Rac GTPase activating protein 1 promotes the glioma growth by regulating the expression of MCM3.

Glioma is the most common tumor of the nervous system. The diffuse growth and proliferation of glioma poses great challenges for its treatment. Here, Transcriptomic analysis revealed that Rac GTPase activating protein 1 (RACGAP1) is highly expressed in glioma. RACGAP1 has been shown to play an important role in the malignant biological progression of a variety of tumors. However, the underlying role and mechanism in glioma remain poorly understood. By using quantitative real-time polymerase chain reaction (qRT-PCR), western blot, immunohistochemistry and Orthotopic mouse xenografts, we confirmed that knockdown of RACGAP1 impeded cell proliferation in glioma and prolonged the survival of orthotopic mice. Interestingly, we also found that inhibiting the expression of RACGAP1 reduced the expression of minichromosome maintenance 3 (MCM3) through RNA-seq and rescue assay, while Yin Yang 1 (YY1) transcriptionally regulated RACGAP1 expression. Furthermore, T7 peptide-decorated exosome (T7-exo) is regard as a promising delivery modality for targeted therapy of glioma, and the T7-siRACGAP1-exo significantly improved the survival time of glioma bearing mice. These results suggested that targeting RACGAP1 may be a potential strategy for glioma therapy.

Analysis of surgical treatment of severe angular kyphosis with keeping the spinal cord length constant in osteotomy area / 中华外科杂志

Objective: To explore the surgical methods and clinical outcomes of severe angular kyphosis with the length of the spinal cord constant in the osteotomy area. Methods: Clinical data from 20 patients with severe angular kyphosis who underwent surgical treatment from January 2017 to December 2020 in the Department of Spinal Surgery,Hangzhou Xiaoshan District Hospital of Traditional Chinese Medicine were retrospectively analyzed. There were 11 males and 9 females, aged (28.5±8.9) years (range:17 to 46 years).There were 15 cases with congenital angular kyphosis,5 cases with tuberculous angular kyphosis.The angle of kyphosis was (107.1±12.9)° (range:93.2° to 131.4°).Frankel classification:2 cases with grade B,4 cases with grade C,3 cases with grade D.The kyphotic vertex is located at the T9 to T12 segments.Pedicle screws were placed in 3 or 4 adjacent segments at the proximal and distal kyphosis apex of the patients using a surgical navigation system.Piezosurgery combined with a grinding drill was used to complete the osteotomy in the apical vertebral region.Titanium mesh or artificial vertebral body was implanted,and the osteotomy surface was closed using this as the fulcrum to complete osteotomy.Spinal X-ray examination was performed before surgery,immediately after surgery and at the last follow-up,and sagittal and coronal Cobb angle,sagittal and coronary balance parameters,anterior vertebral height,posterior vertebral height,and spinal cord length were measured.Pulmonary function,visual analogue scale (VAS),and Oswestry's disability index (ODI) were collected and estimated before and after treatment.The analysis of variance of repeated measurement data was used for each evaluation index before and after treatment,and the t test was used for pairwise comparison. Results: All patients successfully completed surgery,with artificial vertebral body in 11 cases and double titanium mesh in 9 cases.The follow-up time was (28.2±2.3) months (range:26 to 31 months).Sagittal vertical axis improved from (46.9±13.7)mm(range:21.7 to 75.7 mm) before surgery to (10.7±5.5)mm (range:3.6 to 28.1 mm) after surgery,and (11.0±5.7)mm(range:3.6 to 29.3 mm) at the last follow-up,the differences were statistically significant compared to before surgery (all P<0.01).The mean kyphotic Cobb angle was corrected from (107.1±12.9) ° (range:93.2 ° to 131.4°) before surgery to (30.6±8.5) ° (range:20.0 ° to 47.8 °) after surgery (all P<0.01),and (32.1±8.7) ° (range:18.2 ° to 50.8°) at the last follow-up,the differences were statistically significant compared to before surgery(all P<0.01).The anterior vertebral height improved from (14.2±2.9)mm(range:11.04 to 23.6 mm) before surgery to (45.3±7.5)mm(range:29.4 to 56.5 mm) after surgery,and (44.3±6.8)mm(range:29.6 to 56.0 mm) at the last follow-up,the differences were statistically significant compared to before surgery (all P<0.01).The posterior vertebral height was improved from (51.8±5.3)mm (range:43.1 to 61.4 mm)before surgery to (57.6±4.7)mm (range:45.7 to 64.1 mm)after surgery,and (56.3±5.0) mm (range:49.7 to 68.5 mm) at the last follow-up,the differences were statistically significant compared to before surgery (all P<0.01).The spinal cord length of the osteotomy segment was (73.1±12.0)mm (range:56.8 to 98.4 mm) before surgery and (74.8±12.8)mm (range:53.5 to 100.2 mm) after surgery and (75.2±13.7)mm (range:53.9 to 102.4 mm) at the last follow-up,the difference was not statistically significant among them(F=0.144,P=0.866).The ODI and VAS scores improved significantly after surgery and at the last follow-up,and the differences were statistically significant (all P<0.01). Conclusion: The posterior vertebral column resection technique combined with titanium mesh or an artificial vertebral body implant for the treatment of severe angular kyphosis can significantly improve the kyphosis,neurological function,and life quality of patients without affecting the length of the spinal cord.

