Objective To evaluate the bioequivalence and safety of ezetimibe tablets in healthy Chinese subjects.Methods The study was designed as a single-center,randomized,open-label,two-period,two-way crossover,single-dose trail.Subjects who met the enrollment criteria were randomized into fasting administration group and postprandial administration group and received a single oral dose of 10 mg of the subject presparation of ezetimibe tablets or the reference presparation per cycle.The blood concentrations of ezetimibe and ezetimibe-glucuronide conjugate were measured by high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS),and the bioequivalence of the 2 preparations was evaluated using the WinNonlin 7.0 software.Pharmacokinetic parameters were calculated to evaluate the bioequivalence of the 2 preparations.The occurrence of all adverse events was also recorded to evaluate the safety.Results The main pharmacokinetic parameters of total ezetimibe in the plasma of the test and the reference after a single fasted administration:Cmax were(118.79±35.30)and(180.79±51.78)nmol·mL-1;tmax were 1.40 and 1.04 h;t1/2 were(15.33±5.57)and(17.38±7.24)h;AUC0-t were(1 523.90±371.21)and(1 690.99±553.40)nmol·mL-1·h;AUC0-∞ were(1 608.70±441.28),(1 807.15±630.00)nmol·mL-1·h.The main pharmacokinetic parameters of total ezetimibe in plasma of test and reference after a single meal:Cmax were(269.18±82.94)and(273.93±87.78)nmol·mL-1;Tmax were 1.15 and 1.08 h;t1/2 were(22.53±16.33)and(16.02±5.84)h;AUC0_twere(1 463.37±366.03),(1 263.96±271.01)nmol·mL-1·h;AUC0-∞ were(1 639.01±466.53),(1 349.97±281.39)nmol·mL-1·h.The main pharmacokinetic parameters Cmax,AUC0-tand AUC0-∞ of the two preparations were analyzed by variance analysis after logarithmic transformation.In the fasting administration group,the 90％CI of the log-transformed geometric mean ratios were within the bioequivalent range for the remaining parameters in the fasting dosing group,except for the Cmax of ezetimibe and total ezetimibe,which were below the lower bioequivalent range.The Cmax of ezetimibe,ezetimibe-glucuronide,and total ezetimibe in the postprandial dosing group was within the equivalence range,and the 90％CI of the remaining parameters were not within the equivalence range for bioequivalence.Conclusion This test can not determine whether the test preparation and the reference preparation of ezetimibe tablets have bioequivalence,and further clinical trials are needed to verify it.

Non-communicable diseases(NCDs),including cardiovascular diseases,cancer,metabolic diseases,and skeletal diseases,pose significant challenges to public health worldwide.The complex pathogenesis of these diseases is closely linked to oxidative stress and inflammatory damage.Nuclear factor erythroid 2-related factor 2(Nrf2),a critical transcription factor,plays an important role in regulating antioxidant and anti-inflammatory responses to protect the cells from oxidative damage and inflammation-mediated injury.Therefore,Nrf2-targeting therapies hold promise for preventing and treating NCDs.Quercetin(Que)is a widely available flavonoid that has significant antioxidant and anti-inflammatory properties.It modulates the Nrf2 signaling pathway to ameliorate oxidative stress and inflammation.Que modulates mitochondrial function,apoptosis,autophagy,and cell damage biomarkers to regulate oxidative stress and inflammation,highlighting its efficacy as a therapeutic agent against NCDs.Here,we discussed,for the first time,the close association between NCD pathogenesis and the Nrf2 signaling pathway,involved in neurodegenerative diseases(NDDs),cardiovascular disease,cancers,organ damage,and bone damage.Furthermore,we reviewed the availability,pharmacokinetics,pharmaceutics,and therapeutic applica-tions of Que in treating NCDs.In addition,we focused on the challenges and prospects for its clinical use.Que represents a promising candidate for the treatment of NCDs due to its Nrf2-targeting properties.

