Xueshuantong improves cerebral microcirculation disorder: action mechanism based on network pharmacology and experimental validation / 药学学报

This study is to explore the mechanism of Xueshuantong improving cerebral microcirculation disorder through the combination of network pharmacology and experimental validation in vivo. Structural formulas of main Panax notoginseng saponins, including notoginsenoside R1, and ginsenoside Rg1, Re, Rb1 and Rd were obtained from Pubchem website and their potential targets were predicted by Swiss Target Prediction database. Potential molecular targets of brain microcirculation disorder were acquired from OMIM and GeneCards database. The overlapped molecular targets between the drug and disease were analyzed. Protein interaction analysis and topology maps were constructed through the STRING online analysis platform and Cytoscape software. Core action targets were selected. GO function and KEGG pathway were analyzed by DAVID database. Immunohistochemical method was used to examine the expression of platelet endothelial cell adhesion molecule-1 (CD31) in the ischemic cortex of middle cerebral artery occlusion and reperfusion (MCAO/R) rats. The levels of mRNA and protein expressions of core action targets in MCAO/R model rats′ brain microvessels were verified by RT-qPCR and Western blot. Based on network pharmacology, 242 targets of Xueshuantong, 425 targets of brain microcirculation disorder, and 35 overlapped targets were obtained. The potential key targets of Xueshuantong, protein kinase B (AKT1), vascular endothelial growth factor A (VEGFA), caspase 3 (CASP3), matrix metallopeptidase 9 (MMP-9), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), signal transducer and activator of transcription 3 (STAT3) involved in the alleviation of cerebral microcirculation disorder were obtained by setting degree and betweenness centrality as screening parameters. Xueshuantong at the dose of 48 mg·kg-1 was shown to significantly improve the injury of neurological behaviors, as well as the density and morphology of microvessels of MCAO/R model rats. Xueshuantong could down-regulate the mRNA levels of AKT1, MMP-9, and STAT3, increase the protein expression levels of CD31, phosphorylated AKT and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), and the ratio of B-cell lymphoma 2/Bcl-2-associated X (Bcl-2/Bax), but decrease the protein expression levels of MMP-9, cleaved caspase-3 and phosphorylated STAT3. In summary, Xueshuantong could improve ischemic cerebral microcirculation disorder and thereby reduce nerve damage in ischemia-reperfusion rats by regulating signaling pathways related with PI3K, AKT, MMP-9, STAT3 and caspase-3 in microvessels. The study strictly adhered to all ethical protocols that experimental animals should follow in the course of medical research.

Adherence to adjuvant with therapy imatinib in patients with gastrointestinal stromal tumor: a national multi-center cross-sectional study / 中华胃肠外科杂志

