[Effective components and mechanism of Qijiao Shengbai Capsules based on fingerprinting and network pharmacology].

Qijiao Shengbai Capsules(QJ) can invigorate Qi and replenish the blood, which is commonly used clinically for adjuvant treatment of cancer and leukopenia due to chemoradiotherapy. However, the pharmacological mechanism of QJ is still unclear. This work aims to combine the high-performance liquid chromatography(HPLC) fingerprints and network pharmacology to clarify the effective components and mechanism of QJ. The HPLC fingerprints of 20 batches of QJ were established. The similarity evaluation among 20 batches of QJ was performed by using Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(version 2012), resulting in a similarity greater than 0.97. Eleven common peaks were identified by reference standard, including ferulic acid, calycosin 7-O-glucoside, ononin, calycosin, epimedin A, epimedin B, epimedin C, icariin, formononetin, baohuoside I, and Z-ligustilide. The "component-target-pathway" network was constructed by network pharmacy, and 10 key components in QJ were identified, such as ferulic acid, calycosin 7-O-glucoside, ononin, and calycosin. The components were involved in the phosphoinositide 3 kinase-protein kinase B(PI3K-Akt), mitogen-activated protein kinase(MAPK), and other signaling pathways by regulating potential targets, including EGFR, RAF1, PIK3R1, and RELA, to auxiliarily treat tumors, cancers, and leukopenia. The molecular docking conducted on the AutoDock Vina platform confirmed the high binding activity of 10 key effective components with core targets, with the binding energy less than-5 kcal·mol~(-1). In this study, the effective components and mechanism of QJ have been preliminary revealed based on HPLC fingerprint and network pharmacology, which provided a basis for quality control of QJ and a refe-rence for further study on its mechanism.

[Chemome profiling of Qijiao Shengbai Capsules by UPLC-IT-TOF-MS].

Qijiao Shengbai Capsules(QJ) are a common Miao medicine serving as an adjuvant cancer therapy in clinical practice.QJ consists of seven medicinal materials such as Astragalus membranaceus and Lespedeza buergeri.Its chemical components have not been clarified and the quality control needs to be improved.In this study, LC-IT-TOF-MS was used to comprehensively collect MS~1 and MS~2 fragment information of QJ and rapidly identify the chemical compositions.The chromatographic separation was performed on the Capcell core ADME column(2.1 mm×150 mm, 2.7 µm) with 0.1% formic acid aqueous solution(A) and acetonitrile(B) as mobile phases for gradient elution.High-resolution mass spectrometric information was obtained by scanning in the positive and negative ion ESI modes.A total of 107 compounds were structurally identified according to the deduced MS fragmentation patterns and comparison with standards and data reported in the literature, including 54 flavonoids, 16 phthalides, 13 alkaloids, 12 phenolic acids, 7 saponins, 2 coumarins, 2 condensed tannins, and 1 purine.This study clarified the chemical composition of QJ and provided references for the improvement of its quality standards and the elucidation of its medicinal substances.

Novel flavonolignans from the roots of Indigofera stachyodes.

Two pairs of new enantiomeric flavonolignans, ±stachyols A and B (±1 and ± 2), along with two novel isoflavanelignans, stachyols C and D (3 and 4) were isolated from the roots of Indigofera stachyodes. Their chemical structures and absolute configurations were determined using nuclear magnetic resonance and comparison of experimental and theoretical electronic circular dichroism (ECD) spectra, as well as quantum chemical calculations. Of those compounds, 1 and 2 represented the first examples of flavonolignans with 5-deoxyflavonoids adduct phenylpropanoids. Moreover, 3 and 4 possess an unprecedented skeleton with isoflavanes adduct phenylpropanoids. The antioxidant activity was evaluated for all compounds in terms of ABTS+ and DPPH bioassays. Compounds 3 and 4 exhibited significant radical-scavenging activity in the ABTS+ assay, with IC50 values of 15.15 and 5.83 µM, respectively.

