ObjectiveTo explore the mechanism by which Ruyan Neixiao cream （RUC） induces ferroptosis in breast precancerous lesion （BPL） cells， and to enrich the theoretical foundation for its use in the treatment of BPL. MethodsThe inhibition of cell proliferation by 1%， 2%， and 4% concentrations of Ruyanneixiao Cream transdermal solution （RUT） was assessed using cell counting kit-8 （CCK-8） and a colony formation assay. Reactive oxygen species （ROS） were measured using the DCFH-DA probe， and the levels of ferrous ions （Fe²⁺）， glutathione （GSH）， and malondialdehyde （MDA） were determined using appropriate kits. Lipid peroxidation was detected with the C11-BODIPY^581/591 fluorescent probe. The expression of nuclear factor E₂-related factor 2 （Nrf2）， solute carrier family 7 member 11 （SLC7A11）， and glutathione peroxidase 4 （GPX4） proteins was analyzed by Western blot. The BPL rat model was constructed using 2，2′-bis（hydroxymethyl）butyric acid （DMBA） combined with estrogen and progesterone， and the rats were treated with RUC for external application. After the 12^th cycle， the rats were euthanized， and histopathological changes in breast tissue were observed by hematoxylin-eosin （HE） staining. Fe²⁺ and MDA levels in breast tissue were measured using corresponding kits. The expression of Nrf2， SLC7A11， and GPX4 proteins in BPL rat breast tissue was detected by immunohistochemistry （IHC） and Western blot. ResultsCompared with the matrix group， the cell viability of MCF-10AT cells in the 1%， 2%， and 4% RUT groups was significantly reduced （P<0.05） in a concentration-dependent manner， with the 24-hour half inhibitory concentration （IC₅₀） being 2.23%. Compared with the 4% RUT group， cell viability in the RUT + Fer-1 group was significantly increased （P<0.05）. Compared with the matrix group， the colony formation rates of MCF-10AT cells in the 1%， 2%， and 4% RUT groups were significantly decreased （P<0.05）. Compared with the 4% RUT group， the cell colony formation rate of the RUT + Fer-1 group was significantly increased （P<0.05）. Compared with the matrix group， the levels of ROS and Fe²⁺ in the 1%， 2%， and 4% RUT groups were significantly increased （P<0.05）， while GSH levels were significantly decreased （P<0.05）， and MDA and lipid peroxidation levels were significantly increased （P<0.05）. Compared with the 4% RUT group， ROS and Fe²⁺ levels in the RUT + Fer-1 group were significantly reduced （P<0.05）， while GSH levels were significantly increased （P<0.05）， and MDA and lipid peroxidation levels were significantly reduced （P<0.05）. Compared with the matrix group， the protein expression levels of Nrf2， SLC7A11， and GPX4 in the 1%， 2%， and 4% RUT groups were significantly decreased （P<0.05）. Compared with the 4% RUT group， the protein expression levels of Nrf2， SLC7A11， and GPX4 in the RUT + Fer-1 group were significantly increased （P<0.05）. In the in vivo experiment， compared with the matrix group， the breast tissue histopathological status of the BPL rats in the RUC group was effectively improved， with less dilatation of the mammary ducts and more orderly duct arrangement. No pathological morphology indicative of invasive cancer was observed. Compared with the matrix group， Fe²⁺ and MDA levels in the mammary tissue of the RUC group were significantly increased （P<0.05）. Compared with the matrix group， the protein expression levels of Nrf2， SLC7A11， and GPX4 in the mammary tissue of the RUC group were significantly reduced （P<0.05）. ConclusionRUC may induce ferroptosis in BPL cells by inhibiting the Nrf2/SLC7A11/GPX4 signaling pathway， increasing Fe²⁺ accumulation， and promoting lipid peroxidation.