Application of Tiaoshen Jianpi acupuncture and moxibustion in hospice care for terminal cancer patients / 中国针灸

To analyze the application feasibility of Tiaoshen Jianpi acupuncture and moxibustion in hospice care for terminal cancer patients. Tiaoshen Jianpi acupuncture and moxibustion adjusts the spirit to regulate emotions and fortifies the spleen to supplement and boost foundation of acquired (postnatal) constitution. And it could relieve adverse reactions after radiotherapy and chemotherapy, alleviate pain and regulate emotions in hospice care for terminal cancer patients, so as to promote the progress of hospice care for terminal cancer patients.

Mechanisms exploration of Angelicae Sinensis Radix and Ligusticum Chuanxiong Rhizoma herb-pair for liver fibrosis prevention based on network pharmacology and experimental pharmacologylogy / 中国天然药物

Angelicae Sinensis Radix (Danggui) and Ligusticum Chuanxiong Rhizoma (Chuan Xiong) herb-pair (DC) have been frequently used in Traditional Chinese medicine (TCM) prescriptions for hundreds of years to prevent vascular diseases and alleviate pain. However, the mechanism of DC herb-pair in the prevention of liver fibrosis development was still unclear. In the present study, the effects and mechanisms of DC herb-pair on liver fibrosis were examined using network pharmacology and mouse fibrotic model. Based on the network pharmacological analysis of 13 bioactive ingredients found in DC, a total of 46 targets and 71 pathways related to anti-fibrosis effects were obtained, which was associated with mitogen-activated protein kinase (MAPK) signal pathway, hepatic inflammation and fibrotic response. Furthermore, this hypothesis was verified using carbon tetrachloride (CCl

A retrospective analysis of long-term follow-up of sacral neuromodulation in the management of refractory interstitial cystitis/bladder pain syndrome / 中华泌尿外科杂志

Objective:To summarize long-term outcome of sacral neuromodulation (SNM) for refractory interstitial cystitis/bladder pain syndrome (IC/BPS).Methods:Between January 2013 and October 2020, 28 patients with IC / BPS who received SNM in Beijing Chaoyang Hospital and Hebei Yanda Hospital were retrospectively analyzed. There were 5 males and 23 females, with median age 63.00 (47.50, 66.75) years old. The urgency score was 4 (3, 4) points, 24-hour micturition frequency was 26 (20.50, 32.50) times, nocturia was 9 (7, 12) times, single urine volume was 59.00 (41.25, 79.50) ml, VAS score was 9.0 (8.0, 9.0) points, O′Leary-Sant score was 31.00 (20.25, 33.00) points, and single maximum urine volume was 100.0 (80.0, 127.5) ml. The improvement of symptoms before operation, test period and last follow-up were compared.Results:The urgency score was 2 (1, 3), the 24-hour micturition frequency was 17.00 (15.00, 22.75), the frequency of nocturia was 5.5 (4.0, 7.0), the single urine volume was 87.50 (70.25, 110.00) ml, the VAS score was 4.0 (3.0, 6.0) and the O′Leary-Sant score was 20.00 (17.00, 23.00) in 28 patients during the test period, which were significantly improved compared with those before operation ( P < 0.05). There was no significant difference in the single maximum urine volume of 135.0 (102.5, 160.0) ml between the two groups ( P > 0.05). 28 patients received SNM Ⅱ permanent stimulator implantation. The median follow-up time was 29.5 (21.25, 61.75) months. Among the 28 patients, 3 patients underwent cystectomy and ileal conduit after removal of the complete SNM system due to the unsatisfied results. Twenty-five cases (89.3%) were still treated with SNM. Among them, 6 cases accepted combinative therapy of oral medicine (antihistamines, sodium pentose polysulfate, hormones, immunosuppressants, etc.). Two cases accepted combinative therapy of intravesical instillation, including heparin in one case and sodium hyaluronate in the other one. Three cases accepted combinative therapy of botulinum toxin injection.One case accepted combinative therapy of bladder augmentation. Two cases accepted combinative therapy of traditional Chinese medicine (TCM). One case accepted combinative therapy of oral medicine and TCM. The remaining 10 cases didn't accept any treatment. Among them, 3 cases were still treated with SNM even though they were not satisfied with the effect, including 1 case due to electrode displacement. At the last follow-up of 25 patients, the urgency score was 2 (1, 3), the 24-hour micturition frequency was 16.50 (13.00, 19.75), the frequency of nocturia was 5.5 (4.0, 9.0), the single urine volume was 105.0 (72.5, 120.0) ml, the VAS score was 4.5 (3.0, 6.0) and the O'Leary Sant score was 16.00 (14.00, 22.50), which were significantly improved compared with those before operation ( P < 0.05), but no difference with those during test period ( P>0.05). There was no significant difference in the single maximum urine volume of 125.0 (102.5, 150.0) ml at the last follow-up compared with preoperative and test period ( P>0.05). Conclusions:As a treatment option for refractory IC / BPS, SNM can improve the symptoms of most patients and maintain good long-term efficacy combined with other.

