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

The alteration of pulmonary artery pressure is an important physiological indicator to reflect the organism's adaptation to acclimatization or the pathological injury in response to high-altitude hypoxic environment. The effects of hypoxic stress at different altitudes for different time on pulmonary artery pressure are different. There are many factors involved in the changes of pulmonary artery pressure, such as the contraction of pulmonary arterial smooth muscle, hemodynamic changes, abnormal regulation of vascular activity and abnormal changes of cardiopulmonary function. Understanding of the regulatory factors of pulmonary artery pressure in hypoxic environment is crucial in clarifying the relevant mechanisms of hypoxic adaptation, acclimatization, prevention, diagnosis, treatment and prognosis of acute and chronic high-altitude diseases. In recent years, great progress has been made in the study regarding the factors affecting pulmonary artery pressure in response to high-altitude hypoxic stress. In this review, we discuss the regulatory factors and intervention measures of pulmonary arterial hypertension induced by hypoxia from the aspects of hemodynamics of circulatory system, vasoactive state and changes of cardiopulmonary function.
Humans ; Altitude ; Arterial Pressure ; Acclimatization ; Hypoxia ; Muscle, Smooth

The present study explored the consistency of the content proportions of active components of Aurantii Fructus and analyzed the influencing factors based on three-dimensional multi-component analysis. A total of 839 Aurantii Fructus samples in 65 research articles were analyzed using the three-dimensional multi-component analysis mode. The content data of flavonoid components(naringin, hesperidin, neohesperidin, narirutin, and nobiletin), coumarin components(meranzin and gluconolactone), and alkaloid(synephrine) in 386 samples which met the criteria of 2020 edition of the Chinese Pharmacopoeia were extracted and adjusted to percentages, and the content ratios between components were calculated. The influencing factors of Aurantii Fructus quality were analyzed. The results showed content ratios of components as follows: neohesperidin∶naringin in the range of 0.4-1.2; narirutin∶naringin in the range of 0.02-0.16; hesperidin∶naringin in the range of 0.01-0.3; nobiletin∶naringin in the range of 0.000 588 3-0.069 68; synephrine∶naringin in the range of 0.02-0.042; gluconolactone∶naringin in the range of 0.001-0.01; meranzin∶naringin in the range of 0.000 4-0.035. The quality of Aurantii Fructus was closely related to the origin, variety, harvesting time, and processing method of medicinal materials. Harvesting time had a greater impact on the quality of Aurantii Fructus, and the origin and variety had a certain impact on the quality of Aurantii Fructus. The findings of this study indicated that the ratios between flavonoid components, flavonoids and coumarin components, and flavonoids and alkaloids fluctuated. The production base should optimize the varieties, harvesting period, and processing methods of Aurantii Fructus to provide a scientific basis for the production of high-quality Aurantii Fructus.
Citrus ; Flavonoids/analysis* ; Drugs, Chinese Herbal ; Fruit/chemistry* ; Coumarins/analysis* ; Chromatography, High Pressure Liquid/methods*

As a large family of transcription factors, the MYB family plays a vital role in regulating flower development. We studied the MYB family members in Lonicera macranthoides for the first time and identified three sequences of 1R-MYB, 47 sequences of R2R3-MYB, two sequences of 3R-MYB, and one sequence of 4R-MYB from the transcriptome data. Further, their physicochemical properties, conserved domains, phylogenetic relationship, protein structure, functional information, and expression were analyzed. The results show that the 53 MYB transcription factors had different conserved motifs, physicochemical properties, structures, and functions in wild type and 'Xianglei' cultivar of L. macranthoides, indicating their conservation and diversity in evolution. The transcript level of LmMYB was significantly different between the wild type and 'Xianglei' cultivar as well as between flowers and leaves, and some genes were specifically expressed. Forty-three out of 53 LmMYB sequences were expressed in both flowers and leaves, and 9 of the LmMYB members showed significantly different transcript levels between the wild type and 'Xianglei' cultivar, which were up-regulated in the wild type. The results provide a theoretical basis for further studying the specific functional mechanism of the MYB family.
Transcription Factors/metabolism* ; Lonicera/metabolism* ; Phylogeny ; Plant Proteins/metabolism* ; Gene Expression Regulation, Plant

