OBJECTIVE: To investigate the effect of zedoarondiol on neovascularization of atherosclerotic (AS) plaque by exosomes experiment. METHODS: ApoE^-/- mice were fed with high-fat diet to establish AS model and treated with high- and low-dose (10, 5 mg/kg daily) of zedoarondiol, respectively. After 14 weeks, the expressions of anti-angiogenic protein thrombospondin 1 (THBS-1) and its receptor CD36 in plaques, as well as platelet activation rate and exosome-derived miR-let-7a were detected. Then, zedoarondiol was used to intervene in platelets in vitro, and miR-let-7a was detected in platelet-derived exosomes (Pexo). Finally, human umbilical vein endothelial cells (HUVECs) were transfected with miR-let-7a mimics and treated with Pexo to observe the effect of miR-let-7a in Pexo on tube formation. RESULTS: Animal experiments showed that after treating with zedoarondiol, the neovascularization density in plaques of AS mice was significantly reduced, THBS-1 and CD36 increased, the platelet activation rate was markedly reduced, and the miR-let-7a level in Pexo was reduced (P<0.01). In vitro experiments, the platelet activation rate and miR-let-7a levels in Pexo were significantly reduced after zedoarondiol's intervention. Cell experiments showed that after Pexo's intervention, the tube length increased, and the transfection of miR-let-7a minics further increased the tube length of cells, while reducing the expressions of THBS-1 and CD36. CONCLUSION Zedoarondiol has the effect of inhibiting neovascularization within plaque in AS mice, and its mechanism may be potentially related to inhibiting platelet activation and reducing the Pexo-derived miRNA-let-7a level.
Animals ; MicroRNAs/genetics* ; Exosomes/drug effects* ; Plaque, Atherosclerotic/genetics* ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Humans ; Blood Platelets/drug effects* ; Apolipoproteins E/deficiency* ; Thrombospondin 1/metabolism* ; CD36 Antigens/metabolism* ; Platelet Activation/drug effects* ; Male ; Mice ; Mice, Inbred C57BL

Hemorrhagic shock is a common clinical emergency that can aggravate cell injury after resuscitation. Astrocytes are crucial for the survival of neurons because they regulate the surrounding ionic microenvironment of neurons. Although hemorrhagic shock and resuscitation (HSR) injury can impair cognition, it remains unclear how this insult directly affects astrocytes. In this study, we established an HSR model by bleeding and re-transfusion in mice. The social interaction test and new object recognition test were applied to evaluate post-operative cognitive changes, and the results suggest that mice experience cognitive impairment following exposure to HSR. In the HSR group, the power spectral density of β and γ oscillations decreased, and the coupling of the θ oscillation phase and γ oscillation amplitude was abnormal, which indicated abnormal neuronal oscillation and cognitive impairment after HSR exposure. In brief, cognitive impairment in mice is strongly correlated with Ca²⁺ signal strength in lateral septum astrocytes following HSR.
Animals ; Astrocytes/metabolism* ; Shock, Hemorrhagic/metabolism* ; Resuscitation/adverse effects* ; Male ; Mice ; Calcium Signaling/physiology* ; Mice, Inbred C57BL ; Septal Nuclei/metabolism* ; Cognitive Dysfunction/etiology* ; Disease Models, Animal ; Cognition Disorders/etiology*

Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited signif-icant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degra-dation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