ObjectiveTo explore the mechanism by which Ruyan Neixiao cream （RUC） induces ferroptosis in breast precancerous lesion （BPL） cells， and to enrich the theoretical foundation for its use in the treatment of BPL. MethodsThe inhibition of cell proliferation by 1%， 2%， and 4% concentrations of Ruyanneixiao Cream transdermal solution （RUT） was assessed using cell counting kit-8 （CCK-8） and a colony formation assay. Reactive oxygen species （ROS） were measured using the DCFH-DA probe， and the levels of ferrous ions （Fe²⁺）， glutathione （GSH）， and malondialdehyde （MDA） were determined using appropriate kits. Lipid peroxidation was detected with the C11-BODIPY^581/591 fluorescent probe. The expression of nuclear factor E₂-related factor 2 （Nrf2）， solute carrier family 7 member 11 （SLC7A11）， and glutathione peroxidase 4 （GPX4） proteins was analyzed by Western blot. The BPL rat model was constructed using 2，2′-bis（hydroxymethyl）butyric acid （DMBA） combined with estrogen and progesterone， and the rats were treated with RUC for external application. After the 12^th cycle， the rats were euthanized， and histopathological changes in breast tissue were observed by hematoxylin-eosin （HE） staining. Fe²⁺ and MDA levels in breast tissue were measured using corresponding kits. The expression of Nrf2， SLC7A11， and GPX4 proteins in BPL rat breast tissue was detected by immunohistochemistry （IHC） and Western blot. ResultsCompared with the matrix group， the cell viability of MCF-10AT cells in the 1%， 2%， and 4% RUT groups was significantly reduced （P<0.05） in a concentration-dependent manner， with the 24-hour half inhibitory concentration （IC₅₀） being 2.23%. Compared with the 4% RUT group， cell viability in the RUT + Fer-1 group was significantly increased （P<0.05）. Compared with the matrix group， the colony formation rates of MCF-10AT cells in the 1%， 2%， and 4% RUT groups were significantly decreased （P<0.05）. Compared with the 4% RUT group， the cell colony formation rate of the RUT + Fer-1 group was significantly increased （P<0.05）. Compared with the matrix group， the levels of ROS and Fe²⁺ in the 1%， 2%， and 4% RUT groups were significantly increased （P<0.05）， while GSH levels were significantly decreased （P<0.05）， and MDA and lipid peroxidation levels were significantly increased （P<0.05）. Compared with the 4% RUT group， ROS and Fe²⁺ levels in the RUT + Fer-1 group were significantly reduced （P<0.05）， while GSH levels were significantly increased （P<0.05）， and MDA and lipid peroxidation levels were significantly reduced （P<0.05）. Compared with the matrix group， the protein expression levels of Nrf2， SLC7A11， and GPX4 in the 1%， 2%， and 4% RUT groups were significantly decreased （P<0.05）. Compared with the 4% RUT group， the protein expression levels of Nrf2， SLC7A11， and GPX4 in the RUT + Fer-1 group were significantly increased （P<0.05）. In the in vivo experiment， compared with the matrix group， the breast tissue histopathological status of the BPL rats in the RUC group was effectively improved， with less dilatation of the mammary ducts and more orderly duct arrangement. No pathological morphology indicative of invasive cancer was observed. Compared with the matrix group， Fe²⁺ and MDA levels in the mammary tissue of the RUC group were significantly increased （P<0.05）. Compared with the matrix group， the protein expression levels of Nrf2， SLC7A11， and GPX4 in the mammary tissue of the RUC group were significantly reduced （P<0.05）. ConclusionRUC may induce ferroptosis in BPL cells by inhibiting the Nrf2/SLC7A11/GPX4 signaling pathway， increasing Fe²⁺ accumulation， and promoting lipid peroxidation.

ObjectivePatients with hepatic glycogen storage disease（GSD）have recurrent episodes of hypoglycemia. This study aimed to investigate and analyze blood glucose and biochemical indicators in pediatric patients with hepatic GSD， thus provide data support for hypoglycemia prevention and its clinical management. MethodsA cross-sectional field study was conducted among patients with hepatic GSD treated in the Department of Pediatrics of Guangdong Provincial People's Hospital on July 14， 2024. We collected the peripheral blood samples of the patients and their healthy family controls on site， then analyzed and compared their blood glucose and biochemical indicators. ResultsOf the 44 patients with hepatic GSD， there were 34 males and 10 females， including GSD Ib（n =14）， GSD Ia（n=15）， GSD Ⅲ（n=2）， GSD Ⅵ（n=7）and GSD Ⅸ（n=6）. The average age was 7.60（5.08-11.98）years. All patients were on uncooked cornstarch（UCCS）therapy. Of the patients， 77.3%（34/44）had hepatomegaly， 61.4%（27/44）had recurrent hypoglycemia， 61.4%（27/44）had blood glucose ≤ 3.9 mmol/L， 18.2%（8/44）had blood glucose ≤ 2.8 mmol/L， and none of the 8 cases was GSD Ib. The lowest blood glucose level was 1.19 mmol/L and no episodes of hypoglycemia occurred. Of the family control subjects， 65.9%（29/44）had blood glucose ≤ 3.9 mmol/L. There was no significant difference in hypoglycemia prevalence between hepatic GSD group and control group（P=0.658）. The hepatic GSD patients had hyperlactacemia， hyperuricemia and hypercholesterolemia prevalence rates of 65.9%， 45.5% and 9.1%， respectively， as compared with 18.2%， 43.2% and 15.9%， respectively， for the family control subjects. No significant difference was found in the prevalence rates of hyperuricemia and hypercholesterolemia between the two groups（P=0.830 and P=0.334， respectively）. ConclusionsAsymptomatic hypoglycemia is common in patients with hepatic GSD， especially in non-GSD-Ib patients. It is necessary to optimize the diet management of UCCS， conduct dynamic blood glucose monitoring and follow a light diet， so as to decrease hyperuricemia and hypercholesterolemia， avoid and reduce the serious adverse reactions and complications caused by severe hypoglycemia.

