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

Objective To investigate whether circular RNA(circRNA)circ_0054633 targets microRNA-375(miR-375)to regulate the oxidative damage of cardiomyocytes induced by hydrogen peroxide(H2O2).Methods H9C2 cardiomyocytes were divided into control group(normal culture without any treatment),hydrogen peroxide(H2 O2)group(150 μmol·L-1 H2 O2 treated cardiomyocytes for 6 h),H2O2+si-NC group,H2O2+si-circ_0054633 group,H2O2+miR-NC group,H2O2+miR-375 group,H2O2+si-circ_0054633+anti-miR-NC group,H2O2+si-circ_0054633+anti-miR-375 group(cardiomyocytes were transfected with si-NC,si-circ_0054633,miR-NC,miR-375 mimics,si-circ_0054633+anti-miR-NC,si-circ_0054633+anti-miR-375,respectively;24 h after transfection,cardiomyocytes were treated with 150 μmol·L-1 H2O for 6 h).Real-time fluorescence quantitative polymerase chain reaction was used to determine the expression of miR-375,the content of malondialdehyde(MDA)and the activity of superoxide dismutase(SOD)were determined by kit,apoptosis was determined by flow cytometry.Results The expression levels of miR-375 in cardiomyocytes of control group,H2O2 group,H2O2+si-NC group,H2O2+si-circ_0054633 group,H2O2+miR-NC group,H2O2+si-circ_0054633+anti-miR-NC group,H2O2+si-circ_0054633+anti-miR-375 group were 1.00±0.00,0.42±0.05,0.40±0.06,0.69±0.08,1.00±0.00,3.41±0.28,1.00±0.00 and 0.26±0.02,respectively;MDA contents were(3.19±0.32),(13.46±1.27),(15.39±1.04),(5.26±0.51),(16.05±1.36),(9.18±0.85),(4.89±0.44)and(10.05±0.92)nmol·L-1,respectively;SOD activities were(64.69±5.81),(18.23±1.33),(17.07±1.41),(55.74±5.13),(17.12±1.64),(47.66±4.59),(56.77±4.71)and(27.95±2.47)U·mL-1,respectively;the apoptosis rates were(6.21±0.59)％,(29.22±2.19)％,(30.94±2.85)％,(10.05±0.92)％,(31.14±2.83)％,(13.74±1.24)％,(10.39±0.88)％and(21.31±1.92)％,respectively.The above indexes of H2O2 group were compared with the control group,the above indexes of H2O2+si-circ_0054633 group was compared with the H2O2+si-NC group,the above indexes of H2O2+miR-375 group was compared with the H2O2+miR-NC group,the above indexes of H2O2+si-circ_0054633+anti-miR-375 group were compared with H2O2+si-circ_0054633+anti-miR-NC group,the differences were statistically significant(all P＜0.05).Conclusion Interfering with the expression of circ_0054633 can reduce the oxidative stress and apoptosis of cardiomyocytes induced by hydrogen peroxide by targeting miR-375,thereby protecting cardiomyocytes from oxidative damage.

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.

Objective To observe the clinical effect of acupuncture combined with Shenqi Huoxue Decoction in the treatment of adenomyosis of qi deficiency and blood stasis type.Methods Seventy patients with adenomyosis of qi deficiency and blood stasis type were randomly divided into observation group and control group,35 cases in each group.The control group was treated with Levonorgestrel-releasing intrauterine system,and the observation group was treated with acupuncture combined with Shenqi Huoxue Decoction on the basis of the treatment of the control group.One menstrual cycle was a course of treatment,and the treatment lasted for three courses.After 3 months of treatment,the clinical efficacy of the two groups was evaluated,and the changes of Endometriosis Health Profile-5(EHP-5)score,serum superoxide dismutase(SOD)and catalase(CAT)were observed in the two groups before and after treatment.The changes of serum carbohydrate antigen CA125,carbohydrate antigen 199(CA199)and human epididymis protein 4(HE4)levels were compared before and after treatment between the two groups.Results(1)The total effective rate was 97.14％(34/35)in the observation group and 77.14％(27/35)in the control group.The clinical efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the levels of serum CA125,CA199 and HE4 in the two groups were significantly improved(P＜0.05),and the improvement of serum CA1 25,CA199 and HE4 levels in the observation group was significantly superior to that in the control group,the difference was statistically significant(P＜0.05).(3)After treatment,the levels of serum SOD and CAT in the two groups were significantly improved(P＜0.05),and the improvement of serum SOD and CAT levels in the observation group was significantly superior to that in the control group,the difference was statistically significant(P＜0.05).(4)After treatment,the EHP-5 score of quality of life in the two groups was significantly improved(P＜0.05),and the EHP-5 score of quality of life in the observation group was significantly superior to that in the control group,the difference was statistically significant(P＜0.05).Conclusion Acupuncture combined with Shenqi Huoxue Decoction in the treatment of adenomyosis of qi deficiency and blood stasis type can significantly improve the clinical symptoms of patients,regulate the levels of SOD and CAT,so as to improve the quality of life of patients,and the curative effect is significant.

