Clinical application value of Huanglian Jiedu Pills in improving syndrome of excess heat and fire toxin based on phase Ⅱ clinical trial study on plasma ATP, 4-HNE, and ACTH levels / 中国中药杂志

A randomized, double-blind, placebo-controlled, multi-center phase Ⅱ clinical trial design was used in this study to recruit subjects who were in line with the syndrome of excess heat and fire toxin, and were diagnosed as recurrent oral ulcers, gingivitis, and acute pharyngitis. A total of 240 cases were included and randomly divided into a placebo group and a Huanglian Jiedu Pills group. The clinical efficacy of Huanglian Jiedu Pills in treating the syndrome of excess heat and fire toxin was evaluated by using the traditional Chinese medicine(TCM) syndrome scale. Enzyme-linked immunosorbent assay(ELISA) was used to determine and evaluate the levels of adenosine triphosphate(ATP), 4-hydroxynonenal(4-HNE), and adrenocorticotropic hormone(ACTH) in plasma of the two groups before and after administration and to predict their application value as clinical biomarkers. The results showed that the disappearance rate of main symptoms in the Huanglian Jiedu Pills group was 69.17%, and that in the placebo group was 50.83%. The comparison between the Huanglian Jiedu Pills group and the placebo group showed that 4-HNE before and after administration was statistically significant(P<0.05). The content of 4-HNE in the Huanglian Jiedu Pills group decreased significantly after administration(P<0.05), but that in the placebo group had no statistical significance and showed an upward trend. After administration, the content of ATP in both Huanglian Jiedu Pills group and placebo group decreased significantly(P<0.05), indicating that the energy metabolism disorder was significantly improved after administration of Huanglian Jiedu Pills and the body's self-healing ability also alleviated the increase in ATP level caused by the syndrome of excess heat and fire toxin to a certain extent. ACTH in both Huanglian Jiedu Pills group and placebo group decreased significantly after administration(P<0.05). It is concluded that Huanglian Jiedu Pills has a significant clinical effect, and can significantly improve the abnormal levels of ATP and 4-HNE in plasma caused by the syndrome of excess heat and fire toxin, which are speculated to be the effective clinical biomarkers for Huanglian Jiedu Pills to treat the syndrome of excess heat and fire toxin.

Comprehensive evaluation system for quality of Chinese medicinal decoction pieces based on "experience-ingredients-activity-electronic sensing" / 中国中药杂志

Quality evaluation of Chinese medicinal decoction pieces is vital for the development of the downstream industries, and is an important channel for implementing the strategy of "higher quality, higher price, and priority for the high quality" for traditional Chinese medicine. At the moment, the quality of Chinese medicinal decoction pieces is mainly evaluated based on chemical component examination. Considering the weak preliminary research foundation and poor research conditions, traditional experience-based evaluation is undervalued in the quality rating of Chinese medicinal decoction pieces. However, traditional experience is a summary of the quality of Chinese medicinal materials based on clinical experience, which thus can be a potential basis for the quality evaluation of the decoction pieces. It is a challenge in the evaluation of Chinese medicinal decoction pieces to objectify the traditional experience-based evaluation from multiple aspects such as chemistry, effect, and characterization via modern techniques. Therefore, this study developed the "experience-ingredients-activity-electronic sensing" evaluation system for Chinese medicinal decoction pieces on the basis of experience-based assessment, chemical ingredients that can truly reflect the traditional experience, biological effect assessment, and electronic sensory evaluation, which is expected to quantify the traditional experience of quality evaluation of Chinese medicinal decoction pieces via chemistry, biology, and sensory simulation. The evaluation system can serve as a reference for clinical experience-based quality evaluation of Chinese medicinal decoction pieces.

A Comparative Study on the Health Status and Behavioral Lifestyle of Centenarians and Non-centenarians in Zhejiang Province, China-A Cross-Sectional Study.

Background: The growth rate of centenarians was unusually rapid in recent decades, ushering in an era of longevity. This study aims to explore the difference between centenarians and non-centenarians using quantitative research, and to scientifically guide residents to develop the correct lifestyle and health care ways. Methods: From October 2013 to August 2017. A cross-sectional survey was conducted on 271 centenarians and 570 non-centenarians by using a questionnaire to assess longevity and health issues which was developed for the needs of the study, who came from 29 counties and districts in 11 cities of Zhejiang province, China. Two hundred and fifty-five valid questionnaires were returned, with an effective response rate of 94.1%. Meanwhile, data of 526 non-centenarians from Zhejiang province was collected as a control group, with an effective response rate of 92.3%. Results: The prevalence rates of tumor, stomach and duodenal ulcer, diabetes, bronchial asthma, and chronic obstructive pulmonary disease, tuberculosis among centenarians were all lower than those among non-centenarians. The oral health of centenarians is better than that of non-centenarians. The consumption of coarse cereals, pasta, other staple foods and fruits among centenarians was higher than that of non-centenarians. The percentage of centenarians who smoke or engage in recreational activities every day was lower than that of non-centenarians. Conclusions: We should give full play to the role of preventive medicine and health management to safeguard the health of residents. Pay attention to oral health, and develop the good habit of loving teeth. The diet should be rich and varied, and increase the intake of grains and fruits. Give up smoking, limit alcohol, spirit-preserving with calming, follow the law of scientific regimen.