Rheumatoid arthritis(RA), as a chronic autoimmune disease, has a high incidence and disability rate, causing significant suffering to patients. Due to its complex pathogenesis, it has not been fully elucidated to date, and its treatment remains a challenging problem in the medical field. Although western medicine treatment options have certain efficacy, they require prolonged use and are expensive. Additionally, they carry risks of multiple infections and adverse reactions like malignancies. The Chinese herbal medicine Rhododendron molle is commonly used in folk medicine for its properties of dispelling wind, removing dampness, calming nerves, and alleviating pain in the treatment of diseases like rheumatic bone diseases. In recent years, modern clinical and pharmacological studies have shown that the diterpenoids in R. molle are effective components, exhibiting immune-regulatory, anti-inflammatory, and analgesic effects. This makes it a promising candidate for treating RA with a broad range of potential applications. However, R. molle has certain toxic properties that hinder its clinical application and lead to the wastage of its resources. This study reviewed recent research progress on the mechanism of R. molle in preventing and treating RA, focusing on its chemical components, anti-inflammatory and analgesic properties and summarized the adverse reactions associated with R. molle, aiming to offer new ideas for finding natural remedies for RA and methods to reduce toxicity while enhancing the effectiveness of R. molle. The study seeks to clarify the safety and efficacy of R. molle and its extracts, providing a theoretical basis for its application prospects and further promoting the development and utilization of R. molle resources.
Humans ; Rhododendron/chemistry* ; Arthritis, Rheumatoid/drug therapy* ; Anti-Inflammatory Agents ; Diterpenes/pharmacology* ; Analgesics

OBJECTIVE: To demonstrate the mechanism of mechanical ventilation (MV) induced endoplasmic reticulum stress (ERS) promoting mechanical ventilation-induced pulmonary fibrosis (MVPF), and to clarify the role of angiotensin receptor 1 (AT1R) during the process. METHODS: The C57BL/6 mice were randomly divided into four groups: Sham group, MV group, AT1R-shRNA group and MV+AT1R-shRNA group, with 6 mice in each group. The MV group and MV+AT1R-shRNA group mechanically ventilated for 2 hours after endotracheal intubation to establish MVPF animal model (parameter settings: respiratory rate 70 times/minutes, tidal volume 20 mL/kg, inhated oxygen concentration 0.21). The Sham group and AT1R-shRNA group only underwent intubation after anesthesia and maintained spontaneous breathing. AT1R-shRNA group and MV+AT1R-shRNA group were airway injected with the adeno-associated virus one month before modeling to inhibit AT1R gene expression in lung tissue. The expressions of AT1R, ERS signature proteins [immunoglobulin heavy chain-binding protein (BIP), protein disulfide isomerase (PDI)], fibrosis signature proteins [collagen I (COL1A1), α-smooth muscle actin (α-SMA)] in lung tissues were detected by immunofluorescence and Western blotting. Hematoxylin-eosin (HE) staining was used to evaluate lung injury and Masson staining was used to evaluate pulmonary fibrosis. RESULTS: Compared with the Sham group, the degree of pulmonary fibrosis and lung injury were more significant in the MV group. In the MV group, the protein expressions of AT1R, BIP, PDI, COL1A1 and α-SMA were increased (AT1R/β-actin: 1.40±0.02 vs. 1, BIP/β-actin: 2.79±0.07 vs. 1, PDI/β-actin: 2.07±0.02 vs. 1, COL1A1/α-Tubulin: 2.60±0.15 vs. 1, α-SMA/α-Tubulin: 2.80±0.25 vs. 1, all P < 0.01). The number of E-cad⁺/AT1R⁺ and E-cad⁺/BIP⁺ cells in lung tissue increased, and the fluorescence intensity of COL1A1 and α-SMA increased. Compared with the MV group, the degree of pulmonary fibrosis and lung injury were significantly relieved in the MV+AT1R-shRNA group. In the MV+AT1R-shRNA group, the protein expressions of AT1R, BIP, PDI, COL1A1 and α-SMA were decreased (AT1R/β-actin: 0.53±0.03 vs. 1.40±0.02, BIP/β-actin: 1.73±0.15 vs. 2.79±0.07, PDI/β-actin: 1.04±0.07 vs. 2.07±0.02, COL1A1/α-Tubulin: 1.29±0.11 vs. 2.60±0.15, α-SMA/α-Tubulin: 1.27±0.10 vs. 2.80±0.25, all P < 0.01). The number of E-cad⁺/AT1R⁺ and E-cad⁺/BIP⁺ cells in lung tissue decreased, and the fluorescence intensity of COL1A1 and α-SMA decreased. There was no statistically significant difference in the indicators between AT1R-shRNA group and Sham group. CONCLUSIONS MV up-regulate the expression of AT1R in alveolar epithelial cells, activate the AT1R pathway, induce ERS and promote the progression of MVPF.
Mice ; Animals ; Pulmonary Fibrosis/chemically induced* ; Lung Injury ; Respiration, Artificial/adverse effects* ; Actins/metabolism* ; Tubulin ; Mice, Inbred C57BL ; Endoplasmic Reticulum Stress ; RNA, Small Interfering

