Recent estimates of global cancer incidence and survival were used to update previous figures of limited duration prevalence to the year 2008. The number of patients with cancer diagnosed between ...2004 and 2008 who were still alive at the end of 2008 in the adult population is described by world region, country and the human development index. The 5‐year global cancer prevalence is estimated to be 28.8 million in 2008. Close to half of the prevalence burden is in areas of very high human development that comprise only one‐sixth of the world's population. Breast cancer continues to be the most prevalent cancer in the vast majority of countries globally; cervix cancer is the most prevalent cancer in much of Sub‐Saharan Africa and Southern Asia and prostate cancer dominates in North America, Oceania and Northern and Western Europe. Stomach cancer is the most prevalent cancer in Eastern Asia (including China); oral cancer ranks as the most prevalent cancer in Indian men and Kaposi sarcoma has the highest 5‐year prevalence among men in 11 countries in Sub‐Saharan Africa. The methods used to estimate point prevalence appears to give reasonable results at the global level. The figures highlight the need for long‐term care targeted at managing patients with certain very frequently diagnosed cancer forms. To be of greater relevance to cancer planning, the estimation of other time‐based measures of global prevalence is warranted.
Herein, we described the first synthesis of the pentasaccharide and decasaccharide of the A. baumannii ATCC 17961 O‐antigen for developing a synthetic carbohydrate‐based vaccine against A. baumannii ...infection. The efficient synthesis of the rare sugar 2,3‐diacetamido‐glucuronate was achieved using our recently introduced organocatalytic glycosylation method. We found, for the first time, that long‐range levulinoyl group participation via a hydrogen bond can result in a significantly improved β‐selectivity in glycosylations. This solves the stereoselectivity problem of highly branched galactose acceptors. The proposed mechanism was supported by control experiments and DFT computations. Benefiting from the long‐range levulinoyl group participation strategy, the pentasaccharide donor and acceptor were obtained via an efficient 2+1+2 one‐pot glycosylation method and were used for the target decasaccharide synthesis.
We described the first synthesis of the pentasaccharide and decasaccharide of the A. baumannii ATCC 17961 O‐antigen for the development of a synthetic carbohydrate‐based vaccine against A. baumannii infection. We found that long‐range levulinoyl group assistance via hydrogen bonding strikingly improves the β‐selectivity of the glycosylation. The proposed mechanism was investigated experimentally and via DFT calculations.
There is increasing evidence that the existence of systemic inflammation response is correlated with poor prognosis in several solid tumors. The aim of this retrospective study was to investigate the ...association between systemic immune-inflammation index (SII) and therapy response and overall survival in patients with stage III non-small cell lung cancer (NSCLC). The prognostic values of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and prognostic nutritional index (PNI) were also evaluated.
In total, 332 patients with new diagnosis of stage III NSCLC were included in this retrospective analysis. SII was defined as platelet counts × neutrophil counts/lymphocyte counts. Receiver operating characteristic (ROC) curve was used to evaluate the optimal cut-off value for SII, NLR, PLR and PNI. Univariate and multivariate survival analysis were performed to identify the factors correlated with overall survival.
Applying cut-offs of ≥ 660 (SII), ≥ 3.57 (NLR), ≥ 147 (PLR), ≤ 52.95 (PNI), SII ≥ 660 was significantly correlated with worse ECOG PS (< 0.001), higher T stage (< 0.001), advanced clinical stage (p = 0.019), and lower response rate (p = 0.018). In univariate analysis, SII ≥ 660, NLR ≥ 3.57, PLR ≥ 147, and PNI ≤ 52.95 were significantly associated with worse overall survival (p
< 0.001). Patients with SII ≥ 660 had a median overall survival of 10 months, and patients with SII < 660 showed a median overall survival of 30 months. In multivariate analysis only ECOG PS (HR, 1.744; 95% CI 1.158-2.626; p = 0.008), T stage (HR, 1.332; 95% CI 1.032-1.718; p = 0.028), N stage (HR, 1.848; 95% CI 1.113-3.068; p = 0.018), SII (HR, 2.105; 95% CI 1.481-2.741; p < 0.001) and NLR ≥ 3.57 (HR, 1.934; 95% CI 1.448-2.585; p < 0.001) were independently correlated with overall survival.
