The compound (E)-1-(4-(3-(5-chloro-6-oxo-3,6-dihydropyridin-1(2H)-yl)-3-oxo-propyl-1-ene-1-yl) phenyl)-3-(4-fluorophenyl) urea (C12), a novel derivative of piperlongumine previously synthesized by our research group, was investigated in this study to examine its effects on human non-small cell lung cancer cell line H1299 in vitro and elucidate its potential mechanism of action. The impact of C12 on the proliferation, migration, and invasion abilities of H1299 cells were assessed using methyl thiazolyl tetrazolium (MTT) assay, wound healing assay, cloning formation assay, and Transwell assay. Flow cytometry was employed to evaluate the influence of C12 on cell cycle progression, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), and apoptosis induction in H1299 cells. Western blot analysis was conducted to investigate the expression levels of p21, Cyclin B1, CDK1, Bax, Bcl-2, JNK, p-JNK, Erk1/2, p-Erk1/2, p38 and p-p38 proteins for exploring the anti-tumor mechanism underlying C12's actions. The results demonstrated that C12 exerted inhibitory effects on the proliferation, migration, and invasion capacities of H1299 cells in a time-dependent and concentration-dependent manner. Moreover, C12 induced G2/M phase arrest in the cell cycle, reduced MMP levels, elevated ROS production, and triggered apoptotic processes. Flow cytometry analysis revealed that C12 downregulated Cyclin B1 and CDK1 protein expressions, resulting in G2/M phase arrest. C12 also upregulated Bax/Bcl-2 ratio, promoting apoptosis. Furthermore, C12 activated MAPK signaling pathway by enhancing phosphorylation levels of JNK, Erk1/2, and p38 proteins. In conclusion, C12 significantly suppressed proliferation, migration, and invasion capabilities while inducing cell cycle arrest and apoptosis in H1299 cells. These effects may be attributed to activation of the MAPK signaling pathway.

Pharmacokinetics of traditional Chinese medicine(TCM)is a discipline that adopts pharmacokinetic research methods and techniques under the guidance of TCM theories to elucidate the dynamic changes in the absorption,distribution,metabolism and excretion of active ingredients,active sites,single-flavour Chinese medicinal and compounded formulas of TCM in vivo.However,the sources and components of TCM are complex,and the pharmacodynamic substances and mechanisms of action of the majority of TCM are not yet clear,so the pharmacokinetic study of TCM is later than that of chemical medicines,and is far more complex than that of chemical medicines,and its development also confronts with challenges.The pharmacokinetic study of TCM originated in the 1950s and has experienced more than 70 years of development from the initial in vivo study of a single active ingredient,to the pharmacokinetic and pharmacodynamic study of active ingredients,to the pharmacokinetic study of compound and multi-component of Chinese medicine.In recent years,with the help of advanced extraction,separation and analysis technologies,gene-editing animals and cell models,multi-omics technologies,protein purification and structure analysis technologies,and artificial intelligence,etc.,the pharmacokinetics of TCM has been substantially applied in revealing and elucidating the pharmacodynamic substances and mechanisms of action of Chinese medicines,research and development of new drugs of TCM,scientific and technological upgrading of large varieties of Chinese patent medicines,as well as guiding the rational use of medicines in clinics.Pharmacokinetic studies of TCM have made remarkable breakthroughs and significant development in theory,methodology,technology and application.In this paper,the history of the development of pharmacokinetics of TCM and the progress of cutting-edge research was reviewed,with the aim of providing ideas and references for the pharmacokinetics of TCM and related research.

Objective To assess the nutritional status and dietary quality of medical students and its influencing factors.Methods Students from Shanghai Medicial College of Fudan University were recruited to complete the 7-day and 24-hour dietary records,with food consumption measured by weight.A comprehensive evaluation of the students'dietary quality was carried out by comparing their actual nutrient intake against recommended levels and calculating the component score of the Chinese Healthy Eating Index(CHEI).Factor analysis was used to extract dietary patterns.All subjects were further divided into high score group and low score group based on total CHEI.Binary Logistic regression was used to determine the factors influencing dietary quality.Results The study participants had an average daily energy intake of(2 057.02±501.87)kcal/d,80%from on-campus canteen meals.Carbohydrates,proteins and fats contributed to 48.90%,16.55%and 36.07%of the total energy intake,respectively.The CHEI median score was 67.55.Component scores for tubers,vegetables,fruits,dairy,fish and seafood,and nuts were below 60%,indicating an unbalanced diet.Being in the graduate stage(OR=0.53,95%CI:0.28-0.98)and having unreasonable body weight expectations(OR=0.37,95%CI:0.17-0.81)were associated with lower CHEI scores.Conversely,higher CHEI scores were associated with the fruit-dairy dietary pattern(OR=8.20,95%CI:3.39-19.84),the tuber-vegetable dietary pattern(OR=3.41,95%CI:1.58-7.32),and lower rates of on-campus dining(OR=1.92,95%CI:1.02-3.59).Conclusion The energy intake of students at Shanghai Medical College of Fudan University appears to be adequate.However,a relatively high proportion of energy supply from fat intake indicates a need for improvement in their dietary structure.The dietary quality of students is mainly influenced by their educational level,weight expectations and dietary patterns.

