ObjectiveTo study the mechanism of compound Xishu granules （CXG） in inhibiting the proliferation of hepatocellular carcinoma cells by regulating ferroptosis. MethodsThe transplanted tumor model of human Huh7 was established with nude mice and the successfully modeled mice were randomized into model， Fufang Banmao （0.21 g·kg^-1）， low-dose （1.87 g·kg^-1） CXG， medium-dose （3.74 g·kg^-1） CXG， and high-dose （7.49 g·kg^-1） CXG groups. Mice were administrated with drinking water or CXG for 28 days， and the body weight and tumor volume were measured every 4 days. Hematoxylin-eosin staining was employed to observe the histopathological changes of tumors. The cell-counting kit-8 （CCK-8） was used to examine the survival rate of Huh7 cells treated with different concentrations （0， 31.25， 62.5， 125， 250， 500， 1 000 mg·L^-1） of CXG for 24 h and 48 h. CA-AM， DCFH-DA， and C11-BODIPY^581/591 fluorescent probes were used to determine the intracellular levels of ferrous ion （Fe²⁺）， reactive oxygen species （ROS）， and lipid peroxide （LPO）， respectively. The colorimetric method was employed to measure the levels of glutathione （GSH） and superoxide dismutase （SOD）. Western blot was employed to determine the protein levels of glutathione peroxidase 4 （GPX4）， transferrin receptor 1 （TFR1）， and ferritin heavy chain 1 （FTH1）， respectively. ResultsIn the animal experiment， compared with the model group， the drug treatment groups showed reductions in the tumor volume from day 12 （P<0.01）. After treatment， the Fufang Banmao and low-， medium-， and high-dose CXG groups had lower tumor volume， relative tumor volume， and tumor weight than the model group （P<0.05）， with tumor inhibition rates of 48.99%， 79.93%， 91.38%， and 97.36%， respectively. Moreover， the CXG groups had lower tumor volume and relative tumor volume （P<0.05 in all the three dose groups） and lower tumor weight （P<0.05 in medium-dose and high-dose groups） than the Fufang Banmao group. Compared with the model group， the drug treatment groups showed reduced number of tumor cells， necrotic foci with karyopyknosis， nuclear fragmentation， and nucleolysis， and the high-dose CXG group showed an increase in the proportion of interstitial fibroblasts. In the cell experiment， compared with the blank group， CXG reduced the survival rate of Huh7 cells in a dose-dependent manner after incubation for 24 h and 48 h （P<0.05）. Compared with the blank group， the RSL3 group and the low-， medium-， and high-dose CXG groups showed a decrease in the relative fluorescence intensity of CA-AM and increases in the fluorescence intensity of DCFH-DA and fluorescence ratio of C11-BODIPY^581/591， which indicated elevations in the levels of Fe²⁺ （P<0.01）， ROS （P<0.05）， and LPO （P<0.01）， respectively. Compared with the blank group， the RSL3 and low-， medium-， and high-dose CXG groups showed lowered levels of GSH and SOD （P<0.05）. In addition， the RSL3 group and the medium- and high-dose CXG groups showed down-regulated expression of GPX4 and FTH1 （P<0.05）， and the low- and high-dose CXG groups presented up-regulated expression of TFR1 （P<0.05）. ConclusionCXG suppresses the proliferation of hepatocellular carcinoma cells by inducing ferroptosis via downregulating the GSH-GPX4 signaling axis and increasing intracellular Fe²⁺and LPO levels.