Objective: To analyze the current adherence to imatinib in patients with gastrointestinal stromal tumors (GIST) in China and its influencing factors. Methods: A cross-sectional survey was conducted. Study period: from October 1, 2020 to November 31, 2020. Study subjects: GIST patients taking imatinib who were diagnosed and treated in public tertiary level A general hospitals or oncology hospitals; those who had not been pathologically diagnosed, those who never received imatinib, or those who had taken imatinib in the past but stopped afterwards were excluded. The Questionnaire Star online surgery platform was used to design a questionnaire about the adherence to adjuvant imatinib therapy of Chinese GIST patients. The link of questionnaire was sent through WeChat. The questionnaire contained basic information of patients, medication status and Morisky Medication Adherence Scale. Results: A total of 2162 questionnaires from 31 provinces, autonomous regions, and municipalities were collected, of which 2005 were valid questionnaires, with an effective rate of 92.7%. The survey subjects included 1104 males and 901 females, with a median age of 56 (22-91) years old. Working status: 609 cases (30.4%) in the work unit, 729 cases (36.4%) of retirement, 667 cases of flexible employment or unemployment (33.3%). Education level: 477 cases (23.8%) with bachelor degree or above, 658 cases (32.8%) of high school, 782 cases (39.0%) of elementary or junior high school, 88 cases (4.4%) without education. Marital status: 1789 cases (89.2%) were married, 179 cases (8.9%) divorced or widowed, 37 cases (1.8%) unmarried. Two hundred and ninety-four patients (14.7%) had metastasis when they were first diagnosed, including 203 liver metastases, 52 peritoneal metastases, and 39 other metastases. One thousand eight hundred and sixty-nine patients underwent surgical treatment, of whom 1642 (81.9%) achieved complete resection. The median time of taking imatinib was 25 (1-200) months. Common adverse reactions of imatinib included 1701 cases (84.8%) of periorbital edema, 1031 cases (51.4%) of leukopenia, 948 cases (47.3%) of fatigue, 781 cases (39.0%) of nausea and vomiting, 709 cases (35.4%) of rash, and 670 cases (33.4%) of lower extremity edema. The score of the Morisky Medication Adherence Scale showed that 392 cases (19.6%) had poor adherence, 1023 cases (51.0%) had moderate adherence, and 590 cases (29.4%) had good adherence. Univariate analysis showed that gender, age, work status, economic income, residence, education level, marriage, the duration of taking medication and adverse reactions were associated with adherence to adjuvant imatinib therapy (all P<0.05). Multivariate analysis showed that female (OR=1.264, P=0.009), non-retirement (OR=1.454, P=0.001), monthly income ≤4000 yuan (OR=1.280, P=0.036), township residents (OR=1.332, P=0.005), unmarried or divorced or widowed (OR=1.362, P=0.026), the duration of imatinib medication >36 months (OR=1.478, P<0.001) and adverse reactions (OR=1.719, P=0.048) were independent risk factors for poor adherence to adjuvant imatinib. Among patients undergoing complete resection, 324 (19.7%) had poor adherence, 836 (50.9%) had moderate adherence, and 482 (29.4%) had good adherence. Meanwhile, 55 patients with good adherence (11.4%) developed recurrence after surgery, 121 patients with moderate adherence (14.5%) developed recurrence, 61 patients with poor adherence (18.8%) developed recurrence, and the difference was statistically significant (P=0.017). Conclusions: The adherence to adjuvant therapy with imatinib in Chinese GIST patients is relatively poor. Females, non-retirement, monthly income ≤4000 yuan, township residents, unmarried or divorced or widowed, the duration of imatinib medication >36 months, and adverse reactions are independently associated with poor adherence of GIST patients. Those with poor adherence have a higher risk of recurrence after surgery. Positive interventions based on the above risk factors are advocated to improve the prognosis of patients with GIST.

Research advance of pharmacological effects of astragalosides on nervous system diseases / 中国中药杂志

Astragali Radix is a traditional Chinese herbal medicine with a long history, which has the functions of tonifying Qi and promoting urination and granulation. Astragalosides are the main effective components of Astragali Radix, and more than 40 triterpenoid saponins have been obtained from Astragalus membranaceus and its related plants, mainly including astragalosides Ⅰ-Ⅷ, isoastragalosides Ⅰ, Ⅱ, and Ⅳ, acetylastragalosides, and soyasaponins. Astragalosides have a wide range of biological activities, such as immunomodulation, antioxidation, and neuroprotection. Nervous system diseases seriously affect people's quality of life, threaten human physical and mental health, and impose a burden on families and society. As natural drugs, astragalosides have good preventive and therapeutic effects on central nervous system diseases. This paper reviews the main pharmacological effects and mechanisms of astragalosides in the treatment of multiple sclerosis, Parkinson's disease, Alzheimer's disease, and cerebral ischemic stroke and proposes the research prospects and potential problems, aiming to provide reference for the clinical application and basic research of astragalosides.

Galangin enhances autophagy by inhibiting NF-κB pathway in gastric cancer MGC-803 cells / 中国中药杂志

This study aimed to explore the effects of galangin on energy metabolism and autophagy in gastric cancer MGC803 cells and the underlying mechanism. Cell counting kit-8(CCK-8) was used to detect the effects of galangin at different concentrations on via-bility of MGC803 cells after 48 h intervention. Western blot was carried out to measure the effects of galangin on expression of proteins related to autophagy, nuclear factor-κB(NF-κB) pathway and energy metabolism, followed by the determination of its effects on mRNA expression of energy metabolism-related proteins by Real-time quantitative PCR(qPCR). The impact of galangin on autophagy was explored using AutophagyGreen dye reagent, with autophagosomes and lysosomes observed under the transmission electron microscope(TEM). Nude mice transplanted with gastric cancer MGC803 cells via subcutaneous injection were randomly divided into the following three groups: control(0.5% sodium carboxymethyl cellulose, once a day), 5-fluorouracil(5-FU, 50 mg·kg~(-1), twice a week), and galangin(120 mg·kg~(-1), once a day) groups. The body weight and tumor volume were measured once every three days with a vernier caliper at the same time point by the same person. After 21-d treatment, the tumor tissue was isolated and weighed for the calculation of the tumor-suppressing rate. The comparison with the control group revealed that galangin inhibited the viability of MGC803 cells, up-regulated the protein expression of microtuble-associated protein 1 light chain 3 B(LC3 B) Ⅱ, inhibited the phosphorylation of NF-κB pathway-related proteins, and promoted the formation of autophagosomes in MGC803 cells. However, it did not obviously affect the expression of energy metabolism-related proteins. Furthermore, galangin at 120 mg·kg~(-1) significantly reduced the tumor weight and volume in mice, enhanced LC3 BⅡ protein expression, and inhibited the phosphorylation of NF-κB pathway-related proteins. All these have suggested that galangin inhibited the growth of gastric cancer MGC803 cells both in vivo and in vitro, possibly by inhibiting the NF-κB pathway and enhancing autophagy.

