[Effect of moxibustion on JAK2/STAT3 signal pathway in synovial tissues of rabbits with adjuvant arthritis under the overexpression of NLRP3 inflammatory bodies].

OBJECTIVE: To observe the effect of moxibustion on Janus protein tyrosine kinase 2/signal transducer and activator of transcription 3 (JAK2-STAT3) signal pathway and interleukin (IL)-1ß and IL-18 in synovial fluid of adjuvant arthritis (AA) rabbits, so as to explore the mechanism of moxibustion in the treatment of rheumatoid arthritis. METHODS: Twenty-eight rabbits were randomized into control, model, moxibustion, and NLRP3 overexpression groups, with 7 rabbits in each group. AA rabbit model was established by injection of Freund's complete adjuvant (FCA, 0.5 mL/kg) into the rabbits' bilateral hind-knee joint cavities. On the third day after modeling, the NLRP3 lentiviral vector (40 µL) were injected into the bilateral hind-knee joint cavities of rabbits in NLRP3 overexpression group. Moxibustion was used to bilateral "Shenshu" (BL23) and "Zusanli" (ST36), 5 cones every time, once daily, 6 days a week for 3 weeks in the moxibustion and NLRP3 overexpression groups. The perimeters of rabbits' hind legs were measured after modeling and after the intervention. The contents of IL-1ß, IL-18 in synovial fluid were detected by ELISA and the expression levels of NLRP3, JAK2 and STAT3 mRNAs in synovial tissue were detected by real-time PCR. RESULTS: In comparison with the control group, the perimeters of bilateral knee joints were significantly increased at each time point (P<0.05),and the contents of IL-1ß, IL-18 in synovial fluid and the expression levels of NLRP3, JAK2, STAT3 mRNA in synovial tissue were significantly increased (P<0.05) in the model group. Compared with the model group, the perimeters of bilateral knee joints were significantly decreased (P<0.05), and the contents of IL-1ß, IL-18 in synovial fluid and the expression levels of NLRP3, JAK2, STAT3 mRNAs in synovial tissue were significantly decreased (P<0.05) in the moxibusion group. Compared with the moxibustion group, the above indexes were higher in the NLRP3 overexpression group (P<0.05). CONCLUSION: Moxibustion may play an anti-inflammatory and detumescent role in AA rabbits by regulating JAK2-STAT3 signal pathway, and its therapeutic effect may be closely related to the expression of NLRP3.

The Beneficial Effects of Edible Kynurenic Acid from Marine Horseshoe Crab (Tachypleus tridentatus) on Obesity, Hyperlipidemia, and Gut Microbiota in High-Fat Diet-Fed Mice.

The marine horseshoe crab (Tachypleus tridentatus) has been considered as food and traditional medicine for many years. Kynurenic acid (KA) was isolated from horseshoe crab in this study for the first time in the world. A previous study in 2018 reported that intraperitoneal administration of KA prevented high-fat diet- (HFD-) induced body weight gain. Now, we investigated the effects of intragastric gavage of KA on HFD mice and found that KA (5 mg/kg/day) inhibited both the body weight gain and the increase of average daily energy intake. KA reduced serum triglyceride and increased serum high-density lipoprotein cholesterol. KA inhibited HFD-induced the increases of serum low-density lipoprotein cholesterol, coronary artery risk index, and atherosclerosis index. KA also suppressed HFD-induced the increase of the ratio of Firmicutes to Bacteroidetes (two dominant gut microbial phyla). KA partially reversed HFD-induced the changes in the composition of gut microbial genera. These overall effects of KA on HFD mice were similar to that of simvastatin (positive control). But the effects of 1.25 mg/kg/day KA on HFD-caused hyperlipidemia were similar to the effects of 5 mg/kg/day simvastatin. The pattern of relative abundance in 40 key genera of gut microbiota from KA group was closer to that from the normal group than that from the simvastatin group. In addition, our in vitro results showed the potential antioxidant activity of KA, which suggests that the improvement effects of KA on HFD mice may be partially associated with antioxidant activity of KA. Our findings demonstrate the potential role of KA as a functional food ingredient for the treatment of obesity and hyperlipidemia as well as the modulation of gut microbiota.