Objective: To explore the relationship between psychological resilience and attention bias towards negative information in secondary vocational school students, so as to provide reference for developing their mental health work. Methods: In May, 2024, 177 secondary vocational students were selected from the technical secondary vocational school by convenient sampling method. The experiment utilized a mixed experimental design of 2 (group: high psychological resilience group, low psychological resilience group) ×2 (type of stimulus: negative stimulus, neutral stimulus). Adolescents were divided into the high psychological resilience group ( n =32) and the low psychological resilience group ( n =31) based on their scores from the Adolescent Psychological Resilience Scale. Both groups completed the classical dot probing task, with correct rate, reaction time serving and attention biasvalues as primary indicators to assess attention bias. Repeated measures ANOVA was used to compare the reaction time and accuracy of attention bias tasks between two groups of participants, and Pearson correlation analysis was performed on the five dimensions of psychological resilience and attention bias values. Results: The low resilience group exhibited significantly faster response time to negative stimuli compared to neutral stimuli [(579.11±85.44, 586.13±78.92)ms, F (1,61)=5.93, P <0.05]. Additionally, the accuracy of responses to negative stimuli in the low resilience group was significantly lower than that of neutral stimuli [(0.93±0.12, 0.95±0.09), F (1,61)=12.81, P <0.01]. Attention bias values were significantly higher in the low resilience group (7.03±18.43) compared to the high resilience group (-2.54±13.39) ( t =2.36, P <0.05). Pearson correlation analysis revealed a marginally significant negative correlation between the interpersonal assistance (2.85±0.77) and attention bias values (2.20±16.65) ( r=-0.25, P <0.05). Conclusion Secondary vocational school students with low psychological resilience showed a significant attention bias towards negative emotional stimuli, which may render them more susceptible to such stimuli.

ObjectiveTo observe the effects of Hirudo， Notoginseng Radix et Rhizoma， and drug pair on renal pathological morphology and protein phosphatase 2A （PP2A）/adenylate activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signal pathway in rats with chronic renal failure （CRF）. MethodThe 55 male SD rats were randomly divided into a normal group （n=11） and a modeling group （n=44）. The normal group was fed conventionally， and the modeling group was given 0.25 g·kg^-1·d^-1 adenine by gavage for 28 days to replicate the CRF model. After successful modeling， rats were randomly divided into model group， Hirudo group （3 g·kg^-1·d^-1）， Notoginseng Radix et Rhizoma group （3 g·kg^-1·d^-1）， and Hirudo + Notoginseng Radix et Rhizoma group （3 g·kg^-1·d^-1）， with 9 rats in each group. The normal group and model group were given a constant volume of normal saline by intragastric administration for 30 days. At the end of the experiment， the levels of serum creatinine （SCr） and urea nitrogen （BUN） in all groups were measured. The renal pathological morphology changes were observed by hematoxylin-eosin （HE） staining， Masson staining， and electron microscopy. The mRNA expressions of PP2A， AMPK， and mTOR were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of PP2A， AMPK， phosphorylation（p）-AMPK， mTOR， and p-mTOR in renal tissue were detected by Western blot. ResultCompared with the normal group， the renal pathological structure changes were obvious， and the levels of SCr and BUN were significantly increased. The mRNA expression of PP2A， protein expression of PP2A， and p-mTOR/mTOR expression were significantly increased， and the p-AMPK/AMPK was significantly decreased in the model group （P<0.05）. Compared with the model group， the renal pathological morphology changes were significantly improved， and the levels of SCr and BUN were significantly decreased. The mRNA expression of PP2A， protein expression of PP2A， and p-mTOR/mTOR expression in the renal tissue were significantly decreased， and the p-AMPK/AMPK was significantly increased （P<0.05） in all groups after drug intervention. In addition， the effect in the Hirudo+Notoginseng Radix et Rhizoma group was better. The mRNA expression levels of AMPK and mTOR in the renal tissue were not significantly different among the normal group， model group， and other groups. ConclusionThe efficacy of Hirudo and Notoginseng Radix et Rhizoma pairs in improving renal fibrosis in rats with CRF is significantly better than that of the single drug， and its improvement on renal fibrosis in rats with CRF may be related to the regulation of PP2A/AMPK/mTOR signaling pathway.