Tripterygium wilfordii polysaccharide induces differentiation of pancreatic stem cells into islet-like cell clusters / 中国组织工程研究

BACKGROUND: Inadequate sources of islet cells mean that islet cell transplantation for diabetes cannot meet the clinical demand.Therefore,in vitro induction of pancreatic stem cells to differentiate into islets has become a focus of research. OBJECTIVE:To study the effect of Tripterygium wilfordii polysaccharides on the differentiation of pancreatic stem cells from islets in mice, so as to explore the effect of traditional Chinese medicine on the differentiation of pancreatic stem cells into pancreatic beta cells. METHODS:Tripterygium wilfordii polysaccharide was used to induce the differentiation of purified mouse pancreatic stem cells into islets in vitro.The islet-like cell clusters then underwent morphologic observation, dithizone (DTZ) staining, and western blot analysis. RESULTS AND CONCLUSION: Cell morphology, cell growth characteristics and immunocytochemical staining showed that mouse pancreatic stem cells were obtained.They were induced by Tripterygium wilfordii polysaccharide into spherical islet-like structures, which had a spindly pedicle connected with the bottom of the culture flask, and were DTZ-stained to iron red. Western blot assay detected β-cytokine proteins in the islet-like cell clusters. These findings confirm that mouse pancreatic stem cells can be induced to differentiate into islet-like cell clusters containing β cells in vitro by Tripterygium wilfordii polysaccharide.

Effects of Electroacupuncture Preconditioning on Apoptosis and Expression of Apoptosis-related Proteins in Rats after Cerebral Ischemia-reperfusion / 中国康复理论与实践

Objective To investigate the effect of electroacupuncture (EA) preconditioning on apoptosis after cerebral ischemia-re-perfusion (I/R). Methods A total of 72 male Sprague-Dawley rats were randomly divided into sham group (n=24), model group (n=24) and EA group (n=24). The rats in latter two groups were occluded the right middle cerebral arteries for two hours and reperfused. EA group was treated with EA at Baihui (GV20) for two weeks before modeling. They were as-sessed with modified Neurological Severity Scores (mNSS) 24 hours after modeling. Then, the cerebral infarct volume was measured with TTC staining, the apoptosis was detected with TUENL assay, and the expression of p53, Bax and Bcl-2 proteins in ischemic penumbra was detected with Western blotting. Results Compared with the model group, the score of mNSS, cerebral infarct volume and the number of TUNEL-posi-tive cells all significantly decreased (P<0.05) in EA group; while the expression of p53 and Bax proteins de-creased (P<0.05), Bcl-2 increased (P<0.05), and Bax/Bcl-2 decreased (P<0.05).Conclusion EA preconditioning can induce tolerance to cerebral I/R injury, which might associate with the inhibition of p53 protein and down-regulation of the Bax/Bcl-2 ratio in ischemic penumbra, to inhibit cerebral cell apoptosis.

Chemical constituents and anti-cancer effect of Semen Alpinia Katsumadai:recent advances / 中国药理学与毒理学杂志

Semen Alpiniae Katsumadai,nearly mature seeds of Alpinia katsumadai Hayata(Zingib-eraceae),mainly contains flavonoids and terpenoids,which have significant anti-tumor effect.The anti-cancer mechanisms of Semen A.katsumadai include anti-proliferation,apoptosis induction,anti-metas-tasis, energy metabolism modulation and anti-inflammation. This paper reviews the latest advances in studies on the anti-tumor components and the underlying mechanisms of Semen A. katsumadai, the purpose of which is to contribute to the study of both chemical constituents and anti-cancer pharmacology of Semen A.katsumadai.