Objective To integrate and analyze the disease burden of esophageal cancer caused by alcohol consumption in China from 1990 to 2019, along with the differences between genders, and predict the trends in disease burden changes from 2020 to 2029 to improve prevention and treatment strategies. Methods The disease burden of esophageal cancer caused by alcohol consumption in China from 1990 to 2019 was extracted and integrated from the 2019 Global Burden of Disease (GBD) database, and the corresponding trend was analyzed using the Joinpoint regression model with Joinpoint 4.9.1.0 software. The gray prediction model [GM (1, 1) ] was used to forecast the disease burden of alcohol-related esophageal cancer in China from 2020 to 2029. Results In 2019, the leading causes of esophageal cancer in China were tobacco, alcohol, high body mass index, and insufficient fruit and vegetable intake, accounting for the first to fifth positions in esophageal cancer deaths. From a gender perspective, in 2019, the death number and standardized mortality rate for males were 18.97 times and 20.00 times higher than for females, respectively. The disability-adjusted life years (DALYs) and standardized DALYs rate for males were 33.08 times and 24.78 times higher than those for females, respectively, indicating a heavier disease burden of alcohol-related esophageal cancer among Chinese males. From 1990 to 2019, the average annual percentage change (AAPC) in deaths and DALYs due to alcohol-related esophageal cancer in China was 2.08% and 1.63%, respectively, showing a continuous upward trend with statistical significance (P<0.05). The AAPC values for standardized mortality rate and standardized DALYs rate from 1990 to 2019 were –0.92% and –1.23%, respectively, showing a continuous downward trend with statistical significance (P<0.05). The population aged ≥55 years was the main group bearing the disease burden among all age groups from 1990 to 2019. The gray prediction model predicted that by 2029, the overall standardized mortality rate and standardized DALYs rate would decrease to 2.94/100 000and 67.94/100 000, with a greater decline in females than in males. Conclusion Over the past 30 years, the disease burden of alcohol-related esophageal cancer in China has slightly decreased. However, the reduction in disease burden is still lower compared to the overall decline in esophageal cancer burden, and the disease burden for males is significantly higher than for females. Focusing on prevention and treatment for males and the elderly population remains a major issue in addressing alcohol-related esophageal cancer in China.

Objective: To analyze the prevalence trends of different types of elevated blood pressure and their association with nutritional status among primary and secondary school students in Inner Mongolia from 2019 to 2024, providing references for targeted prevention strategies. Methods: From September 2019 to 2024, a stratified random cluster sampling method was used to select 12 primary and secondary schools from each league city in Inner Mongolia Autonomous Region. A total of 177 108, 137 758, 190 182, 180 084 , 188 056, 180 351 primary and secondary school students (excluding grades one to three of primary school) were included for physical examination. The correlation between their nutritional status and high blood pressure was analyzed based on the basic situation of 129 821 primary and secondary school students who completed a questionnaire survey at the same time in 2024. Statistical analysis was conducted using a Chi-square test and multiple Logistic regression model. Results: From 2019 to 2024, the detection rates of elevated blood pressure were 13.60%, 13.68%, 17.60%, 17.24%, 14.77% and 15.96%, respectively. The rates for isolated systolic hypertension were 4.24%, 5.83%, 7.26%, 7.19%, 6.24% and 6.93%; isolated diastolic hypertension rates were 6.38%, 4.99%, 6.23 %, 6.41%, 5.39% and 5.66%; and combined systolic and diastolic hypertension rates were 2.97%, 2.86%, 4.11%, 3.65%, 3.14 % and 3.36%. Multivariate Logistic regression analysis showed that girls, junior high school, senior high school, overweight, and obesity were positively associated with elevated blood pressure risk ( OR =1.27, 1.25, 1.32, 1.66, 3.07, all P <0.05); conversely, county residence, Mongolian ethnicity, and other ethnicities showed negative associations ( OR =0.90, 0.93, 0.90, all P <0.05). Conclusions Overweight and obesity among children and adolescents are closely related to various types of elevated blood pressure. Prevention strategies should prioritize effectively controlling weight issues among children and adolescents, thereby effectively reducing the incidence of elevated blood pressure.

