Standardization, objectification, and essence research of traditional Chinese medicine syndrome: A 15-year bibliometric and content analysis from 2006 to 2020 in Web of Science database.

The standardization, objectification, and essence research of traditional Chinese medicine (TCM) syndrome influence the modernization and international development of TCM syndrome. A total of 253 relevant publications collected from the Web of Science Core Collection database from 2006 to 2020 were analyzed by bibliometric and content methods. The co-occurrence analysis of countries, institutions, journals, authors, and keywords analysis were carried out by using Citespace software. The high-yield institutions and high-impact authors contributed to TCM syndrome publications were concentrated in China. Since 2012, driven by some groundbreaking publications, the number of TCM syndrome literatures has increased rapidly. According to the results of bibliometric and content analysis, research hotspots in TCM syndrome in the last 15 years can be summarized in six aspects: (a) objectification research of four TCM diagnostic methods, (b) omics technology for the essence research of TCM syndrome, (c) research on TCM syndrome evaluation scale, (d) metagenomic technology for the essence research of TCM syndrome, (e) data mining technology for TCM syndrome differentiation, and (f) systematic research on TCM syndromes of chronic hepatitis B. Emerging trends can be identified according to the most recent keywords bursts: (a) TCM syndrome diagnostic models with multiple indexes should be constructed to develop personalized medicine. (b) The connotation of TCM syndrome should be verified through "syndrome detecting from recipe used," and the screened potential markers of TCM syndrome need clinical verification. (c) The intervention and integration of multi-disciplines is expected to find a new breakthrough in the research of TCM syndrome.

Inflammation-nutritional markers of peripheral blood could predict survival in advanced non-small-cell lung cancer patients treated with PD-1 inhibitors.

BACKGROUND: Inflammation-nutritional markers of peripheral blood are easily assessed and can predict survival. The aim of this study was to investigate the association between inflammation-nutritional parameters and survival of anti-programmed death-1 (PD-1) therapy in non-small-cell lung cancer (NSCLC) patients. METHODS: We performed a retrospective study from March 2017 to April 2020 in advanced NSCLC patients treated with PD-1 inhibitors. Univariable and multivariable analyses were conducted to evaluate the relationship between peripheral blood parameters (absolute lymphocyte count [ALC], absolute neutrophil count [ANC], absolute monocyte count [AMC], absolute eosinocyte count [AEC], lactic dehydrogenase [LDH], plasma-albumin [ALB], neutrophil/lymphocyte ratio [NLR], and platelet/lymphocyte ratio [PLR]) measured before therapy initiation and prognosis. RESULTS: Among 184 evaluable patients, 134 (72.8%) were male and the median age was 58 years (range 33-87) with 31 (16.8%) ≥70 years. An elevated ANC (≥7500/ul), NLR (≥5), and PLR (≥200) was significantly associated with worse objective response rate (ORR), progression-free survival (PFS), and overall survival (OS), while increased ALC (≥1000/ul) and ALB (≥3.5 g/dl) could significantly improve survival in terms of ORR, PFS, and OS. In multivariate analyses, higher AEC (≥150/ul) and AMC (≥650/ul) could significantly decrease the risk of death (hazard ratio [HR] 0.363, 95% confidence interval [CI] 0.141-0.931, p = 0.035; HR 0.370, 95% CI 0.203-0.675, p = 0.001). A higher NLR and PLR, and lower ALB were independent predictors of poor prognosis for OS (HR 1.964, 95% CI 1.027-3.755, p = 0.041; HR 4.255, 95% CI 2.364-7.658, p = 0.000; HR 1.962, 95% CI 1.213-3.174, p = 0.006, respectively). CONCLUSION: Our research illustrated that pretreatment AEC, AMC, ALB, NLR, and PLR are independent predictors for survival in advanced NSCLC patients treated with PD-1 inhibitors.

[Purification and component identification of total proanthocyanidins in Choerospondias axillaris pericarp].