Clinical Efficacy of Didangtang Combined with Gemcitabine in Postoperative Patients with Non-muscle-invasive Bladder Cancer / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of Didangtang combined with gemcitabine chemotherapy in postoperative patients with non-muscle invasive bladder ctraditional chinese medicineancer （NMIBC）. Method:A total of 100 patients with NMIBC in Jiangsu Provincial Second Chinese Medicine Hospital and Jiangsu Province Hospital of Chinese Medicine from January 2015 to September 2020 were randomly divided into control group and treatment group. 50 cases in the treatment group received Didangtang combined with intravesical infusion of gemcitabine， and 50 cases in the control group received placebo combined with intravesical infusion of gemcitabine. Before and after the treatment cycle， the blood biochemistry， immune cell subsets（CD3⁺，CD4⁺ and CD4⁺/CD8⁺） were detected to assess the safety and immune function changes in treatment group. Quality of life scale for patients with bladder cancer prepared by European Organization for the Research and Treatment of Cancer （EORTC QLQ-C30） and Specificity scale for patients with superficial bladder cancer （EORTC QLQ-BLS24） were scored to assess the changes in physical， role， emotional and social functioning of the patients， symptomatic conditions such as fatigue， pain， nausea and vomiting， shortness of breath， insomnia， loss of appetite， diarrhea and constipation， as well as bladder cancer-specific symptoms such as treatment-generated problems， future concerns， bowel symptoms and urinary tract symptoms. Result:There were no differences in terms of age， sex， disease duration and tumor states. During the treatment period， both groups had no recurrence or adverse events. The traditional Chinese medicine（TCM） efficacy in the treatment group was significantly better than that in the control group（<italic>χ²</italic>= 7.23，<italic>P </italic>= 0.02）. After treatment， the number of CD3⁺，CD4⁺ ，CD8⁺ cells and the CD4⁺/CD8⁺ ratio in the treatment group were significantly higher than those in control group（<italic>P</italic><0.05）. Both groups showed significant improvements in the domains of role functioning， social functioning， and general health after treatment （<italic>P</italic><0.05）. In addition， fatigue， diarrhea， constipation， intestinal symptoms， and urinary tract symptoms in the treatment group were significantly better than those in the control group after treatment （<italic>P</italic><0.05）. Conclusion:Didangtang can reduce adverse clinical symptoms during postoperative gemcitabine infusion chemotherapy in patients with NMIBC， reduce urethral and intestinal discomfort reactions， improve immune function and enhance quality of life for patients.

Research progress of sulfation modification of chondroitin sulfate and chondroitin sulfate preparation in Kashin-Beck disease and osteoarthritis / 中华地方病学杂志

Chondroitin sulfate (CS) is a sulfurated glycosaminoglycan, a major component of the extracellular matrix, widely distributed in skin, cartilage and vascular tissue. CS plays an important role in the physiological state regulation of articular cartilage, which affects tensile strength and elasticity of tissues by influencing aggrecan. Previous studies have shown that CS sulfate modification may be related to the growth and development disorders of cartilage tissue and the occurrence of osteoarticular diseases. At the same time, CS is also a common joint supplement, often used in the treatment of osteoarthritis and Kashin-Beck disease. In this paper, the research progress of CS sulfate modification characteristics in Kashin-Beck disease and osteoarthritis and the application of the preparation in the treatment of Kashin-Beck disease and osteoarthritis are reviewed, aiming to provide help for the investigation of the etiology of Kashin-Beck disease and the treatment of osteoarthritis and Kashin-Beck disease.

ASBT(SLC10A2): A promising target for treatment of diseases and drug discovery.

Bile acids has gradually become a new focus in various diseases, and ASBT as a transporter responsible for the reabsorption of ileal bile acids, is a key hinge associated to the bile acids-cholesterol balance and bile acids of enterohepatic circulation. The cumulative studies have also shown that ASBT is a promising target for treatment of liver, gallbladder, intestinal and metabolic diseases. This article briefly reviewed the process of bile acids enterohepatic circulation, as well as the regulations of ASBT expression, covering transcription factors, nuclear receptors and gut microbiota. In addition, the relationship between ASBT and various diseases were discussed in this paper. According to the structural classification of ASBT inhibitors, the research status of ASBT inhibitors and potential ASBT inhibitors of traditional Chinese medicine (such resveratrol, jatrorrhizine in Coptis chinensis) were summarized. This review provides a basis for the development of ASBT inhibitors and the treatment strategy of related diseases.