This study demonstrates that the SII is an independent prognostic indicator of poor outcomes for patients with stage III NSCLC and is superior to other inflammation-based factors in terms of prognostic ability.
The aim of this study was to investigate the differences in main characteristics, reporting and methodological quality between prospectively registered and nonregistered systematic reviews.
PubMed ...was searched to identify systematic reviews of randomized controlled trials published in 2015 in English. After title and abstract screening, potentially relevant reviews were divided into three groups: registered non-Cochrane reviews, Cochrane reviews, and nonregistered reviews. For each group, random number tables were generated in Microsoft Excel, and the first 50 eligible studies from each group were randomly selected. Data of interest from systematic reviews were extracted. Regression analyses were conducted to explore the association between total Revised Assessment of Multiple Systematic Review (R-AMSTAR) or Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) scores and the selected characteristics of systematic reviews.
The conducting and reporting of literature search in registered reviews were superior to nonregistered reviews. Differences in 9 of the 11 R-AMSTAR items were statistically significant between registered and nonregistered reviews. The total R-AMSTAR score of registered reviews was higher than nonregistered reviews mean difference (MD) = 4.82, 95% confidence interval (CI): 3.70, 5.94. Sensitivity analysis by excluding the registration-related item presented similar result (MD = 4.34, 95% CI: 3.28, 5.40). Total PRISMA scores of registered reviews were significantly higher than nonregistered reviews (all reviews: MD = 1.47, 95% CI: 0.64-2.30; non-Cochrane reviews: MD = 1.49, 95% CI: 0.56-2.42). However, the difference in the total PRISMA score was no longer statistically significant after excluding the item related to registration (item 5). Regression analyses showed similar results.
Prospective registration may at least indirectly improve the overall methodological quality of systematic reviews, although its impact on the overall reporting quality was not significant.
Compound Kushen Injection (CKI) is a Traditional Chinese Medicine (TCM) preparation that has been clinically used in China to treat various types of solid tumours. Although several studies have ...revealed that CKI can inhibit the proliferation of hepatocellular carcinoma (HCC) cell lines, the active compounds, potential targets and pathways involved in these effects have not been systematically investigated. Here, we proposed a novel idea of "main active compound-based network pharmacology" to explore the anti-cancer mechanism of CKI. Our results showed that CKI significantly suppressed the proliferation and migration of SMMC-7721 cells. Four main active compounds of CKI (matrine, oxymatrine, sophoridine and N-methylcytisine) were confirmed by the integration of ultra-performance liquid chromatography/mass spectrometry (UPLC-MS) with cell proliferation assays. The potential targets and pathways involved in the anti-HCC effects of CKI were predicted by a network pharmacology approach, and some of the crucial proteins and pathways were further validated by western blotting and metabolomics approaches. Our results indicated that CKI exerted anti-HCC effects via the key targets MMP2, MYC, CASP3, and REG1A and the key pathways of glycometabolism and amino acid metabolism. These results provide insights into the mechanism of CKI by combining quantitative analysis of components, network pharmacology and experimental validation.
A synthetic strategy based on biogenetic building blocks for the collective and divergent biomimetic synthesis of cleistoperlones A−F, a cinnamoylphloroglucinol collection discovered from ...Cleistocalyx operculatus, has been developed. These syntheses proceeded successfully in only six to seven steps starting from commercially available 1,3,5‐benzenetriol and involving oxidative activation of stable biogenetic building blocks as a crucial step. Key features of the syntheses include a unique Michael addition/ketalization/1,6‐addition/enol‐keto tautomerism cascade reaction for the construction of the dihydropyrano3,2‐dxanthene tetracyclic core of cleistoperlones A and B, and a rare inverse‐electron‐demand hetero‐Diels–Alder cycloaddition for the establishment of benzopyran ring in cleistoperlones D−F. Moreover, cleistoperlone A exhibited significant antiviral activity against acyclovir‐resistant strains of herpes simplex virus type 1 (HSV‐1/Blue and HSV‐1/153).
