The AP2/ERF transcription factor family is a class of transcription factors widely present in plants, playing a crucial role in regulating flowering, flower development, flower opening, and flower senescence. Based on transcriptome data from flower, leaf, and stem samples of two Lonicera macranthoides varieties, 117 L. macranthoides AP2/ERF family members were identified, including 14 AP2 subfamily members, 61 ERF subfamily members, 40 DREB subfamily members, and 2 RAV subfamily members. Bioinformatics and differential gene expression analyses were performed using NCBI, ExPASy, SOMPA, and other platforms, and the expression patterns of L. macranthoides AP2/ERF transcription factors were validated via qRT-PCR. The results indicated that the 117 LmAP2/ERF members exhibited both similarities and variations in protein physicochemical properties, AP2 domains, family evolution, and protein functions. Differential gene expression analysis revealed that AP2/ERF transcription factors were primarily differentially expressed in the flowers of the two L. macranthoides varieties, with the differentially expressed genes mainly belonging to the ERF and DREB subfamilies. Further analysis identified three AP2 subfamily genes and two ERF subfamily genes as potential regulators of flower development, two ERF subfamily genes involved in flower opening, and two ERF subfamily genes along with one DREB subfamily gene involved in flower senescence. Based on family evolution and expression analyses, it is speculated that AP2/ERF transcription factors can regulate flower development, opening, and senescence in L. macranthoides, with ERF subfamily genes potentially serving as key regulators of flowering duration. These findings provide a theoretical foundation for further research into the specific functions of the AP2/ERF transcription factor family in L. macranthoides and offer important theoretical insights into the molecular mechanisms underlying floral phenotypic differences among its varieties.
Plant Proteins/chemistry* ; Gene Expression Regulation, Plant ; Transcription Factors/chemistry* ; Lonicera/classification* ; Flowers/metabolism* ; Phylogeny ; Gene Expression Profiling ; Multigene Family

OBJECTIVE To investigate the antidepressant mechanism of Shugan hewei tang （SGHWT） based on the metabolomics of prefrontal cortex （PFC）-nucleus accumbens （NAc）-ventral tegmental area （VTA） neural circuit. METHODS Male SD rats were randomly divided into blank group， model group， SGHWT low-， medium- and high-dose groups [3.67， 7.34， 14.68 g/（kg·d）， by raw material]， and fluoxetine group [1.58 mg/（kg·d）， positive control]， with 12 rats in each group. Except for the blank group， the depression model was established by chronic unpredictable mild stress combined with individual cage housing in the remaining groups， and the corresponding drug solution or normal saline was administered via gavage during modeling， once a day， for 6 consecutive weeks. After the last administration， the body weight， sucrose preference rate， total moving distance， frequency into the center and immobility time of rats in each group were detected. Samples of PFC， NAc and VTA areas of rats in the blank group， model group， SGHWT medium-dose group and fluoxetine positive control groups were collected，and their histomorphological features were observed， and non-targeted metabolomics analysis （except for fluoxetine group）were performed and validated. RESULTS Compared with model group， the cytolysis， structural damage and other pathological damages in three brain regions of rats were significantly alleviated in each drug group， while their body weight， sucrose preference rate， total moving distance and frequency into the center were all significantly higher or longer （P＜0.05）， and immobility time was significantly shorter （P＜0.05）. The results of non-targeted metabolomics showed that a total of 78 endogenous differential metabolites were identified， with 40， 35 and 24 in the PFC， NAc and VTA regions respectively， mainly involved in amino acid， lipid and sphingolipid metabolism. The results of metabolic pathway enrichment analysis showed that SGHWT affected the neural circuits of depressed rats by regulating sphingolipid metabolism， alanine， aspartic acid and glutamic acid metabolism， saturated fatty acid biosynthesis， among which alanine， aspartic acid and glutamic acid metabolism was predominantly involved. Validation experiments showed that SGHWT significantly increased the phosphorylation levels of protein kinase B （Akt） and mammalian target of rapamycin （mTOR）， and decreased the protein expression of N-methyl-D-aspartic acid receptor 1 （NMDAR1） in the NAc region of rats. CONCLUSIONS SGHWT significantly improves the depression-like behavior and attenuates pathological damage of PFC-NAc-VTA neural circuit of model rats， the mechanism of which is associated with inhibiting NMDAR1 expression and activating the Akt/mTOR signaling pathway.