[Experimental study on preventive effect of Yougui drink on femoral head necrosis in rats under micro CT].

OBJECTIVE: To explore the preventive effect of Yougui drink on femoral head necrosis in rats under micro CT. METHODS: Twenty-five SD rats were divided into steroid hormone group (group A, 10 rats ), Yougui drink group (group B,10 rats) and normal group (group C,5 rats)with random number table. Endotoxin were injected into abdominal cavity of rats in group A and B for 2 days, methylprednisolone sodium succinate were injected by gluteus for twice a week continued for 6 weeks; group B were gavaged by Yougui drink (veryday for 8 weeks; group C did not do any processing. All rats were killed on the 10th weeks,m icro CT were used to scan femoral head in vitro and preventive effect of Yougui drink (n femoral head necrosis in rats. RESULTS: There was statistical significance in BMD, BV/TV, Tb.N, Tb, Th, Thb, Sp, BS/TV and DA but no significance in SMI between group A and B. Comparison between A and C, there was significant meaning in BMD, BV/TV, Tb.N, Tb, Th, Tb, Sp, BS/TV, DA and SMI. CONCLUSION: Yougui drink on femoral head necrosis in rats under micro CT has preventive effect from BMD BV/TV, Tb.N, Tb, Th, Tb, Sp, BS/TV and DA.

[Effects of Yougui recipe on the behavioral changes in rat of steroid-induced avascular necrosis of the femoral head].

OBJECTIVE: To explore the effect of Yougui Recipe, a kidney-supplementing and yang-activating formula which on the behavioral changes of rat of steroid-induced avascular necrosis of the femoral head (SANFH). METHODS: Thirty Wistar rats were involved and were randomly divided into the blank control group (group A), the model group (group B) and the Yougui Recipe group (group C). SANFH models were established by injection of colibacillus endotoxin and prednisolone intramuscularly. Group C was lavaged with Yougui Recipe (10 ml/kg), while group A and group B were lavaged with the same amount of saline. The behavior of catch force, independent activities, the tail suspension, field experiment and water cleans maze experiment were observed after 6 weeks. RESULTS: Compared with Yougui Recipe, rats in model group: catch force and independent activity decreases; the tail suspension activities was less time. In the desert field experiments, the total distance in 10 min movement reduced significantly. In the water maze experiment, incubation period of escape had a long time obviously, total distance of activities reduced. CONCLUSION: Yougui Recipe can relieve the ethologic change of rat model of steroid-induced avascular necrosis of the femoral head.

Epimedium-derived flavonoids modulate the balance between osteogenic differentiation and adipogenic differentiation in bone marrow stromal cells of ovariectomized rats via Wnt/ß-catenin signal pathway activation.

OBJECTIVE: To observe the function of wnt/ß-catenin signal pathway on the process that epimedium-derived flavonoids (EFs) regulate the balance between osteogenic differentiation and adipogenic differentiation in bone marrow stromal cells of ovariectomized rats, and to provide an experimental evidence for the mechanism of EFs on treating postmenopausal osteoporosis. METHODS: Bone marrow stromal cells from ovariectomized rats were separated and cultivated in the condition of osteoinductive medium or liquid medium for 15 days. Low- (1 µg/mL), medium- (10 µg/mL) and high- (100 µg/mL) dose EFs were administrated correspondingly. Alkaline phosphatase (ALP) staining, ALP activity determination, oil red O staining and realtime polymerese chain reaction (RT-PCR) were used to determine the effect of EFs on osteogenic differentiation and adipogenic differentiation in bone marrow stromal cells of ovariectomized rats. Moreover, in order to explore the mechanism of EFs on osteogenic differentiation and adipogenic differentiation in bone marrow stromal cells of ovariectomized rats, Dickkopf-related protein 1 (DKK1) was used in the medium group. Enzymelinked immunosorbent assay (ELISA) and RT-PCR were used to determine mRNA levels of ß-catenin, low density lipoprotein receptor-related protein 5 (LRP5) and T cell factor (TCF) protein, known as wnt/ß-catenin signal pathway related factors. RESULTS: EFs increased mRNA expression levels of ALP and early osteoblast differentiation factors, such as runt-related transcription factor 2 (Runx2), osteocalcin and collagen I, and decreased mRNA expression levels of fat generation factors, such as peroxisome proliferator activated receptor gamma 2 (PPARγ-2) and CCAAT enhancer-binding protein-α (C/EBPα) in a dose-dependent manner. While osteoblast differentiation factors were down-regulated, fat generation factors were up-regulated when DKK1 was applied. Also EFs up-regulated mRNA expression levels of ß-catenin, LRP5 and TCF protein which could be blocked by DKK1. CONCLUSION: EFs regulate the balance between osteogenic differentiation and adipogenic differentiation in bone marrow stromal cells of ovariectomized rats by activating wnt/ß-catenin signal pathway, which may be an important molecular mechanism of EFs on treating postmenopausal osteoporosis.

