Four pyrazines were isolated from the n-butanol fraction of Hypecoum erectum L. by using various chromatographic methods, including MCI gel, ODS, silica gel and semi-preparative HPLC. The structures of the isolated compounds were identified as hyperectpyrazin A (1), 1′S-(6-methylpyrazin-2-yl)-ethane-1′,2′-diol (2), 2-hydroxymethyl-6-methylpyrazin (3) and pyrazine-2-carboxylic acid (4) by spectroscopy methods (1D NMR, 2D NMR, UV, IR, MS, etc.). The absolute configuration of compound 2 was determined by using the Mo₂(OAc)₄ induced CD analysis for the first time. Compound 1 was a new compound, compounds 2-4 were isolated from H. erectum for the first time. Compounds 1-4 were evaluated for their inhibition against acetylcholinesterase and nitric oxide generation induced by lipopolysaccharide-RAW264.7 macrophage cells. At a concentration of 50 μmol·L^-1, compounds 2 and 4 displayed inhibitory effects on acetylcholinesterase with the inhibition rates of 44.40% and 43.99%, respectively.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objectives:To establish a comprehensive system of Cardiovascular Academic Performance Evaluation(CAPE)and rank global TOP100 medical institutions in the fields of cardiovascular diseases(CVD). Methods:CVD-related terms were extracted from Medical Subject Headings(MeSH),Embase thesaurus(EMtrees)and International Classification of Diseases(ICD)by CVD-related professionals,as well as by librarians and information professionals.Terminology databases(named as Fuwai Subject Headings)were established,and nine sub-disciplines were proposed,including ischemic heart diseases,hypertension,vascular diseases,arrhythmia,pulmonary vascular diseases,heart failure,congenital heart diseases,cardiomyopathy,and valvular heart diseases.The mapping patterns of sub-discipline,cardiovascular terminology and entry terms were pre-defined.The CVD-related research literature published from January 1,2016 to December 31,2022 were retrieved from Web of Science,PubMed and Scopus.Based on this,metadata were fused and duplicates were excluded.Fuwai Subject Headings were searched and matched into four respects for each literature,including subject words,titles,keywords,and abstracts,which was used to generate an information table of"Position—CVD terminology—Frequency",and to calculate CVD correlation scores and sub-discipline scores.We standardized the names of medical institutions and scholars,and make a ranking system for CAPE based on original articles with strong cardiovascular correlation(correlation score≥4).When evaluating the science and technological performance for Chinese hospitals in cardiovascular diseases,National Natural Science Foundation Projects,authorized invention patents,prize achievements,research platforms,and registered data of drug clinical trials in Center for Drug Evaluation(CDE)were considered besides research papers. Results:During 2016 and 2022,1 545 103 CVD research literatures were found worldwide.After excluding meeting abstracts,books,biographies,news,videos,audio texts,retracted publications,and corrections,1 178 019 CVD research literatures were further evaluated.518 058 literatures were indexed as"strongly correlated to CVD"using Fuwai Subject Headings.Besides papers,other data sources were also collected,including 11 143 CVD-related Natural Science Foundation Projects,19 382 CVD-related effective authorized invention patents,103 CVD-related national prize achievements,24 CVD-related national research platforms,and 2 084 CDE registered data of CVD-related drug clinical trials.Research teams from nine sub-disciplines reviewed and validated research literature in respective fields,and classification rules of corresponding sub-disciplines were created and improved based on their opinions.Finally,eleven individual indexes were chosen to construct CAPE system for ranking global TOP100 medical institutions in overall CVD field and TOP30 in nine sub-disciplines.From 2016 to 2022,the number of cardiovascular disease research papers published by Chinese institutes has increased by 123.5%,with a total of approximately 76.8 thousands papers published(about 30 papers per day on average),ranked the second under the United States(approximately 114.1 thousands papers).However,the proportion of papers published by the Chinese Journal Citation Reports(JCR)and the Chinese Academy of Sciences only ranked eighth in the world.In the comprehensive academic performance of original cardiovascular research papers in global hospitals from 2020 to 2022,only two Chinese medical institutions ranked in the TOP20 as evaluated by CAPE system. Conclusions:Based on multi-source data from 2016 to 2022,CAPE initiated to establish a cardiovascular academic performance evaluation system.