Effects of mindfulness-based cognitive therapy on breast cancer survivors with insomnia: A randomised controlled trial.

OBJECTIVE: We investigated the effects of mindfulness-based cognitive therapy on insomnia (MBCT-I) in breast cancer survivors. METHODS: In total, 136 participants were allocated randomly to a MBCT-I group or a waitlist control (WLC) group. Indicators of insomnia and mindfulness were evaluated using the Insomnia Severity Index, actigraphy and the Five Facet Mindfulness Questionnaire. Data were collected at baseline (T1), post-intervention (T2), 3-month follow-up (T3) and 6-month follow-up (T4) time points. RESULTS: Insomnia severity decreased significantly in the MBCT-I group, compared with the WLC group, at T2, T3 and T4 (all p < .001). We found that 59.6% of the MBCT-I group with moderate and severe insomnia improved to no insomnia and subclinical insomnia at T4 relative to T1, accounting for 7.9% and 55.3%, respectively. Compared with the WLC group, the MBCT-I group improved on actigraphy measures of sleep; they exhibited a pattern of decreased sleep onset latency and waking after sleep onset, as well as increased total sleep time and sleep efficiency. Mindfulness also increased more in the MBCT-I group than in the WLC group at T2, T3 and T4 (all p < .001). CONCLUSIONS: MBCT-I may be an efficacious non-pharmacologic intervention to improve sleep quality in breast cancer survivors.

Establishing a rapid classification and identification method for the major triterpenoids of Alisma orientale.

INTRODUCTION: Alismatis Rhizoma (AR) has been widely used to treat various diseases. Its complex chemical composition has caused certain difficulties in the analysis of this traditional Chinese medicine. Therefore, it is necessary to establish a method for the rapid classification and identification of the chemical constituents of AR. OBJECTIVE: This article describes a method for the rapid classification and identification of major triterpenoids in AR. METHODOLOGY: The samples were analysed by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The assay was performed on a Waters ACQUITY UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 µm) with 0.1% formic acid in water (A), and acetonitrile (B) as mobile phase by gradient elution at a flow rate of 0.3 mL/min. In the positive ion mode, the fragment information was obtained and compared with the characteristic fragments and neutral losses described in the literature. Then, the rapid classification and identification of the chemical components from AR were achieved. RESULTS: Finally, 25 triterpene compounds of AR were identified. CONCLUSIONS: The method established in this study achieved the rapid classification and identification of chemical components in AR, which promotes the development of research methods to study the constituents of traditional Chinese medicine.

Mechanism of Didangtang in Treatment of Bladder Cancer Based on Network Pharmacology / 中国实验方剂学杂志

Objective:To investigate the targets and possible mechanism of Didangtang in the treatment of bladder cancer. Method:Based on multiple traditional Chinese medicine and disease databases, the network pharmacology was used to screen potential targets, analyze the biological functions of potential targets, and construct a network of "Chinese medicine-target-path-disease". Bioinformatics analysis was applied in population and gene databases, in order to explore the differential expressions of core targets in tissues, distribution in the population and the correlation with prognosis. The in vitro experiment was used to verify the biological function of Didangtang. The underlying mechanism of Didangtang on the candidate target was detected. Result:A total of 21 core target genes and 16 highly enriched pathways were screened out. A functional network of Didangtang was constructed systematically. At the same time, six targets, namely cadherin 1 (CDH1), CAMP responsive element binding protein 1 (CREB1), colony stimulating factor 2 (CSF2), AP-1 transcription factor (JUN), matrix metalloproteinase 2 (MMP2), and prostaglandin-endoperoxide synthase (PTGS2), were differentially expressed in bladder cancer tissues (P<0.05). Furthermore, JUN and MMP2 were also differentially distributed in population (P<0.05). At the same time, the expression level of JUN was correlated with the prognosis of patients with bladder cancer (P<0.05). The in vitro experiment revealed that Didangtang inhibited the proliferation of bladder cancer cells and decreased the expression of candidate target JUN (P<0.01). Conclusion:Didangtang has the characteristics of multiple targets and multiple pathways in treatment of bladder cancer. It is initially confirmed that Didangtang can affect the expression of target JUN and inhibit the proliferation of bladder cancer, which lays a good foundation for further studies on mechanism.