[Experimental study on invigorating kidney and activating blood on preventing and curing SD rats with knee osteoarthritis].

OBJECTIVE: To explore the effects and mechanism of invigorating kidney and activating blood, invigorating kidney and expelling wind on hemorheology, IL-1ß and TNF-α of SD rats with knee osteoarthritis, then definite the evolution of muscle certified turning into heumatism and compare the effect of Chinese herbal. METHODS: One hundred and eighty SD rats with 3-month-old (each weight was 185 to 215 g) received intra-articular injection of papain solution for establishing knee OA models. All rats were randomly divided into activating blood group, preventing group, expelling wind group, invigorating kidney group, invigorating kidney and activating blood group and model group. Laboratory indexes were obtained at the 30th, 60th, 90th days after gastric perfusion, which including state of mind, activity, fur, weight, joint swelling, largely image, hemorheology, inflammation and HE pathological appearance. RESULTS: After operation, rats appeared blood stasis and swelling and difficulty crawling. There was significant difference of hemorheology in invigorating kidney and activating blood group the content of IL-1ß and TNF-α was obviously lower than model group (P < 0.05 ). While the content of IL-1ß and TNF-α on the early stage was obviously higher than late stage (P < 0.05). CONCLUSION: Knee osteoarthritis mainly show synovial inflammation at the early stage, inflammation at early stage is more severe than late; invigorating kidney and activating blood decoction can inhibit the knee cartilage injury, improve blood circulation and prevent local inflammatory reaction. Activating blood decoction and invigorating kidney and activating blood Decoction have certain curative effect in early time, but the effects of invigorating kidney and activating blood Decoction is more effective than other on the late stage.

Study on the effect of Youguiyin () on regulating gene expression profile of the rats with femoral head necrosis induced by steroid.

OBJECTIVE: To observe the regulation of Youguiyin (YGY, ) on the gene expression profile of the rat with steroid-induced femoral head necrosis (sFHN), for the sake of investigating its molecular mechanism of sFHN prevention and treatment. METHODS: All the 30 rats were randomly divided into three groups, the normal control group (A), the model control group (B), and the YGY treated group (C), 10 in each group. After rats in Groups B and C were being made into FHN models with steroid injection, they received a daily intragastric administration of saline and YGY respectively in equal volume for a total of 6 weeks, while to the unmodeled normal rats in Group A, saline was administered instead. The rats were sacrificed at the terminal of administration; their mRNA from femoral head tissue was extracted and prepared to cDNA probe through inverse transcription for detecting gene expression profile by microarray, outcomes of which was passing fluorescence quantitative PCR verification, and the differential expressed genes were analyzed adopting gene ontology (GO) method. RESULTS: Compared with Group A, the numbers of differential genes found in Groups B and C were 190 and 92, respectively, but the changing trend in the two groups was opposite, mainly manifested as down-regulating in Group B/Group A (GB/GA) and up-regulating in Group C/Group B (GC/GB). The analysis showed that these differential genes were mainly assigned to cell apoptosis, signal transduction, metabolism, cell proliferation and differentiation, cell cycle, blood coagulation, antioxidant activity, etc. CONCLUSIONS: sFHN was regulated by various genes; the regulation of YGY on expressions of these genes and the intra/extra-cellular signaling processes was possibly the molecular mechanism of YGY for preventing/treating sFHN. This study gave an explanation to the effectiveness of Chinese medicine in preventing/treating FHN from aspects of gene expression and enriched the Chinese medicine theory of "Kidney (Shen) governing bones".

[Experimental study on Yougui recipe in preventing osteolysis surrounding artificial prosthesis].