Therapeutic effect of nape cluster acupuncture combined with swallowing function training on post-stroke dysphagia / 中国针灸

OBJECTIVE@#To observe the effect on swallowing function in patients with post-stroke dysphagia treated with nape cluster acupuncture and the immediate effect of acupuncture at Fengchi (GB 20).@*METHODS@#A total of 60 patients with post-stroke dysphagia were randomized into an observation group and a control group, 30 cases in each one.On the basis of conventional western medication treatment, swallowing function training was applied in the control group, once a day.On the base of the treatment as the control group, nape cluster acupuncture was applied at Fengchi (GB 20), Tianzhu (BL 10), Wangu (GB 12), Lianquan (CV 23), Panglianquan (Extra), Jinjin (EX-HN 12) and Yuye (EX-HN 13) in the observation group, once a day. Additionally, pricking blood was applied at Jinjin (EX-HN 12) and Yuye (EX-HN 13), 2 times a week. The treatment was given 30 min each time, a week as one course and 4 courses were required. Before and after treatment, the standardized swallowing assessment (SSA) score and video fluoroscopic swallowing study (VFSS) score were compared in the two groups. The ultrasonic diagnostic device of swallowing and surface electromyography were used to observe the immediate effect on swallowing related muscles of acupuncture at Fengchi (GB 20).@*RESULTS@#Compared before treatment, the SSA scores were reduced after treatment in the two groups (<0.05), and the change of the observation group was larger than the control group (<0.05). Compared before treatment, the VFSS scores were increased after treatment in the two groups (<0.05), and the change of the observation group was larger than the control group (<0.05). Acupuncture at Fengchi (GB 20) immediately increased the amplitude of submental muscles and infrahyoid muscles in the observation group (<0.05), the geniohyoid muscle movement time was reduced and geniohyoid muscle displacement was increased (<0.05).@*CONCLUSION@#On the base of the routine treatment, nape cluster acupuncture could improve swallowing function in patients with post-stroke dysphagia. Acupuncture at Fengchi (GB 20) could immediately affect swallowing related muscles, improve muscle amplitude and reduce swallowing time.

Protective effects and action mechanism of extract from Tibetan medicine Yajima(Chrysosplenium nudicaule) on mice with intrahepatic cholestasis induced by ANIT / 中国中药杂志