Objective:To study the reversal effect of NVP-BEZ235 on doxorubicin resistance in Burkitt lymphoma RAJI cell line.Methods:The doxorubicin-resistant cell line was induced by treating RAJI cells with a concentration gradient of doxorubicin.The levels of Pgp,p-AKT,and p-mTOR in cells were detected by Western blot.Cell viability was detected by MTT assay.IC50 was computed by SPSS.Results:The doxorubicin-resistant Burkitt lymphoma cell line,RAJI/DOX,was established successfully.The expression of Pgp and the phosphorylation levels of AKT and mTOR in RAJI/DOX cell line were both higher than those in RAJI cell line.NVP-BEZ235 downregulated the phosphorylation levels of AKT and mTOR in RAJI/DOX cell line.NVP-BEZ235 inhibited the proliferation of RAJI/DOX cell line,and the effect was obvious when it was cooperated with doxorubicin.Conclusion:The constitutive activation of PI3K/AKT/mTOR pathway of RAJI/DOX cell line was more serious than RAJI cell line.NVP-BEZ235 reversed doxorubicin resistance of RAJI/DOX cell line by inhibiting the PI3K/AKT/mTOR signal pathway.

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.

Objective:To investigate the efficacy of different doses of bortezomib combined with chemotherapy for multiple myeloma (MM).Methods:A prospective case series study was performed. A total of 81 MM patients at Leshan People's Hospital from February 2022 to May 2023 were collected as study subjects. According to the random number table method, patients were divided into high-dose bortezomib group (39 cases treated with 1.6 mg/m 2 bortezomib combined with dexamethasone and thalidomide) and low-dose bortezomib group (42 cases treated with 1.3 mg/m 2 bortezomib combined with dexamethasone and thalidomide). The clinical efficacy after 4 courses of treatment, adverse reactions, C-reactive protein (CRP), β 2 microglobulin (β 2-MG) and serum creatinine levels before and after treatment, survival and prognosis of patients in both groups were compared. Results:There were 29 males and 10 females in the high-dose bortezomib group and the age was (59±5) years; there were 31 males and 11 females in the low-dose bortezomib group and the age was (59±6) years. The differences in the general data of both groups were statistically significant (all P > 0.05). The overall effectiveness rate was 87.2% (34/39) and 80.9% (34/42), respectively in the high-dose bortezomib group and the low-dose bortezomib group, and the difference was not statistically significant of both groups ( χ2 = 0.58, P = 0.446). The incidence rate of adverse reactions was 30.8% (12/39), 19.0% (8/39), respectively in the high-dose bortezomib group and the low-dose bortezomib group, and the difference was not statistically significant of both groups ( χ2 = 1.49, P = 0.222). Before treatment, there were no statistically significant differences in the levels of CRP, β 2-MG and serum creatinine between the 2 groups (all P > 0.05); after treatment, there were statistically significant differences in the levels of CRP [(23.6±2.2) g/L vs. (31.5±3.6) g/L)], β 2-MG [(2 317±63) μg/L vs. (4 212±114) μg/L] and serum creatinine [(70±5) μmol/L vs. (79±7) μmol/L] in the high-dose bortezomib group and the low-dose bortezomib group ( t value was 4.28, 18.29, 4.00, all P<0.05); and the levels of above 3 indicators after treatment were lower than those before treatment of both groups (all P < 0.05). The mortality rate was 10.3% (4/39) and 14.3% (6/42), respectively in the high-dose bortezomib group and the low-dose bortezomib group 1-year follow-up after treatment, and the difference was not statistically significant ( χ2 = 0.30, P = 0.582). Conclusions:The efficacy and safety of high-dose bortezomib combined with chemotherapy are comparable to those of low-dose bortezomib combined with chemotherapy in treatment of MM, while the former could improve renal function and inflammatory status of MM patients.

Hip fracture is considered as the most severe osteoporotic fracture characterized by high disability and mortality in the elderly. Improved surgical techniques and multidisciplinary team play an active role in alleviating prognosis, which places higher demands on perioperative nursing. Dysfunction, complications, and secondary impact of anaesthesia and surgery add more difficulties to clinical nursing. Besides, there still lack clinical practices in perioperative nursing for elderly patients with hip fracture in China. In this context, led by the Orthopedic Nursing Committee of Chinese Nursing Association, the Expert consensus on clinical practice in perioperative nursing for elderly patients with hip fracture ( version 2023) is developed based on the evidence-based medicine. This consensus provides 11 recommendations on elderly patients with hip fracture from aspects of perioperative health education, condition monitoring and inspection, complication risk assessment and prevention, and rehabilitation, in order to provide guiding advices for clinical practice, improve the quality of nursing and ameliorate the prognosis of elderly patients with hip fracture.