The present study determined the quantitative markers of total proanthocyanidins in the purification of the industrial waste Choerospondias axillaris pericarp based on the comparison results of high-performance liquid chromatography(HPLC) and mass spectrometry(MS) and optimized the purification process with two stable procyanidins as markers. The adsorption and desorption of five different macroporous adsorption resins, the static adsorption kinetics curve of NKA-Ⅱ resin, the maximum sample load, and the gradient elution were investigated. The UPLC-Q-TOF-MS/MS was employed for qualitative analysis of the newly-prepared total proanthocyanidins of C. axillaris pericarp. As revealed by the results, NKA-Ⅱ resin displayed strong adsorption and desorption toward total proanthocyanidins. The sample solution(50 mg·mL~(-1)) was prepared from 70% ethanol crude extract of C. axillaris pericarp dissolved in water and 7-fold BV of the sample solution was loaded, followed by static adsorption for 12 h. After 8-fold BV of distilled water and 6-fold BV of 10% ethanol were employed to remove impurities, the solution was eluted with 8-fold BV of 50% ethanol, concentrated, and dried under reduced pressure, and purified total proanthocyanidin powder was therefore obtained. Measured by vanillin-hydrochloric acid method, the purity and transfer rate of total proanthocyanidins were 47.67% and 59.92%, respectively, indicating the feasibi-lity of the optimized process. UPLC-Q-TOF-MS/MS qualitative analysis identified 16 procyanidins in C. axillaris total proanthocyanidins. The optimized purification process is simple in operation and accurate in component identification, and it can be applied to the process investigation of a class of components that are difficult to be separated and purified. It can also provide technical support and research ideas for the comprehensive utilization of industrial waste.

[Comparative of functional components, antioxidant and α-glucosidase inhibition activities between Choerospondias axillaris fruit peel vinegar and apple vinegar].

Based on the idea of plant metabolomics, ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) was used to compare the chemical composition between 6 batches of fruit vinegar brewed from Choerospondias axillaris fruit peel and 6 batches of apple vinegar purchased from 3 companies. Antioxidant and α-glucosidase inhibition activities were also tested in vitro. A total of 43 compounds were identified by reference substance, liquid chromatography-mass spectrometry(LC-MS/MS) fragmentation information or literature data. A total of 40 compounds were identified in the C. axillaris fruit peel vinegar. A total of 16 compounds were identified in apple vinegar. There were 13 common ingredients including organic acids and esters such as citric acid, 2-isopropyl malic acid, and triethyl citrate. The results of partial leastsquares-discriminant analysis(PLS-DA) indicated that they had 33 significantly different compounds such as proanthocyanidin oligomer, quercetin-3-O-rhamnoside and heptadecanoic acid. The proanthocyanidins and flavonoid glycosides in C. axillaris peel vinegar were more abundant than apple vinegar, so it had better health function than ordinary fruit vinegar. The results showed that C. axillaris fruit peel vinegar had stronger antioxidant and α-glucosidase inhibition activities in vitro. The vinegar brewed from waste C. axillaris fruit peel had more chemical ingredients than the apple vinegar. C. axillaris fruit peel vinegar had better biological activity and health function, so it had good development prospect. This study provided the scientific evidence for exploiting the C. axillaris fruit peel into high value-added products. It also provided ideas for the comprehensive development and utilization of similar Chinese medicine waste.

The green tea polyphenol EGCG potentiates the antiproliferative activity of sunitinib in human cancer cells.

Sunitinib is a promising drug for clinical applications; however, the efficacy is reduced by the feedback activation of many signaling cascades. In this study, we investigated the ability of (-)-epigallocatechin-3-gallate (EGCG) to synergize with sunitinib and inhibit insulin receptor substrate (IRS)/mitogen-activated protein kinase (MAPK) pathway activation. MCF-7, H460, and H1975 cell lines with PIK3CA mutations were treated with sunitinib or mock treated 0-24 h and then pulsed with 0-50 µM EGCG for another 12 h; cell proliferation and vascular endothelial growth factor (VEGF) secretion were then evaluated. To analyze angiogenesis and VEGF levels in vivo, MCF-7 and H460 xenograft tumors were established. Cell growth signaling cascades were assessed via western blotting in vitro, and tumors were subjected to immunohistochemical analyses to evaluate signaling cascades in vivo. EGCG enhanced the antiproliferation and VEGF secretion-reducing effects of sunitinib in the three tested cell lines. In vivo, EGCG administration at 4 h after sunitinib treatment resulted in greater tumor shrinkage and antiangiogenesis than with sunitinib alone. We further demonstrated that sunitinib exposure induces insulin receptor substrate-1 (IRS-1) upregulation and activation of MAPK signaling. More strikingly, EGCG treatment downregulated IRS-1 levels and suppressed mitogenic effects. In vivo, immunohistochemical analyses demonstrated marked suppression of the IRS/MAPK/p-S6K1 signaling cascade by EGCG, especially after sunitinib treatment. EGCG potentially synergizes with sunitinib due to its ability to suppress the IRS/MAPK signaling induced by sunitinib. We conclude that administration of EGCG after sunitinib treatment represents a promising strategy for the treatment of cancer.

