Mechanism of Glycyrrhizae Radix et Rhizoma Alleviating Tripterygium wilfordii Polyglycoside Tablets-induced Liver Injury / 中国实验方剂学杂志

ObjectiveTo investigate the protective effect of cytochrome P4502D6 （CYP2D6） and cytochrome P4503A4 （CYP3A4）， key enzymes of drug metabolism in liver， on acute liver injury in water extract of Glycyrrhizae Radix et Rhizoma （WEOGRR）. MethodHealthy male Kunming mice were divided into normal group， model group， WEOGRR low-， medium- and high-dose groups （5， 10， 15 g·kg-1·d-1） and positive drug group （diammonium glycyrrhizinate， 75 mg·kg-1·d-1）， with 10 in each group. One week after preventive administration， acute liver injury model was induced by single intragastric administration of 270 mg·kg-1 Tripterygium Glycosides tablets， and samples were collected after 18 h. The pathological changes of liver were observed by hematoxylin-eosin （HE） staining. Serum liver function indexes including alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， γ-glutamyl transpeptadase （γ-GT）， alkaline phosphatase （ALP）， and total bilirubin （TBIL） as well as the levels of oxidative stress indexes including malondialdehyde （MDA） and superoxide dismutase （SOD） in hepatocytes were determined by biochemical method. Real-time polymerase chain reaction （Real-time PCR） and Western blot were performed to detect the mRNA and protein expression levels of CYP2D6 and CYP3A4， respectively. ResultCompared with normal group， model group had significant hepatocyte swelling and inflammatory cell infiltration （P<0.01）， increased AST， ALT， γ-GT， ALP and TBIL （P<0.05）， elevated MDA and decreased SOD （P<0.01） as well as down-regulated mRNA and protein expression levels of CYP2D6 and CYP3A4 （P<0.05）. Compared with the model group， the normal group had intact liver structure without obvious abnormality， and the WEOGRR groups and positive drug group presented alleviated hepatocyte swelling and inflammatory cell infiltration （P<0.01）， reduced AST， ALT， γ-GT， ALP and TBIL （P<0.01）， lowered MDA and increased SOD （P<0.01） as well as up-regulated expression levels of CYP2D6 and CYP3A4 （P<0.01）. ConclusionThe protective effect of WEOGRR on acute liver injury induced by Tripterygium glycosides tablets may be related to reducing the contents of AST， ALT， γ-GT， ALP and TBIL in serum， inhibiting MDA and increasing the activity of SOD in liver cells， and enhancing the activities of CYP2D6 and CYP3A4， thus accelerating the metabolism of toxic substances.

Discovery and repurposing of artemisinin / 医学前沿

Malaria is an ancient infectious disease that threatens millions of lives globally even today. The discovery of artemisinin, inspired by traditional Chinese medicine (TCM), has brought in a paradigm shift and been recognized as the "best hope for the treatment of malaria" by World Health Organization. With its high potency and low toxicity, the wide use of artemisinin effectively treats the otherwise drug-resistant parasites and helps many countries, including China, to eventually eradicate malaria. Here, we will first review the initial discovery of artemisinin, an extraordinary journey that was in stark contrast with many drugs in western medicine. We will then discuss how artemisinin and its derivatives could be repurposed to treat cancer, inflammation, immunoregulation-related diseases, and COVID-19. Finally, we will discuss the implications of the "artemisinin story" and how that can better guide the development of TCM today. We believe that artemisinin is just a starting point and TCM will play an even bigger role in healthcare in the 21st century.

