A Randomized, Open-Label, Multicenter, Phase 3 Study of High-Dose Vitamin C Plus FOLFOX ± Bevacizumab versus FOLFOX ± Bevacizumab in Unresectable Untreated Metastatic Colorectal Cancer (VITALITY Study).

PURPOSE: To compare the efficacy and safety of high-dose vitamin C plus FOLFOX ± bevacizumab versus FOLFOX ± bevacizumab as first-line treatment in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Between 2017 and 2019, histologically confirmed patients with mCRC (n = 442) with normal glucose-6-phosphate dehydrogenase status and no prior treatment for metastatic disease were randomized (1:1) into a control (FOLFOX ± bevacizumab) and an experimental [high-dose vitamin C (1.5 g/kg/d, intravenously for 3 hours from D1 to D3) plus FOLFOX ± bevacizumab] group. Randomization was based on the primary tumor location and bevacizumab prescription. RESULTS: The progression-free survival (PFS) of the experimental group was not superior to the control group [median PFS, 8.6 vs. 8.3 months; HR, 0.86; 95% confidence interval (CI), 0.70-1.05; P = 0.1]. The objective response rate (ORR) and overall survival (OS) of the experimental and control groups were similar (ORR, 44.3% vs. 42.1%; P = 0.9; median OS, 20.7 vs. 19.7 months; P = 0.7). Grade 3 or higher treatment-related adverse events occurred in 33.5% and 30.3% of patients in the experimental and control groups, respectively. In prespecified subgroup analyses, patients with RAS mutation had significantly longer PFS (median PFS, 9.2 vs. 7.8 months; HR, 0.67; 95% CI, 0.50-0.91; P = 0.01) with vitamin C added to chemotherapy than with chemotherapy only. CONCLUSIONS: High-dose vitamin C plus chemotherapy failed to show superior PFS compared with chemotherapy in patients with mCRC as first-line treatment but may be beneficial in patients with mCRC harboring RAS mutation.

[Correlations between content of linarin in Chrysanthemum indicum and climatic factors in habitats].

Chrysanthemi Indici Flos(CIF), the capitulum of Chrysanthemum indicum, is widely used in proprietary Chinese medicine and daily chemical products. At present, CIF is mainly produced from wild resources and rarely cultivated. This study aims to reveal the correlations between linarin content in CIF and climatic factors in different habitats, and provide a theoretical basis for suitable zoning and rational production of medicinal materials. The content of linarin in CIF was determined by HPLC. Grey relational analysis and Pearson correlation analysis were carried out for linarin content with climatic factors. The results showed that the content of linarin in CIF was significantly different among different habitats. The grey relational degrees of climatic factors with linarin content was in an order of average annual precipitation>annual average sunshine hours>annual average temperature>longitude>annual frost-free period>latitude>altitude. Longitude, annual average temperature and average annual precipitation had significantly positive correlations with the content of linarin in CIF, whereas latitude and altitude showed negative correlations with it. The annual frost-free period and annual average sunshine hours had no significant correlation with the content of linarin in CIF. The content of linarin in CIF varied significantly in different habitats. High longitude, low latitude, low altitude, high annual average temperature and high annual average precipitation could be used as indicators for the habitats of high-quality Ch. indicum. This study provides a reference for selecting suitable producing areas of Ch. indicum and establishing artificial cultivation system.

[Comprehensive antioxidant and anti-inflammatory activity of alcohol extracts from Chrysanthemum indicum in different areas based on entropy weight and TOPSIS methodology].