The early response of plant auxin gene family Aux/IAA (auxin/indole-3-acetic acid) and its interaction with auxin response factor (ARF) are important pattern to regulate plant growth and development. This work identified 28 StoIAA and 24 StoARF members based on the whole genome data of the medicinal plant Senna tora L., which were classified into 10 and 8 subfamilies, respectively. Phylogenetic tree and collinearity analysis showed that S. tora has close evolutionary relationship with the IAA and ARF homologous genes of Glycine max, Medicago truncatula, and the segment duplication events dominate the expansion of StoIAA and StoARF. Gene structure analysis showed that the vast majority of StoIAA and StoARF contain characteristic conserved domain. Transcriptome data showed that StoIAAs and StoARFs were expressed in leaves, roots and seeds, some members had tissue specific expression. The StoIAA and StoARF promoter region most contain functional elements related to stress response, growth and development, hormone induction and secondary metabolism. In addition, gene expression analysis showed that many StoIAAs and StoARFs can quickly respond to drought and salt stress and exhibited same expression patterns under both stress condition. The yeast two-hybrid experiment confirmed that StoARF8 and StoARF10 exhibit varying degrees of interaction with multiple StoIAA proteins, respectively. The above results provide a basis for further biological functional analysis of the Aux/IAA and ARF gene family of S. tora.

BACKGROUND: The effects of acupuncture have varied in different randomized controlled trials (RCTs), and there are many factors that influence treatment effect of acupuncture in different outcomes, with conflicting results. OBJECTIVE: To identify factors and their impact on the treatment effect of acupuncture in different outcomes. METHODS: Acupuncture RCTs were searched from 7 databases including Medline (PubMed), Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and China Biology Medicine disc between January 1st, 2015 and December 31st, 2019. Eligible studies must compare acupuncture to no acupuncture, sham acupuncture, or waiting lists, and report at least 1 patient-important outcome. A multi-level meta-regression was conducted using a 3-level robust mixed model and univariate analyses were performed for all independent variables, even those excluded from the multivariable model due to collinearities. We used thresholds of 0.2 and 0.4 for the difference of standardized mean differences (SMDs), categorising them as small (<0.2), moderate (0.2-0.4), or large (>0.4) effects. RESULTS: The pain construct analysis involved 211 effect estimates from 153 studies and 14 independent variables. High-frequency acupuncture treatment sessions produced larger effects compared to low-frequency sessions [large magnitude, the difference of adjusted SMDs 0.46, 95% confidence interval (CI) 0.07 to 0.84; P=0.02]. The non-pain symptoms construct analysis comprised 323 effect estimates from 231 studies and 15 independent variables. Penetrating acupuncture showed moderately larger effects when compared to non-penetrating acupuncture (0.30, 95% CI 0.06 to 0.53; P=0.01). The function construct analysis included 495 effect estimates from 274 studies and 14 independent variables. Penetrating acupuncture and the flexible acupuncture regimen showed moderately larger effects, compared to non-penetrating acupuncture and fixed regimen, respectively (0.40, 95% CI 0 to 0.80; P=0.05; 0.29, 95% CI 0.06 to 0.53; P=0.01). CONCLUSIONS High-frequency acupuncture sessions appear to be a more effective approach to managing painful symptoms. Penetrating acupuncture demonstrated greater effect in relieving non-painful symptoms. Both penetrating acupuncture type and flexible acupuncture regimen were linked to significant treatment effects in function outcomes. Future studies should consider the factors that are significantly associated with the effects of acupuncture in patient-important outcomes.
Humans ; Randomized Controlled Trials as Topic ; Acupuncture Therapy/methods* ; Pain ; Pain Management ; China

