Background Recently,the study on the cause of optic nerve damage induced by glaucoma is of concern in ophthalmology.Some research showed that the immune system is associated with glaucoma-induced optic neuropathy.Acute ischemia-reperfusion is an ideal model of studying optic neuropathy.ObjectiveThe present study investigates the effect of T and B lymphocyte deficiency on the retinal neurocytes of mice with acute intraocular hypertension.Methods Sixteen SPF CB-17/Icr.Cg-Prkdc~(scid)Lyst~(bg)/CrlVR mice 6-8 week-old (severe combined immunodeficiency mouse,SCID) were used in this study and 16 age-matched SPF wild type (C57BL/6) mice served as controls.The ischemia-reperfusion injury models were induced in the right eyes of 10 SCID mice and 10 C57BL/6 mice through intra-anterior chamber infusion of balanced saline solution for 45minutes to increase the intraocular pressure to 104mmHg,and the left eyes served as model controls.The other 6 SCID mice and 6 C57BL/6 mice served as normal control group.10g/L (2μL) of FlouroGold was injected into the brains of the mice for the labeling of surviving retinal ganglion cells 21 days after ischemia-reperfusion.The thickness of retinal inner nuclear layer was measured by H&E staining under the fluorescent microscope 21 days after ischemic insult.The use of the animals followed the Standard of Association for Research in Vision and Ophthalmology.Results In normal control mice,the morphology of retinal ganglion cells (RGCs) and retinal structure were similar between SCID mice and C57BL/6 mice.The differences in the numbers of RGCs and retinal thickness were insignificant between the two types of mice(P＞0.05).In the experimental mice,the surviving RGCs were strikingly increased in SCID mice (91%±5%) compared with C57BL/6 mice(78%±5%)(P=0.003).The thickness of the retinal inner nuclear layer was obviously thinner in the model eyes (22.44±1.70μm) compared to model control eyes (31.06±3.75μm) in C57BL/6 mice(P=0.004),but no statistically significant difference was found between the model eyes and model control eyes in SCID mice (33.52±2.13μm vs 34.06±3.00μm) 21 days after ischemia-reperfusion injury(P＞0.05).Conclusion T and B lymphocytes deficient mice show a better tolerance to acute intraocular hypertension than the wild type C57BL/6 mice.

Objective To investigate the compatible stability of alanylglutamine by using continuous series infusion device,and provide experimental evidence for reasonable clinical use of alanylglutamine. Methods pH,osmolality and quantity of insoluble particles were measured by using pH meter, automatic freezing osmometer and intelligent particle detector respectively.A HPLC method was built for the determination of the content of alanylglutamine. Results pH and quantity of insoluble particles of the two tested groups did not change significantly over time. Osmolality and the content of alanylglutamine fluctuated greatly in the first half an hour. Conclusion Continuous series infusion device may not mix each bottle of solution very well.It is suggested to premix these solutions to ensure the stability of the dilution ratio and the osmotic pressure of the mixture in the process of the infusion.

Objective To investigate effect of glucose and lipid metabolism on acute cerebral infarction patients by Rhodiola injection. Methods 201 cases of acute cerebral infarction patients were selected,and divided into experiment group and control group.The control group of 101 cases were treated by clinical routine therapy,the experiment group 100 cases were treated with Rhodiola injection.The clinical efficacy, blood rheology and blood lipids, blood glucose index were compared before and after treatment.Results After 2 weeks of treatment, the total effective rate in experimental group was significantly higher than the control group(χ2 =12.596, P<0.05), with statistical difference.Patients in the experimental group,FBG was significantly lower than the control group, the difference was statistically significant (t=8.830, P<0.05).Patients in the experimental group TG, TC, LDL-C were significantly lower than that of control group, HDL-C was significantly higher than control group (P<0.05).Blood rheology indexes decreased significantly better than the control group ( P<0.05 ) .Conclusion Rhodiola injection on patients with acute cerebral infarction has good clinical curative effect, and can effectively improve the blood lipid, blood glucose level, reduce blood viscosity, is of great significance to the clinical treatment of cerebral infarction.