The study is aiming at investigating the application of entropy weight TOPSIS method in the comparison of the scavenging effect of DPPH, ABTS and hydroxyl radical and the inhibition effect of xanthine oxidase(XOD) and lipoxygenase(LOX) of Chrysanthemum indicum. The DPPH, ABTS, salicylic acid and spectrophotometry were used to determine the scavenging effect of DPPH, ABTS and hydroxyl radical and the inhibition effect of xanthine oxidase(XOD) and lipoxygenase(LOX) of Ch. indicum from 31 different areas in vitro. Take the half inhibition rate of as the evaluation index, two principal components were extracted by the principal component analysis, and their cumulative contribution rate reached at 92.4%. The different areas of Ch. indicum could be divided into Dabei Mountain and Qinling-Taihang Mountain by use principal component to analysis. The entropy weight TOPSIS method was used to objectively assign weights to five indexes, calculate the weight of each index and set up the best and worst scheme of the evaluation object, and the relative proximity(C_i) was used as the measure to construct the multi-index comprehensive evaluation model of Ch. indicum. And then sort with the relative proximity value. The results showed that the relative proximity was between 0.098 and 0.983 which represents there were significant differences in the scavenging effect of DPPH, ABTS and hydroxyl radical and the inhibition effect of xanthine oxidase(XOD) and lipoxygenase(LOX) between extracts of Ch. indicum from different areas. The Ch. indicum from Dabie Mountain area have a relatively high relative degree of measurement and high-quality ranking. Taken together, the quality of Ch. indicum.from the Dabie Mountain area is better. The index weight coefficient and the classification result of producing area are basically consistent with the result of principal component analysis. The results show that the TOPSIS method based on entropy weight method can be used to evaluate the comprehensive quality of Ch. indicum.

The clinical research of 5 steps sequential method for whole treatment of hemorrhagic radiation cystitis in china.

Background: Curing hemorrhagic cystitis remains a challenge. We explore a continuous and effective treatment for hemorrhagic radiation cystitis. Methods: The data of patients in 6 provincial cancer hospital urology departments between April 2015 and December 2019 was reviewed retrospectively. Patients were classified as moderate and severe groups. The 5-steps sequential method was adopted. Two groups were initiated with step 1 and step 3 respectively. Step 1 was symptomatic treatment. Thrombin solution or sodium hyaluronate was administrated for bladder irrigation in step 2. Step 3 was transurethral electrocoagulation. Step 4 was interventional embolization. Step 5 was HBO therapy. OABSS was used to assess the improvement of patients' symptoms. The outcome was evaluated after at least 6 months of follow-up. Results: A total of 650 patients (56 men and 594 women), mean age 71.2 years, were enrolled in the 5 steps sequential method. 582 patients were classified as moderate and 68 severe group. In moderate group, the cure rate of step 1 was 61.2% (356/582), 80.4% (468/582) after step 2, 93.1% (542/582) after step 3, 96.2% (560/582) after step 4, and 99.8% (581/582) after step 5. In severe group, the cure rate was 54.4% (37/68) after step 3, 76.5% (52/68) after step 4, and 94.1% (64/68) after the step 5 respectively. The mean OABSS scores of both groups significantly decreased after 5 steps sequential method treatment (P<0.01). Conclusions: Our results show hemorrhagic radiation cystitis can be cured in 5 steps, and the 5 steps sequential method is welcomed and effective. Therapy efficacy depends on the number of steps adopted and the severity of hematuria.

[Cloning and prokaryotic expression of CHI in Chrysanthemum morifolium cv.'Hangju'].

Three Chrysanthemum-chalcone-isomerase genes( CmCHI) were successfully cloned by PCR from the database of Chrysanthemum transcriptome and named CmCHI1,CmCHI2 and CmCHI3,respectively. Bioinformatics analysis showed that the base numbers of CmCHI1-3 open reading frame were 708,633 and 681 bp,encoding 235,210 and 226 amino acids,respectively. Three fusion proteins of about 30 kDa were successfully induced by prokaryotic expression technology,and the corresponding recombinant fusion proteins were isolated and purified by Ni-NTA resin column. Clustering analysis showed that the 3 CmCHI were homologous with Compositae plants,and CmCHI1 and CmCHI3 belonged to type Ⅰ CHI. CmCHI2 belongs to type Ⅳ CHI. Using ß-actin as an internal reference gene,RT-qPCR was used to detect and analyze the expression of CmCHI1-3 genes in Hangju. The results showed that the expression levels of CmCHI1 and CmCHI3 were higher,while the expression levels of CmCHI2 were lower. It was concluded that CmCHI1 and CmCHI3 were the main chalcone isomerase genes involved in the synthesis of flavonoids in Hangju,and CmCHI2 was a helper gene. Flooding treatment significantly promoted the expression of CmCHI1 and CmCHI3 genes,but had no regulatory effect on CmCHI2. The above results provided a basis for further study of the molecular regulation mechanism of CHI gene in the metabolism of flavonoids in Hangju,which laid a foundation for improving the content of flavonoids in Hangju and finally improving the medicinal quality of Hangju.

[Study on wild tending of Chrysanthemum indicum].