bstract: Objective To elucidate the distribution characteristics of mosquito species and the population genetic diversity of important mosquito species in the Wuyi Mountain Nature Reserve, with the aim of providing a scientific basis for the prevention and control of mosquito-borne diseases in the region. Methods Within Wuyi Mountain Nature Reserve 2022- 2023, 16 sampling sites were selected, where larvae were collected using the pipette method and adult mosquitoes were collected using the mosquito trap lamp method. Mosquito species identification was accomplished by integrating morphological characteristics and molecular identification techniques based on CO Ⅰ and CO Ⅱ gene sequences. Software tools such as ClustalX, DnaSP v5.0, and Network v4.6.1.0 were utilized to analyze the genetic differentiation (Fst), gene flow (Nm) among populations of Aedes japonicus, Aedes albopictus and Armigeres subalbatus. Results The mosquito specimens collected from the Wuyi Mountain Nature Reserve were identified as 30 species belonging to 8 genera within the Culicidae family. Among them, there were 10 species of Aedes, 13 species of Culex, 1 species each of Armigeres, Orthopodomyia, Uranotaenia, Tripyeroides, and Anopheles, and 2 species of Toxorhynchites. Analysis of the genetic structure of important mosquito populations showed that the haplotype diversity index (Hd) of Ae. japonicus was 0.994 7, with a generally moderate degree of differentiation between populations and a higher degree of genetic differentiation between populations 6 and 12; Aedeslbopictus had a haplotype diversity index of 0.634 0, with significant genetic differentiation between populations 1 and 2 compared to other groups; Armigeres subalbatus had a haplotype diversity index of 0.703 3, with substantial genetic differentiation and limited gene flow between population 2 and populations 3, 4, 6, and 7. Conclusions The mosquito species are rich in Wuyi Mountain Nature Reserve. A comprehensive survey of the composition and distribution of mosquito populations was carried out, and the characteristics of the population genetic structure of the important species of Ae. japonicus, Ae. Albopictus, and Ar. subalbatus populations were analyzed, providing valuable scientific data reference for local mosquito-borne ecological research and disease prevention and control.

OBJECTIVES: To evaluate the report quality, methodological quality and evidence quality of the systematic reviews and meta-analyses (SRs/MAs) of acupuncture for in vitro fertilization-embryo transfer (IVF-ET). METHODS: The SRs/MAs of acupuncture for IVF-ET were searched electronically from databases of CNKI, Wanfang, VIP, SinoMed, PubMed, Embase, Cochrane Library, from inception of each database to September 27th, 2022. Two reviewers independently screened the literature and extracted the data. Using PRISMA statement, the AMSTAR 2 scale and the GRADE system, the report quality, methodological quality and evidence quality of the included SRs/MAs were assessed. RESULTS: A total of 28 SRs/MAs were included, with PRISMA scores ranging from 8.5 points to 27 points. The problems of report quality focused on protocol and registration, retrieval, risk of bias in studies, additional analysis, limitations and funding. The methodological quality of included studies was generally low, reflecting on items 2, 3, 7, 10, 12 and 16. A total of 85 outcome indexes were included in the GRADE system for evidence grade evaluation. Most of the evidences were low or very low in quality. The reasons for the downgrade were related to study limitations, inconsistency, imprecision and publication bias. CONCLUSIONS Acupuncture therapy improves the outcomes of IVF-ET, but the methodological quality and evidence quality of related SRs/MAs are low. It is recommended to conduct more high-quality studies in the future to provide more reliable evidences.
Acupuncture Therapy/methods* ; Databases, Factual ; Embryo Transfer ; Fertilization in Vitro ; Publication Bias ; Systematic Reviews as Topic

Objective: To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. Methods: The clinical data of 656 ENKTL patients diagnosed at 11 medical centers in the Huaihai Lymphoma Working Group from March 2014 to April 2021 were retrospectively analyzed. The patients were randomly divided into two groups: a training set (460 cases) and a validation set (196 cases) at 7∶3, and the prognostic factors of the patients were analyzed. A prognostic scoring system was established, and the predictive performance of different models was compared. Results: Patients' median age was 46 (34, 57) years, with 456 males (69.5% ) and 561 nasal involvement (85.5% ). 203 patients (30.9% ) received a chemotherapy regimen based on L-asparaginase combined with anthracyclines, and the 5-year overall survival rate of patients treated with P-GEMOX regimen (pegaspargase+gemcitabine+oxaliplatin) was better than those treated with SMILE regimen (methotrexate+dexamethasone+cyclophosphamide+L-asparaginase+etoposide) (85.9% vs 63.8% ; P=0.004). The results of multivariate analysis showed that gender, CA stage, the Eastern Cooperative Oncology Group performance status (ECOG PS) score, HGB, and EB virus DNA were independent influencing factors for the prognosis of ENKTL patients (P<0.05). In this study, the predictive performance of the prognostic factors is superior to the international prognostic index, Korean prognostic index, and prognostic index of natural killer lymphoma. Conclusion: Gender, CA stage, ECOG PS score, HGB, and EB virus DNA are prognostic factors for ENKTL patients treated with pegaspargase/L-asparaginase.
Male ; Humans ; Middle Aged ; Asparaginase/therapeutic use* ; Prognosis ; Retrospective Studies ; Lymphoma, Extranodal NK-T-Cell/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Etoposide ; Cyclophosphamide ; Methotrexate/therapeutic use* ; DNA/therapeutic use* ; Treatment Outcome