[Condensed tannins from roots of Indigofera stachyodes].

Eleven condensed tannins were isolated from the roots of Indigofera stachyodes by various column chromatography techniques including silica gel, octadecyl silica(ODS), Sephadex LH-20, and semi-preparative high performance liquid chromatography(HPLC). These compounds were identified on the basis of physicochemical properties, nuclear magnetic resonance(NMR) and mass spectrometry(MS) data as stachyotannin A(1), epicatechin-(2ß→O→7,4ß→8)-epiafzelechin-(4ß→8)-catechin(2), cinnamtannin D1(3), cinnamtannin B1(4), epicatechin-(2ß→O→7,4ß→8)-epiafzelechin-(4α→8)-epicatechin(5), gambiriin C(6), proanthocyanidin A1(7), proanthocyanidin A2(8), aesculitannin B(9), proanthocyanidin A4(10), and procyanidin B5(11). Compound 1 is a new compound. Compounds 2-11 were isolated from Indigofera for the first time. Furthermore, compounds 1, 2, and 4-11 showed inhibitory effects on thrombin-induced ATP release in platelets.

c-KIT: potential predictive factor for the efficacy of sorafenib in metastatic renal cell carcinoma with sarcomatoid feature.

BACKGROUND: Vascular endothelial growth factor-targeted therapy has been standard care for metastatic renal cell carcinoma for years. However, little clinical experience on these agents in the treatment of sarcomatoid tumors has been documented. The aim of the present study was to detect the expression of c-KIT in the primary tumor of metastatic renal cell carcinoma with sarcomatoid feature, and to reveal its potential value of predicting the efficacy of sorafenib treatment and survival of the patients. PATIENTS AND METHODS: Seventeen patients were enrolled and treated with sorafenib as a second-line treatment after cytokine therapy. The expressions of c-KIT was tested immunohistochemically in the 17 specimens of primary renal tumors. The correlation between c-KIT status and treatment effect was compared. Univariate and multivariate analysis were employed to determine the survival difference between c-KIT-positive and c-KIT-negative patients. RESULTS: Twelve of 17 specimens (70.6%) were detected to be overexpressing c-KIT. c-KIT positive patients had higher disease control rate (75%) compared with c-KIT-negative patients (25%), P = .036. Median overall survival time was 92 weeks for c-KIT positive patients and 44 weeks for c-KIT negative patients, log rank χ(2) = 9.566, P = .002. Multivariate Cox regression model analysis only revealed number of metastatic organs and c-KIT as independent prognostic factors. CONCLUSION: Our findings suggest that c-KIT can be a potential predictive factor for metastatic renal cell carcinoma with sarcomatoid feature in treatment using sorafenib, and patients with positive c-KIT expression might have better responses and obtain longer overall survival time.

Prognostic factors in Chinese patients with metastatic castration-resistant prostate cancer treated with docetaxel-based chemotherapy.

This study aims to evaluate the potential value of patient characteristics in predicting overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with docetaxel-based thermotherapy. A total of 115 patients with mCRPC undergoing a docetaxel q3w regimen were enrolled in this study. A survival analysis was performed using the Kaplan-Meier method. Cox proportional hazards models were used to evaluate the prognostic value of all covariates for OS. OS was also analysed after stratifying patients according to the results of multivariate analysis. The median OS for the entire cohort was 17.0 months. The multivariate analysis showed that the prostate-specific antigen doubling time (PSADT), baseline haemoglobin (Hb) concentration, alkaline phosphatase (ALP) concentration, cycles of chemotherapy and time to castration resistance were independent prognostic factors of OS. According to the presence of PSADT <46.3 days and baseline ALP ≥ 110 IU l(-1), all patients were divided into three risk groups: low-risk group (no risk factors), intermediate-risk group (one risk factor) and high-risk group (two risk factors). Median OSs for patients in low-, intermediate- and high-risk groups were 28.0 months (95% CI: 23.8-32.2), 21.0 months (95% CI: 18.9-23.1) and 11.0 months (95% CI: 7.6-14.4), respectively (P<0.001). In conclusion, PSADT, baseline Hb concentration, ALP concentration, cycles of chemotherapy and time to castration resistance were independent prognostic factors of OS in Chinese patients with mCRPC treated with docetaxel. PSADT combined with the baseline ALP concentration could be a useful risk stratification parameter for evaluating survival outcomes.