To provide theoretical basis for the formation of Chrysanthemum indicum resource and quality,the differences in biology,ecology,yield and quality of Ch. indicum population in the wild tending,the cultivated and the wild were analyzed and compared in this study. The results showed that in the aspect of biology,there was no significant difference between the condition of wild tending and cultivated Ch. indicum at the height of plant,both were significantly higher than wild Ch. indicum. In the aspect of ecology,in the condition of wild tending is less likely to occur water logging than cultivated Ch. indicum. In the condition of wild tending is less likely to occur plant diseases and insect pests than Ch. indicum in the condition of wild. In the aspect of production,the average output of the sample of the condition of wild tending was significantly higher than that the condition of artificial cultivation and wild quadrat. There was no significant difference between the three kinds of condition on the traits of capitulum dichasium,the content of buddleoside of the wild tending Ch. indicum was significantly higher than that of 0. 80% required by the Chinese Pharmacopoeia( 2015 edition). Therefore,the artificial supplement and the appropriate artificial management of wild tending is a mode of production to increase the population density of Ch. indicum and obtain high quality and high yield medicinal materials.

[Effect of short-day treatment on expression of CO gene in Chrysanthemum indicum].

This experiment studied the expression pattern of key gene CO in the photoperiod of Chrysanthemum indicum. The CDS sequence of the Ch. indicum CO gene was cloned by RT-PCR. The open reading frame was 1 380 bp in length and encoded 459 amino acids. The bioinformatics analysis results showed that the Ch. indicum CO had higher homology with Ch. lavandulifolium and Artemisia annua,and the CO was more conservative in the same family. The molecular weight of the predicted protein encode by CO is 52. 04 k Da,the p I is 4. 81,the α-helix structure accounted for 17. 65%,the random coil accounted for 76. 69%,the extension chain accounted for 5. 66%,there are no ß-fold and signal peptide. The experimental results showed that short-day treatment could increase the expression level of CO gene in Ch. indicum and induce its flowering. The results of qRT-PCR showed that the relative expression of CO gene in different tissues and different treatment periods of Ch. indicum was significantly different. In this paper,we studied the effect of short-day treatment on the expression of key genes in the flowering cycle of Ch. indicum,providing a basis for photoperiod regulation and harvesting period of Ch.indicum.

[Identification of Chrysanthemum indicum and its adulterants based on ITS2 barcode].

DNA barcode technology was used to establish a rapid identification method of Chrysanthemum indicum based on ITS2 sequences. The total DNA was extracted from 22 collected samples,and the ITS2 sequence was amplified by PCR and sequenced,and the information of ITS2 sequence was obtained. Another 14 items of the same family or the same genus were downloaded from Gen Bank.We aligned all 36 sequences,calculated the intraspecific and interspecific distances,and constructed Neighbor Joining( NJ) phylogenetic tree,using MEGA 7. 0. The difference of the secondary structure between the ITS2 sequences was compared. The results showed that the genetic distance of Ch. indicum and Ch. morifolium was overlapped,but the maximum intraspecific distance was far less than the minimum interspecific distance between and among Ch. indicum and other species,with an obvious barcoding gap. The NJ tree showed that Ch. indicum and Ch. morifolium shared a clade,and most of Ch. morifolium with some Ch. indicum were shared a subclade,while Inula lineariifolia,Sinosenecio oldhamianus and Senecio scandens belonged to one clade separately. ITS2 secondary structures for I. lineariifolia,S. oldhamianus and S. scandens were significantly different enough to identify completely but Ch. indicum and Ch. morifolium shared two secondary structures of A and B. It was proved that Ch. indicum was one of the evolutionary sources of Ch.morifolium. Therefore ITS2 sequence as DNA barcode can identify Ch. indicum and its adulterants accurately and quickly. The study provides an important basis for Ch. indicum for the identification of germplasm resources and the safety of clinical medication.

A meta-analysis of randomized controlled trials: Efficacy of selenium treatment for sepsis.

