OBJECTIVE To examine the herbal evidence of “Agaru” Tibetan medicines,conduct biopharcological studies and proveide a basis for the corrent origin and quality control. METHODS Through literature research, combined with field visits and expert consultations, variety classification, origins, characteristics and effects, compound preparation,and quality standards of “Agaru” type Tibetan medicines were compiled and summarized. The morphological and microscopic characteristics of “Aerma” medicinal materials were observed. Physicochemical identification was carried out based on thin-layer chromatography and determination of volatile oil components and content using GC-MS technology. RESULTS The name “Agaru” has evolved from Sanskrit loanwords and is a typical Tibetan medicine characterized by “multiple varieties and multiple origins”. Tibetan medicine often classifies it based on color into three categories: white (transliterated as “A Er Jia” or “A Jia Ga Bu”), black (transliterated as “A Er Na” or “A Ga Na Bao”), and red (transliterated as “A Er Ma” or “A Ga Ku Ao”). There is a significant difference in the varieties and origins of “Agaru” type Tibetan medicines used by Tibetan doctors in different regions, involving about 15 species (including varieties and forms) of plants from 5 families and 7 genera. Among them, “Alma” is widely used clinically, and its mainstream base is the heartwood of Camphora glandulifera (Wall.) Nees. Biopharmacological research was carried out on “Aerma” [C. glandulifera (Wall.) Nees], a clinically used variety of the “Agaru” group of Tibetan medicines, providing basic data for the establishment of its quality standards. CONCLUSION This study completes the botanical verification of the Tibetan medicine “Agaru” and the pharmacognostical research on “Aerma” [C. glandulifera (Wall.) Nees]. This will provide an important basis for the scientific evaluation of quality and in-depth development of “Agaru”.

OBJECTIVE To prepare methotrexate (MTX)-nicotinamide (NIC) coamorphous (MTX-NIC CA), evaluate its pharmacokinetic behavior in rats, and explore its solubilization mechanism. METHODS The coamorphous complex was prepared by melting method and characterized by powder X-ray diffraction and other techniques; the physical stability and thermodynamic stability of MTX-NIC CA were examined. The solubilization mechanism was studied by solubility profile method. The concentration of MTX in rat plasma was determined by high-performance liquid chromatography and the pharmacokinetic curve was drawn. RESULTS The physical stability of MTX-NIC CA was good; the reaction of MTX with NIC was a spontaneous enthalpy-driven reaction, and the mechanism of NIC for enhancing the solubility of MTX was that a soluble A_L-type complex with a ligand-to-metal ratio of 1∶1 was formed in solution. Compared with the raw drug MTX, the t_max of MTX-NIC CA was prolonged, and the c_max, AUC_0-t, AUC_0-∞ and F were significantly increased (P<0.05). CONCLUSION The MTX-NIC CA is successfully prepared by melting method with good stability, and the formation of co-amorphous complex improves the bioavailability of poorly soluble drugs.

Sleep disorders are increasingly prevalent within the population, and optimal sleep is essential for overall health. The sleep-wake cycle is a multifaceted process influenced by a variety of factors, including several neurotransmitters such as acetylcholine, norepinephrine, serotonin, histamine, dopamine, orexin, and gamma-aminobutyric acid (GABA). The activity of these neurotransmitters is further modulated by numerous nutrients involved in their metabolic pathways. In recent years, GABA has garnered significant attention due to its critical role in sleep regulation. This review aims to examine the mechanisms through which GABA affects sleep, its clinical implications, as well as recent advancements in research and future directions in this field.

OBJECTIVE To investigate the clinical efficacy of aspirin combined with Huoxue Quyu decoction in the treatment of lower extremity arteriosclerosis obliterans (ASO). METHODS A total of 136 patients with lower extremity ASO admitted to our hospital were selected as the research objects, aged 49-87 years, with an average age of (65.00±6.54) years. According to treatment methods, 68 cases of conventional aspirin treatment were included in the control group, and 68 cases of Huoxue Quyu prescription combined with aspirin were included in the study group. The platelet function, hemodynamic index, blood lipid index, arteriosclerosis index, health status and clinical effect of the two groups were compared before and after treatment. Generalized estimation equation (GEE) model was used to analyze the factors affecting the clinical efficacy of ASO in the lower extremities, and GEE model was used to analyze the interaction effects of ankle-brachial index(ABI) at different time points, different groups and different stages. RESULTS After 6 weeks of treatment, the platelet function, hemodynamic indexes, lipid indexes and arteriosclerosis indexes of the two groups were significantly different compared with those before treatment (P<0.05). PAR, D-D, FIB, HWBV, LWBV, ESR, TC, TG and LDL-C levels in the study group were significantly lower than those in the control group (P<0.05), while BT, HDL-C, ABI, TBI, lameness distance, health status score and clinical efficacy were significantly higher than those in the control group (P<0.05). GEE model analysis showed that treatment method, treatment time and Fontaine stage significantly affected the therapeutic effect of ASO in lower limbs (P<0.05). In the interaction effect analysis, after 2 and 4 weeks of treatment, the ABI values of ASO patients in the study group and the control group were significantly different (P<0.05). After 6 weeks of treatment, different treatment methods had statistically significant effects on ABI values of ASO patients in stage Ⅱ, Ⅲ and Ⅳ (P<0.05). CONCLUSION Aspirin combined with Huoxue Quyu decoction is better than aspirin alone in the treatment of lower extremity ASO in the aspect of improvement of platelet function, hemodynamics, blood lipids and arteriosclerosis. After 6 weeks of treatment, the total effective rate and health status SF-36 score of the study group with combined medication are significantly higher than those of the control group. Treatment method, treatment time and Fontaine stage significantly affect the therapeutic effect of lower extremity ASO.

OBJECTIVE To explore the characteristics of the inhibitory effect of low concentrations of deguelin on the proliferation of activated T cells. METHODS Human peripheral blood mononuclear cells were isolated by Ficoll-Hypaque density gradient centrifugation, human T cells were purified using immunomagnetic beads, and T cells were activated with Anti-CD3/CD28 antibodies. Flow cytometry was used to detect T cell survival rate, proliferation index, apoptosis progression, CD25 expression level, and cell division ratio; ELISA was used to detect cytokines IL-2, IL-4, IL-6, IL-17, and IFN-γ secretion levels. RESULTS Low concentrations of deguelin inhibit T cell proliferation activated by anti-human CD3/CD28 antibodies, with an IC₅₀ of (73±12) nmol·L^-1, and a concentration of 400 nmol·L^-1 has no cytotoxicity. Low concentrations of deguelin do not affect the expression of CD25 and secretion of IL-2 in activated T cells but increases the proportion of G₀/G₁ phase cells. Low concentrations of deguelin promote the secretion of anti-inflammatory cytokine IL-4 and inhibit the production of pro-inflammatory cytokines IL-6, IL-17, and IFN-γ in T cells. CONCLUSION Low concentrations of deguelin significantly inhibit T cell proliferation in the G₀/G₁ phase and effectively suppress the secretion of pro-inflammatory cytokines, suggesting its potential role in the treatment of autoimmune diseases.

OBJECTIVE To establish a population pharmacokinetic (PK) model for rosuvastatin and investigate the effects of demographic data, clinical characteristics, and genetic polymorphisms (ABCG2, SLCO1B1, SLCO1B3, SLCO10A1, ABCB1, CYP2C9) on its PK parameters in Chinese population. METHODS A total of 944 steady-state concentration data were collected from 944 patients with hyperlipidemia. UPLC-MS/MS was used to determine the plasma concentration of rosuvastatin. DNA was extracted and measured for concentration, and the Sequenom MassArray technology platform was utilized for genetic typing. Eventually a population PK model was established with non-linear mixed-effects modeling software (NONMEM). RESULTS The population estimates for the apparent clearance, apparent volume of distribution and absorption rate constant were 253 L·h^-1, 1 810 L and 0.318 h^-1, respectively. The datasets were best described by a one-compartment model with first-order elimination. The steady-state concentration of rosuvastatin increased as estimated glomerular filtration rate(eGFR) decreased and the variant allele for rs2199936 increased, under the same dosage regimen. Carrying one or two variant alleles for the ABCG2 rs2199936 showed a decrease of 32.6% and 53.2% in apparent clearance relative to the value in individuals without the variant allele. CONCLUSION Both ABCG2 rs2199936 and the eGFR were found to be significant covariates for apparent clearance. The results suggest that Chinese individuals with renal impairment and one or two variant alleles for the rs21999336 polymorphism (ABCG2) who are undergoing coronary angiography (CAG) should avoid high doses of rosuvastatin.

OBJECTIVE To establish a quality control method of human chain-activated immune cell preparations. METHODS The ability to secrete cytokines and in vitro cytotoxicity were detected by co-culture and flow cytometry analysis. Purity was determined by flow cytometry. The concentration of live cells and cell viability were determined by AO/PI dual fluorescence cell counter. The residual cytokines were determined by enzyme-linked immunosorbent assay. Mycoplasma nucleic acid was detected by probe real-time PCR.Other detection items were carried out according to the provisions of the 3rd part of Chinese Pharmacopoeia 2020. RESULTS The detection of human chain-activated immune cell preparations was carried out using the established method,and the results of biological activity research, physical and chemical characteristics research, and cytokine residual detection were normally distributed. The detection results were valid,and the coefficient of variation(CV) was less than 20%. All other indicators met the requirements of the Chinese Pharmacopoeia 2020. CONCLUSION A preliminary quality control method of human chain-activated immune cell preparations are established, which has the characteristics of ensuring the quality control lability, safety, and effectiveness of the cell preparations. It can be used for the quality control of the human chain-activated immune preparations.

OBJECTIVE To evaluate the safety characteristics of Rehmannia glutinosa leaf total glycosides capsules in juvenile Wistar rats, and provide reference for the use of Rehmannia glutinosa leaf total glycosides capsules in child and adolescent patients. METHODS Twenty-seven-day-old Wistar rats were randomly divided into control and low-, medium-, and high-dosage groups. Each dosage group was given the Rehmannia glutinosa leaf total glycosides by gavage repeatedly for 8 weeks, followed by a 4 week recovery. The clinical symptoms, body weight, food consumption, hematological and serum biochemical indexes, central nervous system function, learning and memory ability, skeletal development, reproductive function, organ weight and histopathological changes of the rats was observed. RESULTS Rehmannia glutinosa leaf total glycosides capsules did not show significant effects on the clinical symptoms, body weight, food consumption, hematological and serum biochemical indexes, main organ weights, central nervous system function, bones, sexual cycle, sperm counts, vitality and form of the rats. No histopathological changes were observed associated with Rehmannia glutinosa leaf total glycosides capsules. CONCLUSION The no-observed-adverse-effect-level (NOAEL) for Rehmannia glutinosa leaf total glycosides capsules in juvenile rats is determined to be 750 mg·kg^-1 in the 8 week feeding study. The data provides reference for the use of Rehmannia glutinosa leaf total glycosides capsules in child and adolescent patients.

OBJECTIVE To study the effect of Puerariae Lobatae Radix on improving coronary microcirculation disorders in ovariectomized rats. METHODS Seventy-two SD female rats were randomly divided into sham-operated group, model group, estradiol valerate group, and Puerariae Lobatae Radix aqueous extract groups(0.8, 1.6, and 3.2 g·kg^-1), and the perimenopausal model of rat was established by bilateral de-ovulation. Two weeks after molding, drugs were continuously administered by gavage for 16 weeks, once a day, and the corresponding dose of saline was given to the sham-operated and model groups. At the end of the 16th week, PowerLab electrophysiological recorder was used to detect systolic blood pressure(SBP), diastolic blood pressure(DBP), mean blood pressure(MBP), left ventricular systolic pressure(LVSP), left ventricular diastolic pressure(LVDP), and maximal left ventricular pressure rising rate (+dp/dt)and maximal left ventricular pressure decline rate(-dp/dt) in the rats. The whole blood high, middle and low shear viscosity, plasma viscosity and hematocrit of rats were detected by blood rheometer. The changes of four items of blood lipid low triglyceride(TG), total cholesterol(TC), high density lipoprotein cholesterol(HDL-C), low density lipoprotein cholesterol(LDL-C) lactate dehydrogenase (LDH), and creatine kinase (CK) in rat plasma; in plasma of rats were detected by automatic biochemical analyzer. HE staining was conducted to observe the pathological changes in rat myocardium. DiI visualization technology was used to observe the changes in the structure and morphology of coronary microvessels. AngioTool software was applied to analyze the vascular area, density, diameter, the degree of empty space, and according to Poisson Leaf's formula the ion of microvascular resistance to blood flow was calculated. The content changes of nitric oxide(NO) in serum were detected by microtiter method. The content changes of endothelin-1(ET-1) and von Willebrand factor(vWF) in serum were detected by Elisa. Western blot was used to detect the expression of estrogen receptor α(ERα), vascular endothelial growth factor(VEGF) and vascular endothelial growth factor receptor 2(VEGFR2) protein in myocardial tissue. RESULTS Compared with the model group, the water extract of Puerariae Lobatae Radix reduced SBP, DBP, MBP, LVSP and LV±dp/dt max in hemodynamics, whole blood high, medium and low shear viscosity, plasma viscosity and hematocrit in hemorheology, blood flow resistance, myocardial enzyme indexes LDH and CK content, vasoconstrictor factor ET-1 and endothelial injury factor vWF content, and HDL-C content in blood lipid four items, which could reduce inflammatory cell infiltration and myocardial cell atrophy. The contents of TG, TC, LDL-C, blood vessel diameter, area, percentage, porosity, NO content, ERα, VEGFR2 and VEGF protein expression were increased. CONCLUSION Puerariae Lobatae Radix extract can improve coronary microcirculation disorder in ovariectomized rats by regulating endothelial function through estrogen receptor.

OBJECTIVE To analyze the distribution frequency of rs2306283 and rs4149056 polymorphisms in the solute carrier organic anion transporter family 1B1(SLCO1B1) gene and investigate the effect of SLCO1B1 gene on the efficacy and safety of different moderate kinds of statins in patients with coronary heart disease(CHD). METHODS A total of 183 blood samples of patients with CHD were collected, and polymerase chain reaction-fluorescence probe technology was used to detect the polymorphism of SLCO1B1 gene. Blood lipid indicators and blood biochemical indexes before and after statin treatment (atorvastatin, rosuvastatin, other statins), such as triglyceride(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), and urea nitrogen(BUN), serum creatinine(Scr), creatine kinase(CK), alanine aminotransferase(ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP), direct bilirubin(DBIL), indirect bilirubin(IBIL), et al, were recorded. The change values of TG, TC, LDL-C, HDL-C, et al, were calculated. The relationships between SLCO1B1 gene polymorphism and the efficacy and safety of different statins in CHD patients were analyzed. RESULTS There was significant difference between Han and Uyghur CHD patients in the distribution frequency of SLCO1B1 A388G genotypes. The difference in LDL-C was significantly increased in SLCO1B1 388AG+GG patients compared with AA(P<0.05). The difference of LDL-C after treatment in 388AA type was significant(P>0.05), and the change of HDL-C in GG type patients treated with rosuvastatin was significantly higher than patients with atorvastatin(P<0.05). The changes of HDL-C in TT genotype patients with other statins were significantly higher than patients with atorvastatin(P<0.05), and the change values of TC and LDL-C in TT genotype patients with atorvastatin were significantly higher than those of the rosuvastatin group (all P<0.05). The ALP levels in SLCO1B1 388AG genotype patients with rosuvastatin were significantly lower than the other statins (P<0.05), and the DBIL levels in GG patients with other statins were significantly higher than the rosuvastatin and atorvastatin (P<0.05). The IBIL, CK levels and the change of ALT in SLCO1B1 521TC patients were higher than TT (all P<0.05). The AST increase in TT genotype patients with atorvastatin was significantly lower than that of other statins (P<0.05), and the IBIL levels in TC genotype patients with rosuvastatin and atorvastatin were significantly lower than the other statins (P<0.05). CONCLUSION There is relevance between SLCO1B1 rs2306283 and rs4149056 gene polymorphisms and efficacy and safety of different statins treatment. SLCO1B1 388G allele enhances the lipid-lowering effect of rosuvastatin, especially on HDL-C. SLCO1B1 521T allele enhances the lipid-lowering effect of atorvastatin, especially for LDL-C and TC, and the 521C allele may increase the risk of myopathy and liver function impairment. There is relevance among SLCO1B1 rs2306283 and rs4149056 gene polymorphisms and efficacy and safety of different statins treatment, which may be a genetic indicator to predict the efficacy and adverse effects of statins.