Inhibitory effect of aliskiren on LPS-induced angiogenesis of HUVECs / 中国病理生理杂志

AIM:To investigate the inhibitory effect of aliskiren on the angiogenesis of human umbilical vein endothelial cells ( HUVECs) induced by lipopolysaccharide ( LPS) and to explore its possible mechanism.METHODS:HUVECs were cultured and randomly divided into blank group and renin group.The levels of tumor necrosis factor-α(TNF-α) and intercellular adhesion molecule-1 (ICAM-1) in the culture supernatant were detected by ELISA.The protein levels of Toll-like receptor 4 ( TLR4) and ICAM-1 in the HUVECs were determined by Western blot.HUVECs were cul-tured and randomly divided into control group, LPS group, low-dose (1μmol/L) aliskiren group, middle-dose (10μmol/L) aliskiren group and high-dose (100 μmol/L) aliskiren group.The proliferation of HUVECs was detected by MTT and BrdU assays.The mobility of HUVECs was measured by Transwell assay.The formation of the vessels was judged by ob-serving the formation of the luminal structure by HUVECs in Matrigel.The levels of TNF-α, ICAM-1 and monocyte chemo-tactic protein 1 ( MCP-1) in the culture supernatant were measured by ELISA.The expression of renin, TLR4, matrix me-talloproteinases-2 (MMP-2) and matrix metalloproteinases-9 (MMP-9) at mRNA and protein levels in the HUVECs was determined by RT-PCR and Western blot.RESULTS:Renin stimulated the expression of inflammatory factors and TLR4 in the HUVECs.Aliskiren inhibited the growth, migration and angiogenesis of HUVECs in a dose-dependent manner, de-creased the levels of TNF-α, ICAM-1 and MCP-1 and the expression of renin, MMP-2 and MMP-9, and inhibited TLR4 expression (P<0.05).CONCLUSION:Aliskiren inhibits LPS-induced angiogenesis of HUVECs, which may be related to the down-regulation of renin expression, the inhibition of TLR4-mediated inflammatory reaction, and the formation of MMP-9 and MMP-2.

Permanent occlusion of bilateral internal carotid arteries after intermittent occlusion of bilateral carotid arteries: a new rat model for vascular dementia / 国际脑血管病杂志

Objective To modify a classic two-vessel occlusion (2VO) modeling method in order to decrease the systematic errors in the behavioral experiments such as Morris water maze.Methods Thirty-two adult male Wistar rats were randomly allocated into classic 2VO model,modified model,sham operation and sham ligation groups (n =8 in each group).Only the bilateral common carotid arteries were ligated in the classic 2VO model group; the common carotid arteries were clipped intermittently,and the origins of pterygopalatine arteries of the internal carotid arteries were high selectively ligated in the modified model group; the common carotid arteries were only ligated intermittently in the sham ligation group; and only the common carotid arteries and the upper segment of pterygopalatine artery branches were separated in the sham operation group.The rat behavior was evaluated using the pupillary light reflex,Morris water maze and eight-arm radial maze.HE staining was used to observe the histological changes.Results The Morris water maze escape latency (F =72.169 - 163.102,all P ＜ 0.001) and the number of reference memory errors of eight-arm radial maze (F =33.515-74.726,all P ＜0.001) in the modified model and the classic 2VO model groups were longer and higher than those in the sham operation group.The pupillary light reflex of the rats was lost in the classic 2VO model group and the pupillary light reflex of the rats was normal in other groups.The reaching platform time in the classic 2VO model group was significantly longer than that in the modified model and sham operation groups (P ＜0.001).The percentage of target quadrant dwell time was also decreased significantly (at day 7 after procedure:F =13.770,P ＜0.001 ; at day 90 after procedure:F =14.780,P ＜0.001).HE staining showed pathological changes such as the cells decrease in hippocampal CA1 region and leukoaraiosis in the modified model and the classic 2VO model groups.In addition,there were more vacuole-like changes in the rat optic nerve region in the classic 2VO model group,while there were no such changes in the modified model group.Conclusions Establishing vascular dementia model with permanent occlusion of bilateral internal carotid arteries after intermittent occlusion of bilateral carotid arteries could avoid severe visual impairment in rats.In the Morris water maze and eight-arm maze test,the modified model rats showed significant decrease in learning and memory abilities and had hippocampal damage.

