The current study aimed to clarify the roles of apolipoprotein A5 (ApoA5) and milk fat globule-epidermal growth factor 8 (Mfge8) in regulating myocardial lipid deposition and the regulatory relationship between them. The serum levels of ApoA5 and Mfge8 in obese and healthy people were compared, and the obesity mouse model induced by the high-fat diet (HFD) was established. In addition, primary cardiomyocytes were purified and identified from the hearts of suckling mice. The 0.8 mmol/L sodium palmitate treatment was used to establish the lipid deposition cardiomyocyte model in vitro. ApoA5-overexpressing adenovirus was used to observe its effects on cardiac function and lipids. The expressions of the fatty acid uptake-related molecules and Mfge8 on transcription or translation levels were detected. Co-immunoprecipitation was used to verify the interaction between ApoA5 and Mfge8 proteins. Immunofluorescence was used to observe the co-localization of Mfge8 protein with ApoA5 or lysosome-associated membrane protein 2 (LAMP2). Recombinant rMfge8 was added to cardiomyocytes to investigate the regulatory mechanism of ApoA5 on Mfge8. The results showed that participants in the simple obesity group had a significant decrease in serum ApoA5 levels (P < 0.05) and a significant increase in Mfge8 levels (P < 0.05) in comparison with the healthy control group. The adenovirus treatment successfully overexpressed ApoA5 in HFD-fed obese mice and palmitic acid-induced lipid deposition cardiomyocytes, respectively. ApoA5 reduced the weight of HFD-fed obese mice (P < 0.05), shortened left ventricular isovolumic relaxation time (IVRT), increased left ventricular ejection fraction (LVEF), and significantly reduced plasma levels of triglycerides (TG) and cholesterol (CHOL) (P < 0.05). In myocardial tissue and cardiomyocytes, the overexpression of ApoA5 significantly reduced the deposition of TG (P < 0.05), transcription of fatty acid translocase (FAT/CD36) (P < 0.05), fatty acid-binding protein (FABP) (P < 0.05), and fatty acid transport protein (FATP) (P < 0.05), and protein expression of Mfge8 (P < 0.05), while the transcription levels of Mfge8 were not significantly altered (P > 0.05). In vitro, the Mfge8 protein was captured using ApoA5 as bait protein, indicating a direct interaction between them. Overexpression of ApoA5 led to an increase in co-localization of Mfge8 with ApoA5 or LAMP2 in cardiomyocytes under lipid deposition status. On this basis, exogenous added recombinant rMfge8 counteracted the improvement of lipid deposition in cardiomyocytes by ApoA5. The above results indicate that the overexpression of ApoA5 can reduce fatty acid uptake in myocardial cells under lipid deposition status by regulating the content and cellular localization of Mfge8 protein, thereby significantly reducing myocardial lipid deposition and improving cardiac diastolic and systolic function.
Animals ; Humans ; Mice ; Myocytes, Cardiac/metabolism* ; Obesity/physiopathology* ; Male ; Apolipoprotein A-V/blood* ; Lipid Metabolism/physiology* ; Milk Proteins/blood* ; Myocardium/metabolism* ; Diet, High-Fat ; Antigens, Surface/physiology* ; Mice, Inbred C57BL ; Cells, Cultured ; Female

The chemical constituents from leaves of Cyclocarya paliurus were isolated and purified by chromatography on silica gel, C_(18) reverse-phase silica gel, and Sephadex LH-20 gel, as well as semi-preparative high-performance liquid chromatography. Six compounds were identified by UV, IR, NMR, MS, calculated ECD, and comparison with literature data as cyclopaloside D(1), boscialin(2),(5R,6S)-6-hydroxy-6-[(E)-3-hydroxybut-1-enyl]-1,1,5-trimethylcyclohexanone(3), 3S,5R-dihydroxy-6R,7-megastigmadien-9-one(4), 3S,5R-dihydroxy-6S,7-megastigmadien-9-one(5), and gingerglycolipid A(6), respectively. Among them, compound 1 was identified as a new tetralone glycoside, and compounds 2-6 were isolated from leaves of C. paliurus for the first time. Furthermore, compound 1 exhibited strong antioxidant activity, with the IC_(50) of(454.20±31.81)μmol·L~(-1) and(881.82±42.31)μmol·L~(-1) in scavenging DPPH and ABTS free radicals, respectively.
Plant Leaves/chemistry* ; Glycosides/isolation & purification* ; Juglandaceae/chemistry* ; Tetralones/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification*

