The 2-(2-phenylethyl)chromones were separated from agarwood of Aquilaria agallocha Roxb. and their anti-KRAS mutant non-small cell lung cancer (NSCLC) activities were evaluated. 2-(2-Phenyethyl)chromones in agarwood were separated and purified by silica gel, RP-18 reverse phase silica gel, MCI gel CH20P, Diol, and semi preparative HPLC chromatography techniques, while the structures of the compounds were identified by extensive spectroscopic analysis, such as 1D and 2D NMR and ESI-MS. The cell counting kit 8 (CCK-8) assay was used to screen the anti-tumor activity of the isolated monomeric compounds on three KRAS-mutant NSCLC cells. The cell proliferation, cloning formation, adhesion ability, and cell cycle arrest activity of compound 8 were analyzed. Molecular docking and Western blot experiments were used to study the mechanism of compound 8. The in vivo anti-tumor activity of the compound 8 was evaluated by zebrafish cell derived xenograft (CDX) model. Nineteen known 2-(2-phenylethyl)chromones were isolated from the ethyl acetate extract of agarwood. On A549 (KRAS G12S) cells, compounds 8, 10, and 19 showed good inhibitory activity, on H23 (KRAS G12C) cells, compounds 7, 8, and 19 showed good inhibitory activity, and on H358 (KRAS G12C) cells, compounds 8, 10, and 16 showed good inhibitory activity. Compound 8 had the best inhibitory activity in all three cell lines. It effectively inhibited cell proliferation, clone formation, adhesion ability, and arrested the H23 cell cycle at G2/M phase. Compound 8 could also inhibit the expression of c-Met and its downstream signaling pathways, effectively inhibiting tumor growth in zebrafish CDX model. In conclusion, among the nineteen known 2-(2-phenylethyl)chromones, compound 8 had the best activity and significantly inhibited the proliferation of KRAS-mutant NSCLC cells by arresting the cells in the G2/M phase.

Objective To explore the relationship between the status of infarct related artery(IRA)occlusion and thrombus types in patients with non-ST-segment elevation myocardial infarction(NSTEMI)using optical coherence tomography(OCT).Methods A total of 170 NSTEMI patients who underwent emergency percutaneous coronary intervention at Henan Provincial People1s Hospital from October 2021 to August 2023 and underwent OCT examination were included in the study.Among them,83 cases were in the total occlusion group and 87 cases were in the non-total occlusion group.The baseline characteristics,coronary angiography findings,and OCT results of the patients were compared and analyzed.Results Compared with the non-total occlusion group,the patients in the total occlusion group were more younger(P=0.013),the proportion of male was higher(P=0.026),and the proportion of patients with hypertension(P=0.010)and diabetes(P=0.033)was lower.In the total occlusion group,left circumflex artery(LCX)served as the main IRA,whereas in the non-total occlusion group,left anterior descending(LAD)was the predominant IRA(P=0.012);In addition,there was a significantly higher occurrence of rentrop grade Ⅱ～Ⅲ in the total occlusion group compared to the non-total occlusion group(P=0.022).The OCT results showed that in most cases,the total occlusion group was caused by plaque rupture events(P=0.014),mainly red/mixed thrombus(P＜0.001);The non-total occlusion group was more commonly associated with plaque erosion events(P=0.014),with white thrombus being the main cause(P＜0.001).Conclusions Total occlusion of infarct-related artery in NSTEMI patients often occurs in the LCX,and the patient is more younger,the thrombus type is mainly red/mixed thrombus,while non-total occlusion lesions are mainly white thrombus.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Glioblastoma is the most common primary cranial malignancy, and chemotherapy remains an important tool for its treatment. Sanggenon C(San C), a class of natural flavonoids extracted from Morus plants, is a potential antitumor herbal monomer. In this study, the effect of San C on the growth and proliferation of glioblastoma cells was examined by methyl thiazolyl tetrazolium(MTT) assay and 5-bromodeoxyuridinc(BrdU) labeling assay. The effect of San C on the tumor cell cycle was examined by flow cytometry, and the effect of San C on clone formation and self-renewal ability of tumor cells was examined by soft agar assay. Western blot and bioinformatics analysis were used to investigate the mechanism of the antitumor activity of San C. In the presence of San C, the MTT assay showed that San C significantly inhibited the growth and proliferation of tumor cells in a dose and time-dependent manner. BrdU labeling assay showed that San C significantly attenuated the DNA replication activity in the nucleus of tumor cells. Flow cytometry confirmed that San C blocked the cell cycle of tumor cells in G_0/G_1 phase. The soft agar clone formation assay revealed that San C significantly attenuated the clone formation and self-renewal ability of tumor cells. The gene set enrichment analysis(GSEA) implied that San C inhibited the tumor cell division cycle by affecting the myelocytomatosis viral oncogene(MYC) signaling pathway. Western blot assay revealed that San C inhibited the expression of cyclin through the regulation of the MYC signaling pathway by lysine demethylase 4B(KDM4B), which ultimately inhibited the growth and proliferation of glioblastoma cells and self-renewal. In conclusion, San C exhibits the potential antitumor activity by targeting the KDM4B-MYC axis to inhibit glioblastoma cell growth, proliferation, and self-renewal.
Humans ; Glioblastoma/genetics* ; Bromodeoxyuridine/therapeutic use* ; Signal Transduction ; Proto-Oncogene Proteins c-myc/metabolism* ; Agar ; Cell Proliferation ; Cell Line, Tumor ; Apoptosis ; Jumonji Domain-Containing Histone Demethylases/metabolism*