Chrysosplenium nudicaule,Tibetan name " Yajima",is recorded as an effective medicine for the treatment of liver and gallbladder diseases by Tibetan Pharmacopoeia published in the past dynasties,but its traditional efficacy has not yet been investigated by means of modern pharmacological research methods. In this paper,the protective effect of extract of C. nudicaule(ECN) on liver injury in mice was observed by using the mice model of intrahepatic cholestasis(IC) induced by α-naphthyl isothiocyanate(ANIT) and the possible mechanism by which ECN work as the therapeutic agent was discussed. The results showed that the serum levels of AST,ALT,ALP,DBIL,TBIL and TBA of the model mice were notably reduced in dose-dependent manner(P<0. 01,P<0. 05). The activity of SOD and GSH-Px in the liver homogenate of mice was increased,while the content of MDA was decreased(P<0. 01,P<0. 05).Pathological examination of liver in mice showed that ECN could improve the pathological changes of liver tissue in mice. The mRNA expression level of genes related to bile acid metabolism were detected by RT-PCR and the results suggested that ECN could significantly increase the expression of genes such as BSEP,FXR and MRP2(P<0. 01,P<0. 05),meanwhile significantly reduce the expression of CYP7 A1(P<0. 01,P<0. 05). These results confirmed the protective effect of ECN on intrahepatic cholestasis-induced liver injury in mice,and indicated that the mechanism may be related to activating FXR and its target genes,reducing bile acid synthesis and increasing bile acid excretion. This study provides a modern pharmacological basis for the clinical application of Yajima in Tibetan medicine.

Lycium barbarum polysaccharide protects against oxygen glucose deprivation/reoxygenation-induced apoptosis and autophagic cell death via the PI3K/Akt/mTOR signaling pathway in primary cultured hippocampal neurons.

Lycium barbarum polysaccharide (LBP) is the main active ingredient of Lycium barbarum, which exhibits several beneficial effects, including neuroprotection, anti-aging and anti-oxidation. However, the mechanism by which LBP protects against cerebral ischemia/reperfusion-induced injury remains obscure. In this study, we found that LBP pretreatment greatly attenuated oxygen glucose deprivation/reperfusion (OGD/R) injury in primary cultured hippocampal neurons. LBP also suppressed OGD/R-induced lactate dehydrogenase (LDH) leakage, and ameliorated oxidative stress. In addition, LBP significantly reduced OGD/R-induced apoptosis and autophagic cell death. LBP caused the down-regulation of cleaved Caspase-3/Caspase-3, LC3II/LC3I and Beclin 1, as well as up-regulation of Bcl-2/Bax and p62. Furthermore, mechanistic studies indicated that LBP pretreatment increased p-Akt and p-mTOR levels after OGD/R. In summary, our results indicated that LBP protects against OGD/R-induced neuronal injury in primary hippocampal neurons by activating the PI3K/Akt/mTOR signaling pathway.

Shugan Liangxue Decoction () Down-Regulates Estrogen Receptor α Expression in Breast Cancer Cells / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the effect of Shugan Liangxue Decoction (, SGLXD) on estrogen receptor α (ERα) in human breast cancer cells.</p><p><b>METHODS</b>The effect of SGLXD (0.85-5.10 mg/mL) on the proliferation of breast cancer cells were evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The nuclear ERα protein levels in MCF-7, T47D and ZR-75-1 cells which treated by SGLXD for 24 h were examined by western blot and immunofluorescence assay. MCF-7 and MDA-MB-231 cells were treated by 17β-estradiol (E2) with or without SGLXD, for 24 h, and the E2 targeted genes c-myc and bcl-2 protein product was evaluated by western blot.</p><p><b>RESULTS</b>SGLXD showed dose-dependent inhibition on the proliferation of MCF-7, T47D and ZR-75-1 cells, but did not inhibit the proliferation of MDA-MB-231 cells. Furthermore, the promotive effect on cell growth induced by E2 was also significantly inhibited by SGLXD treatment. With the treatment of 1.70, 3.40, 5.10 mg/mL SGLXD, the nuclear ERα protein level was reduced to 88.1%, 70.4% and 60.9% in MCF-7 cells, and was decreased to 43.0%, 38.4% and 5.9% in ZR-75-1 cells as compared with the control group. In T47D cells, the nuclear ERα protein was down-regulated to 51.3% and 4.3% by 3.40 and 5.10 mg/mL SGLXD treatment. The down-regulative effect of SGLXD on nuclear ERα was confirmed by immunofluorescence assay. SGLXD decreased the protein product of c-myc and bcl-2.</p><p><b>CONCLUSIONS</b>SGLXD may exhibit selective inhibition effect on the proliferation of ER positive breast cancer cells. SGLXD reduced the nuclear ERα expression and the protein product of E2 target gene c-myc and bcl-2.</p>

Saponin 6 derived from Anemone taipaiensis induces U87 human malignant glioblastoma cell apoptosis via regulation of Fas and Bcl­2 family proteins.