BACKGROUND: To understand the clinical outcomes of selenium therapy in patients with sepsis syndrome, we conducted a meta-analysis of randomized controlled trials (RCT). METHODS: A total of 13 RCTs comparing selenium and placebo for patients with sepsis were reviewed systematically. RESULTS: However, we could not detect the association of selenium treatment with a decreased mortality at different time course (relative risk [RR] [95% confidence interval, CI]: 0.94 [0.82-1.06] at day 28; 0.73 [0.36-1.47] at day 90; 1.16 [0.78-1.71] at 6 months; respectively). Selenium supplementation did not show favorable efficacy in the incidence of renal failure, secondary infection or duration of mechanical ventilation (RR [95% CI]: 0.65 [0.41-1.03]; 0.96 [0.87-1.06]; standard mean difference [SMD] [95% CI]: 0.17 [-0.30-0.63]; respectively). Interestingly, we found that selenium therapy was benefit for sepsis patients with reduced duration of vasopressor therapy, staying time in intensive care unit and hospital, and incidence of ventilator-associated pneumonia (SMD [95% CI]: -0.75 [-1.37 to -0.13]; -0.15 [CI: -0.25 to -0.04]; -1.22 [-2.44 to -0.01]; RR [95% CI]: 0.61 [0.42-0.89]; respectively). CONCLUSION: Based on our findings, intravenous selenium supplementation could not be suggested for routine use.

Hierarchical virtual screening of the dual MMP-2/HDAC-6 inhibitors from natural products based on pharmacophore models and molecular docking.

The dual-target inhibitors tend to improve the response rate in treating tumors, comparing with the single-target inhibitors. Matrix metalloproteinase-2 (MMP-2) and histone deacetylase-6 (HDAC-6) are attractive targets for cancer therapy. In this study, the hierarchical virtual screening of dual MMP-2/HDAC-6 inhibitors from natural products is investigated. The pharmacophore model of MMP-2 inhibitors is built based on ligands, but the pharmacophore model of HDAC-6 inhibitors is built based on the experimental crystal structures of multiple receptor-ligand complexes. The reliability of these two pharmacophore models is validated subsequently. The hierarchical virtual screening, combining these two different pharmacophore models of MMP-2 and HDAC-6 inhibitors with molecular docking, is carried out to identify the dual MMP-2/HDAC-6 inhibitors from a database of natural products. The four potential dual MMP-2/HDAC-6 inhibitors of natural products, STOCK1 N-46177, STOCK1 N-52245, STOCK1 N-55477, and STOCK1 N-69706, are found. The studies of binding modes show that the screened four natural products can simultaneously well bind with the MMP-2 and HDAC-6 active sites by different kinds of interactions, to inhibit the MMP-2 and HDAC-6 activities. In addition, the ADMET properties of screened four natural products are assessed. These found dual MMP-2/HDAC-6 inhibitors of natural products could serve as the lead compounds for designing the new dual MMP-2/HDAC-6 inhibitors having higher biological activities by carrying out structural modifications and optimizations in the future studies.

[Prokaryotic expression and in vitro enzyme activity analysis of flavonol synthase in Chrysanthemum morifolium cv. 'Hangju'].

We cloned flavonol synthase gene (named as CmFLS) by RACE from Chrysanthemum morifolium cv. 'Hangju' based on transcriptome database. Sequencing results showed that 1 235 bp sequence was acquired with the largest open reading frame (ORF) of 1 008 bp, which encoded 335 amino acids. The predicted CmFLS encoded protein had an isoelectric point (pI) of 5.41. The phylogenetic tree analysis indicated that CmFLS was highly homologous to other FLSs, which identified from the species of Compositae. The recombinant fusion protein, with a molecular mass of 43 kDa, was successfully expressed by prokaryotic expression system. Meanwhile, Ni-NTA resin was used to purify the recombinant fusion protein, and the Ni-Native Buffer containing 250 mmol·L⁻¹ imidazole was most favorable for elution. The purified recombinant fusion protein was subjected to in vitro catalytic reaction, and then the products were extracted and analyzed by HPLC. The results showed that the recombinant fusion protein CmFLS was able to catalyze the production of quercetin by dihydroquercetin under specific buffer and reaction conditions, which indicated that the functional protein encoded by CmFLS had dioxygenase activity in the biosynthetic pathway of flavonoids biosynthesis in Ch. morifolium cv. 'Hangju'. The above results laid the foundation for further studying on CmFLS, and provided new ideas for the regulation of flavonoids metabolism from the molecular level and the catalytic synthesis of flavonols in vitro.

[Comparative study on content of heavy metals in Chrysanthemum indicum and soil in different areas].

