OBJECTIVE: To observe the effect of electroacupuncture (EA) pretreatment of "biaoben acupoint combination" on cardiomyocyte mitochondrial fission in the rats with myocardial ischemia-reperfusion injury (MIRI) and explore its mechanism. METHODS: Fifty male SD rats were randomly divided into a sham-operation group, a model group, an EA pretreatment group, an EA pretreatment + Compound C group and an EA pretreatment+ML385 group, 10 rats in each group. In the EA pretreatment, the EA pretreatment + Compound C group and the EA pretreatment+ML385 group, EA was delivered at bilateral "Neiguan" (PC6), "Zusanli" (ST36) and "Guanyuan" (CV4) for 20 min, with continuous wave and 2 Hz of frequency, 1 mA of current, once daily for consecutive 7 days. On day 8, in the EA pretreatment + Compound C group and the EA pretreatment+ML385 group, 30 min before model preparation, the intraperitoneal injection with Compound C (0.3 mg/kg) and ML385 (30 mg/kg) was administered respectively. Except in the sham-operation group, the ligation of the left anterior descending coronary artery was performed to prepare MIRI rat model in the rest groups. In the sham-operation group, the thread was not ligated. After modeling, the content of reactive oxygen species (ROS) in the ischemic area was measured by flow cytometry, superoxide dismutase (SOD) was detected using xanthine oxidase method, and malondialdelyde (MDA) was detected using thiobarbituric acid (TBA) chromatometry. The morphology of myocardial tissue in the ischemic area was observed with HE staining, and the mitochondria ultrastructure of cardiomyocytes observed under transmission electron microscopy. Using immunofluorescence analysis, the positive expression of mitochondrial fission factor (MFF), mitochondrial fission 1 protein antibody (Fis1) and dynamin-related protein 1 (Drp1) was detected; and with immunohistochemical method used, the protein expression of adenosine monophosphate-activated protein kinase (AMPK), nuclear factor E2-associated factor2 (Nrf2) and Drp1 in the ischemic area was detected. RESULTS: Compared with the sham-operation group, the content of ROS and MDA in the myocardial tissue of the ischemic area, and the positive expression of MFF, Fis1 and Drp1 increased in the model group (P<0.01); the content of SOD and the protein expression of AMRK and Nrf2 decreased (P<0.01), and the protein expression of Drp1 elevated (P<0.01). Compared with the model group, the content of ROS and MDA in the myocardial tissue of the ischemic area, and the positive expression of MFF, Fis1 and Drp1 were dropped in the EA pretreatment group (P<0.01); the content of SOD and the protein expression of AMRK and Nrf2 rose (P<0.01), and the protein expression of Drp1 declined (P<0.01); and in the EA pretreatment+Compound C group and the EA pretreatment+ML385 group, the positive expression of MFF, Fis1 and Drp1, and the protein expression of Drp1 were all reduced (P<0.01). When compared with the EA pretreatment + Compound C group and the EA pretreatment+ML385 group, the content of ROS and MDA in the myocardial tissue of the ischemic area, and the positive expression of MFF, Fis1 and Drp1 were dropped in the EA pretreatment group (P<0.01); the content of SOD and the protein expression of AMRK and Nrf2 rose (P<0.01, P<0.05), and the protein expression of Drp1 decreased (P<0.05). In comparison with the model group, the EA pretreatment+Compound C group and the EA pretreatment+ML385 group, the cardiac muscle fiber rupture, cell swelling and mitochondrial disorders were obviously alleviated in the EA pretreatment group. The morphological changes were similar among the model group, the EA pretreatment+Compound C group and the EA pretreatment+ML385 group. CONCLUSION Electroacupuncture pretreatment of "biaoben acupoint combination" attenuates myocardial injury in MIRI rats, probably through promoting the phosphorylation of AMPK and Nrf2, inhibiting the excessive mitochondrial fission induced by Drp1, and reducing mitochondrial dysfunction caused by mitochondrial fragmentation and vacuolation.
Animals ; Electroacupuncture ; Male ; Rats, Sprague-Dawley ; Myocardial Reperfusion Injury/physiopathology* ; Myocytes, Cardiac/cytology* ; Rats ; Acupuncture Points ; Mitochondrial Dynamics ; Humans ; Reactive Oxygen Species/metabolism* ; NF-E2-Related Factor 2/genetics* ; Superoxide Dismutase/metabolism*