A boy,aged 7 months,presented with severe global developmental delay(GDD),refractory epilepsy,hypotonia,nystagmus,ocular hypertelorism,a broad nasal bridge,everted upper lip,a high palatal arch,and cryptorchidism.Genetic testing revealed a de novo heterozygous missense mutation of c.364G>A(p.E122K)in the EEF1A2 gene,and finally the boy was diagnosed with autosomal dominant developmental and epileptic encephalopathy 33 caused by the EEF1A2 gene mutation.This case report suggests that for children with unexplained infancy-onset severe to profound GDD/intellectual disability and refractory epilepsy,genetic testing for EEF1A2 gene mutations should be considered.This is particularly important for those exhibiting hypotonia,nonverbal communication,and craniofacial deformities,to facilitate a confirmed diagnosis.

Objective To investigate the health education needs and available resources in schistosomiasis-endemic areas based on integration of community resources, and to explore the operation pathways for health education and promotion during the stage of schistosomiasis elimination. Methods A community was selected from Nanji Township, Xinjian District, Nanchang City, Jiangxi Province around the Poyang Lake areas as the study site, and a questionnaire survey on health education needs for schistosomiasis control was conducted among permanent residents at ages of 20 years in the community during the period between June and July, 2022 using face-to-face interviews. In addition, the resources available for the community-based schistosomiasis control health education were investigated among workers in township-level specialized institutions, members of civil society organizations, villagers, teachers and high and primary school students through field observations, field surveys and thematic interviews. Results A total of 304 individuals participated in the questionnaire survey on community-based health education needs for schistosomiasis control, and 94.41% (287/304) and 93.42% (284/304) of the respondents were most interested in knowing/understanding knowledge of the morphology of schistosomes and knowledge associated with the transmission route of schistosomiasis. The four most popular patterns for disseminating schistosomiasis control knowledge included live broadcasting of schistosomiasis control videos (94.41%, 287/304), printed brochures (89.80%, 273/304), special lectures by doctors (62.50%, 190/304) and physical health education materials for schistosomiasis control (61.51%, 187/304). There were 96.71% (294/304) and 77.63% (236/304) of respondents that accepted the participation of township healthcare center and township government/village committees in dissemination of schistosomiasis control knowledge, and there were 95.72% (291/304) and 80.59% (245/304) of respondents that mainly acquired schistosomiasis control knowledge through village allocation of leaflets and volunteer schistosomiasis control activities, respectively. There was 96.71% (294/304) of respondents participating in the dissemination activities of schistosomiasis control knowledge held by village committees, township healthcare centers, and high and primary schools/kinder-gartens, and 61.25% (177/289) of respondents were willing to participate in volunteer schistosomiasis control activities. A total of 115 individuals participated in the survey of available resources for community-based schistosomiasis control health education, and there were a large number of organizational, human and cultural resources in the community that were useful for health communication services. Conclusions The abundant human and material resources from rural communities in schistosomiasis-endemic areas may be integrated into schistosomiasis control health education to generate a rural health education pathway with the joint participation of schistosomiasis control institutions, township governments, community departments and community residents, which may provide insights into the future development of schistosomiasis control health education.

Objective:To summarize the clinical characteristics,therapeutic effect and prognostic factors of patients with Hodgkin's lymphoma(HL).Methods:A total of 129 patients with HL diagnosed in Peking University Third Hospital from January 2010 to March 2021 who were given at least one efficacy assessment after treatment were enrolled,and their clinical data,including sex,age,pathological type,Ann Arbor stage,ECOG score,blood test,β2-microglobulin,lactate dehydrogenase level,albumin level were collected.The clinical characteristics,therapeutic effect and long-term prognosis of the patients were summarized and analyzed.Results:In classical HL,nodular sclerosis HL accounted for the highest proportion of 51.6％,followed by mixed cellularity HL(36.5％),lymphocyte-rich classical HL(3.2％),and lymphocyte depletion HL(0.7％),while nodular lymphocyte predominant HL accounted for 4.8％.The 3-year overall survival(OS)rate of HL patients was 89.8％,and 5-year OS was 85.0％.The 3-year progression-free survival(PFS)rate was 73.4％,and 5-year PFS was 63.1％.Multivariate regression analysis indicated that IPI score was an independent negative factor,while hemoglobin(Hb)level was an independent positive factor for OS in HL patients.When the mediastinal mass size was 9.2 cm,it was most significant to judge the survival status of HL patients.5-year OS and 5-year PFS were 97.4％and 76.0％in early-stage HL patients without large mass,respectively,while in patients with advanced-stage HL was 83.4％and 55.9％(both P＜0.05).After 2-4 courses of treatment,the overall response rate(ORR)of patients who received chemotherapy combined with radiotherapy was 95.0％,while that was 89.6％in those with chemotherapy alone.Conclusions:The overall prognosis of patients with HL is satisfactory,especially those in early-stage without large mass.IPI score and Hb level are independent risk factors for the prognosis of HL patients.A 9.2 cm mediastinal mass can be used as the cut-off value for the prognosis of Chinese HL patients.