Aim To study the effect of paeonol on macrophage phenotvpe conversion based on estrogen receptora (ERa).Methods The macrophage Ml polarization model was established by 100 jjig • L"' LPS and 20 pug • L_1 I FN-7.ELISA was used to examine the effects of paeonol on tumor necrosis factor-a ( TNF-cx ) , interleukin-1 £ ( 1L-1 £ ) , interleukin-10 (IL-10), superoxide dismutase (SOD) , and malondi- aldehyde ( MDA).Western blot was used to detect the expression of M1 phenotvpe markers iNOS, CD86 and M2 phenotvpe markers Arg-1 and CD 163 in macrophages.Further, the methods of blockers and shRNA interference were used to verify whether the effect of paeonol was mediated by ERa.Results ELISA results shower] that paeonol reduced the content of TNF-a, IL- lp and MDA, and increased the content of IL-10 and SOD.Western blot results showed that paeonol reduced the expression of iNOS and CD86 proteins in model group, and increased the expression of Arg-1 and CD163 proteins.Both ERa selective blocker MPP and ERa shRNA reduced the efficacy of paeonol, while ERp selective blocker PHTPP had no significant effect on paeonol.Conclusion Paeonol can induce the transformation of macrophages into M2 type by ERa and alleviate the progression of atherosclerosis.

Objective: The aim of this study is to discover the possible working mechanisms of Ardisiae Japonicae Herba (AJH) on hepatoma carcinoma (HCC). Methods: In this study, ethanol extract of AJH was prepared and used to treat HCC cell in vitro. Furthermore, a genomic wide RNA sequencing (RNA-seq) was performed to screen deregulated genes in HCC cells after the treatment of AJH extract. The gene and protein expression related to lipid metabolism in HCC cells were also investigated to validate the results obtained from RNA-seq. Results: AJH extract could inhibit HCC cell proliferation in vitro. RNA-seq analysis has identified 1,601 differentially expressed genes (DEGs, fold change ≥ 2.0 or fold change ≤ 0.5, P < 0.05) in HCC after AJH extract treatment, which included 225 up-regulated genes and 1,376 down-regulated genes. KEGG pathway analysis of DEGs demonstrated that lipid metabolism was a potential pathway related to AJH treatment. In agreement with the RNA-seq data, qPCR and Western-blot analysis indicated that expression of genes and proteins related to lipid metabolism (SREBP1, ACC, ACLY and FASN) were significantly down-regulated in AJH treatment group as compared with the control group. Furthermore, AJH extract could also decrease lipid contents and cellular free fatty acid levels in HCC cells. Conclusion: Ethanol extract of AJH could inhibit HCC cell proliferation in vitro, the possible mechanism may be related to the inhibition of lipid metabolism.

