This study aimed to investigate the correlation between changes in intestinal toxicity and compositional alterations of Euphorbiae Ebracteolatae Radix(commonly known as Langdu) before and after milk processing, and to explore the detoxification mechanism of milk processing. Mice were intragastrically administered the 95% ethanol extract of raw Euphorbiae Ebracteolatae Radix, milk-decocted(milk-processed), and water-decocted(water-processed) Euphorbiae Ebracteolatae Radix. Fecal morphology, fecal water content, and the release levels of inflammatory cytokines tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in different intestinal segments were used as indicators to evaluate the effects of different processing methods on the cathartic effect and intestinal inflammatory toxicity of Euphorbiae Ebracteolatae Radix. LC-MS/MS was employed to analyze the small-molecule components in the raw product, the 95% ethanol extract of the milk-processed product, and the milky waste(precipitate) formed during milk processing, to assess the impact of milk processing on the chemical composition of Euphorbiae Ebracteolatae Radix. The results showed that compared with the blank group, both the raw and water-processed Euphorbiae Ebracteolatae Radix significantly increased the fecal morphology score, fecal water content, and the release levels of TNF-α and IL-1β in various intestinal segments(P<0.05). Compared with the raw group, all indicators in the milk-processed group significantly decreased(P<0.05), while no significant differences were observed in the water-processed group, indicating that milk, as an adjuvant in processing, plays a key role in reducing the intestinal toxicity of Euphorbiae Ebracteolatae Radix. Mass spectrometry results revealed that 29 components were identified in the raw product, including 28 terpenoids and 1 acetophenone. The content of these components decreased to varying extents after milk processing. A total of 28 components derived from Euphorbiae Ebracteolatae Radix were identified in the milky precipitate, of which 27 were terpenoids, suggesting that milk processing promotes the transfer of toxic components from Euphorbiae Ebracteolatae Radix into milk. To further investigate the effect of milk adjuvant processing on the toxic terpenoid components of Euphorbiae Ebracteolatae Radix, transmission electron microscopy(TEM) was used to observe the morphology of self-assembled casein micelles(the main protein in milk) in the milky precipitate. The micelles formed in casein-terpenoid solutions were characterized using particle size analysis, fluorescence spectroscopy, ultraviolet spectroscopy, and Fourier-transform infrared(FTIR) spectroscopy. TEM observations confirmed the presence of casein micelles in the milky precipitate. Characterization results showed that with increasing concentrations of toxic terpenoids, the average particle size of casein micelles increased, fluorescence intensity of the solution decreased, the maximum absorption wavelength in the UV spectrum shifted, and significant changes occurred in the infrared spectrum, indicating that interactions occurred between casein micelles and toxic terpenoid components. These findings indicate that the cathartic effect of Euphorbiae Ebracteolatae Radix becomes milder and its intestinal inflammatory toxicity is reduced after milk processing. The detoxification mechanism is that terpenoid components in Euphorbiae Ebracteolatae Radix reassemble with casein in milk to form micelles, promoting the transfer of some terpenoids into the milky precipitate.
Animals ; Mice ; Milk/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Male ; Tumor Necrosis Factor-alpha/immunology* ; Intestines/drug effects* ; Interleukin-1beta/immunology* ; Tandem Mass Spectrometry ; Female