ICP-MS was used to determine the contents of five heavy metals such as lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As) and copper (Cu) in Chrysanthemum indicum and soil samples. Pearson correlation and path analysis were used to analyze the effects of latitude and longitude and altitude on the content of heavy metal elements in Ch. indicum. To explore the relationship between geographical location of heavy metal content in Ch. indicum and the content of heavy metal elements in soil. The results showed that the Ch. indicum had high enrichment of Cd and had a synergistic effect on the absorption of five heavy metal elements. Elevation directly affected the accumulation of Pb and Cd in Ch. indicum and was a positive effect. The direct positive effect of latitude acts on the accumulation of Hg and Cu in Ch. indicum. The effect of longitude on the Cd content was the negative effect of longitude. The geographical location had different effects on the accumulation of heavy metal elements in Ch. indicum. There was a certain interaction between direct and indirect effects. Ch. indicum had different absorption and enrichment characteristics for different heavy metal species. When controlling the heavy metal content and medicinal material quality of Ch. indicum, we must fully consider the influence of geographical location on the quality of medicinal materials, select suitable geographic regions to carry out acquisitions, and choose a good ecological environment. Regional establishment of Chinese herbal medicine planting bases, or adopting certain agricultural measures to reduce the absorption of heavy metal elements in Ch. indicum herbs, while conducting research on chemical composition, strengthening the research on the effective forms of heavy metals, and paying attention to the safety of medicinal herbs.

[Cloning and expression analysis of F3'H and quantification of downstream products in Chrysanthemum morifolium under flooding stress].

To investigate the effects of the expression of flavonoid 3' hydroxylase gene (F3'H) and active ingredients in Chrysanthemum morifolium under flooding stress, we cloned F3'H from Hangju (temporarily named CmF3'H) and conducted bioinformatics analysis. During the flower bud differentiation stage, we flooded the Ch. morifolium and then used the Real-time PCR to detect the relative expression of CmF3'H; Finally, active ingredients of the inflorescence were measured by HPLC.The sequencing results showed that 1 562 bp sequence was acquired with the largest open reading frame of 1 527 bp, which encoded 508 amino acids. The phylogenetic tree found that CmF3'H was highly homologous to other species of Compositae. Real-time PCR results showed that CmF3'H had a significant response to flooding stress and had the highest expression level after flooding for 24 h, which was about 9 times as that of the control group. The results of HPLC showed that luteolin and luteoloside, the downstream products catalyzed by the F3'H, were significantly higher than those in the control group. It was also found that the contents of chlorogenic acid and 3,5-O-di-caffeoylquinic acid were also significantly higher than those of the control group. Therefore, Ch. morifolium regulates the synthesis of downstream products by regulating the expression of CmF3'H in the flavonoid synthesis pathway under flooding stress, thereby responding to flooding stress. The flooding stress during flower bud differentiation can significantly enhance the accumulation of active ingredients.

[Clinical efficacy of integrated traditional Chinese and Western medicine for castration-resistant prostate cancer].

OBJECTIVE: To investigate the clinical effects of integrated traditional Chinese and Western medicine in the treatment of castration-resistant prostate cancer (CRPC). METHODS: A total of 54 CRPC patients were randomly divided into a control and a trial group, all treated by endocrine therapy (oral Bicalutamide at 50 mg per d plus subcutaneous injection of Goserelin at 3.6 mg once every 4 wk) and chemotherapy (intravenous injection of Docetaxel at 75 mg/m2 once every 3 wk plus oral Prednisone at 5 mg bid), while the latter group by Fuyang Huayu Prescription (a Traditional Chinese Medicine ï¼»TCMï¼½ prescription for tonifying yang and dispersing blood stasis) in addition, for a course of 24 weeks. Comparisons were made between the two groups of patients in the level of serum prostate-specific antigen (PSA), Karnofsky physical condition scores, function assessment of cancer therapy-prostate (FACT-P) scores, and TCM symptoms scores before and after 12 or 24 weeks of treatment. RESULTS: Compared with the baseline, the serum PSA level was significantly decreased after 12 weeks of treatment both in the control (ï¼»25.9 ± 39.3ï¼½ vs ï¼»20.0 ± 21.1ï¼½ µg/L, P <0.05) and in the trial group (ï¼»22.1 ± 33.9ï¼½ vs ï¼»17.9 ± 19.1ï¼½ µg/L, P <0.05), with no statistically significant differences between the two groups (P >0.05). At 24 weeks, however, the PSA levels in the control and trial groups were slightly increased to (23.1 ± 28.4) and (19.6 ± 23.5) µg/L, respectively, with no statistically significant differences in between (P >0.05). Karnofsky, FACT-P and TCM symptoms scores were all markedly improved in the trial group after 12 weeks of treatment (P <0.05) and remained stable at 24 weeks, but not in the control group either at 12 or at 24 weeks (P >0.05). CONCLUSIONS: TCM Fuyang Huayu Prescription combined with endocrine therapy and chemotherapy is effective for CRPC.