Objective:To evaluate the correlation of dietary patterns with low muscle mass, strength and quality in Chinese adults.Methods:Based on the second resurvey of China Kadoorie Biobank, factor analysis was conducted to derive dietary patterns from 20 food groups. Low muscle mass, strength, and quality were defined as the sex-specific lowest quintile of appendicular skeletal muscle mass index (ASMI), total skeletal muscle mass index (TSMI), handgrip strength and arm muscle quality (AMQ) according to Asian Working Group for Sarcopenia recommendations. Logistic regression models were used to evaluate the correlation of dietary patterns with low muscle mass, strength, and quality.Results:Two major dietary patterns were extracted. The balanced dietary pattern was characterized by the intake of a variety of foods, whereas the rice-meat dietary pattern was characterized by high intakes of rice, meat, poultry and fish. Individuals who had the highest quintile score of the balanced dietary pattern were less likely to have low TSMI, handgrip strength or AMQ( OR=0.83, 95% CI: 0.74-0.95 for low TSMI; OR=0.64, 95% CI: 0.56-0.74 for low handgrip strength; OR=0.82, 95% CI: 0.72-0.93 for low AMQ; for trend P<0.05). And those who scored higher on the rice-meat dietary pattern had lower risk of low muscle mass and strength ( OR=0.67, 95% CI: 0.55-0.82 for low ASMI; OR=0.69, 95% CI: 0.56-0.85 for low TSMI; OR=0.74, 95% CI: 0.60-0.91 for low handgrip strength; for trend P<0.05). Conclusion:Individuals followed the balanced dietary pattern, as well as those who followed the rice-meat dietary pattern, had better levels of skeletal muscle mass, strength and quality.

Objective:To explore the correlation between chronic diseases and muscle mass, strength and quality in adults in China.Methods:Based on the second resurvey of China Kadoorie Biobank (CKB) in 2013-2014, logistic regression models were used to analyze the correlation of different types, number and duration of chronic diseases with low muscle mass, handgrip strength and muscle quality.Results:The prevalence rate of diabetes, coronary heart disease (CHD), stroke and chronic obstructive pulmonary disease (COPD) were 9.6%, 5.8%, 3.2% and 26.8%, respectively, and 38.8% of the participants had at least one disease, and they were more likely to have low handgrip strength and low arm muscle quality (AMQ), and the longer the chronic diseases duration, the higher the risk. The ORs (95% CIs) for low handgrip strength and low AMQ in patients with 1 chronic disease for more than 10 years was 1.64 (1.42-1.90) and 1.83 (1.60-2.10), respectively. The ORs (95% CIs) for low handgrip strength were 1.26 (1.17-1.37), 1.42 (1.23-1.64) and 2.27 (1.55-3.32) and the ORs (95% CIs) for low AMQ were 1.28 (1.18-1.38), 1.67 (1.46-1.92) and 2.41(1.69-3.45), respectively, in patients with 1, 2, ≥3 chronic diseases, the correlation showed a linear trend ( P for trend <0.001). Diabetes, CHD and stroke were positively correlated with low handgrip strength and low AMQ. Compared with participants without COPD, COPD patients were more likely to have low appendicular skeletal muscle mass index (ASMI), low total skeletal muscle mass index (TSMI) and low handgrip strength, and the risk was positively correlated with disease duration. Conclusions:Patients with chronic diseases were more likely to have lower muscle strength and muscle quality, especially the patients with multi diseases and longer disease duration. The proportion of low handgrip strength and low AMQ was higher in patients who reported multi-prevalence and longer duration of chronic diseases.