Key points of poverty alleviation of Chinese herbal medicine industry and classification of recommended Chinese herbal medicines / 中国中药杂志

To build a well-off society in an all-round way, eliminate poverty, improve people's livelihood and improve the level of social and economic development in poverty-stricken areas is the frontier issues of the government and science and technology workers at all levels. Chinese herbal medicine is the strategic resource of the people's livelihood, Chinese herbal medicine cultivation is an important part of China's rural poor population income. As most of the production of Chinese herbal medicine by the biological characteristics of their own and the interaction of natural ecological environment factors, showing a strong regional character.the Ministry of Traditional Chinese Medicine and the State Council Poverty Alleviation Office and other five departments jointly issued the "China Herbal Industry Poverty Alleviation Action Plan (2017-2020)", according to local conditions of guidance and planning of Chinese herbal medicine production practice, promote Chinese herbal medicine industry poverty alleviation related work In this paper, based on the relevant data of poverty-stricken areas, this paper divides the areas with priority to the poverty alleviation conditions of Chinese herbal medicine industry, and analyzes and catalogs the list of Chinese herbal medicines grown in poverty-stricken areas at the macro level. The results show that there are at least 10% of the poor counties in the counties where the poverty-stricken counties and the concentrated areas are concentrated in the poverty-stricken areas. There is already a good base of Chinese herbal medicine industry, which is the key priority area for poverty alleviation of Chinese herbal medicine industry. Poverty-stricken counties, with a certain degree of development of Chinese medicine industry poverty alleviation conditions, the need to strengthen the relevant work to expand the foundation and capacity of Chinese herbal medicine industry poverty alleviation; 37% of poor counties to develop Chinese medicine industry, the basic conditions of poverty alleviation. It is suggested that: prioritized priorities, counties that have a good foundation for Chinese herbal medicine industry will implement the "Poverty Alleviation Action Plan for Chinese Herbal Medicine Industry" through nearly 100 counties with priority development.

Study on distribution division of Codonopsis Radix / 中国中药杂志

This paper is aimed to clarify the distribution of Codonopsis Radix in China and search the main ecological factors that affect the suitability distribution. Through literature reading, National Specimen Information Infrastructure researching, field investigation and general survey of Chinese medicine resources, the distribution information was acquired. The MaxEnt model and ArcGIS technology were applied to analyze the main environmental factors influencing the suitability of Codonopsis Radix with integrated 55 environmental factors. The results showed the precipitation and altitude were the major factors impacting the ecology suitable of Codonopsis Radix. The ecological suitable region of C. pilosula was mainly concentrated in south Gansu, Shanxi, Shanxi, Ningxia and, and the ecological suitable region of C. pilosula var. modesta was mainly concentrated in south Gansu, northwest Guizhou, northeast Sichuan, and the ecological suitable region of C. tangshen was mainly concentrated in west Hubei, east Chongqing, middle Sichuan. Combined with the investigation and cultivation of Codonopsis Radix distribution information, the results of ecological suitability of Codonopsis Radix were verified. The ecological suitability distribution result of Codonopsis Radix was consistent with each species actual distribution, which could provide scientific basis for carrying out the rational cultivation of Codonopsis Radix.

20(S)-Protopanaxadiol enhances angiogenesis via HIF-1α-mediated VEGF secretion by activating p70S6 kinase and benefits wound healing in genetically diabetic mice

Impaired angiogenesis is one of the crucial factors that impede the wound healing process in diabetic foot ulcers (DFUs). In this study, we found that 20(S)-protopanaxadiol (PPD), an aglycone of ginsenosides in Panax notoginseng, stimulated angiogenesis and benefited wound healing in genetically diabetic mice. In HUVECs, PPD promoted cell proliferation, tube formation and VEGF secretion accompanied by increased nuclear translocalization of HIF-1α, which led to elevated VEGF mRNA expression. PPD activated both PI3K/Akt/mTOR and Raf/MEK/ERK signaling pathways in HUVECs, which were abrogated by LY294002 and PD98059. Furthermore, these two pathways had crosstalk through p70S6K, as LY294002, PD98059 and p70S6K siRNA abolished the angiogenic responses of PPD. In the excisional wound splinting model established in db/db diabetic mice, PPD (0.6, 6 and 60 mg ml−1) accelerated wound closure, which was reflected by a significantly reduced wound area and epithelial gaps, as well as elevated VEGF expression and capillary formation. In addition, PPD activated PI3K/Akt/ERK signaling pathways, as well as enhanced p70S6K activity and HIF-1α synthesis in the wounds. Overall, our results revealed that PPD stimulated angiogenesis via HIF-1α-mediated VEGF expression by activating p70S6K through PI3K/Akt/mTOR and Raf/MEK/ERK signaling cascades, which suggests that the compound has potential use in wound healing therapy in patients suffering from DFUs.

