant difference from the sensitivity of TCT combined with HPV test(P=0.078).However,the specificity reached 77.50％,which was significantly higher than that of HPV test combined with TCT(P＜0.001).The SOX1/PAX1 gene methylation level in the CIN2+group was higher than those in the normal cervical tissue and the CIN1 group(P＜0.001).The cut-off values of SOX1 and PAX1 gene methylation for CIN2+detection were-11.81 and-11.98,respectively.Conclusion Adding the detection of SOX1/PAX1 gene methylation in secondary triage significantly improves the efficiency and accuracy of CIN2+detection.

Objective To explore the categories of dyadic mental health literacy among stroke patients and their caregivers,and to analyze the differences in the characteristics of different classes of stroke patients and their caregivers.Methods A convenient sampling method was used to select 287 dyads of stroke patients and their caregivers who were treated at a tertiary general hospital in Henan province from July to October 2020.The general information questionnaire,Multicomponent Mental Health Literacy and Social Support Rating Scale were used for investigation.Latent profile analysis was adopted to explore the categories of dyadic mental health literacy,and multiple logistic regression was used to analyze the influencing factors of each category.Results Stroke patients and their caregivers were divided into 4 categories based on scores of mental health literacy:dyadic low resource group(19.86％),dyadic low literacy group(54.36％),dyadic low belief group(11.15％),dyadic high literacy group(14.63％).The patient's age,average monthly household income,the caregiver's age,the caregiver's Social Support Rating Scale score,the caregiver's educational level,daily care time and total time length of care were the factors influencing the categories of dyadic mental health literacy among stroke patients and their caregivers(P＜0.05).Conclusion Stroke patients and their caregivers were divided into 4 categories based on scores of mental health literacy.Medical staff should carry out comprehensive psychological interventions for stroke patients and their caregivers with different dyadic mental health literacy characteristics,so as to improve dyadic mental health literacy.

In recent years, the field of genetics has witnessed a burgeoning interest in the non-coding region, an area previously dubbed the"dark matter"of the genome. This once enigmatic domain is now progressively revealing its secrets, emerging as a rich terrain for genetic diagnosis and treatment. This editorial centers on diverse diagnostic analyses and intervention techniques associated with the non-coding region, delving into its significance in the etiology, diagnosis, and treatment of both monogenic and polygenic disorders within the nervous system. In doing so, it offers a comprehensive perspective for the exploration of genetic disorders in the nervous system.

Acute amnestic syndrome manifests as transient or persistent symptoms of single amnesia,which may also be accompanied by other neurological symptoms,eventually leading to irreversible brain damage.The typical symptoms of acute ischemic stroke include hemiplegia,aphasia,sensory disturbances,and so forth.Acute amnesia is not a typical symptom of acute ischemic stroke,and it is easy to misdiagnose or delay diagnosis in the emergency department.The authors retrospectively analyzed the clinical data of a patient with acute cerebral infarction who started with acute amnesia syndrome,and combined with relevant literature,to explore its clinical characteristics and pathogenesis.The purpose of this article is to provide reference for emergency physician and neurologist in the diagnosis and treatment of similar cases.

Objective:To analyze the time needed for active breathing coordinator (ABC) coaching in tumor patients, and to explore the influencing factors of coaching time.Methods:A retrospective study was conducted on 93 patients who received ABC treatment led by the same staff at the Cancer Hospital of Chinese Academy of Medical Sciences from September 2019 to April 2021. The effects of education level, body mass index (BMI), age, gender and disease type on the couching time were analyzed. The coaching time was expressed as Mean ± SD. Independent sample t-test or rank sum test was used for comparison between different groups. P<0.05 was considered statistically significant. Results:Statistical significance was observed in the effect of education level, BMI and age on coaching time. The coaching time in the higher education group was (9.74±3.80) min, significantly shorter than the (13.79±6.03) min ( P=0.001) of the primary education group and the (13.03±5.14) min ( P=0.021) of the middle education group. The couching time in the BMI<24 kg/m 2 group was (10.27±3.98) min, significantly shorter compared with (12.74±5.60) min ( P<0.001) in the BMI≥24 kg/m 2 group. The coaching time in the ≥60 years old group was (14.12±5.06) min, significantly longer than the (9.86±3.76) min ( P=0.002) of the ≤40 years old group and the (11.30±5.10) min ( P=0.021) of the 40-60 years old group. No significant differences were noted in the effect of gender, disease type and tumor staging on the coaching time. The coaching time in males and females was (13.54±5.89) and (10.94±4.61) min, respectively ( P=0.071). The coaching time of patients with breast cancer, lung cancer, liver cancer, mediastinal lymphoma and pancreatic cancer was (10.75±4.72), (15.30±5.57), (11.69±4.96), (9.86±3.61) and (12.15±0.07) min, respectively ( P=0.071). The coaching time of stageⅠ,Ⅱ,Ⅲ and Ⅳ patients was (10.35±4.37), (11.88±5.30), (9.52±2.51) and (14.32±5.27) min ( P=0.060). Conclusions:Patients with higher education level and BMI<24 kg/m 2 require less ABC coaching time. Patients aged≥60 years require longer coaching time. Gender, disease type and clinical stage exert no significant effect on the duration of coaching.