Objective To investigate the effects of Simo decoction on duodenal microinflammation and NOD-like receptor thermal protein domain associated protein 3(NLRP3)/cysteinyl aspartate-specific proteinase-1(Caspase-1)/gasdermin D(GSDMD)signaling pathway in rats with functional dyspepsia(FD).Methods The FD model was established by multifactorial method.SD rats were randomly divided into normal group,model group(FD model),positive control group(gavage administration of 0.305 mg·kg-1 mosapride injection)and experimental-H,-M,-L groups(gavage administration of 5.62,2.81,1.40 g·kg-1 Simo decoction).Small intestinal advancement rate and gastric emptying rate was determined;the levels of interleukin(IL)-1 β and IL-18 in serum were determined by enzyme linked immunosorbent assay(ELISA);the protein expression of NLRP3 and GSDMD in duodenal tissue was detected by Western blotting.Results The gastric emptying rates of normal,model,positive control and experimental-H,-M,-Lgroupswere(58.34±5.72)％,(29.16±8.37)％,(48.77±6.10)％,(48.35±6.04)％,(48.20±3.49)％and(39.24±4.20)％;the small intestinal propulsion rates were(82.01±7.55)％,(41.95±9.53)％,(64.61±10.18)％,(75.04±9.76)％,(60.58±7.13)％and(45.89±7.40)％;serum IL-1 β expression were(12.86±0.88),(43.73±4.60),(18.84±0.86),(24.61±1.57),(19.14±0.77)and(29.04±0.72)pg·mL-1;IL-18 expressions were(95.00±3.74),(170.60±8.78),(108.50±3.05),(118.90±3.45),(99.90±8.70)and(141.00±3.71)pg·mL-1;the relative expression levels of NLRP3 proteins were 0.32±0.02,0.84±0.05,0.42±0.03,0.48±0.02,0.61±0.04 and 0.62±0.05;the relative expression levels of GSDMD proteins were 0.34±0.05,0.93±0.06,0.35±0.03,0.52±0.02,0.53±0.06 and 0.55±0.05,respectively.Compared with the normal group,the above indexes in the model group have statistical significance;compared with the model group,the above indexes in the experimental-H group and the positive control group also have statistical significance(P＜0.01 or P＜0.05).Conclusion Simo decoction can effectively improve the general condition and duodenal microinflammation in FD rats,and the mechanism may be related to the inhibition of duodenal NLRP3/Caspase-1/GSDMD signaling pathway.

AIM To establish a GC-MS method for the simultaneous content determination of sixteen pesticide residues in Lycii Fructus and perform safety assessment.METHODS The analysis was performed on DB-5MS chromatographic column(30 m×0.25 mm,0.25 μm)subjected to the programmed heating,with splitless injection of 1.0 μL dissolved sample at a flowing rate of 1.0 mL/min.Other parameters were as follows:injection port temperature of 250℃,electron impact ionization(EI),electron energy of 70 eV;ion source temperature of 230℃,multi-reaction monitoring mode,and collision gas.of high-purity N2.Pesticide residues with relatively high dietary risk were analyzed and discussed with regard to residue levels,dietary intake risk,risk ranking and cumulative exposure assessment.RESULTS Sixteen pesticides showed good linear relationships within their own ranges(r≥0.994 4),whose average recoveries were 70%-114%,with the RSDs of less than 2%.The highest average cyfluthrin residue of 0.999 2 mg/kg in Lycii Fructus of production regions and the highest average cypermethrin residue of 0.088 4 mg/kg in Lycii Fructus commodities were both detected.In Lycii Fructus of production regions with chronic hazard index(HI)value of 0.012 9 and acute HI value of 0.065 5 and their commodities with chronic HI of 0.001 2 and acute HI of 0.005 4,the pesticide residue of cypermethrin was the leading cause of chronic and acute dietary risk,and additionally,pyridaben within maximum residue limit(MRL)was the only detectectable highly toxic pesticide among the other most concerning pestcides of deltamethrin,pyridaben,chlorpyrifos,dichlorvos and methidathion.CONCLUSION There exist pesticide residues within MRL values in some samples of Lycii Fructus and the use of cypermethrin should be well-controlled.