Clinical observation of heat-sensitive moxibustion treatment for coronavirus disease 2019 / 中国针灸

OBJECTIVE@#To observe clinical effect of heat-sensitive moxibustion on coronavirus disease 2019 (COVID-19) and to discusses the effective moxibustion treatment program.@*METHODS@#A total of 42 patients with COVID-19 (general type) were treated with heat-sensitive moxibustion at the acupoint area of Shenque (CV 8) and Tianshu (ST 25). The treatment was conducted under the standards of heat-sensitive moxibustion manipulation, which were "locating acupoint by feeling, moxibustion by differentiate sensation, dosage varies individually, ending after sufficient dosage". The incidence of after first heat-sensitive moxibustion, the reduction of negative emotions, the improvement of chest distress and impaired appetite, and the active acceptance rate of moxibustion before and after treatment were observed.@*RESULTS@#① The rate of heat-sensitive moxibustion for 20 min、40 min、1 h were respectively 52.4% (22/42), 90.5% (38/42), 100.0% (42/42). ② The incidences of feeling relaxed and comfortable immediately after the first, second, and third heat-sensitive moxibustion were 61.9% (26/42), 73.8% (31/42), and 92.9% (39/42), which were higher than 42.9% (18/42) before heat-sensitive moxibustion treatment (<0.05). ③ The incidences of chest distress after the first, second, and third heat-sensitive moxibustion were 23.8% (10/42), 16.7% (7/42), and 9.5% (4/42), which were lower than 50.0% (21/42) before heat-sensitive moxibustion treatment (<0.05); the incidences of impaired appetite after the first, second, and third heat-sensitive moxibustion were 26.2% (11/42), 19.0% (8/42), 9.5% (4/42), which were lower than 57.1% (24/42) before heat-sensitive moxibustion treatment (<0.05). ④ After the first treatment, the active acceptance rate of patients for heat-sensitive moxibustion was 100.0% (42/42), which was higher than 11.9% (5/42) before heat-sensitive moxibustion (<0.05).@*CONCLUSION@#The heat-sensitive moxibustion can effectively reduce the negative emotions and improve the symptoms of chest distress and impaired appetite with COVID-19. It is generally accepted by patients, and worthy of popularization and application in clinical treatment.

Galectin 3 inhibition attenuates renal injury progression in cisplatin-induced nephrotoxicity.

Nephrotoxicity is a major toxic effect in chemotherapy, which constitutes up to 60% of hospitalized acute kidney injury (AKI). Very few treatment options exist to slow the transition from AKI to subsequent chronic kidney diseases (CKD). Here, we demonstrate that galectin-3 (Gal-3), a ß-galactoside binding lectin that plays an important role in kidney fibrosis and renal failure, is one of the key factors for renal injury progression. Ectopic overexpression of Gal-3 significantly decreased the viability of HEK293, simultaneously inducing of cell cycle arrest and apoptosis. However, inhibition of Gal-3, mediated by modified citrus pectin (MCP), predominantly antagonized the pro-apoptotic effects. Mice were pre-treated with normal or 1% MCP-supplemented drinking water 1 week before cisplatin injection. Analyses of serum creatinine and renal tissue damage indicated that MCP-treated mice demonstrated increased renal function and attenuated renal fibrosis after cisplatin-induced injury. MCP-treated mice also demonstrated decreased renal fibrosis and apoptosis, as revealed by masson trichrome staining and Western blot analysis of cleaved caspase-3. Additionally, the protective role of Gal-3 inhibition in the kidney injury was shown to be mediated by protein kinase C α (PKC-α), which promoted cell apoptosis and collagen I synthesis in HEK293 cells. These results demonstrated the potential Gal-3 and PKC-α as therapeutic targets for the treatment of AKI and CKD.

[Pharmacokinetics mechanism of ABC efflux proteins-mediated seven features of compatibility].