To satisfy the growing healthcare demands of the public, it is essential to develop a public service platform for vaccination. This initiative aligns with national policies, optimizes resource allocation, innovates service models, enhances service efficiency, and reduces service costs. Drawing on relevant national policies and regulatory requirements, as well as the notable achievements and practical experiences gained through the exploration and innovation of vaccination service models across various regions, this paper proposes expert recommendations. It defines the essential components and functional specifications for public service platforms, focusing on public needs such as electronic vaccination record management, appointment management, the promotion of electronic vaccination certificates, vaccination certificate verification for school enrollment, vaccination site navigation, and science communication and public engagement. The recommendations aim to serve as a reference for the development of vaccination public service platforms nationwide.

To satisfy the growing healthcare demands of the public, it is essential to develop a public service platform for vaccination. This initiative aligns with national policies, optimizes resource allocation, innovates service models, enhances service efficiency, and reduces service costs. Drawing on relevant national policies and regulatory requirements, as well as the notable achievements and practical experiences gained through the exploration and innovation of vaccination service models across various regions, this paper proposes expert recommendations. It defines the essential components and functional specifications for public service platforms, focusing on public needs such as electronic vaccination record management, appointment management, the promotion of electronic vaccination certificates, vaccination certificate verification for school enrollment, vaccination site navigation, and science communication and public engagement. The recommendations aim to serve as a reference for the development of vaccination public service platforms nationwide.

AIM:To evaluate the bioequivalence of the two rivaroxaban tablets in Chinese healthy subjects.METHODS:Twenty-eight subjects under fasting status and twenty-eight subjects under fed status were enrolled in the study.This study was designed as a four period,fully repetitive,cross-over study.All subjects were administered test(T)and reference(R)rivaroxaban tablets(10 mg)un-der fasting and fed condition respectively.Liquid chromatography-tandem mass spectrometry was used to detect the concentrations of rivaroxaban in plasma.WinNonlin 7.0 was used to calculate the main pharmacokinetic parameters(PK)and to eval-uate the bioequivalence.RESULTS:In fasting group,the main pharmacokinetic parameters of T and R preparation were as follows:Cmax were(186.57±56.41)and(187.61±50.89)ng/mL;AUC0-t were(1 156.21±335.85)and(1 177.59±343.72)h·ng·mL-1;AUC0-∞ were(1 235.77±384.03)and(1223.53±392.10)ng·h·mL-1.The 90％confidential interval(CI)of the three main parameters were 90.81％-105.67％,92.83％-103.85％and 95.04％-107.13％.The upper limit of the 90％CI for the test-to-reference ratio of the within-subject of Cmax,AUC0-t and AUC0-∞ were 1.56,1.41 and 1.73.In fed group,the main pharmacokinetic parameters of T and R preparation were as follows:Cmax were(207.81±45.26)and(211.04±36.62)ng/mL;AUC0-t were(1 271.26±260.92)and(1 233.23±201.85)h·ng·mL-1;AUC0-∞ were(1 290.76±264.90)and(1251.68±203.73)ng·h·mL-1.The 90％CI of the three main parameters were 92.82％-102.28％,97.68％-106.68％and 97.71％-106.68％.The upper limit of the 90％CI for the test-to-reference ratio of the within-subject of Cmax,AUC0t and AUC0-∞were 1.76,1.47 and 1.47.CONCLUSION:The two preparations of rivaroxaban tablets were bioequiva-lent.