Objective:To analyze the application effect of intelligent acceptance equipment for orthopedic medical equipment combined with medical device unique device identifier(UDI)code in the management of orthopedic medical devices.Methods:Based on the UDI code,the UDI application process of orthopedic medical devices was formulated,and all operations such as inspection and accurate billing of orthopedic medical devices were completed through the identification and comparison of intelligent acceptance equipment for orthopedic medical devices.A total of 8 317 orthopedic instruments used in orthopedic surgery in Wangjing Hospital of China Academy of Chinese Medical Sciences from September to December 2023 were selected.According to the different time of the implementation of intelligent acceptance equipment for orthopedic medical devices,the 4 072 orthopedic devices used from September to October 2023 was marked as before implementation and adopted the traditional management mode,the 4 245 orthopedic devices used from November 2023 to December 2023 were marked as before implementation and adopted the intelligent acceptance management mode.The management effect and incidence of adverse events were compared before and after the implementation of intelligent acceptance equipment for orthopedic medical devices.Results:The total effective rate of management after the implementation of intelligent acceptance equipment for orthopedic medical instruments was 98.78%,which was significantly higher than that before the implementation,the difference was statistically significant(x2=272.03,P<0.01).The total incidence of adverse events after the implementation of the intelligent acceptance equipment for orthopedic medical devices was 8.83%,which was significantly lower than that before the implementation,the difference was statistically significant(x2=281.38,P<0.01).Conclusion:The intelligent acceptance device combined with UDI code for orthopedic medical devices can achieve efficient distribution,accurate acceptance and billing,reduce the occurrence of adverse events,meet the requirements of the whole process traceability management of one thing and one code,and improve the management level orthopedic medical devices.

Objective:To investigate the relationship between the duration of the second stage of labor and the amount of postpartum hemorrhage within 2 hours in primiparas using epidural analgesia.Methods:A retrospective study was conducted on the clinical data of pregnant women who delivered vaginally in the obstetrics department of the Affiliated Hospital of Jining Medical University from January 1, 2020, to December 31, 2020. The data included maternal age, pre-pregnancy body mass index (BMI), gravidity, gestational age at delivery, weight gain during pregnancy, common pregnancy complications (such as gestational hypertension, gestational diabetes, hypothyroidism, and pregnancy-related anemia), types of uterotonics, duration of each stage of labor, delivery outcomes, perineal conditions, postpartum hemorrhage within 2 hours, and neonatal birth length and weight. The exposure variable was the duration of the second stage of labor, and the outcome was the amount of postpartum hemorrhage within 2 hours. Potential risk factors were analyzed using univariate analysis. After adjusting for potential confounding factors, a generalized additive model was used for linear regression analysis, smooth curve fitting, and threshold effect analysis to observe the relationship between the duration of the second stage of labor and postpartum hemorrhage within 2 hours.Results:A total of 2 067 primiparas were included in the study. The mean age of the participants was 26.5±3.6 years, the median duration of the second stage of labor was 54 min (range: 35-81 min), and the median amount of postpartum hemorrhage within 2 hours was 230 ml (range: 200-300 ml). After adjusting for factors such as maternal age, pre-pregnancy BMI, gestational age at delivery, vaginal delivery, duration of the first and third stages of labor, perineal conditions, types of uterotonics used within 2 hours postpartum, and neonatal birth length and weight, a positive relationship was found between the duration of the second stage of labor and the amount of postpartum hemorrhage within 2 hours ( ?=0.20, 95% CI: 0.00-0.30, P<0.05). The smooth curve fitting results showed a non-linear relationship between the duration of the second stage of labor and postpartum hemorrhage within 2 hours. Threshold effect analysis indicated that the two-segment regression model (Model Ⅱ) was more suitable for fitting the correlation compared to the univariate linear regression model (Model Ⅰ), with a log-likelihood ratio test P-value of 0.001, and the inflection point was 115 min for the second stage of labor (95% CI: 99-125 min). Conclusions:In primiparas using epidural analgesia, there is a non-linear relationship and threshold effect between the duration of the second stage of labor and the amount of postpartum hemorrhage within 2 hours. When the second stage of labor exceeds 115 min, the extension of the second stage may increase the amount of postpartum hemorrhage within 2 hours.