Phase I study of postoperative radiotherapy concurrent with S-1 in patients with gastric cancer.

Postoperative chemoradiotherapy (CRT) with concurrent 5-fluorouracil is the standard care for gastric cancer patients after curative surgery. The previous studies revealed that the subgroup of patients with high recurrence risk would benefit most from adjuvant CRT. S-1, a novel oral fluorouracil, has showed very effective in metastatic gastric cancer and became the standard option for gastric cancer with D2 dissection. The safety and dosage of S-1 combined with postoperative radiotherapy have not yet been evaluated. This study is to determine the maximum tolerate dose (MTD) and dose-limiting toxicity (DLT) of S-1 given concurrently with postoperative high-dose radiotherapy in gastric cancer. Patients with more advanced stage (pT4 and/or pN+) after R0 resection were recruited. Eligible patients received one cycle standard SOX (S-1 plus oxaliplatin) chemotherapy, then S-1 monotherapy with concurrent radiotherapy for 6 weeks, followed by additional three cycles of SOX. During the concurrent CRT, S-1 was administered on every radiotherapy treatment day according to a predefined dose-escalation schedule. Radiotherapy (3D-RT or IMRT) was given to a total dose of 50.4 Gy in 28 fractions. DLT was defined as grade 3 or 4 hematologic and non-hematologic toxicity. From March 2011 to October 2012, 21 patients were enrolled at five dose levels: 40 (n = 3), 50 (n = 3), 60 (n = 6), 70 (n = 6) and 80 mg/m(2)/day (n = 3). D2-dissection was performed in 18 patients (85.7 %) and 15 patients (71.4 %) had stage III disease. The most common dose-related toxicity was anorexia, nausea and vomiting, fatigue and leucopenia. DLT was occurred in one patient at 60 mg/m(2)/day (grade 3 fatigue), one patient at 70 mg/m(2)/day (grade 3 vomiting and anorexia), two patients at 80 mg/m(2)/day (one with grade 3 vomiting and anorexia; another with grade 3 febrile leucopenia). Four patients did not complete CRT as planned. Overall, this phase I study demonstrated that postoperative CRT with daily S-1 was feasible in gastric cancer and the MTD of S-1 concurrent with radiotherapy was 70 mg/m(2)/day. This S-1-based postoperative CRT will be investigated in a multicenter phase III study in West China.

Interaction of green tea polyphenol epigallocatechin-3-gallate with sunitinib: potential risk of diminished sunitinib bioavailability.

Sunitinib, a novel oral multi-targeted tyrosine kinase inhibitor for patients with metastatic renal cell carcinoma (mRCC) and advanced gastrointestinal stromal tumor, has a good prospect for clinical application and is being investigated for the potential therapy of other tumors. We observed the phenomenon that drinking tea interfered with symptom control in an mRCC patient treated with sunitinib and speculated that green tea or its components might interact with sunitinib. This study was performed to investigate whether epigallocatechin-3-gallate (EGCG), the major constituent of green tea, interacted with sunitinib. The interaction between EGCG and sunitinib was examined in vitro and in vivo. (1)H nuclear magnetic resonance ((1)H-NMR) spectroscopy and mass spectrometry (MS) were used to analyze the interaction between these two molecules and whether a new compound was formed. Solutions of sunitinib and EGCG were intragastrically administered to rats to investigate whether the plasma concentrations of sunitinib were affected by EGCG. In this study, we noticed that a precipitate was formed when the solutions of sunitinib and EGCG were mixed under both neutral and acidic conditions. (1)H-NMR spectra indicated an interaction between EGCG and sunitinib, but no new compound was observed by MS. Sticky semisolid contents were found in the stomachs of sunitinib and EGCG co-administrated mice. The AUC(0-∞) and C (max) of plasma sunitinib were markedly reduced by co-administration of EGCG to rats. Our study firstly showed that EGCG interacted with sunitinib and reduced the bioavailability of sunitinib. This finding has significant practical implications for tea-drinking habit during sunitinib administration.