Oligodendrocytes are myelin-forming cells of the central nervous system(CNS).The processes extending from each oligodendrocyte are capable of wrapping axon to form multiple myelin sheaths to ensure efficient and rapid conduction of action potentials along the axon.Recent studies have shown that myelin changes are quite active although most of the myelin sheaths in the adult brain are in a stable state.On the one hand,oligodendrocyte precursor cells continue to differentiate to form new myelin sheaths;On the other hand,a small portion of the formed myelin sheaths degenerate over time.Dynamic changes in myelin sheaths are thought to be a form of neural plasticity in the adult brain,which aims to regulate the function of neural circuits for adapting of new environments or acquiring new skills.In the brains with Alzheimer's disease(AD),myelin degeneration can lead to a compensatory increase in myelin regeneration,but it is still insufficient to compensate for the loss of myelin,and the promotion of new myelin formation is expected to be a new strategy to improve AD-related cognitive dysfunction.

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.

italic>Lonicera Linn. is the largest genus of family Caprifoliaceae, which has a long history and abundant resources in China. Due to its ornamental and medicinal properties, the species of Lonicera shows outstanding economic value. However, affected by the huge demand and high price stimulation, there is a serious mixing phenomenon on the market. In this study, high-throughput sequencing technology was used to analyze the analysis of L. angustifolia Wallich ex Candolle var. myrtillus (Hook. f. & Thomson) Q. E. Yang, L. myrtillus Hook. f. et Thoms. var. cyclophylla Rehd, L. szechuanica Batal and L. tangutica Maxim to sequence and assemble their chloroplast (CP) genomes, and to conduct structural comparisons and phylogenetic studies. The results showed that the chloroplast genomes of the four species showed a typical circular tetrad structure, with a total length of 154 608-163 413 bp and a total GC content of 37.93%-38.42%. A total of 128-129 genes were annotated, including 83-84 protein-coding genes, 8 rRNA genes, and 37 tRNA genes. A total of 53-68 SSRs and 133-745 long repeats were detected by chloroplast repeat structure analysis. Phylogenetic studies showed that 21 species of Lonicera medicinal plants could be significantly clustered into one branch, among which the relatives of L. angustifolia and L. szechuanica were close, and the kinship of L. myrtillus and L. tangutica was close. This study is the first comprehensive study of the chloroplast genome and phylogenetic relationship of Loicera species, and the experimental results provide a scientific basis for revealing the genetic information, species evolution and genetic diversity of Lonicera species.