Aim To investigate the effect of piperazinyl estrone(PE) on estrogen receptor expression and the transcriptional regulation of target genes.Methods Ovariectomized mice were given with PE in different doses (0.5 mg·kg~(-1),1 mg·kg~(-1),2 mg·kg~(-1))and estrone(0.71 mg·kg~(-1)) for 42 days,the protein expressions of Ers(Erαand Erβ)were shown by immunohistochemical method; To study transcriptional regulation of PE, PACT2-hERα and ERE2-TATA-LUC were co-transfected into MCF-7 cells by using Tfx 50 cationic liposome.Results Compared with ovx group, the groups with PE could up-regulate Ers of uteri in a dose-dependent manner,but its effect on Erα subtype was obvious.The classical ER signaling pathways could be activated by PE in co-transfected MCF-7 cells,but activation of PE was feebler than estrone with the same dose.Conclusion PE can up-regulate estrogen receptors in uteri. PE can transactivate ERE reportor gene through Erα and Erβ in MCF-7 cells, but its effect is feeble.

P2Y12 receptor antagonists and morphine are often recommended in patients with acute myocardial infarction.P2Y12 receptor antagonists can rapidly and potently reduce the platelet activity and prevent future thrombotic events.Meanwhile,combined morphine is used to relieve symptoms of angina.A number of studies have confirmed that morphine can decrease plasma concentrations of clopidogrel and impair its anti-platelet activity,which may lead to poor response in clopidogrel-treated patients with acute coronary syndrome.The randomized trials in healthy volunteers and patients with acute myocardial infarction also confirmed the similar drug-drug interaction between morphine and ticagrelor or prasugrel.Although the P2Y12 receptor antagonists combined with morphine are still used for myocardial infarction patients,there are few report on the objective evaluation of this drug interaction.This review,based on the findings of experimental as well as observational and randomized clinical studies,summarizes completely the drug interactions between oral P2Y12 receptor antagonists and morphine.

Abstract Traditional Chinese medicine (TCM) has demonstrated unique advantages in the prevention and treatment of chronic diseases such as glycolipid metabolism disorder. However, its widespread application has been hindered by the unclear biological essence of TCM syndromes and therapeutic mechanisms. As an emerging interdisciplinary field, phenomics integrates multi-dimensional data including genome, transcriptome, proteome, metabolome, and microbiome. When combined with TCM's holistic philosophy, it forms TCM phenomics, providing novel approaches to reveal the biological connotation of TCM syndromes and the mechanisms of herbal medicine. Taking glycolipid metabolism disorder as an example, this paper explores the application of TCM phenomics in glycolipid metabolism disorder. By analyzing molecular characteristics of related syndromes, TCM phenomics identifies differentially expressed genes, metabolites, and gut microbiota biomarkers to elucidate the dynamic evolution patterns of syndromes. Simultaneously, it deciphers the multi-target regulatory networks of herbal formulas, demonstrating their therapeutic effects through mechanisms including modulation of insulin signaling pathways, improvement of gut microbiota imbalance, and suppression of inflammatory responses. Current challenges include the subjective nature of syndrome diagnosis, insufficient standardization of animal models, and lack of integrated multi-omics analysis. Future research should employ machine learning, multimodal data integration, and cross-omics longitudinal studies to establish quantitative diagnostic systems for syndromes, promote the integration of precision medicine in TCM and western medicine, and accelerate the modernization of TCM.

Objective:To evaluate the inhibitory effect of 5 Chinese herbal medicinal ingredients baicalin, andrographolide, hes-peridin, polyphenols and daidzein on the activity of carboxylesterase 1 (CES1) and carboxylesterase 2 (CES2). Methods: The spe-cial probes respectively for CES1 and CES2, namely imidapril and CPT-11, imidaprilat and SN-38, were used to investigate the poten-tial effect of the above drugs on CES1 and CES2 in rat liver microsomes incubation system. Results:Compared with that in the control group, the activity of CES1 and CES2 was not significantly influenced by the above 5 Chinese herbal medicinal ingredients ( P <0. 05). Conclusion:Baicalin, andrographolide, hesperidin, polyphenols and daidzein exhibit no inhibitory effect against CES1 and CES2, and further studies should be conducted to confirm the effect in vivo.

