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Background: Hepatocellular carcinoma (HCC) is one of the most common cancers in the world and is particularly prevalent in China. China is also a hyperendemic area for hepatitis B virus (HBV) infection. Although a strong association between HBV infection and HCC has been established previously, the role of hepatitis C virus (HCV) infection and the interaction between HBV and HCV in the development of HCC has not been adequately explored. The major objective of this study is to determine the relationship between HBV or HCV infection and HCC by use of case-control study in Henan, China.Method: In all, 152 HCC patients and 115 control patients were collected from four hospitals in Henan, China between January 1994 and October 1995. The demographic characteristics of the two groups were comparable. In further analysis, a 1:1 pair-matched case-control study was performed. Of 152 HCC patients, 113 were randomly selected to be pair-matched by sex and age (+/-5 years) to controls with non-hepatic disease. All the cases and controls were interviewed during hospitalization by two specially trained interviewers using a standard questionnaire. All sera were tested for HBV and HCV markers. Odds ratios (OR) and 95% CI for HCC risk factors were calculated by logistic regression model controlling for possible confounding factors such as sex and age. The multivariate analysis was done on the basis of the univariate analysis.Results: The results of this study indicated that the prevalence of hepatitis B surface antigen (HBsAg) and antibody to HCV (anti-HCV) were much higher in HCC patients (63.2% and 11.2% respectively) than in the control patients (5.2%, 3.5%). The difference between two groups was significant (P < 0.05). Risk factor analysis revealed that both HBV and HCV infection were important factors for HCC in Henan, China and HBV appeared to have a key role in the development of HCC. Odds ratios of HBsAg and HBV infection were 28.82 (95% CI: 11.18-78.78) and 31.22 (95% CI: 13.86-72.15), respectively. Moreover, the risk of developing HCC increased significantly and showed an additive effect when both viral markers of HBV and HCV infection were considered (OR = 42.85). Results from the 1:1 pair-matched case-control study also showed that HBV infection was an important risk factor for HCC, which was consistent with the results from the group-matched case-control study.Conclusion: This is the first reported case-control study of HCC in Henan, China. This study provides further evidence that chronic HBV infection is strongly associated with the development of HCC among this population. Our results have demonstrated that HCV and HBV infection are independent and probably additive risk factors for HCC. [ABSTRACT FROM AUTHOR]

Phytochemical investigation of the 70% ethanol extract of Isodon henryi Kudô afforded fifteen ent-kaurane diterpenoids, including nine previously undescribed compounds, named isohenolides C-K (1-9). Compounds 1-6 featured an unusual 6,7;8,15-diseco-7,20-olide ent-kaurane diterpenoid scaffold, in which 1 also possessed an 11,15-lactone ring while 2-6 all contained a free α-methylene-γ-carboxylic acid. Compound 6 was also a rare 6,8-cyclo-7,20-olide ent-kauranoid. Their structures were elucidated primarily by HRESIMS, 1D and 2D NMR spectroscopy, electronic circular dichroism and X-ray diffraction (Cu Kα) methods. Additionally, most compounds were also screened for anti-inflammatory actions against lipopolysaccharide-induced RAW 264.7 cells, and compounds 9 and 13 exhibited stronger nitric oxide inhibition, with IC 50 values of 15.99 ± 0.75 and 18.19 ± 0.42 μM, respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study comprehensively analyzes the chemical constituents of Zanthoxylum avicennae leaves and branches using UPLC-Q-Orbitrap HRMS. A total of 64 components were identified, with fragmentation patterns summarised for key compounds. Notably, 51 of these components were newly discovered in this plant. The predominant compound classes were alkaloids (31.25%) and flavonoids (25.00%). Visualisation results revealed significant differences in chemical composition between leaves and branches, with an overlap rate of only 26.60%. Leaves were rich in flavonoids such as neohesperidin, while branches contained more alkaloids, such as schinifoline. Antioxidant activity, assessed using DPPH and ABTS assays, indicated that methanol extracts had notable antioxidant potential. The leaf extract demonstrated superior antioxidant activity (ABTS: IC 50 = 0.098 ± 0.006 mg/mL; DPPH: IC 50 = 3.624 ± 0.070 mg/mL) compared to the branch extract (ABTS: IC 50 = 0.303 ± 0.004 mg/mL; DPPH: IC 50 = 3.265 ± 0.075 mg/mL), likely due to differences in the content and variety of flavonoids.

A group of previously undescribed diarylheptanoids with mono/di-glucose substitution, diodiarylheptosides A-F (1-6), together with six known diarylheptanoids (7-12) were isolated from the rhizomes of Dioscorea nipponica. Their structures were established by comprehensive UV, IR, HR-ESI-MS and NMR analyses, and their absolute configurations were determined by a comparison of calculated and experimental ECD, some with optical rotations, after acid-hydrolysis. Moreover, bioassay results showed that compounds 3 and 11 exhibited stronger NO inhibitions on lipopolysaccharides-induced RAW 264.7 cells, with the IC 50 values of 14.91 ± 0.62 and 12.78 ± 1.12 μM., Competing Interests: Declaration of competing interest No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described is original research and don't publish previously., (Copyright © 2024. Published by Elsevier B.V.)