BACKGROUND: Myocardial ischemia-reperfusion (I/R) is a serious and irreversible injury. Bone marrow-derived mesenchymal stem cells (MSCs) is considered to be a potential therapy for I/R injury due to the paracrine effects. High-mobility group box 1 (HMGB1) is a novel mediator in MSC and regulates the response of inflammation injury. Signal Transduction and Transcription Activator 3 (STAT3) is a critical transcription factor and important for release of paracrine factors. However, the relationship between HMGB1 and STAT3 in paracrine effect of MSC remains unknown. METHODS: In vitro, hypoxia/reoxygenation injury model was established by AnaeroPack System and examined by Annexin V flow cytometry, CCK8 assay and morphology observation. Detection of apoptotic proteins and protein expression of HMGB1 and STAT3 by Western blot. RESULTS: The conditioned medium of MSCs with or without LPS pretreatment was cocultured with H9C2 cells for 24 h before hypoxia treatment and MSC showed obvious cardiomyocytes protect role, as evidence by decreased apoptosis rate and improved cells viability, and LPS pretreated MSC exhibited better protect role than untreated MSC. However, such effect was abolished in HMGB1 deficiency group, silencing HMGB1 decreased the secretion of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), insulin growth factor (IGF), cell viability, and the expression of STAT3. Furthermore, STAT3 silence attenuated the protective effect of LPS in MSC. CONCLUSIONS These findings suggested that LPS improved MSC-mediated cardiomyocytes protection by HMGB1/STAT3 signaling.

italic>Artemisia argyi (A. argyi) is a Chinese herbal medicine in China. The main active components are volatile oils, flavonoids, and other compounds, which have various pharmacological activities. Methoxylated flavonoids are the main active ingredients in A. argyi. Flavonoid O-methyltransferase (FOMT) is a key enzyme in the O-methylation of flavonoids. In order to further understand the function and characteristics of FOMT proteins, this paper carried out the whole genome mining and identification of FOMT genes in A. argyi and performed phylogenetic, chromosomal localization, gene sequence characterization, subcellular localization prediction, protein structure, gene structure analysis, and expression pattern analysis. The results showed that a total of 83 FOMT genes were identified in the genome of A. argyi. The phylogenetic tree shows that FOMT genes are divided into two subgroups, CCoAOMT (caffeoyl CoA O-methyltransferase) subfamily (32 genes) and COMT (caffeic acid O-methyltransferase) subfamily (51 genes). Gene sequence analysis showed that the number of amino acids encoded by FOMT was 70-734 aa, the molecular weight was 25 296.55-34 241.3 Da, and the isoelectric point was 4.51-9.99. Compared with 32 members of the CCoAOMT subfamily, nearly 1/3 of the 51 members of the COMT subfamily were hydrophobic proteins and 2/3 were hydrophilic proteins. Subcellular localization prediction showed that more than 80% of CCoAOMT subfamily members were located in the cytoplasm, and 96% of COMT subfamily members were located in the chloroplast. COMT subfamily members have more motifs than CCoAOMT subfamily members. The N-terminal motifs of COMT subfamily proteins are relatively variable, while the C-terminal motifs are relatively conserved. Expression pattern analysis showed that CCoAOMT subfamily members were mainly expressed in roots, while COMT members were mainly expressed in leaves. Some FOMTs showed the tissue expression specificity by real-time quantitative PCR analysis, especially in leaves. In this study, we identified and analyzed the FOMT gene family in A. argyi, and provided a theoretical basis for further research on the function of FOMTs and the biosynthesis of methylated flavonoids in A. argyi.

Human-animal parasitic diseases caused by medical helminths are hazardous to human health. Genetic polymorphism studies on medical helminth populations can not only understand the biological characteristics and genetic structure of their populations, but also help reveal how they adapt to their parasitic environment, thus contributing to deepen our understanding of the epidemiological patterns of parasitic diseases and improve our understanding of accurate prevention and control of parasitic diseases. With the development of molecular biology, molecular markers such as DNA barcodes, simple sequence repeats, and single nucleotide polymorphism markers have been widely used to study the genetic relationships among parasite populations and individuals, and to reveal the genetic variation of parasite populations and the evolution of species origins. In this paper, we systematically review the application of three molecular markers commonly used in the study of genetic polymorphism in medical helminths, with a view to laying the foundation for related research.