With the advent of bezoar substitutes, bezoar compound has been widely used in clinics. Bezoar is commonly applied in the traditional prescriptions for emergency. Due to the complex compositions and difficult soluble constituents, the prescriptions show the disadvantages of low bioavailability and slow onset in clinical application, and the effectiveness is usually related with the adminis-tration route and characteristics of dosage form of the preparations. The exiting bezoar compound and its new dosage forms were summa-rized in the paper, and the existing bezoar compound preparations were stated according to the characteristics of dosage forms and com-pound clinical application in order to promote the development and application of bezoar new dosage forms.

Carboxylesterases (CESs) play important roles in the metabolism of endogenous and foreign compounds in physiological and pharmacological responses. The aim of this study was to investigate the effect of dexamethasone at different doses on the expression of CES1 and CES2. Imidapril and irinotecan hydrochloride (CPT-11) were used as special substrates for CES1 and CES2, respectively. Rat hepatocytes were cultured and treated with different concentrations of dexamethasone. The hydrolytic activity of CES1 and CES2 was tested by incubation experiment and their expression was quantitated by real-time PCR. A pharmacokinetic study was conducted in SD rats to further evaluate the effect of dexamethasone on CESs activity in vivo. Western blotting was performed to investigate the regulatory mechanism related to pregnane X receptor (PXR) and glucocorticoid receptor (GR). The results showed that exposure of cultured rat hepatocytes to nanomolar dexamethasone inhibited the imidapril hydrolase activity, which was slightly elevated by micromolar dexamethasone. For CES2, CPT-11 hydrolase activity was induced only when dexamethasone reached micromolar levels. The real-time PCR demonstrated that CES1 mRNA was markedly decreased by nanomolar dexamethasone and increased by micromolar dexamethasone, whereas CES2 mRNA was significantly increased by micromolar dexamethasone. The results of a complementary animal study showed that the concurrent administration of dexamethasone significantly increased the plasma concentration of the metabolite of imidapril while the ratio of CPT-11 to its metabolite SN-38 was significantly decreased. PXR protein was gradually increased by serial concentrations of dexamethasone. However, only nanomolar dexamethasone elevated the level of GR protein. The different concentrations of dexamethasone required suggested that suppression of CES1 may be mediated by GR whereas the induction of CES2 may result from the role of PXR. It was concluded that dexamethasone at different concentrations can differentially regulate CES1 and CES2.

Objective To explore the influence of different administration time on antidepressant effect of seven clinical common antidepressants. Methods Male mice were randomly divided into eight groups:venlafaxine (75 mg/kg), sertraline (20 mg/kg), fluoxetine (20 mg/kg), doxepin (15 mg/kg), mirtazapine (15 mg/kg), citalopram (40 mg/kg), trazodo?ne (50 mg/kg) and control (saline) groups. Each group contained 36 mice. Drugs were administered to 6 mice per group 30 min before forced swimming test at the 6 time points (9:00, 13:00 and 17:00 as light phase and 21:00, 1:00 and 5:00 as dark phase). Forced swimming test was applied to determine the influence of dosing time on anti-immobility effect of seven antidepressants at each time point. Results Immobility time in venlafaxine group and sertraline group significant?ly decreased compared with that of control group at all time points(all P<0.05). Moreover, anti-immobility effects of ven?lafaxine, fluoxetine, mirtazapine and doxepin were better during the dark phase than during the light phase (all P<0.05). In addition, immobility time in sertraline group decreased at the late part of dark phase (5:00) and the early part of light phase (9:00) compared with other phases (P<0.05). Conclusions Most antidepressants show 24-h rhythm dependent an?ti-immobility effects, but rhythmic patterns are not completely consistent among different antidepressants. Further study is needed to explore the chronopharmacological mechanism and clinical applications of these antidepressants.