The fungal bioluminescence pathway (FBP) is a metabolic pathway responsible for the generation of bioluminescence derived from fungi. This pathway utilizes caffeic acid as the substrate, generating a high-energy intermediate, and the decomposition of which yields green fluorescence with a wavelength of approximately 520 nm. The FBP is evolutionally conserved in luminescent fungal groups. Unlike other bioluminescent systems, the FBP is particularly suitable for engineering applications in eukaryotic organisms, especially in plants. Currently, metabolically engineered luminescent plants are able to emit visible light to illuminate its surroundings, which can be visualized clearly in the dark. The fungal bioluminescent system could be explored in various applications in molecular biology, biosensors and glowing ornamental plants, and even green lighting along city streets.
Luminescence ; Light ; Fluorescence ; Eukaryota ; Green Light

BACKGROUND: In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. METHODS: A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. RESULTS: MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05). CONCLUSIONS The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/genetics* ; China ; Prognosis ; Transcription Factors

Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal cavity. However, no reliable method is currently available to assess its impact on delivery performance. In this study, a biomimetic nasal model based on three-dimensional (3D) reconstruction and three-dimensional printing (3DP) technology was developed for visualizing the deposition of drug powders in the nasal cavity. The results showed significant differences in cavity area and volume and powder distribution in the anterior part of the biomimetic nasal model of Chinese males and females. The nasal cavity model was modified with dimethicone and validated to be suitable for the deposition test. The experimental device produced the most satisfactory results with five spray times. Furthermore, particle sizes and spray angles were found to significantly affect the experimental device's performance and alter drug distribution, respectively. Additionally, mometasone furoate (MF) nasal spray (NS) distribution patterns were investigated in a goat nasal cavity model and three male goat noses, confirming the in vitro and in vivo correlation. In conclusion, the developed human nasal structure biomimetic device has the potential to be a valuable tool for assessing nasal drug delivery system deposition and distribution.

【Objective】 To analyze nutrition-related factors that affect the prevalence of myopia in adolescents, in order to provide reference for primary prevention of myopia. 【Methods】 A stratified sampling method was used to select 385 adolescents from Zhengding County in October 2021. Adolescents in this study took vision testing, physical examination and completed a questionnaire survey. One-way analysis of variance and lasso regression were used to screen the variables, and Logistic regression was used to determine the possible influencing factors of myopia. Factor analysis was adopted to extract the dietary patterns of adolescents in Zhengding County, then the association between dietary patterns and myopia was analyzed. 【Results】 A total of 385 adolescents were surveyed, with the prevalence rate of myopia of about 68.6%. Multivariate analysis revealed that fried food(OR=8.480, 95%CI:1.058 - 67.971) was a risk factor for myopia, while intake of milk and dairy products(OR=0.994, 95%CI:0.991 - 0.999), soybeans and nuts(OR=0.997, 95%CI:0.994 - 0.999), no myopia in either parent(OR=0.312, 95%CI:0.115 - 0.845), physical education class 4 times per week(OR=0.269, 95%CI:0.074 - 0.984) were statistically associated with a lower risk of myopia(P<0.05). Three dietary patterns was extracted through factor analysis, including diversified dietary pattern, soy-hybrid dietary pattern, and snack and beverage dietary pattern. Logistic analysis results indicated that soy-hybrid dietary pattern(OR=0.85, 95%CI:0.73 - 0.99,P<0.05) was statistically associated with myopia. 【Conclusions】 The problem of myopia among adolescents in Zhengding County is more serious. Increasing the intake of milk and dairy products, soybeans and nuts, reducing the intake of fried foods, and adjusting the overall dietary structure should be recommended in order to prevent the development of myopia in adolescents.