Macroporous resin adsorption column chromatography, silica gel column chromatography, ODS column chromatography, and semi-preparative high-performance liquid chromatography, combined with analytical methods such as NMR and MS, were employed to separate and identify compounds from the 70% ethanol extract of Ajania purpurea. A total of 30 compounds were isolated and identified, including 13 phenolic acids, 7 coumarins, 2 lignans, 1 flavonoid, 2 sesquiterpenes, 1 steroid, and 4 others. Among them, compounds 1 and 2 were newly discovered compounds, and compounds 4, 6, 8, 12, 14-23, 25, 28, and 30 were isolated from Ajania plants for the first time. Bioactivity screening showed that multiple compounds significantly inhibited the production of nitric oxide in lipopolysaccharide-stimulated RAW264.7 cells in a dose-dependent manner. Furthermore, compound 2 elevated the levels of glutathione in LPS-induced BEAS-2B cells, reduced the expression of pro-inflammatory cytokines such as tumor necrosis factor(TNF)-α, interleukin(IL)-6, and IL-1β, enhanced the mRNA of GPX4, HMOX1, NFE2L2, and enhanced protein levels of GPX4, HO-1, Nrf2, and SLC7A11, demonstrating potential anti-ferroptotic effect.
Mice ; Animals ; Lignans/isolation & purification* ; RAW 264.7 Cells ; Humans ; Nitric Oxide ; Tumor Necrosis Factor-alpha/immunology* ; Drugs, Chinese Herbal/isolation & purification* ; NF-E2-Related Factor 2/metabolism* ; Macrophages/metabolism* ; Interleukin-6/immunology*

This paper explored the specific mechanism of ginsenoside Rg_1 in regulating mitochondrial fusion through the neurogenic gene Notch homologous protein 1(Notch1) pathway to alleviate hypoxia/reoxygenation(H/R) injury in HL-1 cells. The relative viability of HL-1 cells after six hours of hypoxia and two hours of reoxygenation was detected by cell counting kit-8(CCK-8). The lactate dehydrogenase(LDH) activity in the cell supernatant was detected by the lactate substrate method. The content of adenosine triphosphate(ATP) was detected by the luciferin method. Fluorescence probes were used to detect intracellular reactive oxygen species(Cyto-ROS) levels and mitochondrial membrane potential(ΔΨ_m). Mito-Tracker and Actin were co-imaged to detect the number of mitochondria in cells. Fluorescence quantitative polymerase chain reaction and Western blot were used to detect the mRNA and protein expression levels of Notch1, mitochondrial fusion protein 2(Mfn2), and mitochondrial fusion protein 1(Mfn1). The results showed that compared with that of the control group, the cell activity of the model group decreased, and the LDH released into the cell culture supernatant increased. The level of Cyto-ROS increased, and the content of ATP decreased. Compared with that of the model group, the cell activity of the ginsenoside Rg_1 group increased, and the LDH released into the cell culture supernatant decreased. The level of Cyto-ROS decreased, and the ATP content increased. Ginsenoside Rg_1 elevated ΔΨ_m and increased mitochondrial quantity in HL-1 cells with H/R injury and had good protection for mitochondria. After H/R injury, the mRNA and protein expression levels of Notch1 and Mfn1 decreased, while the mRNA and protein expression levels of Mfn2 increased. Ginsenoside Rg_1 increased the mRNA and protein levels of Notch1 and Mfn1, and decreased the mRNA and protein levels of Mfn2. Silencing Notch1 inhibited the action of ginsenoside Rg_1, decreased the mRNA and protein levels of Notch1 and Mfn1, and increased the mRNA and protein levels of Mfn2. In summary, ginsenoside Rg_1 regulated mitochondrial fusion through the Notch1 pathway to alleviate H/R injury in HL-1 cells.
Ginsenosides/pharmacology* ; Receptor, Notch1/genetics* ; Signal Transduction/drug effects* ; Mice ; Animals ; Mitochondrial Dynamics/drug effects* ; Mitochondria/metabolism* ; Cell Line ; Reactive Oxygen Species/metabolism* ; Oxygen/metabolism* ; Cell Hypoxia/drug effects* ; Cell Survival/drug effects* ; Membrane Potential, Mitochondrial/drug effects* ; Humans