OBJECTIVE: To explore effects of Yougui recipe (see text) and salmon calcitonin acetate in preventing osteolysis surrounding artificial prosthesis. METHODS: Thirty-two SD male rats with weighted (250 +/- 20) g, aged 8 weeks, were randomly divided into four groups: blank group, model group, salmon calcitonin acetate group and Yougui recipe (see text) group, and 8 rats in each group. Blank group did not undergo any process, other 24 rats underwent anesthesia by chloral hydrate, their knee joints were exposed through medial patellar side,drilling from fermoral condyle nest to marrow cavity,high density of polythlene particles were injected into hole, titanium nail were put into, bone wax closed the window, then suturing step by step. After the molding, saline were used to gavaged in blank group and model group, Yougui recipe (see text) for Yougui recipe (see text) group, salmon calcitonin maximus injection for calcitonin group. After 10 weeks' mediation, rats were executed, and arterial blood and bilateral femoral organization were collected to biochemical, imaging morphology, tissue pathology and molecular biology detection. RESULTS: The key gene expression of activiting osteoclast were inhibited in Yougui recipe (see text) group and calcitonin group. The level of OPG, Ca, ALP in Yougui recipe group were higher than calcitonin group (P<0.01); the content of RANKL were lower (P<0.01). There were no significance meaning in RANK, Trap5b, P between two groups. CONCLUSION: Both of Yougui recipe (see text) and calcitonin can slow and treat surrounding osteolysis of artificial joint prosthesis, and Yougui recipe (see text) has better effect in promoting bone formation. The effect of Yougui recipe (see text) in promoting bone formation, inhibiting osteoclasts to provide a new method to treating surrounding osteolysis of artificial joint prosthesis.

Establishment of drug screening assay and pharmacodynamic evaluation method targeting influenza RNA polymerase / 药学学报

Influenza virus RNA-dependent RNA polymerase (RdRP) is essential for replication and expression of influenza virus genome. Viral genomic sequences encoding RdRP are highly conservative, thus making it a potential anti-influenza drug target. A cell-based influenza RdRP inhibitor screening assay was established by a luciferase reporter system to analyze the activity of RdRP. Specificity study and statistic analysis showed that the screening assay is sensitive and reproducible.

[Effects of yougui drink on the osteogenic differentiation of mesenchymal stem cells in the proximal femur in steroid-induced avascular necrosis of femoral head].

OBJECTIVE: To investigate the effects of Yougui drink on osteogenic differentiation of bone mesenchymal stem cells (BMSCs) in the proximal femur in steroid-induced avascular necrosis of femoral head in vitro. METHODS: The BMSCs were induced to osteoblasts in vitro with a conditional medium. The cells cultured with Yougui drink serum were compared with the ordinary one, which both were examined by microscopy, MTU method, ALP and calcium node. RESULTS: Microscopy and MTU studies showed that Yougui drink could improve proliferation of the osteoblasts. ALP and calcium node studies showed that Yougui drink could improve the activity of the osteoblasts (P < 0.01). CONCLUSION: Yougui drink has positive effects on osteogenic differentiation of mesenchymal stem cells in the proximal femur in steroid-induced avascular necrosis of femoral head in vitro.

[Study on the application of Aconitum in clinical orthopedics].

Aconitum is important in clinical orthopedics. From ancient times to the present day,there were many famous doctors who used this herb to cure many diseases in orthopedics. However, the toxicity always connect with its effect. This will limit its application in clinics. So now the important thing is how to use this herb correctly. This article will give some suggestions about how to use aconitum in orthopedics and to make sure it can be used correctly in future. It has four parts: application in orthopedics, pharmacology, factors related to toxicity and the prospect of the use of aconitum.

[Effect of jingui shenqi pill on morphology of injured spinal cell apoptosis in rats caused by brachytherapy].

OBJECTIVE: To study the effect of Jingui Shenqi Pill (JSP) on morphology of spinal cell apoptosis in rats injured by 192Ir irradiation. METHODS: One hundred and twenty rats were randomly divided into four groups: the model group, the JSP group, the prednisone group and the normal group. Corresponding pharmaceutics were given to rats once a day for 14 days respectively. Then except rats in the normal group, the others received 192Ir interstitial irradiation with the dosage of 22 Gy using back-fixing technology. The injured segments of spinal cord were taken out for HE staining, TUNEL examination and observation with electron microscope 8 hrs, 24 hrs and 4 weeks after irradiation. RESULTS: HE staining examination showed no obvious histological change in rats 8 and 24 hrs after irradiation, but pathological changes, as tissue rarefaction and hemorrhage did found in white matter of spinal cord shown by TUNEL 4 weeks later. Electron microscopic examination and TUNEL staining showed that as compared with the model group, the apoptotic index in the JSP and predinisone treated groups was significantly lower (P < 0.01) 8 hrs after radiation, but it showed insignificant difference between groups at the time points of 24 hrs and 4 weeks after radiation (P > 0.05). CONCLUSION: JSP could act against apoptosis of gliocyte in spinal cord of rats in early stage after brachytherapy, indicating that JSP possessing a prednisone-like action.