Pulmonary fibrosis is end-stage of variety of heterogeneous interstitial lung disease, characterizedby excessive proliferation of fibroblasts and extracellular matrix deposition and destruction of lung parenchyma. Thyroid and lung are derived from the same endodermal cells, thyroid hormone affect the occurrence、development and prognosis of the chronic obstructive pulmonary disease, lung cancer and other lung diseases, This article reviews the role and mechanism of thyroid hormone in pulmonary fibrosis in order to provide new idea for the study of the role and mechanism of thyroid hormone in silicosis.
Humans ; Pulmonary Fibrosis/pathology* ; Lung/pathology* ; Silicosis ; Lung Diseases, Interstitial ; Fibroblasts ; Thyroid Hormones ; Fibrosis

Natural products are an important source for the development of antitumor lead compounds, but the pharmacological effects and regulatory mechanisms of natural products in osimertinib resistance in non-small cell lung cancer (NSCLC) are not well understood. The natural product ligustroflavone was used as the research object to analyze its efficacy in osimertinib-resistant NSCLC cells by cell proliferation assay and cell cycle detection. The potential targets of ligustroflavone in osimertinib-resistant NSCLC cells were screened by public databases and bioinformatics, molecular docking and microscale thermophoresis were used to identify the interaction between privet and target molecules. Western blot was used to detect the effect of privet on the target molecules and their downstream pathways. Ligustroflavone reduced the proliferation of osimertinib-resistant NSCLC cells, and could arrest the cell cycle. Cyclin-dependent kinase 6 (CDK6) was the potential target of ligustroflavone in osimertinib-resistant NSCLC cells. Ligustroflavone inhibited the activation of CDK6-Rb axis. Together, ligustroflavone could regulate osimertinib resistance in NSCLC cells by binding cell cyclin-related molecules. This study provides a theoretical basis for the targeted drug resistance of NSCLC with natural products, and also provides a new idea for the development of clinical drug combination.

Objective:To summarize and sort out the best evidence for sleep disorders management in children with autism spectrum disorder.Methods:Literatures related to sleep disorders management in children with autism spectrum disorder were systematically retrieved on UpToDate, BMJ Best Practice, National Guidelines Clearinghouse, Registered Nurses' Association of Ontario, Scottish Intercollegiate Guidelines Network, National Institute for Health and Clinical Excellence, Guidelines International Network, World Health Organization website, Medlive, Joanna Briggs Institute evidence-based healthcare center database, Web of Science, Cochrane Library, PubMed, Embase, CINAHL, PsychInfo, China Biology Medicine disc, Wanfang Database, CNKI, VIP, Association for Science in Autism Treatment website, Autism Society website, National Autism Society website and other domestic and foreign databases and websites. Literature types included guidelines, systematic review/Meta-analysis, evidence summary, clinical decision making and expert consensus. The search deadline was from the establishment of the databases to November 30, 2022. Two researchers trained in systematic evidence-based knowledge evaluated literature quality and extracted evidence.Results:A total of 14 literatures were included, including 1 clinical decision, 4 guidelines, 7 expert consensus and 2 systematic reviews. A total of 32 pieces of evidence were formed from 8 aspects, including screening, assessment, sleep planning, treatment goals, intervention, follow-up, caregiver support and team management of children with autism spectrum disorder.Conclusions:This study summarizes and forms the best evidence on the management of sleep disorders in children with autism spectrum disorder, and provides an evidence-based basis for the management of sleep disorders in them.