ObjectiveBased on the conjoint analysis of transcriptome and metabolome， the key genes in the phenylpropanoid biosynthesis pathway of Lonicera macranthoides were explored， which provided a basis for further exploring the synthesis and regulation mechanism of phenylpropanoid compounds in "Xianglei" L. macranthoides. MethodsThe stem， leaves， and three flowering flowers of "Xianglei" L. macranthoides were selected as experimental materials to construct transcriptome and metabolome. The transcriptome and metabolomics were conjointly analyzed by the Kyoto Encyclopedia of Genes and Genomes （KEGG） database and weighted correlation network analysis （WGCNA）， and the key genes in the phenylpropanoid biosynthesis pathway of L. macranthoides were explored. ResultsIn this study， 77 differential phenylpropanoids and 315 differential genes were found. Through the joint analysis of transcription and metabolism， nine key differential metabolites and four key genes related to them were finally discovered. Among them， cinnamic acid， 5-O-caffeoylshikimic acid，sinapyl alcohol， and chlorogenic acid were higher in flowers， and the content of the iconic effective component， namely chlorogenic acid，decreased sharply during the withering period. Caffeic acid，ferulic acid， 5-hydroxyconiferaldehyde，p-coumaryl alcohol， and syringin were higher in leaves. These four key genes belong to the cinnamic alcohol dehydrogenase （CAD） family， 4-coumaric acid： Coenzyme A （4CL） family， hydroxycinnamyl transferase （HCT） family， and L-phenylalanine ammonlyase （PAL） family genes. ConclusionAmong the four key genes excavated from L. macranthoides， TRINITY_DN42767_c0_g6 is related to the synthesis of p-coumaryl alcohol and sinapyl alcohol. TRINITY_DN43525_c4_g1 uses caffeic acid，ferulic acid，and cinnamic acid as substrates to catalyze the next reaction. TRINITY_DN47958_c3_g4 correlates with the synthesis of 3-p-coumaroyl quinic acid and caffeoyl-CoA， and TRINITY_DN52595_c1_g2 correlates with cinnamic acid synthesis. These findings provide a basis for further exploring the synthesis and regulation mechanism of phenylpropanoids in "Xianglei" L. macranthoides.

Cardiovascular disease remains the leading cause of death in China, with its morbidity and mortality continue to rise. Ferroptosis, a unique form of iron-dependent cell death, plays a major role in many heart diseases. The classical mechanisms of ferroptosis include iron metabolism disorder, oxidative antioxidant imbalance and lipid peroxidation. Recent studies have found many additional mechanisms of ferroptosis, such as coenzyme Q10, ferritinophagy, lipid autophagy, mitochondrial metabolism disorder, and the regulation by nuclear factor erythroid 2-related factor 2 (NRF2). This article reviews recent advances in understanding the mechanisms of ferroptosis and its role in heart failure, myocardial ischemia/reperfusion injury, diabetic cardiomyopathy, myocardial toxicity of doxorubicin, septic cardiomyopathy, and arrhythmia. Furthermore, we discuss the potential of ferroptosis inhibitors/inducers as therapeutic targets for heart diseases, suggesting that ferroptosis may be an important intervention target of heart diseases.
Ferroptosis/physiology* ; Humans ; Heart Diseases/physiopathology* ; NF-E2-Related Factor 2/physiology* ; Animals ; Myocardial Reperfusion Injury/physiopathology* ; Lipid Peroxidation ; Heart Failure/physiopathology* ; Iron/metabolism* ; Diabetic Cardiomyopathies/physiopathology* ; Ubiquinone/analogs & derivatives*