ABC efflux proteins are a kind of transporters mediating diversified endogenous and exogenous efflux protein substrates across the plasma membrane by depending on the chemical energy released by ATP hydrolysis. As a vitally important functional membrane, it is widely found in various tissues and organs. The drug changes the expressions and/or functions of the transport proteins, which will affect the disposal process of substrate drugs corresponding to transporters in vivo, and finally lead to the pharmacokinetic interactions. The efflux proteins take part in the absorption, distribution, metabolism and excretion of drugs, and mainly consist of P-glycoprotein(P-gp), multidrug resistance associated protein(MRP) and breast cancer resistance protein(BCRP). The induction effect or inhibition effect of drugs on efflux protein plays a greatly significant role in the drug interaction produced by the compatibility of traditional Chinese medicine, which may be one of the important mechanisms of the theory of seven features of compatibility. In this article, the effects of seven features of compatibility on the ABC efflux transporters were reviewed, in order to reveal the roles of efflux protein in the herb-pairs compatibility, and provide new ideas for the mechanism and rationality of herb compatibility.

Efficacy of Weitan Waifu patch on the postsurgical gastroparesis syndrome of gastrointestinal cancer: a multi-center trial / 中华肿瘤杂志

Objective@#To investigate the safety and efficacy of the Weitan Waifu patch on the postsurgical gastroparesis syndrome (PGS) of gastrointestinal cancer.@*Methods@#The multi-center, double-blind, randomized controlled trial was conducted with superiority design. Patients with PGS of gastrointestinal cancer diagnosed in 4 AAA hospitals and the abdominal symptom manifested as cold syndrome by Chinese local syndrome differentiation were recruited. These patients were randomly divided into two groups according to 1∶1 proportion. Placebo or Weitan Waifu patch was applied in control group or intervention group, respectively, based on the basic treatments, including nutrition support, gastrointestinal decompression, promoting gastric dynamics medicine.Two acupuncture points (Zhongwan and Shenque) were stuck with placebo in control group or patch in treatment group. The intervention course was 14 days or reached the effective standard.@*Results@#From July 15, 2013 to Jun 3, 2015, 128 participants were recruited and 120 eligible cases were included in the full analysis set (FAS), and 60 cases in each group. 88 cases were included in the per-protocol set (PPS), including 45 cases in the treatment group and 43 cases in the control group. In the FAS, the clinical effective rate in the treatment group was 68.3%, significantly superior than 41.7% of the control group (P=0.003). The medium time of effective therapy in the treatment group was 8 days, significantly shorter than 10 days in the control group (P=0.017). In the FAS, 3 adverse events occurred in the treatment group, including mild to moderate decrustation, pruritus and nausea. The incidence rate of adverse events was 5.0% (3/60) and these symptoms were spontaneously remitted after drug withdrawal. No severe adverse events were observed in the control group. There was no significant difference between these two groups (P=0.244).@*Conclusion@#Weitan Waifu patch is a safely and effectively therapeutic method for patients with PGS (cold syndrome) of gastroenterological cancer.@*Trial registration@#International Standard Randomized Controlled Trial Number Register, ISRCTN18291857

Potassium supplementation and long-term outcomes in chronic peritoneal dialysis patients with end-stage renal disease: a propensity score matching study.

OBJECTIVE: In this retrospective matched-cohort study, the association between potassium supplementation and long-term outcomes was determined. METHODS: Chronic peritoneal dialysis (PD) patients, aged ≥ 16 years, being referred to four PD centers in China, with serum potassium levels ≤ 3.5 mEq/L on three consecutive monthly in Q4 2008 and without receiving oral potassium supplementation in the prior three months were included in this study. Patients were divided into two groups, either to receive (test group) or not (control group) oral potassium supplementation in both Q4 2008 and the subsequent follow-up period, until 31 December 2014. The patients from the test group were matched to those from the control group using a propensity score. The clinical outcomes for all-cause and cardiovascular mortality were estimated by Matched Cox regression models during 61.5 months of median follow-up. All patients were also categorized according to serum potassium correction levels (<3.0, 3.0 to <4.0, 4.0 to <5.0 and ≥5.0 mEq/L) after the whole follow-up. The hazard ratios (HRs) were used to assess the relationship between corrected potassium levels and all-cause and cardiovascular mortality in PD patients. Subgroup analysis was used to determine the homogeneity of the associations between potassium supplementation and all-cause mortality. RESULTS: All-cause mortality occurred in 108 patients (605/10,000 person-years) in the test group and 114 patients (677/10,000 person-years) in the control group during 1786- and 1685-year follow-up, respectively [hazard ratio (HR), 0.89; 95% confidence interval (CI), 0.68-1.16; p = 0.38]. Cardiovascular mortality occurred in 97 patients (542/10,000 person-years) in the test group and 101 patients (598/10,000 person-years) in the control group (HR, 0.89; 95% CI, 0.67-1.18; p = 0.43). There were no significant interactions between potassium supplementation and any of the subgroups, except for diabetes mellitus and volume overload. During a median follow-up of 61.5 months, adjusted all-cause mortality hazard ratio (HR) and 95% confidence interval (CI) for corrected serum potassium of <3.0, 3.0 to < 4.0, and ≥5.0 mEq/L, compared with 4.0 to < 5.0 mEq/L (reference), were 2.23 (1.17-3.72), 1.35 (0.89-1.81), and 1.74 (1.05-3.72), respectively. CONCLUSION: The use of potassium supplementation in chronic PD patients is not associated with mortality. While it may be necessary for the correction of hypokalemia or the maintenance of normokalemia, and the consequent reduction of hypokalemia-associated mortality. Additionally, use of aldosterone antagonists may be preferable for the handling of hypokalemia in PD patients.