Corni fructus (CF) is always subjected to wine processing before prescription in clinic, for an enhancing effect of nourishing liver and kidney. While, the underlying mechanism for this processing on CF remains obscure. In this study, a sensitive ultra-high-performance liquid chromatography mass spectrometry (UPLC-MS/MS) method combined multi-dimensional analyses was established to monitor chemical characterizations of raw and wine-processed CF (WCF) and hence reveal the effects and underlying mechanism of wine processing on CF. As indicated, a total of 216 compounds were tentatively identified, including 98 structurally complex and variable home/hetero-polymers, that were composed of iridoid glucosides, gallic acids, caffeic acid and/or 5-HMF. Interestingly, 53 of these compounds probably characterized potential novel, including 35 iridoid glucosides or their dimers, 9 iridoid glucoside-gallic acid dimers, 7 gallic acids derivatives and 2 gallic acid-caffeic acid dimers, which provides ideas for natural product researchers. Meanwhile, the multi-dimensional analyses including principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and linear regression analysis were used to explore the differences between CF and WCF. The results showed that 23 compounds as chemical markers greatly contributing to the distinction were screened out, and 3 of which (7α/β-O-ethyl-morroniside, gallic acid and 5-HMF) in WCF indicated an increasing trend in intensities in relative to those in CF. Additionally, linear regression analysis showed that in WCF 53 compounds exhibited an increasing in intensities, while 132 ones did a decreasing trend, compared with those in CF. As our investigation demonstrated, acetal reaction of morroniside, ester hydrolysis in different organic acid derivatives as well as glycoside bond cleavage during wine processing probably resulted in the distinctions. The findings of this study provide a further understanding of the effect and mechanism of wine processing on CF., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Ethnopharmacological Relevance: Atherosclerosis (AS), a lipid-induced inflammatory condition of the arteries, is a primary contributor to atherosclerotic cardiovascular diseases including stroke. Arctium lappa L. leaf (ALL), an edible and medicinal herb in China, has been documented and commonly used for treating stroke since the ancient times. However, the elucidations on its anti-AS effects and molecular mechanism remain insufficient., Aim of the Study: To investigate the AS-ameliorating effects and the underlying mechanism of action of an ethanolic extract of leaves of Arctium lappa L. (ALLE)., Materials and Methods: ALLE was reflux extracted using with 70% ethanol. An HPLC method was established to monitor the quality of ALLE. High fat diet (HFD) and vitamin D3-induced experimental AS in rats were used to determine the in vivo effects; and oxidized low-density lipoprotein-induced RAW264.7 macrophage foam cells were used for in vitro assays. Simvatatin was used as positive control. Biochemical assays were implemented to ascertain the secretions of lipids and pro-inflammatory mediators. Haematoxylin-eosin (H&E) and Oil red O stains were employed to assess histopathological alterations and lipid accumulation conditions, respectively. CCK-8 assays were used to measure cytotoxicity. Immunoblotting assay was conducted to measure protein levels., Results: ALLE treatment significantly ameliorated lipid deposition and histological abnormalities of aortas and livers in AS rats; improved the imbalances of serum lipids including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C); notably attenuated serum concentrations of inflammation-associated cytokines/molecules including TNF-α, IL-6, IL-1β, VCAM-1, ICAM-1and MMP-9. Mechanistic studies demonstrated that ALLE suppressed the phosphorylation/activation of PI3K, Akt and NF-κB in AS rat aortas and in cultured foam cells. Additionally, the PI3K agonist 740Y-P notably reversed the in vitro inhibitory effects of ALLE on lipid deposition, productions of TC, TNF-α and IL-6, and protein levels of molecules of PI3K/Akt and NF-κB singnaling pathways., Conclusions: ALLE ameliorates HFD- and vitamin D3-induced experimental AS by modulating lipid metabolism and inflammatory responses, and underlying mechanisms involves inhibition of the PI3K/Akt and NF-κB singnaling pathways. The findings of this study provide scientific justifications for the traditional application of ALL in managing atherosclerotic diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Cardiovascular diseases are the leading cause of death among patients on hemodialysis, with approximately 40% of the cardiovascular deaths linked to acute coronary syndrome. We aimed to investigate the incidence and risk factors of acute coronary syndrome in patients undergoing hemodialysis., Methods: Patients undergoing hemodialysis were prospectively enrolled from January 2018. Data regarding hospitalization due to acute coronary syndrome were collected at 3-month intervals through December 31, 2021. Cox regression model was used to estimate the association between baseline factors and incident acute coronary syndrome during follow-up., Results: Patients' mean age was 66 years, 48% were men, and 16% had a history of coronary artery disease at enrolment. Over a median follow-up of 1,187 days, 85 patients were hospitalized due to acute coronary syndrome. Left main or triple vessel disease was identified in 67 patients. Risk factors associated with incident acute coronary syndrome included aging, male sex, smoking, low diastolic blood pressure, and baseline comorbidities, in addition to dialysis factors including low urea clearance, central venous catheter use, and history of dialysis access dysfunction. After multivariate analysis, age, diabetes, hyperlipidemia, smoking, and frequent interventions for vascular access remained significant risk factors., Conclusions: A high acute coronary syndrome incidence was observed in our cohort, with traditional risk factors playing a consistent role with that in the general population. A history of frequent dialysis access dysfunction was also associated with incident acute coronary syndrome., Competing Interests: All the authors declare no conflict of interest.

