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 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.

Objective To develop a multicolor photoelectroencephalography evoked flash to identify photosensitive epilepsy patients during the selection of naval aircraft pilots.Methods The multicolor photoelectroencephalography evoked flash was composed of a main body,a control box and a bracket.There were four rows of LED lights in the main body,which emitted four colors of light including red,yellow,green and orange,respectively;there were three sockets for signal,light and power and one color changeover switch on the body of the control box,and a control circuit board was fixed at the bottom inside the control box;the bracket had a double-jointed arm folding structure.The flash developed was compared with the coventional photoelectroencephalography evoked flash to verify its effect for inducing photosensitive epilepsy.Results There were no significant differences between the two flashes in the numbers of identified cases with photosensitive epilepsy when the subjects were under awake and closed-eye conditions(P＞0.05).Condusion The flash developed can make up for the deficiency of the coventional photoelectroencephalography evoked flash when selecting naval aircraft pilots.[Chinese Medical Equipment Journal,2024,45(7):112-114]

With the widespread use of carbapenem antibiotics,the clinical detection rate of carbapenem-resistant Gram-negative bacilli has shown a significant increase.Carbapenem-resistant Gram-negative bacilli isolates are often extensively or fully resistant,resulting in limited antimicrobial treatment options and high morbidity and mortality rates,posing a serious public health threat.The clinical treatment of carbapenem-resistant Gram-negative bacilli includes the use of single or combination antimicrobials such as polymyxin,tigecycline,and fosfomycin.A number of new antimicrobials and therapeutic approaches are under development.The clinical management of carbapenem-resistant Gram-negative infections is severely challenged by the limited choice of antimicrobial agents.Therefore,this article reviews the current status and progress of antimicrobial treatment for carbapenem-resistant Gram-negative bacilli to providing clinical reference.

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

In order to improve the management level of medicine list of medical institutions in China ，and help medical institutions build a medicine list of medical institutions with reasonable drug use structure ，standardized adjustment procedures ， convenient operation and application and scientific evaluation methods ，so as to meet the needs of clinical rational drug use to the greatest extent ，with the support of the Pharmaceutical Care Professional Committee of the Chinese Pharmaceutical Association ， China-Japan Friendship Hospital and the First Affiliated Hospital of University of Science and Technology of China （Anhui Provincial Hospital ）jointly initiate and complete Guideline for the Evaluation of Medicine List in Chinese Medical Institutions jointly with a number of medical institutions. In strict accordance with the methodological requirements of World Health Organization standard guidelines ，based on the Delphi method ，the guideline formulation working group has constructed the quality evaluation index system and quantitative scoring table of medicine list management in medical institutions from the 5 dimensions of organization and management ，structure，adjustment，application and e valuation of the list. It is used to help medical institutions evaluate the quality of their medicine list management ，so asto play a positive role in the fine management of medicine list in medical institutions.

The effects of Chloriti Lapis on metal elements in plasma and lung tissue of acute exacerbation of chronic obstructive pulmonary disease( AECOPD) rats were studied. The rat AECOPD model with phlegm heat syndrome was established by smoking combined with Klebsiella pneumoniae infection. After the rats were treated by Chloriti Lapis,the contents of metal elements in plasma and lung tissue were determined by inductively coupled plasma-optical emission spectroscopy( ICP-OES) and inductively coupled plasma mass spectrometry( ICP-MS). The changes in the contents of metal elements were analyzed by SPSS 18. 0. Further,the correlations of differential metal elements( including Cu/Zn ratio) with differential metabolites in plasma,lung tissue and urine of AECOPD rats treated with Chloriti Lapis were analyzed. The results showed that Chloriti Lapis significantly up-regulated the contents of Fe,Al,Mn,Cu,Zn,Sn( P<0. 05),V,Co( P< 0. 01) and Cu/Zn ratio( P< 0. 05),and significantly down-regulated the contents of Ti( P< 0. 05)and Pb( P<0. 05) in the model rat plasma. It significantly increased the content of Be( P<0. 05) and decreased the contents of Mg,Ti and Al( P<0. 01) in model rat lung tissue. The element profiles of normal group,model group and Chloriti Lapis group can be well separated. Chloriti Lapis group and other groups were clustered into two categories. The taurine in plasma and phytosphingosine in lung tissue had the strongest correlations with differential metal elements. The Fe,Al,Mg,Be,Ti,V,Mn,Cu,Zn,Sn,and Co in Chloriti Lapis may directly or indirectly participate in the intervention of AECOPD rats. This group of metal elements may be the material basis of Chloriti Lapis acting on AECOPD rats,and reduce the Cu/Zn value in vivo. It was further confirmed that Chloriti Lapis could interfere with the metabolic pathways of taurine and hypotaurine in plasma and urine as well as the sphingolipid metabolism pathway in lung tissue of AECOPD rats. In addition,this study confirmed that long-term smoking can cause high-concentration Cd accumulation in the lung and damage the lung tissue.
Animals ; Lung ; Medicine, Chinese Traditional ; Minerals ; Pulmonary Disease, Chronic Obstructive ; Rats ; Spectrum Analysis ; Trace Elements/analysis*

To study the effect of mineral Chloriti Lapis on pulmonary metabolites and metabolic pathways in lung tissues of rats with acute exacerbation of chronic obstructive pulmonary disease(AECOPD). The AECOPD rat model of phlegm heat syndrome was replicated by the method of smoking combined with Klebsiella pneumoniae infection. Except for using UPLC-Q-TOF-MS analysis, SPSS 18.0, SIMCA 13.0 and other software were also used for statistical analysis. Through literature search and online database comparison, the differential metabolites were identified, and the possible metabolic pathways were analyzed. After 15 days of administration, PLS-DA analysis was carried out on lung tissue samples of rats in each group. The results showed that the metabolic profiles of lung tissues of rats in each group could be well separated, which indicated that Chloriti Lapis and aminophylline had significant intervention effect on the lung metabolic profile of rats with AECOPD. Moreover, the metabolic profile of Chloriti Lapis group was closer to that of control group, and the intervention effect was better than that of aminophylline group. As a result, 15 potential differential metabolites were identified: phytosphingosine, sphinganine, tetradecanoylcarnitine, L-palmitoylcarnitine, elaidic carnitine, lysoPC[18∶2(9Z,12Z)], lysoPC(16∶0), lysoPC[18∶1(9Z)], lysoPC(18∶0), stearic acid, lysoPC(15∶0), arachidonic acid, docosapentaenoic acid, linoleic acid and palmitic acid. Among them, Chloriti Lapis could significantly improve the levels of 10 differential metabolites of phytosphingosine, tetradecanoylcarnitine, L-palmitoylcarnitine, elaidic carnitine, lysoPC[18∶2(9Z,12Z)], lysoPC(16∶0), lysoPC[18∶1(9Z)], stearic acid, lysoPC(15∶0), and palmitic acid(P<0.05). The intervention effect of Chloriti Lapis group was better than that of aminophylline group. Analysis of metabolic pathways showed that there were 8 possible metabolic pathways that could be affected, and three of the most important metabolic pathways(pathway impact>0.1) were involved: linoleic acid metabolism, arachidonic acid metabolism, and sphingolipid metabolism. Chloriti Lapis had obvious intervention effects on lung tissue-related metabolites and metabolic pathways in rats with AECOPD, and the effect was better than that of aminophyllinne.
Animals ; Lung ; Medicine, Chinese Traditional ; Metabolomics ; Minerals ; Pulmonary Disease, Chronic Obstructive ; Rats