(2R,3S)-Pinobanksin-3-cinnamate improves cognition and reduces oxidative stress in rats with vascular dementia.

This study investigated the neuroprotective effects of (2R,3S)-pinobanksin-3-cinnamate (PNC) in rats with occlusion-damaged bilateral common carotid arteries. Administration with PNC (5 and 10 mg/kg/day) for 5 weeks significantly improved the behavioral performance of rats with vascular dementia, as showed in the Morris water maze test by shortening the escape latency and latency of crossing, completing more platform crossings, as well as spending more time in the target zone. Further evaluations found that PNC could markedly decrease malondialdehyde levels, enhance superoxide dismutase activity and glutathione levels, and decrease the release of cytochrome c as well as the activities of caspases. Moreover, PNC increased Nrf2 and anti-apoptotic bcl-2 protein expression, while Nox1 and pro-apopotic bax protein expression was decreased. PNC may exert its neuroprotective effects through counteracting oxidative stress and has the potential to treat vascular dementia.

Targeted metabolomic study indicating glycyrrhizin's protection against acetaminophen-induced liver damage through reversing fatty acid metabolism.

The present study aimed to give a short report on a possible mechanism of glycyrrhizin to acetaminophen-induced liver toxicity. Seven-day intraperitoneal administration of glycyrrhizin (400 mg/kg/day) to 2- to 3-month-old male C57BL/6N mice (mean weight 27 g) significantly prevents acetaminophen-induced liver damage, as indicated by the activity of alanine transaminase and aspartate aminotransferase. Metabolomics analysis and principal component analysis (PCA) using ultra-fast liquid chromatography coupled to triple time-of-flight mass spectrometer were performed. PCA separated well the control, glycyrrhizin-treated, acetaminophen-treated, and glycyrrhizin+acetaminophen-treated groups. Long-chain acylcarnitines were listed as the top ions that contribute to this good separation, which include oleoylcarnitine, palmitoylcarnitine, palmitoleoylcarnitine, and myristoylcarnitine. The treatment of glycyrrhizin significantly reversed the increased levels of long-chain acylcarnitines induced by acetaminophen administration. In conclusion, this metabolomic study indicates a significant glycyrrhizin protection effect against acetaminophen-induced liver damage through reversing fatty acid metabolism.

[Effects of moxibustion intervention on inflammatory reactions and expression of suppressor of cytokine signaling proteins of synovium cells in rheumatoid arthritis rabbits].