The compilation instructions for the Expert Consensus on Clinical Application of Yifei Zhike Capsules systematically expound the development background， methodological framework， and core achievements of this consensus. In view of the problems existing in the clinical application of Yifei Zhike Capsules， such as insufficient efficacy evidence and lack of standardized syndrome differentiation， the Institute of Basic Research in Clinical Medicine， China Academy of Chinese Medical Sciences took the lead and collaborated with 21 tertiary grade-A hospitals and research institutions across China to form a multidisciplinary expert group （comprising 30 experts in clinical medicine， pharmacy， and methodology）. The compilation work was carried out in strict accordance with the World Health Organization （WHO） guidelines， the GB/T 1.1-2020 standard， and the writing specifications for the explanatory notes of expert consensus on clinical application of Chinese patent medicines. Through systematic literature retrieval （including 32 studies， with 24 clinical studies）， Grading of Recommendations Assessment， Development and Evaluations （GRADE）-based evidence grading， and multiple rounds of discussions using the nominal group method （25 experts voted to determine 17 clinical questions）， 5 evidence-based recommendations and 11 expert consensus suggestions were formed. It is clarified that this medicine （Yifei Zhike Capsules） is applicable to the treatment of expectoration/hemoptysis in acute and chronic bronchitis and the adjuvant treatment of pulmonary tuberculosis. It is recommended that it can be used alone or in combination with anti-tuberculosis drugs. The safety evaluation shows that this medicine mainly induces the following adverse reactions： mild gastrointestinal reactions （such as nausea and abdominal pain） and rashes. The contraindicated populations include pregnant women and women during menstruation. The compilation process of the consensus underwent three rounds of expert letter reviews， two rounds of peer reviews， and quality control assessments to ensure methodological rigor and clinical applicability. In addition， through policy alignment， academic promotion， and a dynamic revision mechanism， the standardization of clinical application was promoted， providing a demonstration for the evidence-based transformation of characteristic therapies of Miao medicine.

Coronavirus disease 2019 (COVID-19) is an acute infectious respiratory disease that has been prevalent since December 2019. Chinese medicine (CM) has demonstrated its unique advantages in the fight against COVID-19 in the areas of disease prevention, improvement of clinical symptoms, and control of disease progression. This review summarized the relevant material components of CM in the treatment of COVID-19 by searching the relevant literature and reports on CM in the treatment of COVID-19 and combining with the physiological and pathological characteristics of the novel coronavirus. On the basis of sorting out experimental methods in vivo and in vitro, the mechanism of herb action was further clarified in terms of inhibiting virus invasion and replication and improving related complications. The aim of the article is to explore the strengths and characteristics of CM in the treatment of COVID-19, and to provide a basis for the research and scientific, standardized treatment of COVID-19 with CM.
Humans ; Drugs, Chinese Herbal/pharmacology* ; COVID-19 Drug Treatment ; SARS-CoV-2/drug effects* ; COVID-19/therapy* ; Medicine, Chinese Traditional/methods* ; Antiviral Agents/pharmacology* ; Animals

Objective To investigate the value of CT perfusion imaging(CTP)and CT angiography(CTA)combined with serum neuron-specific enolase(NSE)in assessing the status and prognosis of collateral circulation(CC)in hemiplegic patients with stroke.Methods A total of 106 patients with stroke hemiplegia were selected in this study.All patients underwent CTA and CTP,and patients were classified into the good CC group(n=67)and the poor CC group(n=39)based on CTA images.Patients were also classified into the good prognostic group(n=56)and the poor prognostic group(n=50)based on modified Rankin Scale(mRS)scores after 3 months of treatment.Enzyme-linked immunosorbent assay(ELISA)was used to detect serum NSE levels.Pearson correlation analysis was used to analyse the correlation between CC scores and CTP parameters and serum NSE levels.The receiver operating characteristic(ROC)curve was used to analyze the evaluation value of serum NSE for the prognosis of hemiplegic patients after stroke.Kappa test was used to analyse the consistency of the prognosis and follow-up results of hemiplegic stroke patients assessed by CTP and CTA alone and in combination with serum NSE.Results The CTP parameters rCBF and rCBV were lower in the poor CC group than those in the good CC group(P＜0.05),and levels of rTTP,rMTT and serum NSE were higher than those in the good CC group(P＜0.01).CC score was positively correlated with rCBF and rCBV,and negatively correlated with rTTP,rMTT and serum NSE levels(P＜0.05).The rCBF and rCBV were lower in the poor prognosis group than those in the good prognosis group,and the proportion of poor CC,rTTP,rMTT,serum NSE level and mRS score were higher than those in the good prognosis group(P＜0.01).The area under the curve of serum NSE alone for predicting poor prognosis in hemiplegic patients with stroke was 0.878(95%CI:0.800-0.934),with a sensitivity of 74.00%and a specificity of 91.07%,which was in good agreement with the results of the follow-up(Kappa value=0.654,P＜0.001).Conclusion CTP,CTA combined with serum NSE have a relatively high evaluation value for the assessment of the CC status and prognosis of stroke patients with hemiplegia.