As an indicator that measures the degree of implementation of intervention measures during the implementation process, fidelity could be used for monitoring and quality evaluation of the completion degree of intervention measures, and plays an important role in improving the degree of intervention implementation and clarifying the factors that affect intervention implementation. This article aims to introduce the connotation and significance, measurement, control, and current application status of fidelity, as well as the current application status of fidelity in acupuncture-moxibustion clinical research and its inspiration for future research. Meanwhile, based on the existing evaluation tool development methods of fidelity and the characteristics of acupuncture-moxibustion clinical research, a preliminary fidelity evaluation framework is proposed. Introducing fidelity into acupuncture-moxibustion clinical research could improve the implementation quality and compliance of acupuncture-moxibustion in clinical research, increase the credibility and effectiveness of clinical research results, and promote the transformation of acupuncture-moxibustion experience into easily learnable and promotable treatment plans.
Moxibustion ; Acupuncture Therapy

Fourteen compounds were isolated from the n-butanol fraction of the 95% aqueous ethanol extract of the stems and twigs of Strychnos cathayensis by D101 macroporous resin, silica gel, ODS, Sephadex LH-20 column chromatography, and semipreparative RP-HPLC. Their structures were elucidated as ethyl 4-O-β-D-allopyranosyl-vanillate (1), n-butyl 4-O-β-D-allopyranosyl-vanillate (2), n-butyl 4-O-(6′-O-syringoyl)-β-D-allopyranosyl-vanillate (3), n-butyl 4-O-(6′-O-vanilloyl)-β-D-allopyranosyl-vanillate (4), n-butyl 4-O-(6′-O-syringoyl)-β-D-glucopyranosyl-vanillate (5), n-butyl 4-O-α-L-rhamnopyranosyl-syringate (6), methyl 3-methoxy-4-(β-D-allopyranosyloxy) benzoate (7), pseudolaroside B (8), butyl syringate (9), glucosyringic acid (10), methyl syringate (11), methyl 4-hydroxy-3-methoxybenzoate (12), clemochinenoside C (13), and clemoarmanoside A (14), respectively, on the basis of spectroscopic data interpretation and by comparison with literature information. Compounds 1-6 are artificial products of phenolic acid esterified by ethanol or n-butanol. It is noted that the precursors (4-O-(6′-O-syringoyl)-β-D-allopyranosyl-vanillic acid and 4-O-(6′-O-vanilloyl)-β-D-allopyranosyl-vanillic acid) of compounds 3 and 4 are new compounds. The hepatoprotective, anti-inflammatory, antioxidant and cytotoxic activities of compounds 1-13 were evaluated in vitro at a concentration of 10 μmol·L^-1. Compounds 1, 2 and 6-10 exhibited potential hepatic protection effects with cell survival rates ranging from 53.6% to 55.5% (acetaminophen, 45.4% at 8 mmol·L^-1). Compound 4 demonstrated anti-inflammatory activity with nitric oxide inhibitory rate of 74.6%. Compounds 3 and 5 showed potential antioxidant activities with malondialdehyde inhibitory rates of 53.2% and 56.1%, respectively.