Familial Haemophagocytic Lymphohistiocytosis Occurs in A Fetus at His Third Trimester-A Case Report / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To analyze the clinical features and pathogenetic gene mutation in a fetus at his third trimester with familial haemophagocytic lymphohistiocytosis (FHL).</p><p><b>METHODS</b>Target region sequencing and high-throughput sequencing were used to detect pathogenetic gene mutations for familial haemophagocytic lymphohistiocytosis in a late onset HLH fetus. Pathogenetic gene mutations of the patient and his parents were verified by Sanger dideoxy sequencing.</p><p><b>RESULTS</b>A male neonate, who had right pleural effusion, hepatomegaly and splenomegaly previously revealed by fetus ultrasound, was delivered at full-term by cesarean section. His clinical presentation showed recurrent fever, tachypenea, decreased breath sounds on right side, hepatosplenomegaly etc., which were gradually aggravating Lab.tests results were as follows: WBC 9.88×10/L, Hb 91 g/L, Plt 13×10/L, ALT 18 U/L,AST 69 U/L,TBIL 207.2 µmol/L, DBIL 183.5 µmol/L, TG 3.05 mmol/L, Fib 0.88 g/L, Serum ferritin 3 120 ng/ml and sIL-2R 57 420 U/ml. FCM showed that CD3CD16CD56cells reached to 3.60% in the pripheral blood. Haemophagocytes were occasionally found in the bone marrow. NK/NKT stimulation test showed a severe damage of degranulation of NK cells. Sequence analysis of genomic DNA from his peripheral blood demonstrated the compound heterozygous mutations of UNC13D gene: c.2448-13 G>A in exon26 and c.1055+1 G>A in exon12, both were pathogenetic mutations. In detailed family survey, it was confirmed that the mutation c.2448-13 G>A in exon26 was inherited from his mother and c.1055+1 G>A in exon12 from his father.</p><p><b>CONCLUSION</b>A rare case of familial haemophagocytic lymphohistiocytosis type 3 (FHL3) with late fetus onset who carried pathogenetic compound heterozygous mutations of UNC13D gene. Those neonates with recurrent fever, serous effusions and multiple organ failure should be screened for FHL. Identifying the pathogenic gene mutations laid the foundation of conceiving disease-free newborns.</p>

Notoginsenoside Ft1 down-regulates HIF-1α, inhibits cell proliferation, decreases migration and promotes apoptosis in breast cancer cells / 药学学报

To investigate the effect of notoginsenoside Ft1(Ft1) on proliferation, migration and apoptosis of breast cancer cells, we conducted several assays including CCK-8 assay, EdU staining, single cell migration assay and Hoechst 33258 staining. The effect of Ft1 on expression of apoptosis related proteins, HIF-1α, PI3K/Akt/mTOR/p70S6K and MAPK pathways was examined with Western blot. Ft1 could significantly reduce cell survival and inhibit cell proliferation in breast cancer cells in a dose-dependent manner. Ft1 also increased chromatin condensation of MDA-MB-231 cells. Furthermore, Ft1 decreased protein expression of Bcl-2 and HIF-1α and increased expression of cleaved caspase 3 in MDA-MB-231 cells after 12 h treatment. Ft1 significantly down-regulated the levels of p-Akt, p-mTOR and p-p70S6K as well as p-ERK1/2, but up-regulated that of p-JNK. Ft1 significantly inhibited the level of p-EGFR (Tyr1068) and p-EGFR (Ser1046/1047) in MDA-MB-231 cells. Finally, Ft1 significantly inhibited the migration path length and velocity of HS578T cells when used at the concentration without affecting cell viability. Thus, Ft1 exhibited multiple antitumor effects including inhibition of cell survival and migration, promotion of cell apoptosis in breast cancer cells. Suppression of HIF-1α via Akt/mTOR/p70S6K and MAPK pathways may be involved in the pharmacological effect of Ft1 on cell proliferation and apoptosis of breast cancer cells.