ABATRACT OBJECTIVE To utilize the pharmacophore model-molecular docking combined with the virtual screening strategy of free energy calculation and the chemical bioinformatics method of traditional Chinese medicine in cell biology experiments to investigate the components of Guiqi Baizhu prescription that target phosphatidylinositol 3-kinase(PI3K) and inhibit the proliferation of uveal melanoma(UM) cells. METHODS The pharmacophore model of PI3K inhibitor was constructed, and the compounds of Guiqi Baizhu prescription were virtual screened. The components that fit the pharmacophore model were calculated by molecular docking and binding free energy, and the potential inhibitory components were selected for biological experimental evaluation. The effects of potential inhibitory components on UM cell proliferation were detected by CCK-8 and clonal formation assay. Flow cytometry was used to detect the cell cycle and apoptosis of UM cells. The mitochondrial membrane potential of UM cells was detected using JC-10 staining. The expressions of PI3K and downstream pathway proteins were detected by Western blotting.RESULTS The pharmacophore model included 2 hydrogen bond receptors, 2 aromatic ring centers, and exclusion volumes. The results of the CCK-8 experiment showed that quercetin, tangerine, and nobiletin at concentrations of 10, 20, 40, 80 μmol·L−1, and cyrtin at concentrations of 20, 40, 80 μmol·L−1, were able to inhibit the proliferation of UM cells. The clonal formation experiment showed that quercetin, tangerine, nobiletin, and morusin, at different concentrations, could significantly inhibit the clonal proliferation of UM cells. Flow cytometry showed that UM cells were arrested in the G0/G1 phase by tangeretin and quercetin, while UM cells were arrested in the G2/M phase by nobiletin and morusin. The results of JC-10 staining showed that quercetin, nobiletin, tangeretin, and morusin could reduce the mitochondrial membrane potential of UM cells. Western blotting results showed that 4 compounds could target PI3K, but their downstream pathways were different.CONCLUSION Based on the method of chemical bioinformatics in traditional Chinese medicine, this study explores the material basis for the inhibition of UM cell proliferation by the Guiqi Baizhu prescription. It also provides insights for the modern development of traditional Chinese medicine prescription.

Objectives:To analyze the disease burden and changing trends of non-rheumatic valvular heart disease(NRVHD)from 1990 to 2019 in China. Methods:Based on the Global Burden of Disease 2019 database,we collected data related to NRVHD in China from 1990 to 2019,analyzed the crude incidence rate,crude prevalence rate,crude disability-adjusted life year(DALY),and age-scaled rate of NRVHD during this period,and analyzed the corresponding trends.The grey prediction model GM(1,1)was used to predict the disease burden of NRVHD in China from 2020 to 2029. Results:The crude incidence,crude prevalence,and crude DALY rates of NRVHD increased in China from 7.87/100 000,123.21/100 000,and 9.83/100 000 in 1990 to 22.85/100 000,374.16/100 000,and 11.95/100 000 in 2019;the age-standardized incidence rate and the age-standardized prevalence rate increased from 9.22/100 000 and 169.04/100 000 in 1990 to 15.30/100000 and 262.85/100 000 in 2019 respectively,with females being higher than males;the age-standardized DALY rate declined from 13.43/100 000 in 1990 to 9.07/100 000 in 2019,with females being higher than males.Joinpoint regression model analysis showed an increasing trend in the age-standardized incidence rate and age-standardized prevalence rate,and a decreasing trend in the age-standardized DALY rate(annual average percentage change[AAPC]values of 1.86%,1.72%and-1.66%,respectively),trend of change was statistically significant(all P<0.05).The burden of disease for all age groups from 1990 to 2019 showed an overall increasing trend,and the crude incidence rate,crude prevalence rate and crude DALY rate all increased with age,and the elderly group over 60 years old was the main group of disease burden.The results of the grey prediction model showed that by 2029,the age-standardized incidence rate and age-standardized prevalence rate would increase to 18.51/100 000 and 303.26/100 000,respectively,and the age-standardized DALY rate would decrease to 7.42/100 000. Conclusions:From 1990 to 2019,the age-standardized incidence rate and age-standardized prevalence rate of NRVHD in China showed an increasing trend,and the age-standardized DALY rate all showed a decreasing trend.The disease burden of NRVHD in China remains high.Women and the senior population are the main target groups needing special attention in China,and more targeted prevention and treatment strategies are needed for high-risk population.