Glioblastoma multiforme (GBM) is the most common and aggressive type of brain tumor, and is associated with a poor prognosis. Saponin 6, derived from Anemone taipaiensis, exerts potent cytotoxic effects against the human hepatocellular carcinoma HepG2 cell line and the human promyelocytic leukemia HL­60 cell line; however, the effects of saponin 6 on glioblastoma remain unknown. The present study aimed to evaluate the effects of saponin 6 on human U87 malignant glioblastoma (U87 MG) cells. The current study revealed that saponin 6 induced U87 MG cell death in a dose­ and time­dependent manner, with a half maximal inhibitory concentration (IC50) value of 2.83 µM after treatment for 48 h. However, saponin 6 was needed to be used at a lesser potency in HT­22 cells, with an IC50 value of 6.24 µM. Cell apoptosis was assessed by flow cytometry using Annexin V­fluorescein isothiocyanate/propidium iodide double staining. DNA fragmentation and alterations in nuclear morphology were examined by terminal deoxynucleotidyl transferase­mediated dUTP nick end labeling and transmission electron microscopy, respectively. The present study demonstrated that treatment with saponin 6 induced cell apoptosis in U87 MG cells, and resulted in DNA fragmentation and nuclear morphological alterations typical of apoptosis. In addition, flow cytometric analysis revealed that saponin 6 was able to induce cell cycle arrest. The present study also demonstrated that saponin 6­induced apoptosis of U87 MG cells was attributed to increases in the protein expression levels of Fas, Fas ligand, and cleaved caspase­3, ­8 and ­9, and decreases in the levels of B­cell lymphoma 2. The current study indicated that saponin 6 may exhibit selective cytotoxicity toward U87 MG cells by activating apoptosis via the extrinsic and intrinsic pathways. Therefore, saponin 6 derived from A. taipaiensis may possess therapeutic potential for the treatment of GBM.

D-allose protects the blood brain barrier through PPARγ-mediated anti-inflammatory pathway in the mice model of ischemia reperfusion injury.

Our early experiments confirmed that D-allose was closely involved in the blood brain barrier (BBB) protection from ischemia reperfusion (IR) injury, but the regulatory mechanism is not fully defined. In this study, we aimed to investigate the role of D-allose in the protection of BBB integrity and the relevant mechanisms involved in the mice model of middle cerebral artery occlusion and reperfusion (MCAO/Rep). D-allose was intravenously injected via a tail vein (0.2mg/g and 0.4mg/g, 1h before ischemia), GW9662 was intraperitoneal injected to the mice (4mg/kg) before inducing ischemia 24h. Pretreatment with D-allose ameliorated the neurological deficits, infarct volume and brain edema in brains of MCAO/Rep mice. D-allose inhibited cell apoptosis in the mice model of MCAO/Rep. We observed that D-allose remarkably decreased BBB permeability and prevented the reduction of ZO-1, Occludin and Claudin-5 in mice brains with MCAO/Rep injury. D-allose also repressed the levels of TNF-α, NF-κB, interleukin (IL)-1ß and IL-8 in inflammatory responses. The increases of intercellular adhesion molecular-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and CD11b/CD18 were significantly inhibited by D-allose during the MCAO/Rep injury. And D-allose decreased the L-selectin and P-selectin levels after MCAO/Rep. Moreover, D-allose induced up-regulation of peroxisome proliferator-activated receptor γ (PPARγ), and down-regulation of TNF-α and NF-κB after MCAO/Rep, which were abolished by utilization of GW9662. In conclusion, we provided evidences that D-allose may has therapeutic potential against brain IR injury through attenuating BBB disruption and the inflammatory response via PPARγ-dependent regulation of NF-κB.

Analysis of Clinical Characteristics of Patients with Drug-induced Liver Injury / 胃肠病学