Inhibitory effects of vina-ginsenoside R7 on activation of rat C6 astrocytes induced by LPS and TNF-α combination / 中国中药杂志

To investigate the inhibitory effect and mechanism of vina-ginsenoside R7 (R7) on the activation of rat C6 astrocytes cells induced by LPS/TNF-α, cells in logarithmic growth phase were cultured in DMEM medium without FBS for 24 h. After dissociated using 0.25% EDTA-trypsin, the cells were seeded into respective plates at the density of 1.5×10⁶ cells per mL and cultured overnight. The cells were divided into the following groups： control group (no treatment), model group (treated with LPS 1 μg•mL⁻¹ and TNF-α 10 μg•L⁻¹ treated for 24 h), R7 groups (pre-treated with 6.25, 12.5, 25, 50, and 75 μmol•L⁻¹ R7, 4 μmol•L⁻¹ L-NMMA for 2 h and then stimulated with LPS 1 mg•L⁻¹ and TNF-α 10 μg•L⁻¹ for 24 h). Cell viability was analyzed by CCK-8 kit. Secretion of nitric oxide (NO) in the medium was measured by Greiss method. Concentrations of interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) were assayed by ELISA kits. Gene expressions of inflammatory factors were examined by quantitative-PCR analysis. Activation of NF-κB was detected by dual luciferase reporter gene assay kit. The results showed that R7 could significantly inhibit the secretion of NO from C6 cells in a dose-effect manner, with an IC₅₀ of 34 μmol•L⁻¹. And it could reduce cell proliferation induced by LPS/TNF-α stimulation. Furthermore, R7 at 50 μmol•L⁻¹ significantly down-regulated gene expressions of iNOS (P<0.001), TNF-α (P<0.001), IL-1β(P<0.05), and COX-2 (P<0.001), but could not change gene expression of IL-6. However, R7 reduced the secretion of TNF-α (P<0.001) and IL-6 (P<0.001). Further studies disclosed that, different concentrations of R7 (25, 50, 100 μmol•L⁻¹) could significantly inhibit the transcription activity of NF-κB(P<0.05, P<0.01, and P<0.001). In conclusion, R7 could inhibit inflammatory responses in C6 cells induced by LPS/TNF-α probably by inhibiting the transcription activity of NF-κB, which indicates its possible therapeutic effect in neurological diseases related to neuroinflammation.

Clinical outcome of treating intractable hematospermia using holmium laser incision through a ureteroscope / 亚洲男科学杂志(英文版)

A conventional procedure for treating hematospermia is to insert a ureteroscope or seminal vesiculoscope into the prostatic utricle through the urethra, and then dilate the ejaculatory duct opening using the scopeor the catheter. However, the ejaculatory duct stenosis may occur after the simple ureteroscopy. We compared the outcomes of treating hematospermia using holmium laser incision through a ureteroscope and using simple ureteroscopy. Retrospective method was used to analyze 67 intractable hematospermia cases. Varying degrees of ejaculatory duct stenosis or obstruction were observed in all the patients. Postoperative follow?up was conducted for 6 months up to 3 years. Two patients who underwent the simple ureteroscopy experienced hematospermia recurrence in 6 and 8 months, respectively. No recurrence was found in all the patients who underwent the holmium laser incision. We have found that the holmium laser incision through a ureteroscope shows a better outcome than the simple ureteroscopy.

Astragaloside IV regulates STAT1/IκB/NF-κB signaling pathway to inhibit activation of BV-2 cells / 中国中药杂志