Pelvic floor electrical stimulation for postprostatectomy urinary incontinence: a meta-analysis.

OBJECTIVE: To evaluate the role of electrical stimulation (ES) in the recovery of postprostatectomy urinary incontinence (UI). METHODS: We performed a meta-analysis of all available randomized controlled trials comparing ES enhanced pelvic floor muscle training (PFMT) with PFMT alone for postprostatectomy UI. We separated in the analysis the continence rate within 3 months or longer than 6 months after operation, which stand for the early and late recovery of UI after operation, respectively. Relative risk (RR) reductions and their 95% confidence intervals (CIs) were calculated for categorical outcomes. RESULTS: Four studies randomizing 210 cases were included in the meta-analysis. Three studies enrolling 186 cases reported the continence rate within 3 months after radical prostatectomy. The pooled analysis did not show that ES improved early recovery of UI better than did PFMT (RR 1.21; 95% CI = 0.95-1.54, P = .12). All 4 studies provided data for 6-12 months after RP; the pooled analysis did not show a relative benefit (RR = 1.03; 95% CI = 0.88-1.20, P = .73). CONCLUSION: Based on available evidence, ES enhanced PFMT did not improve the return to continence more than PFMT in men with postprostatectomy UI.

Tumor cytoreduction results in better response to androgen ablation--a preliminary report of palliative transurethral resection of the prostate in metastatic hormone sensitive prostate cancer.

OBJECTIVES: To investigate the oncologic influence of transurethral resection of the prostate (TURP) as a cytoreductive surgery in metastatic hormone sensitive prostate cancer (mHSPC), in the setting of continuous complete androgen blockade (CAB). MATERIALS AND METHODS: Medical histories of 146 consecutive Chinese males with newly diagnosed mHSPC, registered in our institution in 2006 and 2007, were reviewed. All of these patients received CAB as initial systematic therapy. Demographics and cancer control outcomes from 39 mHSPC patients who underwent TURP for a relief of bladder outlet obstruction were compared with those of the other 107 who received CAB only when they were still hormone-sensitive. Median follow-up was 15 months (3 to 27 months). RESULTS: Age at diagnosis, baseline PSA, and biopsy Gleason score were comparable between the 2 groups. Patients who underwent a TURP had lower PSA nadir (median 0.15 ng/ml vs. 0.82 ng/ml, P = 0.015) and longer time to PSA nadir (11.2 months vs. 6.4 months, P < 0.001). More patients in the non-TURP group developed hormone refractory prostate cancer (P = 0.007). The TURP group had a tendency towards longer disease-specific survival and overall survival (24.4 months vs. 24.1 months and 24.4 months vs. 22.9 months, respectively), though this did not reach statistical significance. CONCLUSIONS: TURP resulted in a better and more prolonged response to hormone therapy in mHSPC, with a trend towards positive influence in disease specific survival and overall survival. To date, our preliminary report is the first study regarding long-term survival of cytoreductive surgery in mHSPC, and further investigations are warranted.

Erythrocyte sedimentation rate kinetics as a marker of treatment response and predictor of prognosis in Chinese metastatic renal cell carcinoma patients treated with sorafenib.