Background:Drug-induced liver injury( DILI)is a kind of commonly seen diseases,in which typical clinical manifestations are lacking and misdiagnosis and missed diagnosis are frequently occurred. Aims:To investigate the clinical characteristics of patients with DILI. Methods:Clinical data of patients with DILI at Zhongshan Hospital,Xiamen University from January 2014 to December 2015 were collected. Clinical characteristics were retrospectively analyzed and the relationship between clinical characteristics and prognosis was investigated. Results:A total of 51 patients with DILI were enrolled,the ratio of male to female was 1∶ 1. 32,the average age at diagnosis was(50. 6 ± 17. 9)years old,the highest proportion(43. 1% )of patients were aged 60 and older. Hepatocellular damage was the main type of liver injury (84. 3% ). Chinese herbs,cardiovascular drugs,hormone and endocrine drugs were the most common drugs causing DILI, which accounted for 51. 0% ,19. 6% and 9. 8% ,respectively. Concomitant diseases of DILI covered many systems. The clinical manifestation of DILI was atypical,and the laboratory examination also lacked specificity. The positivity rate of autoimmune antibody was 5. 9% . Most patients had good prognosis,and the cure rate and improvement rate were 21. 6%and 66. 7% ,respectively. The mortality rate was 5. 9% with the cause of death being liver failure. Levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),albumin,prothrombin time(PT) and international normalized ratio( INR) at admission were correlated significantly with prognosis( P ﹤ 0. 05 ). Conclusions:DILI commonly occurs in elderly population,and inappropriate use of Chinese herbs maybe the important cause. The clinical manifestation of DILI is not typical,and most patients have good prognosis. Levels of ALT,AST, TBIL,albumin,PT and INR at admission are correlated significantly with prognosis.

HPLC fingerprint of Guanxin Shutong Capsule / 中草药

Objective: To establish an HPLC method for fingerprint analysis of Guanxin Shutong Capsule (GSC) for its quality control. Methods: The chromatographic behaviors were obtained by an Agilent TC-C18 column (250 mm × 4.6 mm, 5 μm) with gradient elution using 0.05% phosphoric acid and acetonitrile as the mobile phase. The column temperature was set at 30 ℃ and the flow rate was 1.0 mL/min. The detection wavelength was set at 280 nm. The common mode of HPLC fingerprint for 10 batches of GSC was established with Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine (2009 edition) and the common peaks were identified by reference compounds. Results: Fingerprints of 10 batches of GSC were established and the similarities to the common mode were above 0.95. Totally 45 common peaks were found, and 34 belonged to herbs. Five mutual peaks were from Choerospondias axillaris, 23 mutual peaks were from Salvia miltiorrhiza, and seven mutual peaks were from Syzigium aromaticum. Based on the retention time of reference substances, 13 constituents including gallic acid (peak 1), danshensu (peak 3), protocatechuic acid (peak 5), procatechuic aldehyde (peak 6), ellagic acid (peak 10), rosmarinic acid (peak 16), salvianolic acid A (peak 19), salvianolic acid B (peak 23), eugenol (peak 24), dihydrotanshinone I (peak 30), cryptotanshinone (peak 34), tanshinone I (peak 35), and tanshinone IIA (peak 39) were identified. Conclusion: This method is specific and reliable, which will be conducive to the quality control of GSC.

[Saponin 6 of Anemone Taipaiensis inhibits proliferation and induces apoptosis of U87 MG cells].

OBJECTIVE: To investigate the effect of saponin 6 of Anemone Taipaiensis on the proliferation of human U87 MG glioma cells and the possible mechanism. METHODS: U87 MG cells were treated with different concentrations of saponin 6 (0.0, 1.6, 3.2, 6.4, 12.8 µg/mL) for 24 hours or 48 hours. Cell viability was measured by MTT assay; the apoptosis rate was detected by flow cytometry combined with annexin V-FITC /PI staining; Western blotting was applied to determine the protein level of activated caspase-3. RESULTS: Compared with control groups, saponin 6 significantly inhibited U87 MG cell proliferation in a time- and dose-depended manner. Apoptosis rate of U87 MG cells and the expression of activated caspase-3 were raised with the increasing concentration of saponin 6. CONCLUSION: Saponin 6 of Anemone Taipaiensis could depress cell proliferation in a dose-depended manner, increase the expression of activated caspase-3 and promote apoptosis in U87 MG cells.

Influence of different processing methods on Lonicerae Japonicae Flos from Donghai cultivation base in Jiangsu province / 中国中药杂志

To study the impact of five different origin processing methods, namely natural drying, drying in baking shop, drying by microwave heating, drying in drum and drying with sulphur fumigation, on the quality of Lonicerae Japonicae Flos from Donghai cultivation base in Jiangsu Province, with the contents of chlorogenic acid and galuteolin and the similarity in HPLC fingerprints as the evaluation indicators. The results showed that different origin processing methods had significant impact on the content of chlorogenic acid and the similarity in HPLC fingerprints, but with no significant difference on the content of galuteolin. By means of drying by microwave heating and drying in drum, the samples showed higher contents of chlorogenic acid, respectively 3.67% and 3.39%. The similarities of HPLC fingerprints were 0.815 and 0.793, respectively. By means of the drying in baking shop and the drying with sulphur fumigation, the contents of chlorogenic acid in the samples were 2. 87% and 2. 53% , respectively. The similarities of HPLC fingerprints were 0.964 and 0.765, respectively. The lowest content of chlorogenic acid in naturally dried samples was 1.92%. The similarity of HPLC fingerprints was 0.940. According to the findings as well as the internal control standards for Lonicerae Japonicae Flos herbs of Jiangsu Kanion Pharmaceutical Co. , Ltd. , the optimum processing method for Lonicerae Japonicae Flos from Donghai cultivation base was the drying in baking shop. This study provided a theoretical basis for determining the processing method for Lonicerae Japonicae Flos from Donghai cultivation base of Jiangsu Province.