Zi goose is a small local variety with high fecundity,good meat quality,roughage resist-ance,strong adaptability and excellent down quality.It is an excellent female parent for cross breeding among varieties.With the rapid development of goose industry,the variety of Zi goose has not been well protected,the variety is hybrid and degraded seriously,and the number of pure Zi goose is decreasing day by day.This paper reviewed the research progress on the breeding distribu-tion and preservation status of Zi goose and the variety characteristics of Zi goose,in order to pro-vide reference for the research,protection and utilization of germplasm resources of Zi goose and the stable development of goose industry.

Objective:To explore the efficacy of quantitative parameters of dual-layer spectral CT in preoperative prediction of Ki-67 expression in esophageal squamous cell carcinoma (ESCC).Methods:From December 2021 to December 2022, 64 patients with histopathologically diagnosed ESCC were retrospectively analyzed at Liaoning Cancer Hospital & Institute. The expression level of Ki-67 in ESCC tumor tissue was detected by the immunohistochemical method. The patients were divided into the Ki-67 high expression group (the Ki-67 expression index≥30%, 47 cases) and the Ki-67 low expression group (the Ki-67 expression index<30%, 17 cases). The quantitative parameters of spectral CT were measured, including traditional 120 kVp CT value, 40 keV CT value, iodine density (ID), normalized iodine density (NID), and Z-effective in arterial and venous phases. Independent sample t test was used to compare the differences in the parameters between the Ki-67 high and low expression groups. The receiver operating characteristic (ROC) curve was drawn to evaluate the efficacy of each parameter in predicting Ki-67 expression. DeLong test was used to compare the area under the curve (AUC). Results:The 120 kVp CT value, 40 keV CT value, ID, and Z-effective in the arterial phase and the 120 kVp CT value, 40 keV CT value, ID, NID, Z-effective in venous phase in the Ki-67 high expression group were all higher than those in the Ki-67 low expression group ( P<0.05). There was no statistically significant difference in arterial phase NID between the two groups ( t=1.85, P=0.070). NID in the venous phase had the highest AUC in predicting high expression of Ki-67 in ESCC (AUC=0.965, 95%CI 0.923-1.000). With a venous phase NID value of 0.28 as the diagnostic threshold, the sensitivity and specificity were 93.6% and 100%. There was no significant difference in AUC between venous phase NID and venous phase ID (AUC=0.926) and Z-effective (AUC=0.909) ( Z=-1.52, 1.81, P=0.128, 0.071), but there was a significant difference of AUC between venous phase NID and 120 kVp CT value (AUC=0.719) and 40 keV CT value (AUC=0.747) ( Z=3.41, 3.30, P=0.001, 0.001). There were statistical differences of AUC between venous phase NID and each parameter of arterial phase ( P<0.05). Conclusion:The three spectral CT parameters (ID, NID, and Z-effective) in the venous phase have high diagnostic efficacy in predicting ESCC Ki-67 expression.

In this study, a new Bacillus velezensis strain Bv-303 was identified and its biocontrol effect against rice bacterial-blight (BB) disease caused by Xanthomonas oryzae pv. oryzae (Xoo) was investigated. Cell-free supernatant (CFS) of strain Bv-303 under different growth conditions were prepared to test the antagonistic activity and stability against Xoo by the Oxford-cup method in vitro. The antibacterial effect of strain Bv-303 to BB disease in rice were further analyzed in vivo by spraying the cell-culture broth (CCB), CFS and cell-suspension water (CSW), respectively, on the rice leaves inoculated with Xoo. Additionally, rice seeds germination rate and seedling growth under the strain Bv-303 CCB treatment were tested. The results showed that the strain Bv-303 CFS significantly inhibited Xoo growth by 85.7%‒88.0% in vitro, which was also stable under extreme environment conditions such as heat, acid, alkali and ultraviolet light. As tested in vivo, spraying the CCB, CFS or CSW of strain Bv-303 on the Xoo-infected leaves enhanced rice plant resistance to BB disease, with CCB showing the highest increase (62.7%) in disease-resistance. Notably, CCB does not have negative effects on rice seed germination and seedling growth. Therefore, strain Bv-303 has great potential for biocontrol of the rice BB disease.
Oryza ; Fatigue Syndrome, Chronic ; Bacillus ; Xanthomonas ; Plant Diseases/microbiology*