The present article was aimed to compare the effectiveness of different induction methods for depression models. Kunming mice were randomly divided into chronic unpredictable mild stress (CUMS) group, corticosterone (CORT) group, and CUMS+CORT (CC) group. The CUMS group received CUMS stimulation for 4 weeks, and the CORT group received subcutaneous injection of 20 mg/kg CORT into the groin every day for 3 weeks. The CC group received both CUMS stimulation and CORT administration. Each group was assigned a control group. After modeling, forced swimming test (FST), tail suspension test (TST) and sucrose preference test (SPT) were used to detect the behavioral changes of mice, and the serum levels of brain-derived neurotrophic factor (BDNF), 5-hydroxytryptamine (5-HT) and CORT were detected with ELISA kits. Attenuated total refraction (ATR) spectra of mouse serum were collected and analyzed. HE staining was used to detect morphological changes in mouse brain tissue. The results showed that the weight of model mice from the CUMS and CC groups decreased significantly. There was no significant change in immobility time of model mice from the three groups in FST and TST, while the glucose preference of model mice from the CUMS and CC groups was significantly reduced (P < 0.05). The serum 5-HT levels of model mice from the CORT and CC groups were significantly reduced, while the serum BDNF and CORT levels of model mice from the CUMS, CORT, and CC groups showed no significant changes. Compared with their respective control groups, the three groups showed no significant difference in the one-dimensional spectrum of serum ATR. The difference spectrum analysis results of the first derivative of the spectrogram showed that the CORT group had the greatest difference from its respective control group, followed by the CUMS group. The structures of hippocampus in the model mice from the three groups were all destroyed. These results suggest that both CORT and CC treatments can successfully construct a depression model, and the CORT model is more effective than the CC model. Therefore, CORT induction can be used to establish a depression model in Kunming mice.
Mice ; Animals ; Depression/etiology* ; Antidepressive Agents/pharmacology* ; Brain-Derived Neurotrophic Factor ; Serotonin

OBJECTIVE: Jiedu Recipe (JR), a Chinese herbal remedy, has been shown to prolong overall survival time and decrease recurrence and metastasis rates in patients with hepatocellular carcinoma (HCC). This work investigated the mechanism of JR in HCC treatment. METHODS: The chemical constituents of JR were detected using liquid chromatography-mass spectrometry. The potential anti-HCC mechanism of JR was screened using network pharmacology and messenger ribonucleic acid (mRNA) microarray chip assay, followed by experimental validation in human HCC cells (SMMC-7721 and Huh7) in vitro and a nude mouse subcutaneous transplantation model of HCC in vivo. HCC cell characteristics of proliferation, migration and invasion under hypoxic setting were investigated using thiazolyl blue tetrazolium bromide, wound healing and Transwell assays, respectively. Image-iT™ Hypoxia Reagent was added to reveal hypoxic conditions. Stem cell sphere formation assay was used to detect the stemness. Epithelial-mesenchymal transition (EMT) markers like E-cadherin, vimentin and α-smooth muscle actin, and pluripotent transcription factors including nanog homeobox, octamer-binding transcription factor 4, and sex-determining region Y box protein 2 were analyzed using Western blotting and real-time polymerase chain reaction. Western blot was performed to ascertain the anti-HCC effect of JR under hypoxia involving the Wnt/β-catenin pathway. RESULTS: According to network pharmacology and mRNA microarray chip analysis, JR may potentially act on hypoxia and inhibit the Wnt/β-catenin pathway. In vitro and in vivo experiments showed that JR significantly decreased hypoxia, and suppressed HCC cell features of proliferation, migration and invasion; furthermore, the hypoxia-induced increases in EMT and stemness marker expression in HCC cells were inhibited by JR. Results based on the co-administration of JR and an agonist (LiCl) or inhibitor (IWR-1-endo) verified that JR suppressed HCC cancer stem-like properties under hypoxia by blocking the Wnt/β-catenin pathway. CONCLUSION JR exerts potent anti-HCC effects by inhibiting cancer stemness via abating the Wnt/β-catenin pathway under hypoxic conditions. Please cite this article as: Guo BJ, Ruan Y, Wang YJ, Xiao CL, Zhong ZP, Cheng BB, Du J, Li B, Gu W, Yin ZF. Jiedu Recipe, a compound Chinese herbal medicine, inhibits cancer stemness in hepatocellular carcinoma via Wnt/β-catenin pathway under hypoxia. J Integr Med. 2023; 21(5): 474-486.
Animals ; Mice ; Humans ; Carcinoma, Hepatocellular/genetics* ; beta Catenin/pharmacology* ; Liver Neoplasms/genetics* ; Drugs, Chinese Herbal/therapeutic use* ; RNA, Messenger/therapeutic use* ; Cell Line, Tumor ; Cell Proliferation ; Cell Movement ; Gene Expression Regulation, Neoplastic