Research Progress on Prevention and Treatment of Traditional Chinese Medicine to Delayed Diarrhea Induced by Irinotecan / 浙江中医药大学学报

Objective To elaborate the progress on prevention and treatment of Chinese medicine to delayed diarrhea induced by Irinotecan. [Methods] In recent 5 years, traditional Chinese medicine treatment of the disease literature was reviewed . [Results] Traditional Chinese Medicine in prevention and treatment of this disease has unique advantages.[Conclusion] Traditional Chinese Medicine in prevention and treatment of this disease should be unified on syndrome type and evaluation criteria,enhance the efficacy, accepted by the majority of patients.

Saponin 1 induces apoptosis and suppresses NF-κB-mediated survival signaling in glioblastoma multiforme (GBM).

Saponin 1 is a triterpeniod saponin extracted from Anemone taipaiensis, a traditional Chinese medicine against rheumatism and phlebitis. It has also been shown to exhibit significant anti-tumor activity against human leukemia (HL-60 cells) and human hepatocellular carcinoma (Hep-G2 cells). Herein we investigated the effect of saponin 1 in human glioblastoma multiforme (GBM) U251MG and U87MG cells. Saponin 1 induced significant growth inhibition in both glioblastoma cell lines, with a 50% inhibitory concentration at 24 h of 7.4 µg/ml in U251MG cells and 8.6 µg/ml in U87MG cells, respectively. Nuclear fluorescent staining and electron microscopy showed that saponin 1 caused characteristic apoptotic morphological changes in the GBM cell lines. Saponin 1-induced apoptosis was also verified by DNA ladder electrophoresis and flow cytometry. Additionally, immunocytochemistry and western blotting analyses revealed a time-dependent decrease in the expression and nuclear location of NF-κB following saponin 1 treatment. Western blotting data indicated a significant decreased expression of inhibitors of apoptosis (IAP) family members,(e.g., survivin and XIAP) by saponin 1. Moreover, saponin 1 caused a decrease in the Bcl-2/Bax ratio and initiated apoptosis by activating caspase-9 and caspase-3 in the GBM cell lines. These findings indicate that saponin 1 inhibits cell growth of GBM cells at least partially by inducing apoptosis and inhibiting survival signaling mediated by NF-κB. In addition, in vivo study also demonstrated an obvious inhibition of saponin 1 treatment on the tumor growth of U251MG and U87MG cells-produced xenograft tumors in nude mice. Given the minimal toxicities of saponin 1 in non-neoplastic astrocytes, our results suggest that saponin 1 exhibits significant in vitro and in vivo anti-tumor efficacy and merits further investigation as a potential therapeutic agent for GBM.

Saponin B, a novel cytostatic compound purified from Anemone taipaiensis, induces apoptosis in a human glioblastoma cell line.

Glioblastoma multiforme (GBM) is one of the most common malignant brain tumors. Saponin B, a novel compound isolated from the medicinal plant, Anemone taipaiensis, has been found to have a strong time- and dose-dependent cytostatic effect on human glioma cells and to suppress the growth of U87MG GBM cells. In this study, we investigated whether saponin B induces the apoptosis of glioblastoma cells and examined the underlying mechanism(s) of action of saponin B. Saponin B significantly suppressed U87MG cell proliferation. Flow cytometric analysis of DNA in the U87MG cells confirmed that saponin B blocked the cell cycle at the S phase. Furthermore, treatment of the U87MG cells with saponin B induced chromatin condensation and led to the formation of apoptotic bodies, as observed under a fluorescence microscope, and Annexin V/PI assay further suggested that phosphatidylserine (PS) externalization was apparent at higher drug concentrations. Treatment with saponin B activated the receptor-mediated pathway of apoptosis, as western blot analysis revealed the activation of Fas-l. Saponin B increased the Bax and caspase-3 ratio and decreased the protein expression of Bcl-2. The results from the present study demonstrate that the novel compound, saponin B, effectively induces the apoptosis of GBM cells and inhibits glioma cell growth and survival. Therefore, saponin B may be a potential candidate for the development of novel cancer therapeutics with antitumor activity against gliomas.