Cloning and functional analysis of a novel ascorbate peroxidase (APX) gene from Anthurium andraeanum.

An 888-bp full-length ascorbate peroxidase (APX) complementary DNA (cDNA) gene was cloned from Anthurium andraeanum, and designated as AnAPX. It contains a 110-bp 5'-noncoding region, a 28-bp 3'-noncoding region, and a 750-bp open reading frame (ORF). This protein is hydrophilic with an aliphatic index of 81.64 and its structure consisting of α-helixes, ß-turns, and random coils. The AnAPX protein showed 93%, 87%, 87%, 87%, and 86% similarities to the APX homologs from Zantedeschia aethiopica, Vitis pseudoreticulata, Gossypium hirsutum, Elaeis guineensis, and Zea mays, respectively. AnAPX gene transcript was measured non-significantly in roots, stems, leaves, spathes, and spadices by real-time polymerase chain reaction (RT-PCR) analysis. Interestingly, this gene expression was remarkably up-regulated in response to a cold stress under 6 °C, implying that AnAPX might play an important role in A. andraeanum tolerance to cold stress. To confirm this function we overexpressed AnAPX in tobacco plants by transformation with an AnAPX expression construct driven by CaMV 35S promoter. The transformed tobacco seedlings under 4 °C showed less electrolyte leakage (EL) and malondialdehyde (MDA) content than the control. The content of MDA was correlated with chilling tolerance in these transgenic plants. These results show that AnAPX can prevent the chilling challenged plant from cell membrane damage and ultimately enhance the plant cold tolerance.

[Effect of coicis semen oil on renal interstitial fibrosis in rats with unilateral urethral obstruction].

OBJECTIVE: To study the effect and mechanism of Coicis Semen oil (Kanglaite injection, KLT) on renal interstitial fibrosis induced by unilateral ureteral obstruction (UUO). METHOD: Fifty-four male SD rats were randomly divided into 3 groups, 6 in each group, the sham operated group, the model group, and the KLT group. Renal interstitial fibrosis model was established in rats by UUO. After administration of KLT (15 mL x kg(-1) x d(-1)) for 3, 7 and 14 days, the dynamic histological changes of renal interstitial tissues were observed and renal damage including tubular impairment and interstitial fibrosis were quantified on HE and Masson stained tissue sections. The expression of alpha-smooth muscle actin (alpha-SMA) and transforming growth factor-beta1 (TGF-beta1) were measured by immunohistochemistry staining sections. The protein expression of p-Smad2 and Smad7 were detected by Western blot respectively. RESULT: The degree of tubular damage in KLT group was much lower than that in UUO group (P < 0.05). The expression of alpha-SMA and TGF-beta1 was decreased in both UUO group and KLT group, while it was significantly lower in KLT group at every time point. The protein expression of p-Smad2 was obviously decreased while the protein expressions of Smad7 was obviously increased in KLT group, compared with the UUO group (P < 0.05). CONCLUSION: Coicis Semen oil could attenuate the tubulo-interstitial fibrosis, probable by intervening the TGF-beta/Smads signal transduction pathway of UUO rats.

Anti-tumour activity of longikaurin A (LK-A), a novel natural diterpenoid, in nasopharyngeal carcinoma.

BACKGROUND: Longikaurin A is a natural ent-kaurene diterpenoid isolated from Isodon genus. The ent-kaurene diterpenoids isolated from medicinal plants have been shown to have anti-disease effects. The present study was designed to examine the anti-tumour effects of longikaurin A (LK-A) in nasopharyngeal carcinoma in vitro and in vivo. METHODS: Apoptosis and cell cycle arrest were determined by flow cytometry analysis of the cells treated with Longikaurin A. The proteins of apoptosis signaling pathway were detected by western blotting analysis. Finally, we examined whether LK-A exhibits anti-tumour activity in xenograft models. RESULTS: Longikaurin A inhibited the cell growth by inducing apoptosis and cell cycle arrest. At low concentrations, longikaurin A induced S phase arrest and at higher concentrations, longikaurin A induced caspase-dependent apoptosis by regulating apoptotic molecules. Finally, longikaurin A significantly inhibited the tumour growth of CNE2 xenografts in vivo and showed no obvious effect on the body weights of the mice. CONCLUSION: Our results suggest that Longikaurin A exhibited anti-tumour activity in nasopharyngeal carcinoma in vitro and in vivo.