AIM:To evaluate the bioequivalence of the two rivaroxaban tablets in Chinese healthy subjects.METHODS:Twenty-eight subjects under fasting status and twenty-eight subjects under fed status were enrolled in the study.This study was designed as a four period,fully repetitive,cross-over study.All subjects were administered test(T)and reference(R)rivaroxaban tablets(10 mg)un-der fasting and fed condition respectively.Liquid chromatography-tandem mass spectrometry was used to detect the concentrations of rivaroxaban in plasma.WinNonlin 7.0 was used to calculate the main pharmacokinetic parameters(PK)and to eval-uate the bioequivalence.RESULTS:In fasting group,the main pharmacokinetic parameters of T and R preparation were as follows:Cmax were(186.57±56.41)and(187.61±50.89)ng/mL;AUC0-t were(1 156.21±335.85)and(1 177.59±343.72)h·ng·mL-1;AUC0-∞ were(1 235.77±384.03)and(1223.53±392.10)ng·h·mL-1.The 90％confidential interval(CI)of the three main parameters were 90.81％-105.67％,92.83％-103.85％and 95.04％-107.13％.The upper limit of the 90％CI for the test-to-reference ratio of the within-subject of Cmax,AUC0-t and AUC0-∞ were 1.56,1.41 and 1.73.In fed group,the main pharmacokinetic parameters of T and R preparation were as follows:Cmax were(207.81±45.26)and(211.04±36.62)ng/mL;AUC0-t were(1 271.26±260.92)and(1 233.23±201.85)h·ng·mL-1;AUC0-∞ were(1 290.76±264.90)and(1251.68±203.73)ng·h·mL-1.The 90％CI of the three main parameters were 92.82％-102.28％,97.68％-106.68％and 97.71％-106.68％.The upper limit of the 90％CI for the test-to-reference ratio of the within-subject of Cmax,AUC0t and AUC0-∞were 1.76,1.47 and 1.47.CONCLUSION:The two preparations of rivaroxaban tablets were bioequiva-lent.

ObjectiveTo explore the effect of tetramethylpyrazine （TMP） on the vascular mimicry （VM） of non-small cell lung cancer A549 stem cell-like cells （CSLCs） in hypoxic state， and on the expression of hepatocyte growth factor （HGF）/mesenchymal-epithelial transition factor （c-Met）. MethodSerum-free sphere culture method was used to separate and enrich A549 CSLCs， and flow cytometry to detect the expression of stem cell marker CD44⁺/CD24^-/low. CoCl₂ was employed to induce hypoxia model. Cell counting kit-8 （CCK-8） assay was employed to examine the influence of 100， 200， 400， 800， 1 600， and 3 200 μmol·L^-1 TMP on the viability of A549 CSLCs. The low， medium， and high concentration （100， 200， 400 μmol·L^-1） of TMP that did not significantly affect the viability of A549 CSLCs was selected for subsequent experiments. Tube formation assay was used to detect the effect of different concentration of TMP on the formation of A549 CSLCs VM under hypoxia condition， and Western blot was applied to measure the expression of HGF/c-Met. ResultThe CD44⁺/CD24^-/low expression ratio of the isolated and enriched CSLCs was （80.3±0.21）%， which was significantly higher than that of the A549 group （P<0.01）. Compared with the control group， TMP groups showed increase in the inhibition rate of CSLCs， particularly the 24 h TMP （800， 3 200 μmol·L^-1） groups and the 48 h TMP （1 600， 3 200 μmol·L^-1） groups （P<0.05）. Compared with blank group and Bevacizumab （Bev） group， each concentration of TMP decreased the number of tubes formed and intersections （P<0.01）. The number of tubes formed and intersections decreased in TMP groups compared with that in the SU11274 group， particularly the 200 μmol·L^-1 TMP group （P<0.05） and 400 μmol·L^-1 TMP group （P<0.01）. Levels of HGF and c-Met in all TMP groups were down-regulated compared with those in the blank group （P<0.05， P<0.01）. ConclusionTMP can inhibit the formation of VM in A549 CSLCs in vitro under hypoxia condition which may act by regulating HGF/c-Met related signaling pathways.

Purpose: We aimed to investigate whether obtaining a higher level of education was causally associated with lower breast cancer risk and to identify the causal mechanism linking them. Methods: The main data analysis used publicly available summary-level data from 2 large genome-wide association study consortia. Mendelian randomization (MR) analysis used 65 genetic variants derived from the Social Science Genetic Association Consortium as instrumental variables for years of schooling. The outcomes from the Breast Cancer Association Consortium (BCAC) were the overall breast cancer risk (122,977 cases/105,974 controls in women) and the two subtypes: estrogen receptor (ER)-positive breast cancer and ER-negative breast cancer. Fixed and random effects inverse variance weighted methods were used to estimate the causal effects, along with other additional MR methods for sensitivity analyses. Results: Results showed that each additional standard deviation of 4.2 years of education was causally associated with a 27% lower risk of ER-negative breast cancer (odds ratio, 0.73; 95% confidence interval, 0.64–0.84; p-value < 0.001). This finding was consistent with the results of the sensitivity analyses. Physical activities can help improve the protective effect of education against breast cancer, with relatively large mediation proportions. Education increases the risk of ER-positive breast cancer due to alterations in high-density lipoprotein level, triglyceride level, height, waist-to-hip ratio, body mass index, and smoking status, with relative medium mediation proportions. Other mediators including low-density lipoprotein, hip circumference, number of cigarettes smoked per day, time spent performing light physical activity, and performing vigorous physical activity for > 10 minutes explain a small part of the causal effect of education on the risk of developing breast cancer, and their mediation proportion is approximately 1%. Conclusion A low level of education is a causal risk factor in the development of breast cancer as it is associated with poor lipid profile, obesity, smoking, and types of physical activity.