OBJECTIVE: To analyze two families with inherited dysfibrinogenemia, and explore the molecular pathogenic mechanisms. METHODS: The coagulation indexes of the probands and their family members were detected. The FGA, FGB, and FGG exons and their flanking sequences were amplified by PCR, and the mutation sites were identified by sequencing. SIFT, PolyPhen2, LRT, ReVe, MutationTaster, phyloP, and phastCons bioinformatics software were used to predict the functional impact of the mutation sites. Protein structure and amino acid conservation analysis of the variant were conducted using PyMOL and Clustal X software. RESULTS: The thrombin time (TT) of the proband in family 1 was prolonged to 37.00 s, and Fg∶C decreased to 0.52 g/L. The TT of the proband in family 2 was 20.30 s, and Fg∶C was 1.00 g/L, which was lower than the normal range. Genetic analysis revealed that the proband in family 1 had a heterozygous mutation c.80T>C in FGA, resulting in the substitution of phenylalanine 27 with serine (Phe27Ser). The proband in family 2 had a heterozygous mutation c.1007T>A in FGG, resulting in the substitution of methionine 336 with lysine (Met336Lys). Bioinformatics software prediction analysis indicated that both mutations were deleterious variants. PyMOL mutation models revealed that the Aα chain mutation (Phe27Ser) in family 1 and γ chain mutation (Met336Lys) in family 2 resulted in alterations in spatial structure and reduced protein stability. Clustal X results showed that both Aα Phe27 and γMet336 were highly conserved across homologous species. CONCLUSION Heterozygous mutations of FGA gene c.80T>C and FGG gene c.1007T>A are both pathogenic variants, causing inherited dysfibrinogenemia.
Female ; Humans ; Male ; Afibrinogenemia/genetics* ; Fibrinogen/genetics* ; Heterozygote ; Mutation ; Pedigree

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Objective To analyze the situation of blood lipid and blood routine parameters in patients with pneumoconiosis,and construct a column chart diagnostic model to explore their diagnostic value for pneumo-coniosis.Methods A total of 456 patients with pneumoconiosis admitted to the First Affiliated Hospital of Chongqing Medical and Pharmaceutical College from January 2022 to January 2024 were selected as the pneu-moconiosis group,while 462 healthy subjects exposed to dust during the same period were chosen as the con-trol group.Serum lipids and blood routine parameters related to pneumoconiosis were measured and compared between two groups.Univariate and multivariate Logistic regression analyzes were conducted to examine ser-um lipids and blood routine parameters associated with pneumoconiosis.A risk prediction model was construc-ted using logistic regression in machine learning,and the diagnostic efficacy of the column chart diagnostic model was evaluated by calculating the C-index through receiver operating characteristic(ROC)curve and plotting the model calibration curve based on Hosmer Lemeshow goodness of fit.Decision curve analysis(DCA)was used to assess the clinical practicality of the column chart diagnostic model.Results The levels of serum high-density ester protein cholesterol(HDL-C),cholesterol(TC),red blood cell(RBC),hematocrit(HCT),hemoglobin concentration(HGB),lymphocyte number(LYM),and lymphocyte percentage(LYM％)in the pneumoconiosis group were lower than those in the control group(P＜0.05).The levels of neutrophil-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),and systemic immune inflammation index(SII)were higher than those in the control group(P＜0.05).Multivariate Logistic regression analysis showed that HDL-C,LYM％,PLR,and SII were independent influencing factors for pneumoconiosis(P＜0.05).A column chart diagnostic model for the occurrence of pneumoconiosis was constructed using HDL-C,TC,LYM％,PLR,and SII as diagnostic factors.The ROC curve C-index of the diagnostic model was 0.84(95％CI:0.81-0.86),with sensitivity for diagnosing pneumoconiosis of 75.29％,specificity of 77.51％,posi-tive predictive value of 83.25％,and negative predictive value of 67.88％.Internal validation was conducted on the constructed column chart diagnostic model,with a validation set ROC curve C-index of 0.84(95％CI:0.80-0.87),sensitivity of 80.91％,specificity of 72.62％,positive diagnostic value of 79.46％,and negative diagnostic value of 74.39％.The calibration positive curve slope of the diagnostic model was close to 1,and in the fit test P＞0.05.DCA analysis showed that the diagnostic model had clinical practical value for risk diag-nosis of pneumoconiosis.Conclusion HDL-C,TC,LYM％,PLR and SII are independent influencing factors for pneumoconiosis.A column chart diagnostic model for the occurrence of pneumoconiosis is successfully constructed based on machine learning principles,and it has been verified to have high diagnostic efficiency.