ObjectiveTo observe the effect of enriched environment (EE) combined with acupuncture at head point (HA) on behavior in rats with autism spectrum disorder. MethodsHealthy female Wistar rats were given peritoneal injection of sodium valproate at 12.5 days of gestation. Twenty-four male offspring rats were randomly selected and then randomly divided into model group (n = 6), EE group (n = 6), HA group (n = 6) and EE combined with HA group (the combined group, n = 6). Six male offspring rats born from female mice injected with the same amount of saline intraperitoneally were as control group. After four weeks of treatment, all the five groups were tested with three-chamber test and marble burying test, and the sociability index, the social novelty index and the number of buried marbles were recorded. The levels of interleukin (IL)-1β and IL-6 in peripheral blood were determined by enzyme-linked immunosorbent assay (ELISA). ResultsAfter treatment, compared with the model group, the sociability index and the social novelty index improved (P < 0.05), the number of buried marbles reduced (P < 0.05), and the levels of IL-6 and IL-1β in peripheral blood decreased in EE group, HA group and the combined group (P < 0.05); while the combined group was the best (P < 0.01). ConclusionBoth EE or acupuncture at HA could improve behavioral symptoms, and reduce the expression of inflammatory factors in rats with autism spectrum disorder. The combination of the two methods showed the best result.

Objective:To explore the clinical changes in levels of the new clinical marker serum hepatitis B virus (HBV) pregenomic RNA (pgRNA) in patients with chronic hepatitis B (CHB) with long-term antiviral therapy.Methods:100 CHB cases who were initially treated with nucleos(t)ide analogues (NAs) at Peking University First Hospital were included. The levels of alanine aminotransferase (ALT), HBV DNA, hepatitis B e-antigen (HBeAg), and hepatitis B surface antigen (HBsAg) during the follow-up period were measured. The TaqMan-based real-time quantitative PCR method was used to detect serum HBV pgRNA levels. The independent sample t-test and Mann-Whitney U test were used to compare continuous variables between groups, while Pearson's χ2 test and Fisher's exact test were used to compare categorical variables. Results:HBV pgRNA levels decreased significantly in patients who developed virological responses at 48 weeks ( n = 54) during subsequent treatment compared to those who did not ( n = 46). The HBV pgRNA level was lower in HBeAg-positive patients than in HBeAg-negative patients ( P < 0.05 or P < 0.01). Patients with higher HBV DNA and HBeAg-positivity levels at baseline had a higher HBV pgRNA level following antiviral therapy. There was no statistically significant difference in HBV pgRNA levels in patients with different HBV pgRNA levels at baseline after antiviral therapy. There was no correlation between serum HBV pgRNA and HBsAg at baseline, but there was a correlation after long-term antiviral therapy, while there was a weak correlation between HBV pgRNA and HBsAg at the fifth and ninth years of antiviral therapy ( r = 0.262, P = 0.031; r = 0.288, P = 0.008). Conclusion:HBV pgRNA levels were higher with higher HBV activity in CHB patients with long-term antiviral therapy.

Objective To investigate the correlation between interleukin 1β gene-511C/T polymorphism of and essential hypertension in the Yi ethnic group of Yunnan province.Methods-511C/T polymorphism of interleukin 1β gene was detected by PCR-RFLP in 85 Yi patients with essential hypertension(EH group)and 106 Yi healthy people(control group)in Shuanghe Township,Jinning County,Yunnan Province.Genotype and allele frequencies were analyzed by SPSS 27.0 software,and association analysis was performed.Results The frequency distribution of CC,CT and TT genotypes at the mutation site 511 of the IL-1βgene in EH group was 18.82%,44.71%and 36.47%,respectively,and it was 5.66%,26.42%and 67.92%in the control group.The difference in genotype frequency between the two groups was statistically significant(P＜0.05).The allele frequency of C and T in EH group was 41.18%and 58.82%,respectively,and the allele frequency of C and T in control group was 18.87%and 81.13%.The frequency difference of alleles between the two groups was statistically significant(P＜0.05).Both genotype frequency and allele frequency found in males and females had statistical differences(P＜0.05).Conclusions The distribution of IL-1β gene-511C/T polymorphism is related to the incident of essential hyper-tension among the Yi ethnic group Yunnan Province,and is the susceptibility gene of the Yi ethnic group to essen-tial hypertension.