ObjectiveTo study the mechanism of Huanglian Jiedutang （HLJDT） in treating mice with atherosclerosis （AS） by improving ferroptosis. MethodsA total of 10 SPF C57BL/6J mice were selected as a normal group， and 50 ApoE^-/- mice were randomly divided into five groups： model group， low-dose group of HLJDT， medium-dose group of HLJDT， high-dose group of HLJDT， and atorvastatin （ATV） group. ApoE^-/- mice were fed a high-fat diet for eight weeks to establish the AS model， and at the 9th week， they were given normal saline， low， medium， and high doses of HLJDT （3.9， 7.8， 15.6 g·kg^-1·d^-1）， and atorvastatin calcium tablets （0.01 g·kg^-1·d^-1）， respectively， for a total of eight weeks. The formation of aortic plaque in mice was observed by gross oil red O staining and Masson staining. The levels of total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， triglyceride （TG）， and high-density lipoprotein cholesterol （HDL-C） in blood fat were measured by the automatic biochemical analyzer， and the mitochondrial structure of the aorta was observed by transmission electron microscopy. The content of serum superoxide dismutase （SOD） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. The content of reduced glutathione （GSH） in serum was detected by the microplate method， and that of malondialdehyde （MDA） in serum was detected by the TBA method. The protein expression of nuclear factor E₂-associated factor 2 （Nrf2）/glutathione peroxidase 4 （GPX4） signaling pathway was detected by Western blot. ResultsCompared with those of the normal group， the contents of TC， LDL-C， TG， HDL-C， and MDA in the serum and the aortic vascular plaque deposition of the model group were significantly increased （P<0.01）， while the expression levels of SOD and GSH in serum， as well as Nrf2， solute carrier family 7 member 11 （SLC7A11）， and GPX4 in aorta were significantly decreased （P<0.01）. Mice in the model group appeared mitochondrial fragmentation and vacuolation in the aorta， volume atrophy， mitochondrial crista reduction， or a loose and disorganized form. Compared with those in the model group， the aortic vascular plaque deposition was significantly decreased in the low-dose， medium-dose， and high-dose groups of HLJDT and ATV group， and the contents of serum TC， LDL-C， TG， and MDA in serum were significantly decreased （P<0.05， P<0.01）. The contents of serum SOD and GSH and the expression levels of Nrf2， SLC7A11， and GPX4 in the aorta were increased （P<0.05， P<0.01）， and the symptoms of aortic mitochondrial vacuolation were alleviated. The number of cristae was increased， and they were ordered neatly. ConclusionHLJDT can reduce aortic vascular plaque deposition， decrease blood lipid and MDA expression， increase SOD and GSH expression， and ameliorate the pathological changes of ferroptosis， the mechanism of which is related to the Nrf2/GPX4 signaling pathway.

ObjectiveTo study the mechanism of astragaloside Ⅳ （AS Ⅳ） on db/db mice with type 2 diabetes mellitus （T2DM） and non-alcoholic fatty liver disease （NAFLD） based on network pharmacology and experimental validation. MethodA total of 24 db/db mice were randomly divided into four groups： model group， metformin group， and low-dose and high-dose AS Ⅳ groups. Six C57 mice were used as the blank group. The low-dose and high-dose AS Ⅳ groups were given AS Ⅳ of 0.015 and 0.030 g·kg^-1 by gavage， and the metformin group was given 0.067 g·kg^-1 by gavage. The blank and model groups were given equal volumes of distilled water by gavage. After intragastric administration， fasting blood glucose （FBG） was detected， and an oral glucose tolerance test was performed. Serum lipid level and liver histopathology were detected. The target and enrichment pathway of AS Ⅳ for treating T2DM and NAFLD were predicted by network pharmacology， and the main enrichment pathway was verified by molecular biology techniques. The protein expressions of AMPK， p-AMPK， sterol regulatory element-binding protein-1 （SREBP-1）， and fatty acid synthetase （FAS） in liver tissue were detected by Western blot. ResultCompared with the blank group， the levels of body mass， liver weight coefficient， fasting blood glucose， serum total cholesterol， triglyceride， and low-density lipoprotein cholesterol in mice treated with AS Ⅳ were decreased （P<0.05， P<0.01）. The pathology of liver tissue showed significant improvement in lipid accumulation， and imaging results showed that the degree of fatty liver was reduced after AS Ⅳ therapy. Network pharmacological prediction results showed that vascular endothelial growth factor α （VEGFA）， galactoagglutinin 3 （LGALS3）， serine/threonine kinase B2 （Akt2）， RHO-associated coiled-coil protein kinase 1 （ROCK1）， serine/threonine kinase B1 （Akt1）， signaling and transcriptional activator protein （STAT3）， and messtimal epidermal transformation factor （MET） were key targets in "drug-disease" network. The results from the Kyoto encyclopedia of genes and genomes （KEGG） enrichment showed that the AMP-dependent protein kinase （AMPK） signaling pathway was strongly associated with T2DM and NAFLD. Western blot results showed that compared with the blank group， the expression levels of p-AMPK/AMPK in the model group were significantly down-regulated， while those of SREBP-1 and FAS proteins were significantly up-regulated （P<0.01）. Compared with the model group， the expression levels of p-AMPK/AMPK in the metformin group and high-dose AS Ⅳ group were significantly up-regulated， while those of SREBP-1 and FAS proteins were significantly down-regulated （P<0.05， P<0.01）. ConclusionAS Ⅳ regulates the expression of lipid proteins by activating the AMPK signaling pathway， thereby improving lipid metabolism.