OBJECTIVE: To observe the effect of moxibustion intervention on inflammatory reactions and expression of suppressor of cyfokine signaling 1 (SOCS 1) and SOCS 2 [Which are involved in inhibition of the Janus Kinase-signal transducer and activator of transcrip-tion (JAK/STAT signaling pathway and in sffenuation of cytokine signaling)] in synovium cells of the hind-knee joint in rheumatoid arthritis (RA) rabbits, so as to study its mechanism underlying improvement of RA. METHODS: Forty-two Japanese big-ear white rabbits were randomized into control, model and moxibustion groups respectively, with 14 cases in each group. RA model was established by injection of Freund's Complete Adjuvant (0. 5 mL/kg) into the rabbits' bilateral hind-knee joint cavities. Moxibustion was applied to bilateral "Shenshu" (BL 23) areas, 5 cones every time, once daily for 3 weeks except the Sundays. The perimeters of rabbits' hind legs were measured before and after modeling and after the therapy. The synovial tissue of joint was sampled for analyzing the expression levels of SOCS 1 and SOCS 3 by immunohistochemistry. RESULTS: Before the therapy, the perimeters of bilateral knee joints of the control, model and moxibustion groups were of no statistical significance (P>0. 05). In comparison with the control group, the perimeters of bilateral knee joints were significantly increased on day 1, 7, 14 and 21 in the model group (P<0. 01). Compared with the model group, the perimeters of bilateral knee joints in the moxibustion group were significantly decreased (P<0. 05), suggesting an improvement of the inflammatory reaction after moxibustion intervention. Correspondingly, synovial SOCS 1 and SOCS 3 expression levels were remarkabely higher in the model group than in the control group (P<0. 01), and obviously decreased in the moxibustion group compared with the model group (P<0. 01). CONCLUSIONS: Moxibustion intervention has an anti-inflammatory and detumescent effects in RA rabbits, which may be closely associated with its effects in down-regulating expression of SOCS 1 and SOCS 3 proteins by suppressing negative feedback regulatory JAK/STAT pathway in synovial cells. [KEY WORDS] Moxibustion; Rheumatoid arthritis; Inflammatory reactions; Synovial cells; Suppressor of cytokine signaling proteins; Negative-feedback regulatory factors

[Effects of heat and cool-producing needling manipulations on rectal temperature and serum endotoxin content in endotoxin-induced heat syndrome rabbits].

OBJECTIVE: To observe the effect of traditional manipulations of "Shaoshanhuo" (heat-producing needling) and "Toutianliang"(cool-producing needling) on body temperature and serum endotoxin level in heat syndrome rabbits. METHODS: Twenty-four Japanese rabbits were randomly divided into control, model, Shaoshanhuo and Toutianliang groups. Heat-syndrome model was established by subcutaneous injection of bacterium coli endotoxin solution (40 microg/mL, 2 mL/kg). Heat-producing and cool-producing needling was applied to bilateral "Quchi" (LI 11) for 5 min, respectively. Rectal temperature was detected by using a thermometer, and serum endotoxin content assayed by using Limulus Ameboyte Lysate kit (luminescence measuring). RESULTS: In comparison with the control group, both rectal temperature and serum endotoxin levels were increased significantly in the model group (P < 0.01). While compared to the model group, the rectal temperature and serum endotoxin levels were down-regulated considerably in both Shaoshanhuo and Toutianliang groups (P < 0.05, P < 0.01). The effect of the Toutianliang group was obviously superior to that of the Shaoshanhuo group in reducing serum endotoxin content (P < 0.01). CONCLUSION: Both heat-producing needling and cool-producing needling can lower rectal temperature and serum endotoxin levels in heat-syndrome rabbits, and the effect of cool-producing needling is relatively better in reducing endotoxin content.

Bioavailability study of berberine and the enhancing effects of TPGS on intestinal absorption in rats.

Berberine chloride (BBR) is a natural isoquinoline alkaloid extracted from medicinal herbs. It has been reported that the intestinal absorption of BBR is very low. In this study, the absolute bioavailability of BBR was studied, and the enhancing effects of D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) on intestinal absorption were investigated in rats. BBR injection was administrated via the femoral vein at a dose of 1.0 mg kg(-1) in intravenous group, and BBR oral formulations were administrated by oral gavage at a dose of 100 mg kg(-1) in BBR control (control) group and BBR-TPGS (test) group, respectively. The result showed that BBR had a very low absolute bioavailability of 0.68%, and TPGS could enhance intestinal absorption of BBR significantly. TPGS at a concentration of 2.5% could improve peak concentration (C(max)) and area under the curve (AUC(0-36)) of BBR by 2.9 and 1.9 times, respectively. The absorption enhancing ability of TPGS may be due to its ability to affect the biological activity of P-glycoprotein and thereby reduce the excretion of absorbed BBR into the intestinal lumen. This study indicated that absolute bioavailability of BBR was 0.68% in rats, and TPGS was a good absorption enhancer capable of enhancing intestinal absorption of BBR significantly.