Objective:To investigate the effect of Chloriti Lapis on metal elements in brain tissue and plasma of epileptic rats kindled by pentylenetetrazol （PTZ）， and to explore the possible material basis of Chloriti Lapis. Method:PTZ kindling method was used to establish epileptic rat model. Inductively coupled plasma mass spectrometry （ICP-MS） and inductively coupled plasma optical emission spectrometer （ICP-OES） were used to determine the contents of metal elements in brain tissue and plasma of the blank group， model group， carbamazepine group （0.1 g·kg^-1） and Chloriti Lapis group （2 g·kg^-1）. The data were statistically analyzed by SPSS 18.0 software. Result:Compared with the blank group， the contents of Sr， Sb and Ba in brain tissue of rats in the model group were significantly increased （P<0.05， P<0.01）， while the contents of Zn， Fe， Cu， K， Li， Co， Sn and Pb were significantly decreased （P<0.05， P<0.01）. Compared with the model group， the contents of Zn， Fe， K， Li， Co， As and Pb in brain tissue of rats in the Chloriti Lapis group were obviously increased （P<0.05， P<0.01）， while the contents of Sr and Sb were significantly decreased （P<0.01）. These results showed that Chloriti Lapis had positive effect on the regulation of the content of metal elements in rat brain tissue to normal level， the intervention effect was clear， and the overall effect was better than that of carbamazepine group. The determination of 21 metal elements in plasma showed that compared with the blank group， the levels of K， Sr and Cd in the model group were significantly increased （P<0.05）， and the contents of Li， Al， Ti and Cr were significantly decreased （P<0.05）. Compared with the model group， the contents of Ca， K， Li， Al and V in the Chloriti Lapis group were obviously increased （P<0.05， P<0.01）， and the contents of Fe， Ti， Sr and Cd were significantly decreased （P<0.05，P<0.01）. The correlation analysis of metal elements among the groups showed that there were 17 pairs of elements had positively correlation in the brain tissue of rats， 2 pairs of elements had significant negative correlation. In the plasma of rats， 8 pairs of elements had significant positive correlation and 6 pairs of elements had significant negative correlation. Conclusion:The metal element groups represented by Zn， Fe， K， Li， Co， As， Pb， Sr， Sb， Ca， Al， V， Ti and Cd may be the effective material basis for Chloriti Lapis to interfere PTZ-kindled epileptic model rats， which may be related to the influence of these metal element groups on the release of neurotransmitters and the electrical balance of neurons， the regulation of abnormal synchronous discharge induced by Na⁺， K⁺， Ca²⁺ channel disorders and intervention of metabolism pathways in brain tissue related to epilepsy. It can make the excitatory and inhibitory activities restrain each other， and finally reach the normal physiological state of neurons and cells. The intervention effect of Chloriti Lapis group was better than that of carbamazepine group.

Objective:To explore the possible mechanism of Chloriti Lapis in the treatment of epilepsy by the metabonomics of brain tissue in pentylenetetrazol （PTZ）-kindled epileptic rats treated with Chloriti Lapis. Method:The epileptic animal model in rats was established by PTZ kindling， and the rats were divided into the control group， model group， carbamazepine group and Chloriti Lapis group. The brain tissue samples were detected by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry（UPLC/Q-TOF-MS）， and the experimental results were statistically analyzed by partial least squares-discriminant analysis （PLS-DA） and SPSS 18.0. Result:The metabolic fingerprints and metabolic profiles of the rat brain tissue were established， which showed that the metabolic profiles of each group had changed significantly and could be separated well among the groups. Moreover， the Chloriti Lapis group had a tendency to be closer to the control group than the carbamazepine group. Seven differential metabolites were screened， including phosphatidylserine （PS） （18∶0/18∶0）， L-glutamic acid， docosahexaenoyl ethanolamide， arachidonic acid， glucosylsphingosine， cholestane-3，7，12，24，25-pentol and lysophosphatidylcholine （LysoPC） （P-18∶0）. Except for docosahexaenoyl ethanolamide and LysoPC （P-18∶0）， Chloriti Lapis had significant intervening and regulating effects on the other five differential metabolites. There were 12 possible metabolic pathways that affected the metabolic disorder of PTZ-kindled rats， and 3 important metabolic pathways （pathway impact>0.1）， namely， D-glutamine and D-glutamate metabolism， alanine， aspartate and glutamate metabolism， and arachidonic acid metabolism， among which D-glutamine and D-glutamate metabolism was the most important metabolic pathways. Conclusion:From this point of view， Chloriti Lapis has a clear intervention effect on PTZ-kindled epileptic rats， which may be related to the intervention of the above differential metabolite contents and related metabolic pathways. It can reduce the toxic effect of excitatory neurotransmitters on neurons in brain tissue and inhibit the development of inflammation in brain tissue， so as to maintain the biological function of brain cells and slow down the occurrence of epilepsy.