Objective: To investigate the incidence and trend of short-term outcomes among preterm infants born <34 weeks' gestation. Methods: A secondary analysis of data from the standardized database established by a multicenter cluster-randomized controlled study "reduction of infection in neonatal intensive care units (NICU) using the evidence-based practice for improving quality (REIN-EPIQ) study". This study was conducted in 25 tertiary NICU. A total of 27 192 infants with gestational age <34 weeks at birth and admitted to NICU within the first 7 days of life from May 2015 to April 2018 were enrolled. Infants with severe congenital malformation were excluded. Descriptive analyses were used to describe the mortality and major morbidities of preterm infants by gestational age groups and different admission year groups. Cochran-Armitage test and Jonckheere-Terpstra test were used to analyze the trend of incidences of mortality and morbidities in 3 study-years. Multiple Logistic regression model was constructed to analyze the differences of outcomes in 3 study-years adjusting for confounders. Results: A total of 27 192 preterm infants were enrolled with gestational age of (31.3±2.0) weeks at birth and weight of (1 617±415) g at birth. Overall, 9.5% (2 594/27 192) of infants were discharged against medical advice, and the overall mortality rate was 10.7% (2 907/27 192). Mortality for infants who received complete care was 4.7% (1 147/24 598), and mortality or any major morbidity was 26.2% (6 452/24 598). The incidences of moderate to severe bronchopulmonary dysplasia, sepsis, severe intraventricular hemorrhage or periventricular leukomalacia, proven necrotizing enterocolitis, and severe retinopathy of prematurity were 16.0% (4 342/27 192), 11.9% (3 225/27 192), 6.8% (1 641/24 206), 3.6% (939/25 762) and 1.5% (214/13 868), respectively. There was a decreasing of the overall mortality (P<0.001) during the 3 years. Also, the incidences for sepsis and severe retinopathy of prematurity both decreased (both P<0.001). However, there were no significant differences in the major morbidity in preterm infants who received complete care during the 3-year study period (P=0.230). After adjusting for confounders, infants admitted during the third study year showed significantly lower risk of overall mortality (adjust OR=0.62, 95%CI 0.55-0.69, P<0.001), mortality or major morbidity, moderate to severe bronchopulmonary dysplasia, sepsis and severe retinopathy of prematurity, compared to those admitted in the first study year (all P<0.05). Conclusions: From 2015 to 2018, the mortality and major morbidities among preterm infants in Chinese NICU decreased, but there is still space for further efforts. Further targeted quality improvement is needed to improve the overall outcome of preterm infants.
Bronchopulmonary Dysplasia/epidemiology* ; Gestational Age ; Humans ; Infant ; Infant Mortality/trends* ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases/epidemiology* ; Patient Discharge ; Retinopathy of Prematurity/epidemiology* ; Sepsis/epidemiology*

Morus alba, a traditional economic crop, is also a significant medicinal plant. The branches(Mori Ramulus), leaves(Mori Folium), roots and barks(Mori Cortex), and fruits(Mori Fructus) of M. alba are rich in chemical components, such as alkaloids, flavonoids, flavanols, anthocyanins, benzofurans, phenolic acids, and polysaccharides, and possess hypoglycemic, hypolipidemic, anti-inflammatory, anti-tumor, anti-microbial, liver protective, immunoregulatory, and other pharmacological activities. This study analyzed the sources, classification, and functions of the main chemical components in M. alba and systematically summarized the latest research results of essential active components in M. alba and their pharmacological effects to provide references for in-depth research and further development as well as utilization of active components in M. alba.
Anthocyanins ; Flavonoids/pharmacology* ; Morus ; Plant Extracts/pharmacology* ; Plant Leaves

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome