Rare Earth Extraction from Phosphogypsum by Aspergillus niger Culture Broth.

The extraction of rare earth elements (REEs) from phosphogypsum (PG) is of great significance for the effective utilization of rare earth resources and enhancing the resource value of PG waste residues. This study used Aspergillus niger (A. niger) fungal culture filtrate as a leaching agent to investigate the behavior of extracting REEs from PG through direct and indirect contact methods. According to the ICP-MS results, direct leaching at a temperature of 30 °C, shaking speed of 150 rpm, and a solid-liquid ratio of 2:1, achieved an extraction rate of 74% for REEs, with the main elements being yttrium (Y), lanthanum (La), cerium (Ce), and neodymium (Nd). Under the same conditions, the extraction rate of REEs from phosphogypsum using an A. niger culture filtrate was 63.3% higher than that using the simulated organic acid-mixed solution prepared with the main organic acid components in the A. niger leachate. Moreover, the morphological changes observed in A. niger before and after leaching further suggest the direct involvement of A. niger's metabolic process in the extraction of REEs. When compared to using organic acids, A. niger culture filtrate exhibits higher leaching efficiency for extracting REEs from PG. Additionally, using A. niger culture filtrate is a more environmentally friendly method with the potential for industrial-scale applications than using inorganic acids for the leaching of REEs from PG.

Recent progresses in novel in vitro models of primary neurons: A biomaterial perspective.

Central nervous system (CNS) diseases have been a growing threat to the health of humanity, emphasizing the urgent need of exploring the pathogenesis and therapeutic approaches of various CNS diseases. Primary neurons are directly obtained from animals or humans, which have wide applications including disease modeling, mechanism exploration and drug development. However, traditional two-dimensional (2D) monoculture cannot resemble the native microenvironment of CNS. With the increasing understanding of the complexity of the CNS and the remarkable development of novel biomaterials, in vitro models have experienced great innovation from 2D monoculture toward three-dimensional (3D) multicellular culture. The scope of this review includes the progress of various in vitro models of primary neurons in recent years to provide a holistic view of the modalities and applications of primary neuron models and how they have been connected with the revolution of biofabrication techniques. Special attention has been paid to the interaction between primary neurons and biomaterials. First, a brief introduction on the history of CNS modeling and primary neuron culture was conducted. Next, detailed progress in novel in vitro models were discussed ranging from 2D culture, ex vivo model, spheroid, scaffold-based model, 3D bioprinting model, and microfluidic chip. Modalities, applications, advantages, and limitations of the aforementioned models were described separately. Finally, we explored future prospects, providing new insights into how basic science research methodologies have advanced our understanding of the CNS, and highlighted some future directions of primary neuron culture in the next few decades.

Genomic and Phenotypic Evolution of Tigecycline-Resistant Acinetobacter baumannii in Critically Ill Patients.

Acinetobacter baumannii is an important opportunistic pathogen of nosocomial infections. A. baumannii presently exhibits increasing antibiotic resistance, which poses great challenges to public health. The occurrence of tigecycline-resistant A. baumannii is related to tigecycline treatment and the within-host evolution of bacteria. We analyzed isogenic A. baumannii isolates from two critically ill patients who underwent tigecycline treatment. Whole-genome sequencing and comparative analyses were performed to determine the characteristics of genomic evolution. We conducted phenotypic studies, including in vitro antibiotic sensitivity tests, biofilm formation tests, growth curve determination, serum bactericidal determination, and Galleria mellonella lethality assays. In vivo emergent tigecycline resistance was observed after tigecycline treatment. After the withdrawal of tigecycline pressure, tigecycline-resistant isolates were not isolated from one patient. Four tigecycline-resistant isolates exhibited lower growth rates. The biofilm formation and virulence characteristics of tigecycline-resistant isolates were reasonably different between the two patients. A special phenotype appeared after tigecycline treatment in both patients, accompanied by reduced serum tolerance, enhanced biofilm formation ability, and reduced virulence of Galleria mellonella. Most of the genomic variation occurred after the tigecycline treatment, primarily involving transcription-, signal transduction-, translation-, ribosomal biogenesis-, and cell wall biogenesis-related genes. We determined that the genomic variations in baeR, wzc, aroQ, rluC, and adeS and acquisition of ISAba1 were associated with tigecycline resistance in vivo. Capsular polysaccharide-related genes, wzc, and itrA2, and aroQ, were the key genes related to the virulence evolution of A. baumannii within the host. IMPORTANCE Multidrug-resistant Acinetobacter baumannii poses a huge challenge to clinical treatment, and tigecycline is considered a last-line drug for the treatment of multidrug-resistant A. baumannii. However, the mechanism of tigecycline resistance in vivo has not been elucidated. This study analyzed the genomic and phenotypic evolution of tigecycline-resistant A. baumannii in two critically ill patients. In this study, after treatment with tigecycline, tigecycline-resistant A. baumannii emerged with higher fitness costs. After the withdrawal of tigecycline pressure, tigecycline-resistant isolates were not isolated from one patient. The in vivo and in vitro virulence of the isolates exhibited diametrically opposite results in the two patients. Genomic variations in baeR, wzc, aroQ, rluC, and adeS and acquisition of ISAba1 were associated with tigecycline resistance in vivo. The capsular polysaccharide-related genes, wzc, itrA2, and aroQ, were the key genes related to the virulence of A. baumannii in hosts. Our research provides a theoretical basis for elucidating the mechanism of tigecycline resistance and presents new clues for future surveillance and treatment of multidrug-resistant A. baumannii.

Clinical Study on Characteristics and Risk Factors of Coronary Artery Lesions in Young Patients with Acute Myocardial Infarction.

Epidemiological evidence suggests that the incidence of acute myocardial infarction (AMI) among people under 40 years of age has an increasing trend in recent years. Smoking, hypertension, diabetes mellitus, family history, and gender (male) are considered as classic risk factors for CHD, but the pathogenesis of CHD in young people is not exactly the same. Moreover, the relationship between the pattern of coronary artery disease and risk factors in young patients with acute myocardial infarction is inconclusive. In this study, we retrospectively studied the clinical data of 150 AMI patients treated in our hospital from January 2020 to May 2021. The patients were divided into the young group and elderly group according to the difference in age. The number of coronary artery lesions, the degree of coronary artery stenosis, the distribution dominance typing, the position of the lesions, and the presence of collateral circulation were observed and compared between the two groups. Multivariate logistic regression analysis was used to investigate the risk factors affecting coronary artery lesions in young patients with AMI. The results showed that the number of coronary lesions in young patients with AMI was mainly single-vessel, and the dominant type of distribution was mainly right dominant type. The stenosis degree is lighter than that of elderly patients, and the incidence of collateral circulation is lower than that of elderly patients, but the position of the lesions has no obvious regular. Smoking, staying up late, HDL-C, and LDL-C/ApoB were independent factors affecting the number of coronary artery lesions, and the changes of HDL-C and LDL-C/ApoB had an important influence on the degree of coronary stenosis in young patients. This provides a new idea for clinical treatment.

UFLC-PDA-MS/MS Profiling of Seven Uncaria Species Integrated with Melatonin/5-Hydroxytryptamine Receptors Agonistic Assay.

Uncariae Ramulus Cum Uncis (Gou-Teng), the dried hook-bearing stems of several Uncaria plants (Rubiaceae), is a well-known herbal medicine in China. The clinical application of Gou-Teng is bewildered for the morphological and chemical similarity between different species. In order to discern their chemical and biological difference, an ultra-fast liquid chromatography equipped with ion trap time-of-flight mass spectrometry (UFLC-IT/TOF-MS) combining with melatonin (MT1 and MT2) and 5-hydroxytryptamine (5-HT1A and 5-HT2C) receptors agonistic assay in vitro was conducted on seven Uncaria species. As a result, 57 compounds including 35 indole alkaloids, ten flavonoids, five triterpenoids, five chlorogenic analogues, and two other compounds were characterized based on their MS/MS patterns and UV absorptions. Specifically, cadambine-type and corynanthein-type alkaloids were exclusively present in U.rhynchophylla and U.scandens, whereas corynoxine-type alkaloids were commonly detected in all the seven Uncaria plants. Three Uncaria species, U. rhynchophylla, U. macrophylla, and U. yunnanensis showed obviously agnostic activity on four neurotransmitter receptors (MT1, MT2, 5-HT1A, and 5-HT2C). This first-time UFLCMS-IT-TOF analyses integrated with biological assay on seven Uncaria plants will provide scientific viewpoints for the clinical application of Gou-Teng.

[Advances in indole alkaloids from traditional Chinese medicine of Uncariae Ramulus Cum Uncis documented in Chinese Pharmacopoeia].

Uncaria genus( Rubiaceae) contains 34 species all over the world,of which 11 species and one variant are present in China. Five species,namely U. rhynchophylla,U. macrophylla,U. hirsuta,U. sinensis and U. sessilifructus,are documented in Chinese Pharmacopoeia as the raw materials of Uncariae Ramulus Cum Uncis. Indole alkaloids are the characteristic constituents of Uncaria plants,in addition to triterpenes,lignans and flavones. This paper reviews the progress of indole alkaloids and their distribution within the five Uncaria species documented in Chinese Pharmacopoeia for better understanding the active constituents of Uncariae Ramulus Cum Uncis.

miR-375 affects the proliferation and invasion of hepatoma cells via targetingYAP / 中国肿瘤生物治疗杂志

@# Objective: To investigate the mechanisms of miR-375 affecting the proliferation and invasion of hepatoma cells via targeting YAP (Yes-associated protein). Methods: The cancerous tissues and corresponding para-cancerous tissues of 70 patients with hepatocellular carcinoma (HCC) who underwent surgical resection at the Second Affiliated Hospital of Henan University of Traditional Chinese Medicine from January 2015 to December 2016, as well as the hepatoma cell lines SMMC-7721, Hb611, HepG2 and BEL-7405 were collected for this study. qPCR method was used to detect the expression level of miR-375 in collected HCC tissues and different hepatoma cell lines; Dual luciferase reporter gene assay was used to verify the interaction between miR-375 and YAP; The relationship between miR-375 and clinicopathological features of HCC patients was also analyzed; MTT assay was used to detect the effect of miR375 on the proliferation of hepatoma cells; Transwell invasion assay was used to detect the invasive ability of hepatoma cells after inhibiting the expression of miR-375; Western blotting was used to detect the expression of YAP in HepG2 cells. The nude mouse model of subcutaneously transplanted xenograft was established, and the tumor volume and mass of transplanted hepatoma cells were detected after inhibiting the expression of miR-375. The expression of YAP in xenograft of nude mice was detected by immunohistochemistry and Western blotting. Results: The expression of miR-375 and YAP in HCC tissues was significantly higher than that in para-cancerous tissues (all P<0.05). The expression of miR-375 in HepG2 cells was the highest (P<0.05). miR-375 could specifically bind to the 3' UTR of YAP and regulate the expression activity of YAP. After inhibiting the expression of miR-375, the proliferation and invasion abilities of HepG2 cells were reduced (all P<0.05); The tumor volume and mass of transplanted xenografts were significantly reduced (both P<0.05); The expression of YAP protein in the transplanted xenografts was down-regulated (P<0.05). Conclusion: miR-375 plays an important role in the occurrence and development of liver cancer, and can influence the malignant biological behaviors of hepatoma cells by targeting and regulating the expression ofYAP.

Prebiotic, Immunomodulating, and Antifatigue Effects of Konjac Oligosaccharide.

Irregular and long time work schedules not only makes people feel fatigue, but also brings great risks of diseases, due to gastrointestinal disorder and immune dysfunction. Therefore, it has positive significance to help challenged people stay energetic and healthy with food supplement. Konjac oligosaccharide has shown various physiological benefits and been recommended in the fortification of functional foods. However, there have been few reports on its application aimed to simultaneously relieve physical fatigue and keep body healthy. In this paper, the potential prebiotic, immunoregulatory, and antifatigue activities of konjac oligosaccharide were evaluated in vitro and in vivo. The results showed that konjac oligosaccharide could promote probiotics growth and short chain fatty acids production in mice cecum. At the concentration of 50 to 200 µg/mL, konjac oligosaccharide could activate murine macrophage RAW 264.7 to secret NO and cytokines of IL-10 and IL-6. Moreover, this oligosaccharide could alleviate physical fatigue by prolonging exhaustive time, improving the level of superoxide dismutases and glutathione peroxidase, increasing the content of blood glucose, and decreasing the content of blood urea nitrogen. The results suggested that konjac oligosaccharide had prebiotic, immunoregulatory, and antifatigue effects, providing its application potential in functional food aimed at people with irregular and long time work.

Maresin 1 improves the Treg/Th17 imbalance in rheumatoid arthritis through miR-21.

OBJECTIVE: Treg/Th17 imbalance plays an important role in rheumatoid arthritis (RA). Maresin 1 (MaR1) prompts inflammation resolution and regulates immune responses. We explored the effect of MaR1 on RA progression and investigated the correlation between MaR1 and Treg/Th17 balance. METHODS: Both patients with RA and healthy controls were recruited into the study. Collagen-induced arthritis (CIA) model was constructed to detect the clinical score, histopathological changes and Treg/Th17 ratio. Purified naive CD4+ T-cells were used to study the effect of MaR1 on its differentiation process and microRNA microarray studies were performed to investigate MaR1 downstream microRNAs in this process. MicroRNA transfection experiments were conducted by lentivirus to verify the mechanism of MaR1 on Treg/Th17 balance. RESULTS: Compared with controls, the MaR1 concentration was higher in the patients with inactive RA and lower in the patients with active RA. Expression of the Treg transcription factor FoxP3 was the highest in inactive RA and the lowest in active RA, while the Th17 transcription factor RORc showed a reverse trend. An inverse correlation was observed between the FoxP3/RORc ratio and Disease Activity Score 28. Intervention of MaR1 in the CIA model reduced joint inflammation and damage, and improved the imbalanced Treg/Th17 ratio. MaR1 increased Treg cells proportion while reduced Th17 cells proportion under specific differentiation conditions. Furthermore, miR-21 was verified as MaR1 downstream microRNA, which was upregulated by MaR1, modulating the Treg/Th17 balance and thus ameliorating the RA progression. CONCLUSIONS: MaR1 is a therapeutic target for RA, likely operating through effects on the imbalanced Treg/Th17 ratio found in the disease.

Structural characterization and immunomodulatory activity of exopolysaccharides from submerged culture of Auricularia auricula-judae.

Submerged culture of Auricularia auricula-judae has been documented, but there have been few studies on the structural characterization and medicinal properties of its exopolysaccharides. In present study, two exopolysaccharides, named CEPSN-1 and CEPSN-2, were isolated from submerged culture of A. auricula-judae, and their structural features as well as immunomodulatory activity were analyzed. The two exopolysaccharides both had a backbone chain composed of (1 → 4)-α-d-glucose residues in glucopyranose type. At the tested concentration range of 50-200 µg/mL, CEPSN-1 and CEPSN-2 not only showed non-toxicity to RAW 264.7 cells, but also could promote the release of NO and cytokines (IL-6, IL-10 and TNF-α) in the cells. The release of NO was significantly enhanced by the two exopolysaccharides at 100 µg/mL (p < 0.05). The IL-10 secretion was significantly increased by 1.80 and 1.61-fold, compared to the control after treatment with 50 µg/mL of CEPSN-1 and CEPSN-2, respectively (p < 0.05). These results demonstrated that, though their structural feature were different from that of polysaccharides from fruit body, exopolysaccharides of A. auricula-judae from submerged culture with the backbone of (1 → 4)-α-D-glucan could be explored as potential immunomodulatory agents for the application in complementary medicine or functional foods.

Dereplication-guided isolation of a new indole alkaloid triglycoside from the hooks of Uncaria rhynchophylla by LC with ion trap time-of-flight MS.

Uncaria rhynchophylla (Gou-Teng) as the monarch herb of many formulae (Fufang), e.g. "Tian-Ma-Gou-Teng-Yin," "Ling-Jiao-Gou-Teng-Yin," and "Yi-Gan-San", is a famous traditional Chinese medicine documented in the Chinese pharmacopoeia for mental and cardiovascular diseases. In the traditional Chinese medicine system, only the hook-bearing stems are used as the crude materials for Gou-Teng, and the hooks are always considered more effective than the stems. Focusing on the mono-herb and its active constituents from combinatorial formulae is the core idea of reductionism of traditional Chinese medicine theory. Detailed liquid chromatography with mass spectrometry analysis on the hooks of U. rhynchophylla was performed to profile the chemical constituents based on tandem mass spectrometry fragmentation and UV absorption. Under the guidance of liquid chromatography with ion trap/time-of-flight mass spectrometry, one new indole alkaloid triglycoside (1), together with five known compounds 2-6 as the main constituents, were isolated from the hooks of U. rhynchophylla by various column chromatography methods. Compound 1 showed moderate activity on MT1 and MT2 melatonin receptors with agonistic rates of 79.6 and 46.3% at the concentration of 1 mM. This dereplication strategy can be equally applicable to rapidly disclose the active constituents of other Chinese herbs through targeted purification.

Chemical and biological comparison of different sections of Uncaria rhynchophylla (Gou-Teng).

Uncaria rhynchophylla (Gou-Teng in Chinese) is officially documented in Chinese pharmacopoeia as one of the authentic sources for the crude drug of Gou-Teng which has long been used for mental and cardiovascular diseases. Indole alkaloids are the characteristic constituents responsible for the desired hypotensive effect; however, the psychiatric active constituents of Gou-Teng are still unclear. According to traditional Chinese medicine theory, only the hook-bearing stems of U. rhynchophylla are used as the crude materials for Gou-Teng, while its leaves and fruits are scarcely used. The present study aimed to compare the metabolic fingerprints of different parts (hooks, stems, leaves and fruits) of U. rhynchophylla by LC-DAD-MS/MS analysis and further evaluate their psychiatric activities on HEK293 cell line in vitro. A total of 38 constituents including 26 alkaloids, six flavonoids, two triterpenoids, two chlorogenic acid analogs and two other compounds were characterized. The different parts of U. rhynchophylla can be well differentiated from their chemical profiles. Leaves displayed the most potent activity on both MT1 and MT2 receptors, with agonistic rates of 39.7% and 97.6%. For 5-HT1A and 5-HT2C receptors, hooks showed the strongest activity with agonistic rates of 92.6% and 83.1%, respectively. This investigation provided valuable information for understanding the chemical divergence between different parts of U. rhynchophylla, and their substantial bases for psychiatric purposes.

The vascular protective effects of Anoectochilus roxburghii polysaccharose under high glucose conditions.

ETHNOPHARMACOLOGICAL RELEVANCE: Anoectochilus roxburghii has been used as a health food and a herb for treatment diabetes in China for hundreds years. Anoectochilus roxburghii polysaccharose (ARP) is the major active component of the plant. AIM OF THE STUDY: The present study investigated the vascular protection of ARP in vivo and in vitro experiments. MATERIALS AND METHODS: Hypoglycemic activity of ARP was examined in diabetic mice. Moreover, the further vascular protective effects in vitro were investigated in human umbilical vein endothelial cells (HUVECs) stimulated by high glucose (HG, 35mM). RESULTS: Compared with untreated diabetic mice, ARP (100 or 300mg/kg) caused a significant decrease in blood glucose levels. Histological examination showed that ARP ameliorated endothelial damage to some extent, especially ARP at dosage of 300mg/kg. In vitro assay, pretreatment with ARP (10, 20 and 30µg/mL) markedly inhibited generations of reactive oxygen species (ROS), monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule-1 (ICAM-1) in HG-induced HUVECs. ARP pretreatment not only suppressed HG-induced matrix metalloproteinases (MMPs) activity via increasing the expression of the tissue inhibitors of MMPs (TIMPs), but also adjusted the MMPs/TIMPs balance to maintain homeostasis of vascular structure. Moreover, pretreatment with ARP could significantly reduce p-NF-κB p65, p-p38 MAPK expression levels in HG-induced HUVECs. CONCLUSIONS: The vascular protective effects of ARP might be associated with NF-κB and p38 MAPK pathway. ARP might be used as useful substance in the treatment of vasculopathy in diabetic patients.

The renal protective effects of Anoectochilus roxburghii polysaccharose on diabetic mice induced by high-fat diet and streptozotocin.

ETHNOPHARMACOLOGICAL RELEVANCE: Anoectochilus roxburghii (Wall.) Lindl. 1832 is an herbal medicine used to treat diabetes in China. Considering that Anoectochilus roxburghii polysaccharose (ARP) is the main constituent of Anoectochilus roxburghii, the present study is aimed to investigate the renal protection of ARP and its possible mechanism in diabetic mice. MATERIALS AND METHODS: Institute of Cancer Research (ICR) mice were induced to diabetes with high-fat diet (HFD) and low-dose streptozotocin (STZ). ARP (100, 300 mg/kg) was orally administrated to diabetic mice once a day for consecutive 15 days. The fasting glucose level, expressions of key proteins of p38 MAP kinase cascade, inflammatory factors, fibronectin (FN) and the activities of matrix metalloproteinases (MMPs) were measured. Furthermore, the histological examination of the separated kidneys was also carried out. RESULTS: Compared with the diabetic mice, ARP administration induced a significant decrease in blood glucose level and improved the body weight of diabetic mice. In addition, ARP inhibited the expression of renal p38 MAP kinase cascade and its downstream inflammatory factors including tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), FN as well as MMP2/9. Moreover, the histological examination showed an apparent reduction of mesangial matrix deposition and damage of microvascular structure after ARP administration. CONCLUSIONS: The protective effects of ARP on diabetic renal damage may be attributed to the inhibition of p38 MAP kinase cascade and then attenuating the inflammatory responses and high glucose-induced renal damage.

Antihyperglycemic activity of Anoectochilus roxburghii polysaccharose in diabetic mice induced by high-fat diet and streptozotocin.

ETHNOPHARMACOLOGICAL RELEVANCE: Anoectochilus roxburghii is a traditional Chinese herb used for treatment of diabetes and some other diseases. Anoectochilus roxburghii polysaccharose (ARP) is the main constituent of Anoectochilus roxburghii. The present study aimed to investigate the antidiabetic effects of ARP in diabetic mice induced by high-fat diet and streptozotocin. MATERIALS AND METHODS: Two doses of ARP (100 or 300 mg/kg) were administered once daily for 25 days to diabetic mice. To evaluate the antidiabetic effects of ARP, the fasting glucose levels, aspartate aminotransferase (AST), alanine transaminase (ALT) and superoxide dismutase (SOD) activities, malondialdehyde (MDA) content, triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and liver glycogen were examined. Furthermore, histological examinations were carried out on the separated pancreas and liver of mice. RESULTS: Compared with untreated diabetic mice, ARP (100 or 300 mg/kg) caused a significant decrease in blood glucose levels, activities of AST and ALT, and MDA contents, and a significant increase in liver glycogen contents, SOD activities, thymus index and spleen index. Simultaneously, the alteration in lipid metabolism was partially attenuated as evidenced by decreased serum TC, TG and LDL-C concentrations in diabetic mice. In addition, histological examinations showed that administration of ARP (100 or 300 mg/kg) significantly attenuated the pathologic lesions in pancreas and liver of diabetic mice, and improved pancreas and liver function. CONCLUSIONS: The antidiabetic activity of ARP may be attributed to the improvement of glucose and lipid metabolism, increase of immune protection and reduction of oxidative stress.

[Effect of jianpi liqi recipe on mRNA expressions of TP, DPD, and CYP3A4 in mice with human gastric cancer transplanted tumor].

OBJECTIVE: To study the effect of Jianpi Liqi Recipe (JLR) on 5-fluorouracil (5-FU) relevant metabolic enzymes and CYP3A4 (the same enzyme of many chemotherapeutics) of mice with human gastric cancer transplanted tumor. METHODS: Totally 80 mice were randomly divided into the model group, the chemotherapy group, the JLR group, and the combination group (using chemotherapy combined JLR), 20 in each group. The human gastric cancer transplanted tumor mouse model was duplicated by hypodermic inoculating MKN-8 tumor cell suspension from the left armpit. Physiological saline or JLR was given to those in the model group or the JLR group at 0.25 mL each time, twice daily by gastrogavage from the 2nd day after transplantation. Mice in the chemotherapy group were given 0.25 mL physiological saline, twice daily by gastrogavage 2 days after transplantation, for 5 days in succession, and then they were peritoneal injected with 5-FU at the daily dose of 20 mg/kg, once daily for 5 days in succession from the 7th day of transplantation. Those in the combination were given 0.25 mL JLR, twice daily by gastrogavage, for 5 days in succession, and then they were peritoneal injected with 5-FU at the daily dose of 20 mg/kg, once daily for 5 days in succession from the 7th day of transplantation. The mRNA expressions of thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), and CYP3A4 were detected using RT-PCR. RESULTS: Compared with the model group and the chemotherapy group, mRNA expressions of TP and CYP3A4 obviously increased, mRNA expression of DPD obviously decreased in the JLR group and the combination group (P < 0.01). There was no statistical difference in mRNA expressions of TP, DPD, and CYP3A4 between the JLR group and the combination group (P > 0.05). CONCLUSION: JLR could promote the activation of 5-FU, suppress the decomposition and inactivation of 5-FU in the tumor tissue of mice, and improve the chemotherapeutic efficacy through up-regulating mRNA expressions of TP and CYP3A4, and suppressing the mRNA expression of DPD.

The vascular protective properties of kinsenoside isolated from Anoectochilus roxburghii under high glucose condition.

Anoectochilus roxburghii is a traditional Chinese herb used for the treatment of diabetes and some other diseases. The vascular protective effect of its major active ingredient, kinsenoside, in high glucose conditions was investigated in in vivo and in vitro experiments. In in vivo tests, kinsenoside (50 and 100mg/kg) efficiently lowered blood glucose and cholesterol levels and it enhanced the oxidation resistance of diabetic mice induced by streptozotocin. In the in vitro assay, kinsenoside (20 and 50 µg/mL) markedly inhibited changes in various biochemical substances (nitric oxide (NO), lactic dehydrogenase (LDH), superoxide dismutase (SOD), and catalase (CAT)) in human umbilical vein endothelial cells (HUVECs) damaged by high glucose (35 mM) and restored vascular endothelial structure by balancing the matrix metalloproteinases-the tissue inhibitors of matrix metalloproteinases (MMP-TIMP) system. The vascular protective effects of kinsenoside were speculated to be attributed to oxidative stress inhibition and the reduction of nuclear factor kappa B (NF-κB) mRNA expression levels in high glucose conditions. Moreover, histological examination, including hematoxylin-eosin (H&E) staining, masson trichrome (Masson) staining, and periodic Schiff-methenamine (PASM) staining, greatly supported the morphological and functional amelioration of diabetes-related changes in mice aortas after kinsenoside (20 and 50 µg/mL) treatment. These results indicated that kinsenoside might be a promising agent for the treatment of diabetic vascular disease.

[Triterpenes from root of Rhaponticum uniflorum].

OBJECTIVE: To study the chemical constituents of the root of Rhaponticum uniflorum. METHOD: Separation and purification were performed on silica gel and Sephadex LH-20 column chromatography. Their structure were elucidated on the basis of physicochemical and spectral analysis. RESULT: Five triterpenoid compounds were isolated and identified as ursolic acid (1), 3-oxo-19alpha-hydroxyurs-12-en-28-oic acid (2), pomolic acid (3), arjunic acid (4) and tormentic acid (5), respectively. CONCLUSION: Compounds 1 approximately 5 were isolated from the genus Rhaponticum for the first time.

Association of apolipoprotein E 4 polymorphism with cerebral infarction in Chinese Han population.

AIM: To study the association between APOE polymorphisms and cerebral infarction through a case-control study among the Chinese Han population. METHODS: First-ever cerebral infarction patients (n=226) whose ages ranged from 40 to 60 years old were recruited from Department of Neurology, Zhongshan Hospital, Shanghai, and Zhejiang Chinese Traditional Medicine Hospital, Zhejiang, China. Unrelated healthy controls (n=201) were selected from the general population in the same area with similar age and sex distribution. APOE was amplified by one-stage PCR using the forward primer: 5'-GGC ACG GCT GTC CAA GGA GCT-3' and reverse primer: 5'-GAT GGC GCT GAG GCC GCG CT-3'. The PCR product was digested directly with 5 U of CfoI and separated by a 20 % polyacrylamide (acrylamide: bis-acrylamide=29:1) nondenaturing gel. RESULTS: Both cerebral infarction patient and control groups were in Hardy-Weinberg equilibrium. The allele frequency of APOE*2, APOE*3, and APOE*4 was 4.6 %, 81.9 %, and 13.5 % respectively in the patients with cerebral infarction; 5.7 %, 87.3 %, and 7.0 % respectively in the healthy control group. Compared with APOE3/3 subjects, APOE4/4 carriers had a 2.1-fold risk of cerebral infarction (odds ratio 2.1, 95 % confidence limits 1.3 to 3.4). The allele frequency of APOE*4 in the cerebral infarction patient group was significantly higher than that in the control group (13.5 % vs 7.0 %; P=0.002). CONCLUSION: APOE 4 is a risk factor for cerebral infarction among the Chinese Han population.

[Interventional therapy combining Seed of Job's-stears with lipiodol for hepatoma-bearing rats].

OBJECTIVE: To study the effect of the interventional therapy of hepatoma-bearing rat by Seed of Job's-stears (SJS) injection combining with lipiodol. METHODS: To evaluate the effect of SJS as a medicament which can be used in interventional therapy, we repeated the hepatoma-bearing rats, and treated them by interventional therapy with SJS referring to the method which Lindel set up, comparing its effect to which of chemical medicines and lipiodol. RESULTS: SJS or lipiodol alone had an inhibiting effect to liver cancer. The tumor growth rates were 13.89%, 14.05%, and the tumor inhibiting rates reached 38.10%, 37.49%. The curative effect of the SJS/lipiodol group was the best, and its growth rate and inhibiting rate were 3.36% and 85.03%, respectively better than the SJS group and lipiodol group (P<0.01). There was no statistically significant difference between the effect of the SJS/lipiodol group and the mitomycin/lipiodol group. The survival period of SJS/lipiodol group was longer than the rest groups (P<0.01 or P<0.05). CONCLUSIONS: The interventional therapy by SJS/lipiodol has obvious inhibitory effect on the growth of hepatoma-bearing rats, which is similar to that of MMC/lipiodol. This inhibiting effect is better than that of the SJS or lipiodol group. SJS/lipiodol can prolong the survival period of hepatoma-bearing rats obviously, and this effect is better than that of single lipiodol, SJS or MMC/lipiodol.