<p><b>OBJECTIVE</b>The study was aimed to investigate the inhibitory effect and mechanism of astragaloside IV (ASI) on the activation of microglial cells.</p><p><b>METHOD</b>After pre-incubated with ASI for 2 h, microglial cells BV-2 were stimulated with interferon-γ (IFN-γ) for 1. 5 h and 24 h, respectively. Secretion of nitric oxide (NO) in the medium was measured by Griess method. Production of tumor necrosis factor alpha (TNF-α) was detected by ELISA approach. Cellular gene expressions of CD11b, TNF-α, interleukin 1β (IL-1β) and induced nitric oxide synthase (iNOS) were examined by quantitative-PCR analysis. Total and phosphorylation of STAT1, IκB and NF-κB was analyzed by Western blot method.</p><p><b>RESULT</b>ASI could significantly inhibit the increased secretion of TNF-α and NO from BV-2 cells upon IFN-γ stimulation (P < 0.001). Further study showed that ASI significantly down-regulated gene expression of IL-1β and TNF-α (P < 0.01, P < 0.05) and exhibited a trend to reduce that of iNOS. IFN-γ and ASI have no obvious effect on gene expression of CD11b. Moreover, ASI inhibited the phosphorylation of STAT1, IκB and NF-κB elicited by IFN-γ stimulation.</p><p><b>CONCLUSION</b>ASI could restrain microglial activation through interfering STAT1/IκB/NF-κB signaling pathway, reducing gene expres- sion of IL-1β and TNF-α, and thus inhibiting the production of proinflammatory mediators such as NO and TNF-α.</p>

Surgery with versus without preoperative concurrent chemoradiotherapy for mid/low rectal cancer: an interim analysis of a prospective, randomized trial / 癌症

<p><b>INTRODUCTION</b>Multimodality therapy, including preoperative chemoradiotherapy (CRT) and total mesorectal excision (TME), has effectively reduced local recurrence rates of rectal cancer over the past decade. However, the benefits and risks of the addition of neoadjuvant CRT to surgery need to be evaluated. This study was to compare the efficacy of TME with versus without preoperative concurrent chemoradiotherapy (CCRT) involving XELOX regimen (oxaliplatin plus capecitabine) in Chinese patients with stages II and III mid/low rectal adenocarcinoma.</p><p><b>METHODS</b>We randomly assigned patients to the TME group (TME without preoperative CCRT) or CCRT + TME group (TME with preoperative CCRT). The primary endpoint was disease-free survival (DFS); the secondary endpoints were overall survival (OS), local and distant recurrence, tumor response to CRT, toxicity, sphincter preservation, and surgical complications. An interim analysis of the potential inferiority of DFS in the CCRT + TME group was planned when the first 180 patients had been followed up for at least 6 months.</p><p><b>RESULTS</b>A total of 94 patients in the TME group and 90 patients in the CCRT + TME group were able to be evaluated. The 3-year DFS and OS rates were 86.3 % and 91.5 % in the whole cohort, respectively. The 3-year DFS rates of the TME and CCRT + TME groups were 85.7% and 87.9 % (P = 0.766), respectively, and the 3-year OS rates were 90.7 % and 92.3 % (P = 0.855), respectively. The functional sphincter preservation rates of the TME and CCRT + TME groups were 71.3 % and 70.0 % (P = 0.849), respectively. In the TME group, 16 (17.0 %) patients were proven to have pTNM stage I disease after surgery. In the CCRT + TME group, 32 (35.6 %) patients achieved a pathologic complete response (pCR).</p><p><b>CONCLUSIONS</b>Preliminary results indicated no significant differences in the DFS, OS, or functional sphincter preservation rates between the TME and CCRT + TME groups. However, preoperative CCRT with XELOX yielded a high pCR rate. Newer techniques are needed to improve the staging accuracy, and further investigation is warranted.</p><p><b>CLINICAL TRIAL REGISTRATION NUMBER</b>Chi CTR-TRC-08000122.</p>

Expression of molecular markers detected by immunohistochemistry and risk of lymph node metastasis in stage T1 and T2 colorecrectal cancers / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the molecular risk factors of lymph node metastasis in stage T1 and T2 colorectal cancers by tissue microarray and immunohistochemistry techniques.</p><p><b>METHODS</b>Two hundred and three patients with stage T1 and T2 colorectal carcinoma who underwent radical surgery from 1999 to 2010 in our department were included in this study. Their clinicopathological data were retrospectively analyzed. Expression of the following 14 molecular markers were selected and assayed by tissue microarray and immunohistochemistry: VEGFR-3, HER2, CD44v6, CXCR4, TIMP-1, EGFR, IGF-1R, IGF-2, IGFBP-1, ECAD, MMP-9, RKIP, CD133, MSI. Chi-squared test and logistic regression were used to evaluate the variables as potential risk factors for lymph node metastasis.</p><p><b>RESULTS</b>The positive expression rates of biomarkers were as following: VEGFR-3 (44.3%), EGFR (30.5%), HER-2 (28.1%), IGF-1R (63.5%), IGF-2 (44.8%), IGFBP-1 (70.9%), ECAD (45.8%), CD44v6 (51.2%), MMP-9 (44.3%), TIMP-1 (41.4%), RKIP (45.3%), CXCR4 (40.9%), and CD133 (49.8%). The positive rate of MSI expression was 22.2%. Both univariate and multivariate analyses showed that VEGFR-3, HER-2, and TIMP-1 were significant predictors of lymph node metastasis. Univariate analysis showed that CD44v6 and CXCR4 were significant significant predictors of lymph node metastasis.</p><p><b>CONCLUSIONS</b>VEGFR-3, HER2 and TIMP-1 are independent factors for lymph node metastasis in stage T1 and T2 colorectal cancers.</p>