Logistic regression analysis of damp-heat and cold-damp impeding syndrome of rheumatoid arthritis: a perspective in Chinese medicine.

OBJECTIVE: To investigate a method for quantitative differential diagnosis of damp-heat and cold-damp impeding syndrome of rheumatoid arthritis (RA) in Chinese medicine (CM). METHODS: Laboratory parameters were collected from 306 patients with RA. The clinical symptoms and laboratory parameters were compared between patients with these two syndromes (158 with RA of damp-heat impeding syndrome, and 148 with RA of cold-damp impeding syndrome), and a regression equation was established to facilitate discrimination of the two RA syndromes. RESULTS: There were significant differences in disease activity score in 28 joints [DAS28 (4)], erythrocyte sedimentation rate (ESR), white blood cell count (WBC), C-reactive protein (CRP), platelet count (PLT), albumin (ALB) and globulin (GLB) between the two syndrome of RA (P<0.05). Logistic regression analysis showed that the parameters ESR, WBC, CRP, joint pyrexia, joint cold, thirst, sweating, aversion to wind and cold, and cold extremities were statistically useful to discriminate damp-heat from cold-damp impeding syndrome. The regression equation was as follows: P=1/{1+exp[-(3.0-0.021X (1)-0.196X (2)-0.163X (3)-1.559X (4)+1.504X (5)-0.927X (6)-1.039X (7)+1.070X (8)+1.330X (9))]}. The independent variables X (1)-X (9) were ESR, WBC, CRP, hot joint, cold joint, thirst, sweating, aversion to wind and cold, and cold limbs. A P value > 0.5 signified cold-damp impeding syndrome, and a P value < 0.5 signified damp-heat impeding syndrome. The accuracy was 90.2%. CONCLUSION: The regression equation may be useful for discriminating damp-heat from cold-damp impeding syndrome of RA.

Generalized propensity score for estimating the average treatment effect of multiple treatments.

The propensity score method is widely used in clinical studies to estimate the effect of a treatment with two levels on patient's outcomes. However, due to the complexity of many diseases, an effective treatment often involves multiple components. For example, in the practice of Traditional Chinese Medicine (TCM), an effective treatment may include multiple components, e.g. Chinese herbs, acupuncture, and massage therapy. In clinical trials involving TCM, patients could be randomly assigned to either the treatment or control group, but they or their doctors may make different choices about which treatment component to use. As a result, treatment components are not randomly assigned. Rosenbaum and Rubin proposed the propensity score method for binary treatments, and Imbens extended their work to multiple treatments. These authors defined the generalized propensity score as the conditional probability of receiving a particular level of the treatment given the pre-treatment variables. In the present work, we adopted this approach and developed a statistical methodology based on the generalized propensity score in order to estimate treatment effects in the case of multiple treatments. Two methods were discussed and compared: propensity score regression adjustment and propensity score weighting. We used these methods to assess the relative effectiveness of individual treatments in the multiple-treatment IMPACT clinical trial. The results reveal that both methods perform well when the sample size is moderate or large.

Gamma knife-treated hepatoma: case of obstructive jaundice and management.

Gamma knife therapy is becoming more frequently applied in solid tumor treatment. This article reports a unique case of severe obstructive jaundice arising as a complication of treatment of hepatoma at the hepatic hilum using a gamma knife.While planning an intervention, some images seem to promise success but actually lead to failure. Radiation damage to specific organs is difficult to predict because of several variables. Radiation-induced fibrosis and necrosis are the most common long-term adverse effects of radiotherapy; they are usually considered irreversible and result in induration and firmness of the tissue.To minimize radiation fibrosis, accurate patient positioning and tumor relocalization are essential for gamma knife use in the liver and other extracranial sites. Even when practiced frequently, any intervention must be delivered with caution if the liver has been treated with radiation. Otherwise, even with much experience, the unwary doctor can be trapped by deceptive images.