Objective To evaluate the efficacy and safety of a novel intravascular lithotripsy(IVL)balloon—Vesscrack shockwave balloon—for vascular preparation before stent implantation in patients with severe coronary artery calcification(CAC).Methods This was a prospective,single-arm,multicenter study conducted in China from June 2022 to October 2022.Patients with severe CAC were treated with the Vesscrack shockwave balloon for lesion preparation,followed by drug-eluting stent(DES)implantation.Of these,33 patients underwent optical coherence tomography(OCT).The primary endpoint was procedural success,defined as successful stent implantation with residual stenosis≤30％and the absence of in-hospital major adverse events,including cardiac death,target vessel-related myocardial infarction,or target lesion revascularization.Results A total of 170 patients[mean age:(65.9±7.9)years,116 males]were enrolled.After treatment with IVL and DES,the minimum lumen diameter increased significantly compared to baseline[(2.34±0.40)mm vs.(0.95±0.33)mm,P＜0.001],the degree of stenosis was significantly reduced[(13.24±6.60)％vs.(65.18±10.59)％,P＜0.001].Procedural success was achieved in 100％of cases,and device success was 98.8％.The 30-day patient-related cardiovascular clinical composite endpoint(POCE)rate was 0.0,with no target lesion failure,no confirmed or potential thrombotic events were observed.The shockwave energy generator demonstrated excellent stability and ease of use.Among the 33 patients assessed with OCT,after IVL intervention,the maximum calcified area of the lumen[(3.51±1.51)mm2 vs.(2.85±1.80)mm2,P＜0.001],and the minimum lumen area within the target lesion[(3.08±1.04)mm2 vs.(2.02±0.75)mm2,P＜0.001],and after DES intervention,the luminal area of the largest calcified site[(6.59±1.64)mm2 vs.(2.85±1.80)mm2,P＜0.001]and the minimum luminal area within the target lesion[(6.19±1.45)mm2 vs.(2.02±0.75)mm2,P＜0.001]were significantly increased,and the differences were statistically significant.Conclusions The Vesscrack shockwave balloon is effective and safe for vascular preparation in patients with severe CAC prior to stent implantation.It achieves significant calcified plaque modification,high procedural success rates,and minimal complications.

Aim To study the mechanism of adipose mesenchymal stem cell exosomes(ASC-exo)inhibition of fluorescein isothiocyanate(FITC)-induced atopic dermatitis(AD).Methods The mouse age,extrac-tion method,and the concentration of a solution of typeⅠ collagen enzyme and other conditions were compared to study the effects on the morphology and quantity of adipose mesenchymal stem cells(ASCs)after extrac-ted.FITC-induced mouse model in vivo was estab-lished and different doses of ASC-exo were given to measure ear thickness,ear weight and ear scratching times of mice.HE staining was used to observe the pathological changes of ear tissue of mice.The non-toxicity of ASC-exo was detected.IgE,IL-5,IL-13 and other cytokines were detected by ELISA.The gene ex-pressions of TSLP,IL-33,occludin,Claudin-1(CLDN-1)and E-cadherin were detected by RT-qPCR.The protein expression was detected by immunohistochemis-try.Results An efficient method for extracting ASCs was established.Compared with the blank group,mice in the model group showed obvious AD symptoms.Compared with the model group,ASC-exo administra-tion group significantly reduced the number of ear scratches,epidermal thickening,inflammatory cell infil-tration and the secretion of Th2 cytokines IL-5 and IL-13.Meanwhile,ASC-exo administration group signifi-cantly increased the expression of structural proteins CLDN-1 and occludin in epithelial cells and decreased the expression of TSLP and IL-33.Conclusions ASC-exo can significantly improve Th2 skin inflamma-tion in AD mice,and its mechanism may be through in-creasing the expression of tight junction proteins and adhesion link protein in epithelial cells,repairing the skin barrier,and inhibiting the key promoters of allergy TSLP and IL-33.