Chimeric antigen receptor-modified T(CAR-T)cell therapy,as a new type of cellular immunotherapy,has shown good clinical efficacy in the treatment of malignant hematological tumors,especially B-cell acute lympho-blastic leukemia.However,there are problems such as antigen loss and immune evasion in single-target selection,so multi-target therapy strategies are gradually gaining attention.Multi-target CAR-T can effectively avoid antigen escape caused by a single target by targeting multiple tumor-associated antigens at the same time,reduce the risk of recurrence,and is expected to improve the therapeutic effect.This paper primarily discusses the structural types of multi-target CAR-T cell therapy and its clinical trial applications in the treatment of B-cell acute lymphoblastic leu-kemia(B-ALL),aiming to provide future references for the treatment of B-ALL.

Objective To investigate the correlation between the total load of cerebral small vessel disease(CSVD)and the early prognosis of patients with acute cerebral infarction(ACI).Methods A total of 150 patients with ACI admitted to the Department of Neurology,the First Hospital of Jiaxing from October 2020 to June 2022 were included,according to modified Rankin scale(mRs)score,patients were classified good prognosis group(mRs≤2 points)and poor prognosis group(mRs≥3 points),baseline data and clinical characteristics were compared between the 2 groups,and total CSVD load was assessed by cranial MRI,single factor and multi-factor analysis were performed with Logistic model.The relativity of CSVD load and early prognosis was analyzed with Pearson method.Results Age,length of stay,National Institute of Health stroke scale(NIHSS),hypersensitivity C-reactive protein,triglyceride and homocysteine were significantly higher in poor prognosis group than those in good prognosis group,the difference was significant(P<0.05).The scores of lacunar,cerebral microhemorrhage,white matter hyperintensity and CSVD in poor prognosis group were significantly higher than those in good prognosis group(P<0.05).Multivariate Logistic regression analysis showed that length of stay(OR=1.278,95％CI=1.054-1.548,P=0.012),admission NIHSS score(OR=1.354,95％CI=1.113-1.647,P=0.002),CSVD total load(OR=2.494,95％CI=1.666-3.735,P<0.001)were independent risk factors for poor early prognosis in patients with acute cerebral infarction.Conclusion CSVD load is associated with poor prognosis in patients with acute cerebral infarction.

This experiment aims to study the taste-masking effects of different kinds of corrigent used individually and in combination on ibuprofen oral solution, in order to optimize the taste-masking formulation. Firstly, a wide range of corrigent and the mass fractions were extensively screened using electronic tongue technology. Subsequently, a combination of sensory evaluation, analytic hierarchy process (AHP)-fuzzy mathematics evaluation, and Box-Behnken experimental design were employed to comprehensively assess the taste-masking effects of different combinations of corrigent on ibuprofen oral solution, optimize the taste-masking formulation, and validate the results. The study received ethical approval from the Review Committee of the Beijing University of Chinese Medicine (ethical code: 2024BZYLL0102). The results showed that corrigent fractions and types were screened separately through single-factor experiments. Subsequently, a Box-Behnken response surface design combined with AHP and fuzzy mathematics evaluation was used to fit a functional model: Z = 688.310 11 - 3 023.722 22X₁ - 11.477 00X₂ + 62.721 67X₃ + 14.600 00X₁X₂ - 179.666 67X₁X₃ - 3.152 00X₂X₃ + 4 031.111 11X₁² + 0.525 28X₂² + 9.772 00X₃². This model is stable and reliable, determining the optimal taste-masking formulation to be 3.9 g·L^-1 of stevioside, 100 g L^-1 of xylitol, and 30 g L^-1 of methyl-β-cyclodextrin. The comprehensive score of the verification test is 88.14, with a relative RSD of 0.39%, indicating the feasibility of this model. This study achieved the improvement of the taste of ibuprofen oral solution through a combination of objective and subjective methods. Three types of corrigent were identified for enhancing drug taste, leading to the selection of the optimal taste-masking formulation for ibuprofen oral solution. This significantly enhanced the taste of the original formulation, improved patient compliance, and offered a new approach to mitigating the undesirable taste of formulations.