Objective:To investigate the relationship between the duration of the second stage of labor and the amount of postpartum hemorrhage within 2 hours in primiparas using epidural analgesia.Methods:A retrospective study was conducted on the clinical data of pregnant women who delivered vaginally in the obstetrics department of the Affiliated Hospital of Jining Medical University from January 1, 2020, to December 31, 2020. The data included maternal age, pre-pregnancy body mass index (BMI), gravidity, gestational age at delivery, weight gain during pregnancy, common pregnancy complications (such as gestational hypertension, gestational diabetes, hypothyroidism, and pregnancy-related anemia), types of uterotonics, duration of each stage of labor, delivery outcomes, perineal conditions, postpartum hemorrhage within 2 hours, and neonatal birth length and weight. The exposure variable was the duration of the second stage of labor, and the outcome was the amount of postpartum hemorrhage within 2 hours. Potential risk factors were analyzed using univariate analysis. After adjusting for potential confounding factors, a generalized additive model was used for linear regression analysis, smooth curve fitting, and threshold effect analysis to observe the relationship between the duration of the second stage of labor and postpartum hemorrhage within 2 hours.Results:A total of 2 067 primiparas were included in the study. The mean age of the participants was 26.5±3.6 years, the median duration of the second stage of labor was 54 min (range: 35-81 min), and the median amount of postpartum hemorrhage within 2 hours was 230 ml (range: 200-300 ml). After adjusting for factors such as maternal age, pre-pregnancy BMI, gestational age at delivery, vaginal delivery, duration of the first and third stages of labor, perineal conditions, types of uterotonics used within 2 hours postpartum, and neonatal birth length and weight, a positive relationship was found between the duration of the second stage of labor and the amount of postpartum hemorrhage within 2 hours ( ?=0.20, 95% CI: 0.00-0.30, P<0.05). The smooth curve fitting results showed a non-linear relationship between the duration of the second stage of labor and postpartum hemorrhage within 2 hours. Threshold effect analysis indicated that the two-segment regression model (Model Ⅱ) was more suitable for fitting the correlation compared to the univariate linear regression model (Model Ⅰ), with a log-likelihood ratio test P-value of 0.001, and the inflection point was 115 min for the second stage of labor (95% CI: 99-125 min). Conclusions:In primiparas using epidural analgesia, there is a non-linear relationship and threshold effect between the duration of the second stage of labor and the amount of postpartum hemorrhage within 2 hours. When the second stage of labor exceeds 115 min, the extension of the second stage may increase the amount of postpartum hemorrhage within 2 hours.

A randomized, double-blind, placebo-controlled, multi-center phase Ⅱ clinical trial design was used in this study to recruit subjects who were in line with the syndrome of excess heat and fire toxin, and were diagnosed as recurrent oral ulcers, gingivitis, and acute pharyngitis. A total of 240 cases were included and randomly divided into a placebo group and a Huanglian Jiedu Pills group. The clinical efficacy of Huanglian Jiedu Pills in treating the syndrome of excess heat and fire toxin was evaluated by using the traditional Chinese medicine(TCM) syndrome scale. Enzyme-linked immunosorbent assay(ELISA) was used to determine and evaluate the levels of adenosine triphosphate(ATP), 4-hydroxynonenal(4-HNE), and adrenocorticotropic hormone(ACTH) in plasma of the two groups before and after administration and to predict their application value as clinical biomarkers. The results showed that the disappearance rate of main symptoms in the Huanglian Jiedu Pills group was 69.17%, and that in the placebo group was 50.83%. The comparison between the Huanglian Jiedu Pills group and the placebo group showed that 4-HNE before and after administration was statistically significant(P<0.05). The content of 4-HNE in the Huanglian Jiedu Pills group decreased significantly after administration(P<0.05), but that in the placebo group had no statistical significance and showed an upward trend. After administration, the content of ATP in both Huanglian Jiedu Pills group and placebo group decreased significantly(P<0.05), indicating that the energy metabolism disorder was significantly improved after administration of Huanglian Jiedu Pills and the body's self-healing ability also alleviated the increase in ATP level caused by the syndrome of excess heat and fire toxin to a certain extent. ACTH in both Huanglian Jiedu Pills group and placebo group decreased significantly after administration(P<0.05). It is concluded that Huanglian Jiedu Pills has a significant clinical effect, and can significantly improve the abnormal levels of ATP and 4-HNE in plasma caused by the syndrome of excess heat and fire toxin, which are speculated to be the effective clinical biomarkers for Huanglian Jiedu Pills to treat the syndrome of excess heat and fire toxin.
Humans ; Adrenocorticotropic Hormone ; Hot Temperature ; Medicine, Chinese Traditional ; Adenosine Triphosphate