New prospective on adjuvant treatment for gastrointestinal stromal tumors / 中华胃肠外科杂志

Gastrointestinal stromal tumor (GIST) represents the most common mesenchymal tumor of the gastrointestinal tract. With decades of development, surgical excision combined with molecular targeted agents is becoming the mode for the GIST treatment. Imatinib mesylate (IM) is the first-line therapy medicine for GIST adjuvant treatment, and it significantly reduces recurrence or metastasis and increases survival. According to the recently results of SSGXVIII/AIO study, imatinib adjuvant therapy should be administered for at least 3 years for the GIST patients with a high estimated risk of recurrence and metastasis after surgery. Nevertheless, the optimal duration of the adjuvant therapy or the follow-up policy remains unclear, and we look forward to standard assessment criteria for individualized treatment.

Study on associated biomarkers influencing recurrence, metastasis and prognosis in patients with gastrointestinal stromal tumors after complete resection / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the associated biomarkers influencing recurrence, metastasis and prognosis in patients with gastrointestinal stromal tumors (GIST) after complete resection.</p><p><b>METHODS</b>Tumor tissue samples of 148 patients with GIST undergoing complete resection from January 1990 to December 2008 in Sun Yat-sen University Cancer Center were collected. The expressions of Ki-67, E-cadherin, MMP7, CD44, nm23, P53, survivin, Cyclin D1, COX-2, and VEGF in tumor tissue samples were detected by tissue microarray and immunohistochemistry (IHC). The association of above factors expressions with recurrence, metastasis and prognosis was examined.</p><p><b>RESULTS</b>Log-rank test showed that Ki-67, E-cadherin, MMP7, CD44, P53 and survivin were associated to disease-free duration after complete GIST resection (all P<0.05), and the Ki-67, E-cadherin, P53 and survivin were associated to overall survival (all P<0.05). Cox multivariate analysis revealed that disease-free survival was associated with Ki-67, CD44 and P53 (all P<0.05), and the overall survival was only associated with Ki-67 (P<0.05).</p><p><b>CONCLUSION</b>Ki-67, CD44 and P53 are closely associated with recurrence and metastasis after complete GIST resection, and Ki-67 can predict the prognosis of GIST.</p>

Compliance and associated factors of postoperative chemotherapy for elderly patients with colorectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the compliance and associated factors of postoperative chemotherapy for elderly patients with colorectal cancer.</p><p><b>METHODS</b>A total of 386 elderly patients (>70 years old) with stage II(-IIII( colorectal cancer underwent surgery between January 2000 and January 2010. The clinicopathological data were retrospectively reviewed. There were 226 patients received postoperative chemotherapy and 160(41.4%) refused. Logistic regression model was used to analyze factors associated with patients compliance to chemotherapy. Patients were followed up by phone call regarding the reason for refusal.</p><p><b>RESULTS</b>Multivariate analysis showed that gender, body mass index (BMI), body surface area (BSA), age, and complication were independent risk factors associated with chemotherapy compliance(All P<0.05). Follow-up phone questionnaire showed that 63.8%(51/80) of patients with stage II( cancer did not received chemotherapy because of the doctor's uncertainty of chemotherapy benefit. For stage III( patients, fear of chemotherapy (31.2%, 15/48), feeling uncomfortable (18.8%, 9/48), and financial issues(18.8%, 9/48) were the main factors. The desperate feeling was the predominant reason for stage IIII( patients(56.2%, 18/32).</p><p><b>CONCLUSIONS</b>Gender, BSA, age, and postoperative complication are the main factors associated with compliance to postoperative chemotherapy. Doctors' recommendation should be emphasized for stage II( patients. For stage III( patients, treatment recommendation should be enthusiastic.</p>