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

BACKGROUND: The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined. METHODS: All CTO vessels treated with successful anatomical PCI in patients from PANDA III trial were retrospectively measured for post-PCI QFR. The primary outcome was 2-year vessel-oriented composite endpoints (VOCEs, composite of target vessel-related cardiac death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization). Receiver operator characteristic curve analysis was conducted to identify optimal cutoff value of post-PCI QFR for predicting the 2-year VOCEs, and all vessels were stratified by this optimal cutoff value. Cox proportional hazards models were employed to calculate the hazard ratio (HR) with 95% CI. RESULTS: Among 428 CTO vessels treated with PCI, 353 vessels (82.5%) were analyzable for post-PCI QFR. 31 VOCEs (8.7%) occurred at 2 years. Mean value of post-PCI QFR was 0.92 ± 0.13. Receiver operator characteristic curve analysis shown the optimal cutoff value of post-PCI QFR for predicting 2-year VOCEs was 0.91. The incidence of 2-year VOCEs in the vessel with post-PCI QFR < 0.91 (n = 91) was significantly higher compared with the vessels with post-PCI QFR ≥ 0.91 (n = 262) (22.0% vs. 4.2%, HR = 4.98, 95% CI: 2.32-10.70). CONCLUSIONS Higher post-PCI QFR values were associated with improved prognosis in the PCI practice for coronary CTO. Achieving functionally optimal PCI results (post-PCI QFR value ≥ 0.91) tends to get better prognosis for patients with CTO lesions.

Objective To explore the efficacy and safety of ticagrelor de-escalation and nicorandil therapy in elderly patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI).Methods A total of 300 elderly patients with ACS were selected from the Sixth and Seventh Medical Center of Chinese PLA General Hospital and Beijing Chaoyang Integrative Medicine Emergency Rescue and First Aid Hospital from November 2016 to June 2019,including 153 males and 147 females,aged>65 years old.All the patients received PCI,and all had double antiplatelet therapy(DAPT)scores≥2 and a new DAPT(PRECISE-DAPT)score of≥25.All patients were divided into two groups by random number table method before operation:ticagrelor group(n=146,ticagrelor 180 mg load dose followed by PCI,and ticagrelor 90 mg bid after surgery)and ticagrelor de-escalation + nicorandil group(n=154,ticagrelor 180 mg load dose followed by PCI,ticagrelor 90 mg bid+nicorandil 5 mg tid after surgery,changed to ticagrelor 60 mg bid+ nicorandil 5 mg tid 6 months later).Follow-up was 12 months.The composite end points of cardiovascular death,myocardial infarction and stroke,the composite end points of mild hemorrhage,minor hemorrhage,other major hemorrhage and major fatal/life-threatening hemorrhage as defined by the PLATO study,and the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding within 12 months in the two groups were observed.Results The comparison of general baseline data between the two groups showed no statistically significant difference(P>0.05).There was also no significant difference in the composite end points of cardiovascular death,myocardial infarction and stroke between the two groups(P>0.05).The cumulative incidence of bleeding events in ticagrelor de-escalation + nicorandil group was significantly lower than that in ticagrelor group(P<0.05),while the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding were also significantly lower than those in tecagrelor group(P<0.05).Conclusion In elderly patients with ACS,the treatment of ticagrelor de-escalation + nicorandil after PCI may not increase the incidence of ischemic events such as cardiovascular death,myocardial infarction or stroke,and it may reduce the incidence of hemorrhagic events.

Objective:To analyze and compare the difference of gene expression profiles in normal colon tissues,colon adenoma and carcinoma tissues by RNA sequencing technology,and re-veal the key genes and potential mechanisms in the development from colon adenoma to carcinoma.Methods:RNA sequencing analysis was carried out on normal colon tissues,colon adenomas and carcinoma tissues of the same patient,and differential genes that were significantly expressed in colon cancer and not significantly expressed in adenoma tissues were obtained,and the GO and KEGG function enrichment analysis was performed.Results:There are 4307 differential genes that are significantly expressed in colon cancer and not significantly expressed in adenoma.The GO and KEGG function enrichment analysis of these genes found that they were mainly enriched in bi-ological processes such as biological process regulation,cell process regulation,protein binding and cancer pathway,PI3K Akt signal pathway MAPK signal pathway.Conclusion:There are many genes involved in the development process from colon adenoma to carcinoma.These genes have the potential to become therapeutic targets for colorectal cancer,providing a new direction for fol-low-up research on colorectal cancer.