Four novel cinnamoylphloroglucinol dimers were discovered from C. operculatus. Biomimetic syntheses of these and two known dimers were developed through a strategy in which the activation of stable biogenetic building blocks was a crucial step and key features included a unique cascade reaction and a rare inverse‐electron‐demand Diels–Alder reaction. One of the dimers showed activity against herpes simplex virus type 1 through a new mode of action.
There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-L1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular ...carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval CI, 8.4-11.0) versus 8.0 months (95% CI, 6.6-9.5) (adjusted hazard ratio HR, 0.70, P = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 16.1-27.3 vs. 15.7 months 13.0-20.2; adjusted HR, 0.63, P = 0.001; ORR, 60.1% vs. 32.0%; P < 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile.
A generalised spatial modulation (SM) scheme with multiple active transmit antennas, named as multiple active-spatial modulation (MA-SM), is proposed in this paper. By allowing multiple transmitting ...antennas in the SM system to transmit different symbols at the same time instant, MA-SM takes advantages of the low complexity of SM and high multiplexing gain of Vertical-Bell Lab Layered Space-Time (V-BLAST) system. In the MA-SM system, the transmitted symbols are mapped into a high dimensional constellation space including the spatial dimension. The general principle for designing the efficient MA-SM for arbitrary number of transmit antennas and modulation scheme is presented. Moreover, a near-optimal detection scheme with low complexity for MA-SM is also proposed and analyzed. A closed form bound for the bit error probability (BEP) of the proposed detection scheme is also derived in this paper. Numerical results with the comparison among the existing multiple-input multiple-output (MIMO) systems such as space time block code (STBC) and V-BLAST demonstrate the efficiency of MA-SM.
With the picolinyl (Pic) group as a C‐1 located directing group and N3 as versatile precursor for C5‐NH2, a novel 1‐Pic‐5‐N3 thiosialyl donor was designed and synthesized, based on which a new ...sialylation protocol was established. In comparison to conventional sialylation methods, the new protocol exhibited obvious advantages, including excellent α‐stereoselectivity in the absence of a solvent effect, broad substrate scope encompassing the challenging sialyl 8‐ and 9‐hydroxy groups of sialic acid acceptors, flexibility in sialoside derivative synthesis, high temperature tolerance and easy scalability. In particular, the applicability to the synthesis of complex and bioactive N‐glycan antennae when combined with the MPEP glycosylation protocol via the “latent‐active” strategy has been shown. Mechanistically, the excellent α‐stereoselectivity of the novel sialylation protocol could be attributed to the dramatic electron‐withdrawing effect of the protonated Pic groups, which was supported by control reactions and DFT calculations.
Sugar building blocks: With 1‐Picolinyl‐5‐azido thiosialoside as donor, a robust sialylation was developed that is applicable to the flexible synthesis of complex sialosides and shows broad substrate scope, good to excellent chemical yield, excellent α‐stereoselectivity, high temperature tolerance, and easy scalability.
Here we report a new type of chiral all‐carbon tetrasubstituted VQMs generated via chiral phosphoric acids catalyzed nucleophilic addition of 2‐alkynylnaphthols to o‐quinone methides or imines, which ...can be captured intramolecularly as a result of cycloaddition reaction. A new class of naphthyl‐2H‐chromenes bearing axially and centrally chiral elements and axially chiral quinone‐naphthols were prepared efficiently with good to excellent yields, diastereoselectivities and enantioselectivities. Noteworthy, the enantioselective cycloaddition of alkynylnaphthols with o‐quinone methides proceeded via a 2+2 cycloaddition, followed by a retro‐4π‐electrocyclization and a 6π re‐cyclization. While the cycloaddition of alkynylnaphthols with imines proceeded via a sequential 2+4 cycloaddition and an auto oxidation reaction. Moreover, the obtained axially chiral naphthols can be converted into valuable phosphine ligands and other functional molecules.
A chiral all‐carbon tetrasubstituted VQM is generated by chiral phosphoric acid catalyzed nucleophilic addition of 2‐alkynylnaphthols to o‐quinone methides or imines, and it can be captured intramolecularly by a cycloaddition reaction. A wide range of naphthyl‐2H‐chromenes bearing axially and centrally chiral elements and axially chiral quinone‐naphthols were prepared efficiently with excellent enantioselectivities.
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