Osthole attenuates spinal cord ischemia-reperfusion injury through mitochondrial biogenesis-independent inhibition of mitochondrial dysfunction in rats.

BACKGROUND: Osthole, the main bioactive compounds isolated from the traditional Chinese medical herb broad Cnidium monnieri (L.) cusson, has been shown to exert spectrum of pharmacologic activities. The aim of this study was to investigate the potential neuroprotective effects of osthole against spinal cord ischemia-reperfusion injury in rats. MATERIALS AND METHODS: Osthole was administrated at the concentration of 0.1, 1, 10, 50, or 200 mg/kg (intraperitoneally) 1 h before spinal cord ischemia. The effects on spinal cord injury were measured by spinal cord water content, infarct volume, hematoxylin and eosin staining, and neurologic assessment. Mitochondria were purified from injured spinal cord tissue to determine mitochondrial function. RESULTS: We found that treatment with osthole (10 and 50 mg/kg) significantly decreased spinal cord water content and infarct volume, preserved normal motor neurons, and improved neurologic functions. These protective effects can be also observed even if the treatment was delayed to 4 h after reperfusion. Osthole treatment preserved mitochondrial membrane potential level, reduced reactive oxygen species production, increased adenosine triphosphate generation, and inhibited cytochrome c release in mitochondrial samples. Moreover, osthole increased mitochondria respiratory chain complex activities in spinal cord tissue, with no effect on mitochondrial DNA content and the expression of mitochondrial-specific transcription factors. CONCLUSIONS: All these findings demonstrate the neuroprotective effect of osthole in spinal cord ischemia-reperfusion injury model and suggest that oshtole-induced neuroprotection was mediated by mitochondrial biogenesis-independent inhibition of mitochondrial dysfunction.

A randomized controlled study comparing omeprazole and cimetidine for the prophylaxis of stress-related upper gastrointestinal bleeding in patients with intracerebral hemorrhage.

OBJECT: Patients with intracerebral hemorrhage (ICH) are at high risk for severe stress-related upper gastrointestinal (UGI) bleeding, which is predictive of higher mortality. The aim of this study was to evaluate the effectiveness of omeprazole and cimetidine compared with a placebo in the prevention and management of stress-related UGI bleeding in patients with ICH. METHODS: In a single-center, randomized, placebo-controlled study, 184 surgically treated patients with CT-proven ICH within 72 hours of ictus and negative results for gastric occult blood testing were included. Of these patients, 165 who were qualified upon further evaluation were randomized into 3 groups: 58 patients received 40 mg intravenous omeprazole every 12 hours, 54 patients received 300 mg intravenous cimetidine every 6 hours, and 53 patients received a placebo. Patients whose gastric occult blood tests were positive at admission (n = 70) and during/after the prophylaxis procedure (n = 48) were treated with high-dose omeprazole at 80 mg bolus plus 8 mg/hr infusion for 3 days, followed by 40 mg intravenous omeprazole every 12 hours for 7 days. RESULTS: Of the 165 assessable patients, stress-related UGI bleeding occurred in 9 (15.5%) in the omeprazole group compared with 15 patients (27.8%) in the cimetidine group and 24 patients (45.3%) in the placebo group (p = 0.003). The occurrence of UGI bleeding was significantly related to death (p = 0.022). Nosocomial pneumonia occurred in 14 patients (24.1%) receiving omeprazole, 12 (22.2%) receiving cimetidine, and 8 (15.1%) receiving placebo (p > 0.05). In patients with UGI bleeding in which high-dose omeprazole was initiated, UGI bleeding arrested within the first 3 days in 103 patients (87.3%). CONCLUSIONS: Omeprazole significantly reduced the morbidity of stress-related UGI bleeding in patients with ICH due to its effective prophylactic effect without increasing the risk of nosocomial pneumonia, but it did not reduce the 1-month mortality or ICU stay. Further evaluation of high-dose omeprazole as the drug of choice for patients presenting with UGI bleeding is warranted. Clinical trial registration no.: ChiCTR-TRC-12001871, registered at the Chinese clinical trial registry (http://www.chictr.org/en/proj/show.aspx?proj=2384).