The accumulation and spread of prion-like proteins is a key feature of neurodegenerative diseases (NDs) such as Alzheimer's disease, Parkinson's disease, or Amyotrophic Lateral Sclerosis. In a process known as 'seeding', prion-like proteins such as amyloid beta, microtubule-associated protein tau, α-synuclein, silence superoxide dismutase 1, or transactive response DNA-binding protein 43 kDa, propagate their misfolded conformations by transforming their respective soluble monomers into fibrils. Cellular and molecular evidence of prion-like propagation in NDs, the clinical relevance of their 'seeding' capacities, and their levels of contribution towards disease progression have been intensively studied over recent years. This review unpacks the cyclic prion-like propagation in cells including factors of aggregate internalization, endo-lysosomal leaking, aggregate degradation, and secretion. Debates on the importance of the role of prion-like protein aggregates in NDs, whether causal or consequent, are also discussed. Applications lead to a greater understanding of ND pathogenesis and increased potential for therapeutic strategies.
Humans ; Prions ; Neurodegenerative Diseases/pathology* ; Amyloid beta-Peptides ; Alzheimer Disease ; alpha-Synuclein ; tau Proteins ; Parkinson Disease

3ʹ-Hydroxy-4ʹ-methoxy-2-hydroxy-5-bromochalcone (hereinafter referred to as C13) is a novel chalcone derivative obtained in the process of structural modification of DHMMF, the antitumor active compound of Resina Draconis, in our laboratory. In this study, we investigated the effects of C13 on the proliferation and apoptosis of human gastric cancer HGC-27 and AGS cells and its potential mechanism of action. Firstly, through methyl thiazolyl tetrazolium (MTT), colony formation assay, and 5-ethynyl-2'-deoxyuridine (EdU) staining, we found that C13 inhibited the proliferation ability of human gastric cancer HGC-27 and AGS cells. Using flow cytometry and Western blot, it was found that C13 induced apoptosis in human gastric cancer HGC-27 and AGS cells, and up-regulated the protein level of cleaved poly ADP-ribose polymerase (cleaved-PARP). The results of RNA sequencing analysis showed that the Erb-b2 receptor tyrosine kinase 4/phosphoinositide 3-kinases/AKT (ErbB4/PI3K/AKT) signaling pathway may be involved in anti-gastric cancer activity of C13. Finally, the results of immunoblotting assay showed that C13 treatment down-regulated the protein levels of ErbB4 and phospho-ErbB4, as well as down-regulated the phosphorylation levels of PI3K and AKT in human gastric cancer HGC-27 and AGS cells, which verified the results from RNA-seq analysis. In conclusion, C13 inhibited the proliferation and induced apoptosis of human gastric cancer cells, which may be related to the down-regulation of ErbB4/PI3K/AKT signaling pathway. This study may provide a candidate drug for the treatment of gastric cancer.

Objective To investigate the effects of miR-4531/CX3CL1 signaling pathway on the vascular injury in preeclampsia, and to search possible targets for early diagnosis and prevention of preeclampsia. Methods Placental tissue samples were obtained from 10 patients with late-onset preeclampsia and 10 normal pregnant women in the Obstetrics and Gynecology Department of Minhang Hospital, Fudan University from October 2021 to December 2022. The levels of miR-4531 and CX3CL1 were evaluated by qRT-PCR. Cell transfection was performed by lipofectamine 2000 in vitro. The binding relationship between miR-4531 and CX3CL1 was determined by luciferase reporter assay. The apoptosis of neutrophils, the migration, repair, colony formation and cell-free DNA (cfDNA) release of human umbilical vein endothelial cells (HUVECs) were detected. Results MiR-4531 was significantly downregulated, and CX3CL1 was upregulated in placental tissues of preeclampsia patients (P＜0.05). Luciferase report assay confirmed the direct binding relationship between miR-4531 and CX3CL1. Upregulation of miR-4531significantly promoted the migration, proliferation, repair, and inhibited cfDNA release of HUVECs and neutrophils apoptosis in medium under hypoxic condition (P＜0.05). However, downregulation of miR-4531 obviously inhibited the proliferation, migration, repair, and enhanced cfDNA release of HUVECs and neutrophils apoptosis in medium under hypoxic condition (P＜0.05). Conclusions The miR-4531is downregulated in placental tissues of preeclampsia parients and is a potential therapeutic target for preeclampsia. It might cause endothelial damage and an abnormal hypercoagulable state under hypoxic condition by targeting and regulating the CX3CL1 pathway.

Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.

The quality control of traditional Chinese medicine(TCM)is the core issue to ensure the modernization,industrialization and internationalization of TCM.Compared with other detection methods,electrochemical analysis method has many advantages such as high sensitivity,fast detection speed and low cost,making it an important means of quality control for TCM and having broad development prospects.This article reviewed the research progress of electrochemical methods in quality control of TCM in recent years,discussed the application of electrochemical fingerprinting technique in identification of TCM,and comprehensively summarized the application of electrochemical technology in analyzing effective components and harmful substances in TCM,including flavonoids,alkaloids,quinones,glycosides,heavy metals and pesticide residues.Finally,the development prospects of electrochemical methods in the field of quality control of TCM were discussed.

Objective To investigate the effect of anti-angiogenic drug Sitravatinib combined with poly(adenosine diphosphate[ADP]-ribose)polymerase inhibitor(PARPi)Niraparib on mucosal melanoma cell lines and its possible mechanism.Methods The CCK8 assay was used to detect the maximal half inhibitory concentration(IC50)of Sitravatinib and Niraparib targeting at mucosal melanoma(MM)cell lines.CompuSyn was used to detect the Combination Index(CI)in different concentrations of the two drugs.Flow cytometry was used to detect the effect of drugs on cell apoptosis.Colony formation assay was used to detect the effect of drugs on cell proliferation.Western blot was used to detect the protein expressions and RT-qPCR was used to detect mRNA expression.Results CI values was respectively 0.19 and 0.15 for Sitravatinib(2 μmol/L)in combination with Niraparib(20 μmol/L)in a human vaginal maligant melanoma cell line(HMVII)and a metastasis inguinal lymph node of vulvar malignant melanoma cell line(GAK).Compared with the control group and single-drug groups,the cell proliferation of the combination group was significantly reduced(P＜0.05 or P＜0.01 or P＜0.001).The cell apoptosis rate was signifi-cantly increased(P＜0.01 or P＜0.001).The protein and mRNA expression of apoptosis-related biomarkers signifi-cantly increased(P＜0.001);In addition,the protein and mRNA expression of cell autophagy biomarkers signifi-cantly increased(P＜0.01 or P＜0.001).The protein expression of DNA damage marker significantly increased.Moreover,compared with the control group,The expression of radiation sensitive protein 51(RAD51)recombinase in the Sitravatinib single-drug group and combination group significantly reduced.As the dose of Sitravatinib gradu-ally increased up to 2 μmol/L,the protein and mRNA expression of RAD51 both significantly reduced(P＜0.05 or P＜0.01),the mRNA expression of BRCA1 and BRCA2 also significantly reduced(P＜0.05 or P＜0.01 or P＜0.001).Conclusions Sitravatinib combined with Niraparib inhibits the proliferation of mucosal melanoma cells,induces cell apoptosis and promotes autophagy.The mechanism is potentially related to the inhibition of ho-mology-dependent recombination repairs(HRR).

Diagnosis and treatment of locally advanced rectal cancer(LARC)must be completed by a collaborative model of a multi-disciplinary team.The neoadjuvant chemoradiotherapy significantly reduced the local recurrence rate of LARC,but did not affect the occurrence of distant metastases and overall survival.Total neoadjuvant therapy(TNT),by strengthening the intensity of chemotherapy and extending the time from radiotherapy to surgery,can improve the tumor response rate as well as disease-free survival rate and metastasis-free survival rate.It offers advantages such as enhancing the compliance with chemotherapy,maximizing tumor regression,improving survival and increasing the chance of organ preservation.TNT is a promising treatment model for LARC patients with high risk of distant metastasis or strong desire for organ preservation.With the application of immunotherapy in the field of TNT,the mode of TNT continues to expand.And the exploration of therapeutic predictive markers will help to provide a personalized treatment for patients.