Objective To observe the effects of Xiaomudan Granules on cholesterol synthesis in rats with non-alcoholic fatty liver disease(NAFLD);To explore its mechanism on the treatment of NAFLD based on mTORC1/USP20/HMGCR pathway.Methods Totally 60 SD rats were randomly divided into blank group,model group,Western medicine group(polyene phosphatidylcholine)and TCM low-,medium-and high-dosage groups(Xiaomudan Granules).The blank group was fed with ordinary diet,and the other groups were fed with high-fat diet for 12 weeks to establish NAFLD rat model.After successful modeling,each administration group was given the corresponding drug intragastric administration,and the blank group and model group were given aseptic distilled water intragastric administration for 4 weeks.Body mass and liver mass of rats were recorded,liver index was calculated,and serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C)contents were detected by automatic biochemical analyzer,the morphological changes of liver tissue were observed by HE staining and oil red O staining,real-time fluorescence quantitative PCR and Western blot were used to detect ribosome S6 kinase(S6K),ubiquitin specific protease 20(USP20),3-hydroxy-3-methylglutaryl CoA reduction enzyme(HMGCR)mRNA and p-S6K,S6K,USP20,HMGCR protein expression in liver tissue.Results Compared with the blank group,the body mass,liver mass and liver index of rats in model group significantly increased(P<0.01,P<0.05),the volume of liver lobe increased,the edge was blunted;the contents of serum ALT,AST,TC,TG and LDL-C significantly increased,while HDL-C content significantly decreased(P<0.01);most hepatocytes showed steatosis,significant vacuole and inflammatory infiltration,increased lipid droplets,and significantly increased mRNA expression of USP20 and HMGCR in liver tissue(P<0.01)and protein expressions of p-S6K,USP20 and HMGCR(P<0.01).Compared with the model group,TCM high-dosage group and Western medicine group could significantly decrease body mass,liver mass and liver index of rats(P<0.01,P<0.05),and improve the appearance of liver;decrease the contents of ALT,AST,TC and LDL-C in serum,and increase the content of HDL-C(P<0.01,P<0.05);alleviate hepatocyte steatosis and balloon-like degeneration,reduce lipid droplet deposition,and decrease USP20,HMGCR mRNA and p-S6K,USP20,HMGCR protein expression in liver tissue(P<0.01,P<0.05).Conclusion Xiaomudan Granules may regulate cholesterol synthesis through mTORC1/USP20/HMGCR pathway,and thus play a role in the treatment of NAFLD in rats.

This article summarizes Professor Xu Zhiyin's experience in treating non-puerperal mastitis from the perspective of mid-dle jiao qi movement and believes that the pathological viscera of non-puerperal mastitis are located in the liver,spleen,and stomach,and closely related to the middle jiao qi movement.According to clinical manifestations,the disease can be divided into lump stage,abscess stage,and fistula stage.The main pathogenesis of the disease is liver depression-spleen deficiency and phlegm obstructing the breast collaterals;long-term heat stagnation and excessive heat corroding the flesh;qi deficiency-evil stagnation and lingering restrai-ning.In terms of treatment,the pathogenesis should be clearly identified according to the different stages of the disease,and the medi-cine should be changed according to the pathogenesis.The key of treatment is to regulate the middle jiao qi movement and adjust the treatment according to the stage.In the lump stage,use pungency to disperse and bitterness to descend,and suppress wood and sup-port soil;in the abscess stage,lower the turbidity and raise the clearness,and discharge the fire and calm the wood;in the fistula stage,mobilize the central prefecture,and cultivate the soil and nourish the wood,so as to obtain satisfactory curative effect.

Objective To investigate the clinical effect of air moxibustion combined with pushpin-like needle acupuncture,which is formulated based on the"suppressing wood-supporting earth"theory in the doctrine of the five elements of Traditional Chinese Medicine(TCM),in the treatment of pain,nausea and vomiting after transcatheter arterial chemoembolization(TACE).Methods A total of 160 patients with hepatocellular carcinoma,who were admitted to the First Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine of China to receive initial TACE between July 2020 and June 2023,were enrolled in this study.The patients were randomly divided into 4 groups with 40 patients in each group.The patients of the control group received TACE with conventional nursing care,the patients of the pushpin-like needle group received pushpin-like needle acupuncture on the basis of the control group,the patients of the air moxibustion group received air moxibustion treatment on the basis of the control group,and the patients of the combination group received air moxibustion combined with pushpin-like needle acupuncture on the basis of the control group.The post-TACE pain degree(VAS scoring)and nausea/vomiting extent(INVR scoring)were compared between each other among the four groups.Results The differences in the VAS score and INVR score(including main effect and interaction effect)between each other among the four groups were statistically significant(all P＜0.05).Statistically significant differences in the VAS score and INVR score existed between the control group and the other three groups(all P＜0.05).The differences in the VAS score and INVR score between combination group and pushpin-like needle group,as well as between combination group and air moxibustion group were statistically significant(both P＜0.05).Conclusion Air moxibustion combined with pushpin-like needle acupuncture can effectively and remarkably relieve post-TACE pain,nausea and vomiting,which is superior to simple use of air moxibustion or pushpin-like needle acupuncture.Therefor,the combination use of air moxibustion and pushpin-like needle acupuncture should be popularized in clinical practice.