Effects of Danshensu on maternal syndrome in phosphatidylserine/phosphatidylcholine microvesicle induced-mouse model: is it a candidate for preeclampsia remedy? / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Up to date, there is few satisfactory pharmacotherapy, except for aspirin and heparin, to stop the preeclampsia progression. Although the mechanism of preeclampsia is poorly understood, it has been proven to be associated with coagulation activation. Researches on prophylactic and therapeutic application of anticoagulants may benefit the clinical aspects of preeclampsia individuals. This study aimed to evaluate the effects of Danshensu on maternal syndrome in phosphatidylserine/phosphatidylcholine (PS/PC) microvesicle induced-mouse model.</p><p><b>METHODS</b>Sixty-six preeclampsia-like pregnant mice, induced by PS/PC microvesicle administration, were randomly divided into six groups. From days 5.5 to 16.5 of pregnancy, each group was respectively treated as follows: a) mice in group C (n = 12, control group) were injected with 100 microl of filtered phosphate-buffered saline into the tail vein every day; b) group PE (n = 15, preeclampsia model group) were injected in the same way with 100 microl of filtered PS/PC vesicle suspension; c) group H (n = 9, group treated with heparin) were injected with 1 unit heparin together with PS/PC vesicle suspension; d) group A (n = 10, group treated with aspirin) were injected with 20 microg/g aspirin-DL lysine as well; e) group LD (n = 10, group treated with low-dose Danshensu) were injected with 10 microg/g Danshensu; and f) group HD (n = 10, group treated with high-dose Danshensu) were injected with 30 microg/g Danshensu. Systolic blood pressure, total urinary protein levels, blood tests for some hemostatic function parameters (mean platelet counts, plasma antithrombin III activity (AT-III), D-D dimmer levels, and thrombin time), fibrin deposition by phosphotungstic acid hematoxylin staining, and thrombomodulin expression by immunohistochemistry staining in placentas were examined as indices for maternal syndrome.</p><p><b>RESULTS</b>Heparin showed significant effects on maternal syndrome of preeclampsia such as hypertension and proteinuria, and different doses of Danshensu also presented the certain effects. High-dose Danshensu and aspirin all demonstrated better effects than low-dose Danshensu on decreasing blood pressure to normal level, while high-dose Danshensu demonstrated better effects than aspirin and low-dose Danshensu on decreasing proteinuria to normal level. As to Danshensu's effects on hemostatic function, high- and low-dose Danshensu's marked effects on increasing the plasma AT-III activity were the same as that of aspirin and inferior to that of heparin. High-dose Danshensu's better effect on elevating the platelet counts was superior to low-dose Danshensu and aspirin. Low-dose Danshensu's obvious effect on decreasing D-D levels was close to heparin and superior to high-dose Danshensu and aspirin. High- and low-dose Danshensu's significant effects on reduced thrombin time level are same to heparin. Different anticoagulants all played improvement roles in placental fibrin depositions, but heparin and high-dose Danshensu's roles on lowering thrombomodulin expression in placentas were superior to low-dose Danshensu and aspirin. However, anticoagulant function of high-dose Danshensu was still inferior to heparin. We found long-term use of heparin and aspirin, in spite of low-dose administration, could raise the risk of bleeding such as placental abruption and intestinal hemorrhage. But no any side effect was observed in mice treated with different doses of Danshensu in our study.</p><p><b>CONCLUSIONS</b>Danshensu has proven to be effective and safe in ameliorating the prognosis of maternal syndrome in a preeclampsia mouse model. We suggest long-term provision of low-dose Danshensu in pregnancy, leading to an improvement of preeclampsia syndrome with considerable maternal safety.</p>

[C21 steroids from the stems of Marsdenia tenacissima].

To study the C21 steroids of the stems of Marsdenia tenacissima (Roxb.) Wight et Arn, various chromatography methods were used for the isolation of the constituents and their structures were identified by spectral analysis. Eight C21 steroids were isolated from the CHCl3 extract, which were identified as 11alpha-O-tigloyl-17beta-tenacigenin B (1), 17beta-tenacigenin B (2), tenacigenoside A (3), 11alpha-O-2-methylbutyryl-12beta-O-acetyl tenacigenin B (4), tenacissoside H (5), marsdenoside A (6), tenacissoside G (7), and tenacissoside I (8). Among them, compound 1 is a new compound.