Objective To investigate the influencing factors of adverse pregnancy outcomes in patients with preeclampsia and the predictive value of serum trace elements in the second trimester.Methods A total of 98 patients with preeclampsia admitted to Qujing First People's Hospital from January 2019 to June 2022 were enrolled in the study.Patients were divided into poor outcome group and good outcome group according to whether they had adverse pregnancy outcomes.The clinical data of all patients enrolled in the study were col-lected and the serum levels of trace elements calcium,copper,zinc and iron were detected in the second trimes-ter.Univariate analysis and multivariate Logistic regression were used to analyze the influencing factors of ad-verse pregnancy outcomes in patients with preeclampsia.The levels of serum trace elements in the second tri-mester of pregnancy were compared between the poor outcome group and the good outcome group.The re-ceiver operating characteristic(ROC)curve was used to evaluate the predictive value of serum trace elements calcium,copper,zinc and iron for adverse pregnancy outcomes in patients with preeclampsia.Results Univari-ate analysis showed that compared with the good outcome group,the poor outcome group had significantly higher systolic blood pressure,24 h urinary protein quantitation,and D-dimer level(P＜0.05)and significantly less gestational age and platelet count at admission(P＜0.05).Multivariate Logistic regression analysis showed that 24 h urinary protein quantification,D-dimer and platelet count were the influencing factors of ad-verse pregnancy outcomes in patients with preeclampsia(P＜0.05).The levels of serum trace elements calci-um,copper,and zinc in the poor outcome group were significantly lower than those in the good outcome group(P＜0.05),and the level of iron was significantly higher than that in the good outcome group(P＜0.05).ROC curve analysis showed that the areas under the curves(AUCs)of serum calcium,copper,zinc,and iron in the second trimester of pregnancy for predicting adverse pregnancy outcomes in preeclampsia patients were 0.830(95％CI:0.780-0.880),0.855(95％CI:0.805-0.905),0.847(0.797-0.897)and 0.861(95％CI:0.811-0.911),respectively.Conclusion Adverse pregnancy outcomes in patients with preeclampsia are re-lated to 24 h urine protein,D-dimer and platelet count.The levels of serum trace elements calcium,copper,zinc and iron in the second trimester of pregnancy change significantly in patients with adverse pregnancy out-comes,which may become predictive markers of adverse pregnancy outcomes.