Ethnic medicine has a rich history of application. Because of the large number of ethnic groups, wide geographical distribution, and unique medical systems in China, the research on the human use experience(HUE) of ethnic medicine should combine the characteristics of ethnic medicine, be based on practical experience, and respect folk practice and tradition. The clinical positioning of ethnic medicine should consider three factors, i.e., population region, dominant diseases, and clinical demand. We should consider the development of traditional preparations that meet the needs of ethnic regions and encourage the development of new drugs that can be popularized and used nationwide for the dominant diseases of ethnic medicines. Attention should be paid to the problems such as a large number of customary articles or substitutes of ethnic medicinal materials, the phenomena of foreign bodies with the same name and different names for the same substance, the different standards of medicinal materials, and the poor processing standards. The name, processing method, source, medicinal parts, and dosage of ethnic medicinal materials or decoction pieces should be determined, and resources should be carefully evaluated to ensure the safety of medicinal resources and ecology. The preparation of ethnic medicine is mostly in the form of pills, powder, ointment, etc., with simple processing technology. The problems of low-quality stan-dards of some preparations, different prescriptions with the same name, and inconsistent processing technology should be overcome, and the process route and main process parameters should be clarified to lay the foundation for the subsequent empirical research on HUE. In the collection and analysis of the HUE data of ethnic medicine, the core guiding ideology of "patient-centered" should be established, and the experience data of patients should be collected. The problems of weak links existing in the inheritance of ethnic medicine should be solved, and flexible and diverse methods should be adopted. Meanwhile, on the premise of complying with the requirements of the principles of medical ethics, we should respect the religion, culture, and customs of ethnic areas to obtain the key HUE information of ethnic medicine. On the basis of the patient preference information and differences in regional disease epidemiology, population characteristics, and medical practice, whether the HUE conclusions of ethnic medicine can be extrapolated to patients outside the region is evaluated from the aspects of clinical benefits, risk tolerance, risk acceptance, etc. The HUE research on ethnic medicine is carried out in a clear way to guide the research and development of new ethnic medicines.
Humans ; Medicine, Chinese Traditional ; China ; Reference Standards ; Technology ; Drugs, Chinese Herbal/therapeutic use*

This study aimed to evaluate the biological effect and mechanism of Vernonia anthelmintica Injection(VAI) on melanin accumulation. The in vivo depigmentation model was induced by propylthiouracil(PTU) in zebrafish, and the effect of VAI on melanin accumulation was evaluated based on the in vitro B16F10 cell model. The chemical composition of VAI was identified according to the high-performance liquid chromatography quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS). Network pharmaco-logy was applied to predict potential targets and pathways of VAI. A "VAI component-target-pathway" network was established, and the pharmacodynamic molecules were screened out based on the topological characteristics of the network. The binding of active molecules to key targets was verified by molecular docking. The results showed that VAI promoted tyrosinase activity and melanin production in B16F10 cells in a dose-and time-dependent manner and could restore the melanin in the body of the zebrafish model. Fifty-six compounds were identified from VAI, including flavonoids(15/56), terpenoids(10/56), phenolic acids(9/56), fatty acids(9/56), steroids(6/56), and others(7/56). Network pharmacological analysis screened four potential quality markers, including apigenin, chrysoeriol, syringaresinol, and butein, involving 61 targets and 65 pathways, and molecular docking verified their binding to TYR, NFE2L2, CASP3, MAPK1, MAPK8, and MAPK14. It was found that the mRNA expression of MITF, TYR, TYRP1, and DCT in B16F10 cells was promoted. By UPLC-Q-TOF-MS and network pharmacology, this study determined the material basis of VAI against vitiligo, screened apigenin, chrysoeriol, syringaresinol, and butein as the quality markers of VAI, and verified the efficacy and internal mechanism of melanogenesis, providing a basis for quality control and further clinical research.
Animals ; Vernonia/chemistry* ; Melanins/metabolism* ; Zebrafish/metabolism* ; Network Pharmacology ; Molecular Docking Simulation ; Apigenin/pharmacology* ; Drugs, Chinese Herbal/pharmacology* ; Chromatography, High Pressure Liquid