AIM:To investigate the ferroptosis-related key genes in the progression of primary open angle glaucoma(POAG)through bioinformatics analysis, aiming to gain a deeper understanding of the biological mechanism of ferroptosis in POAG.METHODS: The GSE27276 dataset, derived from the trabecular meshwork, was obtained from the GEO database. It consisted of 19 trabecular meshwork tissue samples and 17 normal trabecular meshwork tissue samples. The ferroptosis-related genes were obtained from the FerrDb database. Then the GSE27276 dataset with the ferroptosis gene set was mapped, differentially expressed ferroptosis-related genes(DE-FRGs)were identified in POAG, and the correlation analysis was performed. Additionally, the gene ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways of DE-FRGs were further analyzed. This study utilized two machine learning algorithms, namely the LASSO regression model and the SVM-RFE model, to identify the ferroptosis-related key genes of POAG. The screening results from both models were intersected to identify the most significant genes. The clinical diagnostic performance of these genes was evaluated using the receiver operating characteristic curve(ROC); the gene set enrichment analysis(GSEA)and gene set variation analysis(GSVA)were conducted on the most significant genes; the expression levels of these genes were validated using the GSE2378 and GSE9944 datasets obtained from the optic nerve head.RESULTS: In comparison to normal trabecular meshwork tissue, a total of 396 ferroptosis genes exhibited differential expression in POAG trabecular meshwork tissue. Among these, 39 genes were up-regulated while 64 genes were down-regulated. Spearman correlation analysis revealed certain correlation between the up-regulated genes and the down-regulated genes. The GO function and KEGG pathway enrichment analysis revealed that the differential genes were primarily enriched in the oxidative stress response and ferroptosis pathways. A total of 18 DE-FRGs were identified as key genes using LASSO and SVM-RFE algorithms, which demonstrated a higher diagnostic value. GSEA and GSVA revealed a significant association between GDF15, MFN2, and OTUB1 genes with the glutathione metabolic pathway. Moreover, it was observed that MFN2 activated the glutathione metabolic pathway in the high expression group, while OTUB1 activated it in the low expression group. The cross-validation of GSE2378 and GSE9944 datasets revealed a significant increase in the expression level of CREB1 in optic nerve specimens compared to normal optic nerve specimens, and it was consistent with the expression observed in trabecular meshwork samples from the GSE27276 dataset.CONCLUSION: Based on bioinformatics analysis, a total of 396 DE-FRGs were identified in POAG. By constructing a machine screening model and cross-validation of external datasets, CREB1 is expected to be the best characteristic gene for potential diagnostic biomarker, and provide targets for further elucidating the molecular mechanism and the diagnosis of ferroptosis in POAG. However, further in vivo and in vitro validation is required to elucidate the biological mechanism of ferroptosis in POAG.

Objective: To compare the clinical characteristics of different types of human adenovirus (HAdV) infection in hospitalized children with acute respiratory infection in Beijing, and to clarify the clinical necessity of adenovirus typing. Methods: In a cross-sectional study, 9 022 respiratory tract specimens collected from hospitalized children with acute respiratory infection from November 2017 to October 2019 in Affiliated Children's Hospital, Capital Institute of Pediatrics were screened for HAdV by direct immunofluorescence (DFA) and (or) nucleic acid detection. Then the Penton base, Hexon and Fiber gene of HAdV were amplified from HAdV positive specimens to confirm their HAdV types by phylogenetic tree construction. Clinical data such as laboratory results and imaging data were analyzed for children with predominate type HAdV infection using t, U, or χ² test. Results: There were 392 cases (4.34%) positive for HAdV among 9 022 specimens from hospitalized children with acute respiratory infection. Among those 205 cases who were successfully typed, 131 were male and 74 were female, age of 22.6 (6.7, 52.5) months,102 cases (49.76%) were positive for HAdV-3 and 86 cases (41.95%), HAdV-7, respectively, while 17 cases were confirmed as HAdV-1, 2, 4, 6, 14 or 21. In comparison of clinical characteristics between the predominate HAdV type 7 and 3 infection, significant differences were shown in proportions of children with wheezing (10 cases (11.63%) vs. 25 cases (24.51%)), white blood cell count >15 ×10⁹/L (4 cases (4.65%) vs.14 cases (13.73%)), white blood cell count <5×10⁹/L (26 cases (30.23%) vs.11 cases (10.78%)), procalcitonin level>0.5 mg/L (43 cases (50.00%) vs. 29 cases (28.43%)), multilobar infiltration (45 cases (52.33%) vs.38 cases (37.25%)), pleural effusion (23 cases (26.74%) vs. 10 cases (9.80%)), and severe adenovirus pneumonia (7 cases (8.14%) vs. 2 cases (1.96%)) with χ²=5.11, 4.44, 11.16, 9.19, 4.30, 9.25, 3.91 and P=0.024, 0.035, 0.001, 0.002, 0.038, 0.002, 0.048, respectively, and also in length of hospital stay (11 (8, 15) vs. 7 (5, 13) d, Z=3.73, P<0.001). Conclusions: HAdV-3 and 7 were the predominate types of HAdV infection in hospitalized children with acute respiratory tract infection in Beijing. Compared with HAdV-3 infection, HAdV-7 infection caused more obvious inflammatory reaction, more severe pulmonary symptoms, longer length of hospital stay, suggesting the clinical necessity of further typing of HAdVs.
Adenovirus Infections, Human/epidemiology* ; Adenoviruses, Human/genetics* ; Beijing/epidemiology* ; Child ; Child, Hospitalized ; Cross-Sectional Studies ; Female ; Humans ; Infant ; Male ; Phylogeny ; Respiratory Tract Infections/epidemiology*