OBJECTIVES: Previous prognostic factor models for metastatic renal cell carcinoma (mRCC) have not included erythrocyte sedimentation rate (ESR). We designed the present study to evaluate the prognostic value of ESR for mRCC patients treated with sorafenib. METHODS: Sorafenib was given to 83 patients with clear cell mRCC. Serum ESR was tested before treatment and every 4 weeks after first administration of sorafenib. Oncological evaluation was carried out every 8 weeks. Analyzed factors included age, sex, performance status, method of nephrectomy, number of metastatic organs, anemia, lactate dehydrogenase, corrected calcium, albumin, baseline ESR level and ESR kinetics status. Kaplan-Meier and Cox regression analyses on progression-free survival (PFS) were carried out. RESULTS: Baseline ESR levels ranged from 3 to 154 mm/h, and 43 (41.0%) patients had an ESR level higher than 40 mm/h. Median PFS was 10.0 months (95% CI 7.6-12.4 months). Dividing the cohort into three groups according to ESR kinetics status, median PFS was 27 months in the decreased ESR group, 12 months in the stable ESR group and 6 months in the increased ESR group. Performance status, time from diagnoses to sorafenib treatment, number of metastatic organs and ESR kinetics were independent predictors for PFS in multivariable Cox regression model analysis, with an area under the curve of 0.865 in a binary logistic regression model of 12-month PFS probability. CONCLUSIONS: ESR kinetics can be useful to monitor the treatment response and to predict PFS for mRCC patients treated with sorafenib as second-line therapy.

[The study of electrical acupuncture stimulation therapy combined with pelvic floor muscle therapy for postprostatectomy incontinence].

OBJECTIVE: To explore the effectiveness and significance of whether electrical acupuncture stimulation combining with pelvic floor muscle therapy (PFMT) can improve the recovery of urinary continence. METHODS: A total of 109 patients took part in the study of novel combination treatment for urinary continence from September 2008 to September 2009. Patients were divided into study group (n = 40) and control group (n = 69). The patients in study group received electrical acupuncture stimulation therapy combined with PFMT one week after removal the catheter. The patients in control group performed PFMT as the only treatment for post prostatectomy incontinence. The patients were followed up closely, with their clinical characteristics recorded, questionnaires of ICI-Q-SF filled up, and all the data for statistical analysis collected. RESULTS: There was a significant difference between the study group and the control group in the urinary control curve (P = 0.029). The difference of continence probability between these two groups became greater from 4 weeks after surgery, and the difference reached the peak at 6 weeks (P = 0.023). Then the difference became smaller, and there was no difference at 16 weeks after surgery. ICI-Q-SF questionnaires showed the same results. CONCLUSION: Electrical acupuncture stimulation therapy combining with PFMT can improve the recovery of patients' urinary continence after radical prostatectomy.

Feasibility and activity of sorafenib and sunitinib in advanced penile cancer: a preliminary report.

INTRODUCTION: We describe our experience with sorafenib and sunitinib in the treatment of chemotherapy-refractory advanced penile squamous cell carcinoma (SCC). PATIENTS AND METHODS: Between May 2008 and June 2009, 6 advanced penile cancer patients were treated with sorafenib or sunitinib in our center. All of them had previously received at least two chemotherapy regimens. Tumor responses were evaluated by radiologic assessment and serum SCC antigen change. Immunohistochemical staining of CD34 and Ki-67 was performed in 3 paired tumor tissues before and after treatment. RESULTS: In the 6 patients, 1 partial response and 4 stable diseases were observed. Three patients showed pain response and had an improvement in quality of life. After molecular-targeted therapies, reduction in microvessel density and Ki-67 labeling index was observed in paired specimens. Serum SCC antigen levels were decreased in 5 patients after 1 week of medication. The patient who achieved partial response had an SCC antigen reduction of nearly 95% after treatment with sunitinib. Serious adverse events were fatal infection and rupture of the femoral vessel, which were unlikely related to the medication. CONCLUSIONS: The feasibility and activity of sorafenib and sunitinib in our series suggest that this approach may be a promising alternative in chemotherapy-refractory advanced penile SCC.