Objective To study the effective composition of Aster ageratoides Turcz for relieving asthma and its toxicity . Methods Seventy‐two qualified male guinea pigs ,body mass(300 ± 20)g ,were randomly divided into the control group ,aminophyl‐line group(0 .047 g/kg) and different ratio group of total saponins and total flavonoids (8∶1 ,4∶1 ,2∶1 ,1∶1 ,1∶2 ,1∶4 ,1∶8) . Every group received at dose of 0 .38 g/kg once a day for 3 days by intragastric administration .The effect of relieving asthma was taken as the indicators for the optimization of compositions ,which was detected by observing the latent period of asthma induced by acetylcholine‐histamine in guinea rats .The relaxation percentage of smooth muscle retracted by acetylcholine was detected by Pow‐erlab biological signal collecting system when aminophylline(1 .25 mg/mL) and different matching drugs(0 .02 g/mL) were added in Krebs′solution .The acute toxicities of total saponins ,total flavonoids and mixture of total saponins with total flavonoids (ratio of 1∶2) were detected by classical acute toxicity test of mice .Results Compared with the control group ,aminophylline group ,each group latent period of inducing asthma significantly or very significantly prolonged (P<0 .05) ,among them ,1∶1 ,1∶2 ,1∶4 group and other matching group were significantly different(P<0 .05) ,but 1∶2 group cited the longest incubation period .Aminophylline group and the ratio could significantly relaxe guinea pig tracheal smooth muscle retracted by acetylcholine .Aminophylline group di‐astolic percentage was the largest(24 .12 ± 1 .20)% ,all the groups were less than the percentage of diastolic aminophylline group (P<0 .05) ,but in 1∶2 group with the closest .Aster ageratoides Turcz ,tatarian aster total saponins ,total flavonoids and the ratio of 1∶2 to mice maximum tolerance was respectively 300 ,345 ,325 g/kg .Conclusion For the same total dosage ,the relieving asth‐ma effects of proportions of 1∶2 Aster ageratoides Turcz were obvious .There are no abnormal changes in the acute toxicity trila with total flavonoids ,total saponins ,as well as the ratio of 1∶2 ,safety is relatively good .

OBJECTIVETo conduct an experimental study on in vitro transdermal absorption of prepared Shangshi Zhitong cataplasm.

METHODFranz diffusing cells and mice were adopted for the percutaneous penetration study. The accumulative percutaneous permeation of total alkaloids, strychnine and atropine in certain time was determined by acid dye colorimetry and HPLC.

RESULTThe accumulative permeation of alkaloids (Q) increased with time (t), with a linear relation between them.

CONCLUSIONThe in vitro percutaneous penetration of Shangshi Zhitong cataplasm complies with the zero-order kinetics.

Administration, Cutaneous ; Alkaloids ; pharmacokinetics ; Animals ; Atropine ; pharmacokinetics ; Drugs, Chinese Herbal ; pharmacokinetics ; Male ; Mice ; Rats ; Rats, Wistar ; Skin Absorption ; Strychnine ; pharmacokinetics

Objective To clone the cDNA encoding human HMGB1, express it in E. coli, and identify its biological activity. Methods Human HMGB1 cDNA was amplified by RT-PCR and cloned into vector pUC19. After sequence analysis, the cDNA was ligated into prokaryotic expression vector pQE-80L and induced by IPTG to express HMGB1. The protein was purified with Ni~(2+)-NTA chromatography and polymyxin B affinity column. To identify the function of purified protein, the product was co-cultured with THP1 cells. Results Recombinant expression plasmid pQE-80L/HMGB1 was constructed successfully. After purification, the protein purity reached 96%. The recombinant HMGB1 stimulated THP1 to secrete TNF-? . Conclusion The highly purified HMGB1 was obtained successfully, which showed biological activity. These results lay the foundation for further research on the function of human HMGB1.