On December 22, 2017, a 35-year-old male hemophilia A patient with a secondary chronic refractory wound after left knee joint surgery was transferred from the Department of Hematology of Maoming People's Hospital to the Department of Burns and Plastic Surgery in the same hospital. The physical examination revealed that the patient's left knee joint was swollen, with a full-thickness skin defect wound of 4 cm×4 cm on the lateral side of the joint and a large number of dark red blood clots at the bottom of the wound. The wound bleeding was controlled by intravenous infusion of plasma, cryoprecipitate, and human coagulation factor Ⅷ. After con- ventional debridement and dressing changes until the wound infection was controlled and necrotic tissue was removed, a subcutaneous cavity wound of 2 cm×2 cm in area and 3 cm in depth remained in the left knee joint and was difficult to heal. Nineteen days after transfer, the patient received autologous platelet-rich plasma (PRP) treatment, and 32 days after PRP treatment, the wound in left knee joint was healed with epithelialization. This case suggests that autologous PRP therapy would be a good option for hemophilia complicated chronic refractory wounds when they could not be repaired by surgery.
Adult ; Hemophilia A/therapy* ; Humans ; Knee Joint/surgery* ; Male ; Platelet-Rich Plasma ; Skin Transplantation ; Soft Tissue Injuries/surgery* ; Treatment Outcome ; Wound Healing

OBJECTIVE: To explore the association between postpartum depression (PPD) and transforming growth factor-β (TGF-β) concentrations in human colostrum. METHODS: Participants were recruited from a maternal and infant cohort established in a tertiary general hospital in Guangdong Province between December, 2020 and September, 2021. In the afternoon of the second postpartum day, the women were evaluated with Edinburgh Postnatal Depression Scale (EPDS) for screening PPD (defined as a score of 10 or higher). The women with PPD were matched at a 1:1 ratio with women without PPD with maternal age difference within 5 years and the same mode of delivery. Colostrum samples were collected in morning on the third postpartum day for measurement of TGF-β concentrations using enzyme-linked immunosorbent assay (ELISA), and the association between EPDS scores and TGF-β concentrations was analyzed in the two groups. RESULTS: A total of 90 women were included in the final analysis. The mean concentrations of TGF-β1, TGF-β2 and TGF-β3 in the colostrum were 684.03 (321.22-859.25) pg/mL, 5116.50±1747.04 pg/mL and 147.84±48.68 pg/mL in women with PPD, respectively, as compared with 745.67 (596.00-964.22) pg/mL, 4912.40±1516.80 pg/mL, and 168.21±48.15 pg/mL in women without PPD, respectively. Compared with women without PPD, the women with PPD had significantly lower concentrations of TGF-β1 (P=0.026) and TGF-β3 (P=0.049) in the colostrum. Spearman correlation analysis revealed that the EPDS scores were negatively associated with the concentrations of TGF-β1 (r=-0.23, P=0.03) and TGF-β3 (r=-0.25, P=0.02) in the colostrum. CONCLUSION PPD is associated with decreased concentrations of TGF-β1 and TGF-β3 in human colostrum, suggesting the need of early PPD screening and interventions during pregnancy and the perinatal period to minimize the impact of PPD on human milk compositions.
Child, Preschool ; Cohort Studies ; Colostrum ; Depression, Postpartum/diagnosis* ; Female ; Humans ; Infant ; Postpartum Period ; Pregnancy ; Transforming Growth Factor beta1 ; Transforming Growth Factor beta2 ; Transforming Growth Factor beta3 ; Transforming Growth Factors