Postoperative chemoradiotherapy in gastric cancer: a phase I study of radiotherapy with dose escalation of oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX regimen).

Concurrent chemoradiotherapy begins to be more and more widely accepted as a standard adjuvant treatment in gastric cancer. And oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) also reveals to be a very effective regimen in gastric cancer. But the safety and the dosages of FOLFOX combining with radiotherapy are still unknown. This study was to determine the maximum-tolerated dose and the dose-limiting toxicity of FOLFOX with higher-dose concurrent radiotherapy (RT) as adjuvant treatment in patients with gastric cancer. Patients with Stage II/III gastric cancer after surgery were recruited. They received one cycle of induction chemotherapy (standard FOLFOX4). Then, they received 50.4 Gy in 1.8-Gy fractions in combination with two cycles of concurrent FOLFOX, and oxaliplatin among this regimen was administered with escalating doses. Dose-limiting toxicity including grade 3 or grade 4 hematologic and nonhematologic toxicities was investigated. Fifteen patients were enrolled at the following dose levels: oxaliplatin 55 mg/m(2) (3 patients), 65 mg/m(2) (6 patients), and 75 mg/m(2) (6 patients). Dose-limiting toxicity was observed in 1 patient at 65 mg/m(2) (grade 4 leukopenia) and in 3 patients at 75 mg/m(2) (1 patient had grade 4 leukopenia, 1 had grade 3 thrombocytopenia, and 1 had grade 3 stomatitis). Combination chemotherapy FOLFOX with oxaliplatin 65 mg/m(2), d 1; leucovorin 200 mg/m(2), 2 h, d1-2; 5-fluorouracil 400 mg/m(2), iv, d 1-2 and 600 mg/m(2) civ, 22 h, d 1-2 given concurrently with RT (50.4 Gy) can be recommended as a safer and preferable regimen for the adjuvant treatment of patients with gastric cancer.

Inhibition of tumor growth with a vaccine based on xenogeneic homologous fibroblast growth factor receptor-1 in mice.

Angiogenesis is important for the growth of solid tumors. The breaking of the immune tolerance against the molecule associated with angiogenesis should be a useful approach for cancer therapy. However, the immunity to self-molecules is difficult to elicit by a vaccine based on autologous or syngeneic molecules due to immune tolerance. Basic fibroblast growth factor (bFGF) is a specific and potent angiogenic factor implicated in tumor growth. The biological activity of bFGF is mediated through interaction with its high-affinity receptor, fibroblast growth factor receptor-1 (FGFR-1). In this study, we selected Xenopus FGFR-1 as a model antigen by the breaking of immune tolerance to explore the feasibility of cancer therapy in murine tumor models. We show here that vaccination with Xenopus FGFR-1 (pxFR1) is effective at antitumor immunity in three murine models. FGFR-1-specific autoantibodies in sera of pxFR1-immunized mice could be found in Western blotting analysis. The purified immunoglobulins were effective at the inhibition of endothelial cell proliferation in vitro and at the antitumor activity in vivo. The antitumor activity and production of FGFR-1-specific autoantibodies could be abrogated by depletion of CD4+ T lymphocytes. Histological examination revealed that the autoantibody was deposited on the endothelial cells within tumor tissues from pxFR1-immunized mice, and intratumoral angiogenesis was significantly suppressed. Furthermore, the inhibition of angiogenesis could also be found in alginate-encapsulate tumor cell assay. These observations may provide a new vaccine strategy for cancer therapy through the induction of autoimmunity against FGFR-1 associated with angiogenesis in a cross-reaction.