This study was aimed at tracing the molecular typing and drug resistance characteristics of a suspected food poi-soning event caused by Clostridium perfringens in a district of Wuhan City.The FilmArray detection system and multiple fluo-rescence quantitative PCR methods were used to rapidly screen for pathogens in samples from the poisoning event.According to the initial screening results,bacteria were isolated,cultured,and identified by mass spectrometry.Fluorescence PCR was used to detect six virulence genes of the isolated Clostridium perfringens strains.On the basis of whole genome sequencing results,we conducted virulence genes,resistance genes,and whole genome single nucleotide polymorphism genetic evolution(wgSNPs)analyses.Antibiotic sensitivity testing was conducted with the agar dilution method.A total of ten strains of Clos-tridium perfringens were isolated,including eight strains from seven anal swab samples,one strain from fecal samples,and one strain from food samples.Food with suspected contamination had a Clostridium perfringens count of 7.8×106 CFU/g.The PLC(a)toxin gene was detected in all ten gas producing capsule isolation strains,but no other 5 tox-in genes such as CPE were detected,thus confirming that all were type A bacteria producing capsule Clostridium.All strains were 100％resistant to clindamycin and almost completely sensitive to antibiotics such as vancomycin,cefoxitin,and meropenem.Ten strains of Clos-tridium perfringens carried resistance genes such as tetB(P),tetA(P),and mprF,followed by ermQ(70％),ant(6)-Ⅰb(10％),and LnuP(10％).Genetic evolution analysis of wgSNPs indicated that the four outbreak strains clustered together and belonged to an independent subbranch with the suspected food sourcestrains,thus indicating close genetic relationships.In con-clusion,this food poisoning incident might have been be caused by hand torn chickens contaminated with Clostridium perfrin-gens,and the molecular types of the strains revealed high genetic diversity.No multiple drug resistance was observed,but all strains were resistant to clindamycin,an aspect requiring further clinical attention.

Objective: To investigate the association of physical activity and screen time with overweight and obesity among children and adolescents with special needs in Tianjin, so as to provide scientific evidence for childhood obesity prevention and intervention measures in the population. Methods: From January 2022 to June 2024, 296 children and adolescents with intellectual disabilities and autism spectrum disorders aged 2-18 years were recruited from special education schools and institutions in Tianjin. Height and weight were measured, and a standardized questionnaire was used to assess physical activity and screen time. Binary Logistic regression analysis was carried out to investigate the association of physical activity and screen time with overweight and obesity. Results: The prevalence of overweight and obesity among children and adolescents with special needs in Tianjin were 17.2% and 21.6%, respectively, and the combined prevalence of overweight and obesity was 38.9%. The median of moderatetovigorous physical activity (MVPA) time was 0.20 h/d, and physical activity sufficiency rate was 7.8%. The median of screen time was 1.79 h/d, and the screen time compliance rate was 68.2%. The binary Logistic regression results showed that lower levels of MVPA time and increased screen time were associated with a higher risk of overweight and obesity among children and adolescents with special needs [OR(95%CI)=1.80(1.06-3.07), 2.40(1.42-4.07),P<0.05]. Conclusions Insufficient physical activity and excessive screen time are associated with an increased risk of overweight and obesity among children and adolescents with special needs. Therefore, comprehensive intervention measures should be implemented as early as possible to prevent and reduce the incidence of overweight and obesity in this population.