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

Objective:To study the predictive values of lung ultrasound (LUS) score and Downes score in selecting respiratory support strategies for newborns with dyspnea.Methods:From September 2021 to July 2022, newborns admitted to our hospital with dyspnea were selected and assigned into the non-invasive respiratory support (N) group, invasive respiratory support (I) group and control (C) group based on the respiratory support strategies on admission. LUS scores and Downes scores at 6, 24, and 48 h after birth were recorded. ROC curves were drawn to determine the predictive values of LUS and Downes scores for respiratory support strategies.Results:A total of 263 cases were enrolled, including 105 cases in N group, 56 cases in I group and 102 cases in C group. The differences of LUS and Downes scores between the three groups at the same timepoint were statistically significant with I group had the highest scores, N group second and C group lowest ( P<0.05). LUS and Downes scores within each group at different timepoints were significantly different ( P<0.05).In all three groups, LUS and Downes scores were decreased with longer duration of treatment. LUS score, Downes score and PaO 2/FiO 2 were positively correlated with each other ( P<0.05). The area under the curve (AUC) of LUS score and Downes score predicting non-invasive respiratory support within 6 h after birth were 0.900 (95% CI 0.861-0.940, P<0.05) and 0.889 (95% CI 0.847-0.931, P<0.05), respectively, with the same cutoff of 2.5. The AUC of the combination of LUS and Downes scores predicting non-invasive respiratory support was 0.944 (95% CI 0.915-0.973, P<0.05). The AUC of LUS score and Downes score predicting invasive respiratory support were 0.979 (95% CI 0.963-0.995, P<0.05) and 0.831 (95% CI 0.760-0.902, P<0.05), respectively, with the same cutoff of 5.5. The AUC of the combination of LUS and Downes scores predicting invasive respiratory support was 0.985 (95% CI 0.972-0.998, P<0.05). Conclusions:Both LUS score and Downes score have certain predictive values for respiratory support strategies in newborns with dyspnea.

Objectives It was a preliminary exploration on rare disease management of comprehensive hospital based on the"Center-Multidisciplinary Team"structure.Methods By applying interrupted time series analysis,the characteristics and related medical service of rare disease patients discharged from sample hospitals from 2021 to 2023 were measured.Results The results showed that the hospital served 19 825 rare disease patients from 2021 to 2023.The proportion of patients whose main diagnosis were rare diseases was approximately 27％.The interrupted time series technique indicated that the expected proportion of rare disease patients increased instantly by 1.89 thousand points.The capability to diagnose has significantly improved,with a growing trend on volume of bioinformatics analysis services for rare diseases patients.Conclusion The rare disease management based on the"Center-Team"structure can increase the attention of medical staff to rare diseases,strengthen the diagnostic capacity of rare diseases,and make patient management more continuous and disciplinary co-operation more efficient without significantly increasing the input burden on hospitals.

Objectives It was a preliminary exploration on rare disease management of comprehensive hospital based on the"Center-Multidisciplinary Team"structure.Methods By applying interrupted time series analysis,the characteristics and related medical service of rare disease patients discharged from sample hospitals from 2021 to 2023 were measured.Results The results showed that the hospital served 19 825 rare disease patients from 2021 to 2023.The proportion of patients whose main diagnosis were rare diseases was approximately 27％.The interrupted time series technique indicated that the expected proportion of rare disease patients increased instantly by 1.89 thousand points.The capability to diagnose has significantly improved,with a growing trend on volume of bioinformatics analysis services for rare diseases patients.Conclusion The rare disease management based on the"Center-Team"structure can increase the attention of medical staff to rare diseases,strengthen the diagnostic capacity of rare diseases,and make patient management more continuous and disciplinary co-operation more efficient without significantly increasing the input burden on hospitals.

Ritlecitinib is an inhibitor that acts on Janus kinase 3 and the hepatocellular carcinoma kinase family.In June 2023,the FDA approved Ritlecitinib for the treatment of severe alopecia areata in patients aged 12 years and above.Multiple clinical studies have observed hair regeneration in patients after using Ritlecitinib,which is generally safe and well tolerated during use.This article introduces its pharmacological effects,pharmacokinetics,clinical research,safety,and usage and dosage.