Safety and efficacy of dalteparin in percutaneous coronary intervention in Chinese patients with non-ST-elevation acute coronary artery syndromes: comparison with unfractionated heparin / 老年心脏病学杂志（英文版）

Objective To prospectively evaluate the safety and therapeutic efficacy ofdalteparin in patients with high risk non-ST-elevation acute coronary syndromes (ACS) during percutaneous coronary intervention (PCI). Methods Atotal of 175 patients with high risk non-ST-elevation ACS were randomly assigned to 2 groups [dalteparin group and unfractionated heparin (UFH) group]. The patients in dalteparin group were given dalteparin at a dose of 5,000U subcutaneously soon after diagnosis and then an additional 60U/ kg intravenous bolus ofdalteparin before emergent PCI. Vascular access sheaths were removed immediately after PCI or coronary artery angiography; the patients in UFH group were given UFH intravenously at a dose of 25mgjust before PCI and an additional 65mg bolus was administered if angiographic findings showed that the patients were suitable for percutaneous transluminai coronary angioplasty (PTCA). Sheaths were removed at 4-6 hours after PCI; Results Eighty-three patients in dalteparin group underwent PCI while 82 patients in UFH group underwent PCI; anti-Xa activities of 52 patients in dalteparin group were measured. The average anti-Xa activity was (0.83±0.26) U/ml at 15 minutes after intravenous injection of dalteparin and anti-Xa>0.5U/ml was obtained in 96.1% of the patients; hematomas at puncture sites were significantly fewer in dalteparin group as compared with UFH group (2.3% vs 9. 2%, P < 0.05); none of the patients in 2 groups suffered major bleeding events. No death, acute arterial reocclusion or emergent revascularization events occurred at 30 days after PCI. Conclusions Our study demonstrated that early subcutaneous injection of dalteparin at a dose 5,000U after diagnosis and an additional 60U/kg intravenous bolus ofdalteparin before PCI is safe and efficacious for patients with high risk non-ST-elevation ACS undergoing emergent PCI

Transfusion of activated immune cells induced fluctuations of HCV titer without mutations in hepatitis C virus core and E2 region CTL epitopes / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the variations of HCV core and E2 region epitopes during transfusion of activated immune cells.</p><p><b>METHODS</b>Four patients receiving transfusion of activated immune cells were under continuously observation. HCV titers were measured by quantitive PCR. HCV core and E2 regions were cloned and sequences were analyzed by computer software.</p><p><b>RESULTS</b>During the follow-up the serum ALT levels and the HCV virus titers fluctuated greatly in each of these persons. After transfusion, no significant variations were observed in HCV core and E2 coding regions.</p><p><b>CONCLUSIONS</b>The alteration of host immune attacks could induce the fluctuations of HCV load without any mutations in the currently observed coding genes of the epitopes.</p>

Positive selection caused change of hepatitis C virus quasispecies distribution in the natural history of he patitis C infection / 中华传染病杂志

Objective To investigate the evolution of hepatitis C virus (HCV) quasispecies in persistent and self limited infection patients. Methods Peripheral blood HCV preserved for 10 years from 8 naive individuals once infected by HCV were analyzed. HCV hypervariable region 1 (HVR1) genes were cloned and sequenced. Entropy, genetic distances, nonsynonymous mutations per nonsynonymous site (K A ), synonymous mutations per synonymous site(K S ) were evaluated for evolutionary analysis. Results The entropy values and genetic distances of HCV quasispecies were lower in self limited infection indivi duals than that of persistent infection individuals. In 3 of the 4 persistent infection individuals there exist no difference between within group and between group genetic distances in HCV HVR1. The ratios of K A /K s were higher than 1 in 7 of these 8 individuals. Conclusions The complexity and diversity degree of HCV quasispecies may affect the outcome of HCV infection. Positive Darwinian selection may be the major cause for the change of HCV quasispecies distribution in hepatitis C infection natural history.

Comparison of Quality Between Cultivated and Wild Species of Desmodium styracifolium / 中草药

To compare the quality of cultivated species with w ild species of Desmodium styracifolium (Osbeck) Merr. TLC and UV were used to study their qualities. Results showed that there was no obvious di fference between them.