Objective To explore the effect of Wenyang Huazhuo Tongluo recipe on pulmonary microvascular injury in mice with scleroderma based on mitophagy.Methods Fifty mice were randomly divided into blank control group(0.9％NaCl,by gavage),control group(0.9％NaCl,by gavage),model group,Wenyang Huazhuo Tongluo recipe group(47mg·kg-1·d-1 Wenyang Huazhuo Tongluo recipe by gavage),positive control group(10 mg·kg-1·d-1 KC7F2 dissolved in phosphate buffer solution intraperitoneal injection),continuous administration for 4 weeks.The expression levels of in vitro membrane translocation enzyme 20(TOMM20),hypoxia inducible factor-1α(HIF-1α),B cell lymphoma-2/adenovirus E1B-19 kDa interacting protein 3(BNIP3),PTEN inducible muscle enzyme protein 1(PINK1)and E3 ubiquitin ligase(Parkin)in lung tissue were detected by immunohistochemistry(IHC).Western blot(WB)was used to detect the expression levels of mitophagy-related proteins(TOMM20,LC3B)and HIF-1α/BNIP3/PINK1/Parkin pathway proteins in pulmonary microvascular endothelial cells.Results The relative content of HIF-1α in microvascular endothelial cells of lung tissue in the control group,model group,Wenyang Huazhuo Tongluo recipe group and positive control group were 0.17±0.02,0.98±0.01,0.66±0.03 and 0.48±0.01;the relative content of BNIP3 were 0.40±0.02,0.74±0.01,0.56±0.01 and 0.60±0.02;the relative content of PINK1 were 0.26±0.04,0.88±0.01,0.65±0.02 and 0.67±0.02;the relative contents of Parkin were 0.33±0.02,0.89±0.01,0.65±0.02 and 0.77±0.02;the relative contents of TOMM20 were 1.10±0.02,0.58±0.01,1.02±0.01 and 0.98±0.03;the relative contents of LC3B-Ⅰ/LC3B-Ⅱ were 0.24±0.01,0.80±0.01,0.53±0.02 and 0.70±0.02,respectively.The content of HIF-1α,BNIP3,PINK1,Parkin and LC3B-Ⅰ/LC3B-Ⅱ in model group was higher than those in control group.Wenyang Huazhuo Tongluo recipe can effectively reduce its content.The content of TOMM20 in the model group was lower than that in control group,and Wenyang Huazhuo Tongluo recipe can effectively increase its content.Conclusion Wenyang Huazhuo Tongluo recipe may inhibit mitophagy and improve SSc pulmonary microvascular injury by increasing TOMM20 and inhibiting the protein expression of LC3B and HIF-1α/BNIP3/PINK1/Parkin signaling pathway.

In order to facilitate the accurate comprehension and correct implemention of the national occupational health standard Health standard for operators of nuclear power plants (GBZ/T 164-2022), this article presents an in-depth elucidation encompassing the significance of the standard promulgation, the background of its revision, the current status of the relevant domestic and international standards, the basis for revision of the principal technical inclusion and the application scope of the standard. The aim is to provide a guidance the selection, appropriate evaluation, and occupational health monitoring of nuclear power plant operators, ultimately ensuring the safe operation of nuclear facilities.

Objective to establish a combined diagnosis model of scleroderma related genes based on gene expression comprehensive database(GEO)and artificial neural network(ANN)and to evaluate its effect and to predict and analyze targeted traditional Chinese medicine.Methods two scleroderma chips GSE23741 and GSE95065 were obtained from the GEO database as the training group data set.Random forest and lasso regression algorithms were used to screen the key genes of scleroderma and construct the ANN model for the diagnosis of scleroderma.The validation data sets GSE76807,GSE32413 and GSE59785 were used to verify the model,and the area under curve(AUC)analysis was used to evaluate the clinical application value of ANN model.The relative expression of key gene mRNA was verified by RT-qPCR experiment.The CIBERSORT algorithm was used to estimate the bioinformatics association between scleroderma and the screened biomarkers.Finally,the key genes were used to screen the targeted traditional Chinese medicine.Results A total of 167 differential genes were obtained.Furthermore,the five most relevant key genes(SERPINE2,SFRP4,SUGCT,FBLN5,NRXN2)were screened by machine learning,and the artificial neural network diagnosis model was constructed.The model was used to draw the subject operating characteristic(ROC)curves diagnosed by the training group and the verification group,and the AUC value of the training group was 1.000.The AUC of verification group were 0.770,0.795 and 0.872 respectively.The result of RT-qPCR experiment is consistent with that of machine learning algorithm.Immune cell infiltration analysis showed that the relative content of memory CD4+T cells was significantly increased in scleroderma group,while the relative content of γ δ T cells in normal group was significantly increased.Key genes are associated with macrophage M1,T cells,memory activated CD4+T cells,resting mast cells,CD8+T cells and so on.According to the key genes,12 traditional Chinese medicines were screened.Most of the four qi and five flavors belong to warm,cold,flat,sweet,pungent and bitter,and most of them belong to the meridians of liver,spleen and lung.Conclusion the artificial neural network diagnosis model of key genes of scleroderma is constructed,which can be used in clinical diagnosis of scleroderma,and the potential targeted traditional Chinese medicine for the treatment of scleroderma is predicted,which provides a new perspective for exploring the pathogenesis of scleroderma.