Objective To investigate the protective effect of silymarin extract(SME)and its complex preparation on ethanol liver injury.Methods An ethanol liver injury model was established by gavage of 12 mL·kg-1 50％ethanol.Male mice were divided into blank group(distilled water),model group(ethanol liver injury model),SME-L,-H groups(6,20 mg·mL-1 SME),SME+Ganoderma lucidum extract(GLE)-L,-H groups(10,30 mg·mL-1 SME+GLE,SME∶GLE=1∶1),Jian An Shi Silymarin Pueraria Mirifica and Tansy tablets(JAS)-L,-H groups(68,204 mg·mL-1 JAS),there were 12 mice in each group.The serum levels of glutamic-oxaloacetic transaminase(GOT)in mice were measured by fully automated biochemical analyzer assay;the serum levels of interleukin-6(IL-6)and tumor necrosis factor-alpha(TNF-α)in mice were measured by enzyme-linked immunosorbent assay(ELASA);the hepatic tissue of oxidative stress indexes[catalase(CAT)and total superoxide dismutase(T-SOD)]were measured by ultraviolet spectrophotometer.Results The T-SOD activity in the blank group,model group,SME-L,SME-H,SME+GLE-L,SME+GLE-H,JAS-L and JAS-H groups were(192.54±49.00),(141.65±34.72),(205.83±32.77),(191.68±25.83),(192.31±28.79),(177.82±32.61),(218.58±74.80)and(210.24±31.65)U·mg·prot-1;CAT activity were(37.78±5.73),(28.92±8.44),(44.12±11.52),(41.41±9.15),(47.01±10.48),(41.63±8.95),(47.14±8.91)and(48.29±10.06)U·mg-1;GPT levels were(47.61±13.00),(97.84±26.00),(62.33±18.92),(51.84±17.91),(70.77±28.00),(58.00±21.27),(52.28±18.78)and(45.55±9.27)U·L-1;IL-6 levels were(21.03±1.52),(28.43±5.75),(21.90±3.24),(21.23±1.55),(22.26±2.58),(21.24±2.91),(22.17±4.14)and(21.14±3.02)pg·mL-1.Comparing the above indexes in the model group with the blank group,and comparing the above indexes in the SME-L,SME-H,SME+GLE-L,SME+GLE-H,JAS-L,JAS-H groups with the model group,the differences were statistically significant(all P＜0.01).The TNF-α levels in blank,model,SME-L,SME-H,SME+GLE-L,SME+GLE-H,JAS-L and JAS-H groups were were(28.07±7.72),(69.02±16.34),(40.29±8.94),(48.84±10.17),(41.91±14.96),(40.07±12.75),(50.72±11.44)and(45.05±11.34)pg·mL-1.Comparing the model group with the blank group,the SME,SME+GLE-L,-M and JAS,-M groups with the model group,the differences were statistically significant(all P＜0.01).Conclusion Silybum marianum extract and its compound preparation can increase the antioxidant level and reduce the inflammation of mouse liver,and have a certain improvement effect on liver injury caused by acute ethanol poisoning.

Objective To construct machine learning models that can be used to predict AUC fold change(FC)using a database of existing pharmacokinetic(PK)and drug-drug interaction(DDI)information,which can be used to explore the possibility of predicting existing drug interactions and to provide certain rational recommendations for clinical drug use.Methods PK data of DDIs and AUC fold change data were extracted from FDA-approved drug labels.Peptide and pharmacodynamic(PD)information related to drug interactions were retrieved through DrugBank,and PPDT identification of relevant peptide IDs was performed using Protein Resource(UniProt),and a matrix normalization code was used to generate multidimensional vector data that were easy to analysis.The effect of PPDT on the AUC,and the resulting multiplicity change was used as the dependent variable for machine learning model construction.The model with the smallest root mean square error(RMES)value was used for model construction to train a bagged decision tree(Bagged)prediction model.The models were tested using the trained models for some of the drug tests.The models were evaluated by reviewing the available literature findings on detection of drug interaction pairs and analyzing and comparing the predicted values.Results A total of 16 pairs of model drug pairs were tested for the effects of 16 drugs on tacrolimus,and it was found that the accuracy of the prediction of the presence or absence of drug interactions was 81.25％;the prediction results were classified according to the FDA standard classification of the strong and weak for the strength of drug interactions,and the results showed that the prediction of the strength of drug interactions,with a large deviation from the larger prediction was less.Conclusion The evaluation of the model to predict the presence or absence of drug interactions was general;however,after classifying the strengths and weaknesses of drug interactions,the prediction of drug interactions was better,and the prediction results indicated that the model prediction performance has a certain reference value for potential DDI assessment before clinical trials.