Six compounds were isolated from aqueous extract of wine-processed Corni Fructus through silica gel, ODS column chromatography, Sephadex LH-20 gel column chromatography, reverse phase preparative HPLC and other chromatographic separation technologies. Their structures were identified with multiple spectroscopical methods including HR-ESI-MS, UV, IR, NMR and ECD and so on. Their structures were established as pinoresinoside B(1), cornusgallicacid A(2),(+)-isolariciresinol-9'-O-β-glucopyranoside(3),(-)-isolariciresinol 3α-O-β-D-glucopyranoside(4),(7R,8S)-dihydrodehydrodiconiferyl alcohol 9-O-β-D-glucopyranoside(5), and(-)-seco isolariciresinol-9'-O-β-D-glucopyranoside(6). Among them, compounds 1 and 2 were two new compounds. The biological activity evaluation results showed that compounds 2 and 6 had strong DPPH free radical scavenging ability, with EC&#95;(50) values of(4.18±1.96) and(21.45±1.19) μmol·L~(-1), respectively. Compounds 1 and 2 had protective effects on H&#95;2O&#95;2-induced oxidative damage in NRK-52E cells in a dose-dependent manner, and the cell survival rate of compound 2 at 100 μmol·L~(-1) was 96.09%±1.77%.

Chemical constituents were isolated and purified from ethyl acetate fraction of Arctium lappa leaves by silica gel, ODS, MCI, and Sephadex LH-20 column chromatography. Their structures were identified with multiple spectroscopical methods including NMR, MS, IR, UV, and X-ray diffraction combined with literature data. Twenty compounds(1-20) were identified and their structures were determined as arctanol(1), citroside A(2), melitensin 15-O-β-D-glucoside(3), 11β,13-dihydroonopordopicrin(4), 11β,13-dihydrosalonitenolide(5), 8α-hydroxy-β-eudesmol(6), syringin(7), dihydrosyringin(8), 3,4,3',4'-tetrahydroxy-δ-truxinate(9),(+)-pinoresinol(10), phillygenin(11), syringaresinol(12), kaeperferol(13), quercetin(14), luteolin(15), hyperin(16), 4,5-O-dicaffeoylquinic acid(17), 1H-indole-3-carboxaldehyde(18), benzyl-β-D-glucopyranoside(19), and N-(2'-phenylethyl) isobutyramide(20). Among them, compound 1 is a new norsesquiterpenoid, and compounds 2-5, 7-8, and 18-20 are isolated from this plant for the first time.

Cinnamomi ramulus (CR) and Cinnamomi cortex (CC), both sourced from Cinnamomum cassia Presl, are commonly used Chinese medicines in the Chinese Pharmacopeia. However, while CR functions to dissipate cold and to resolve external problems of the body, CC functions to warm the internal organs. To clarify the material basis of these different functions and clinical effects, a simple and reliable UPLC-Orbitrap-Exploris-120-MS/MS method combined with multivariate statistical analyses was established in this study with the aim of exploring the difference in chemical compositions of aqueous extracts of CR and CC. As the results indicated, a total of 58 compounds was identified, including nine flavonoids, 23 phenylpropanoids and phenolic acids, two coumarins, four lignans, four terpenoids, 11 organic acids and five other components. Of these compounds, 26 significant differential compounds were identified statistically including six unique components in CR and four unique components in CC. Additionally, a robust HPLC method combined with hierarchical clustering analysis (HCA) was developed to simultaneously determine the concentrations and differentiating capacities of five major active ingredients in CR and CC: coumarin, cinnamyl alcohol, cinnamic acid, 2-methoxycinnamic acid and cinnamaldehyde. The HCA results showed that these five components could be used as markers for successfully distinguishing CR and CC. Finally, molecular docking analyses were conducted to obtain the affinities between each of the abovementioned 26 differential components, focusing on targets involved in diabetes peripheral neuropathy (DPN). The results indicated that the special and high-concentration components in CR showed high docking scores of affinities with targets such as HbA1c and proteins in the AMPK-PGC1-SIRT3 signaling pathway, suggesting that CR has greater potential than CC for treating DPN.

Background: As an autoimmune systemic disorder, rheumatoid arthritis (RA) features chronic inflammation as well as synovial infiltration of immune cells. This study was designed with the purpose of discussing the hidden mechanism of SPTBN1 and exploring favorable molecular-targeted therapies., Methods: With the application of RT-qPCR and western blot, the expressions of SPTBN1 and PIK3R2 before or after transfection were estimated. Besides, Cell Counting Kit-8, Edu, wound healing, transwell, enzyme-linked immunosorbent assay, and TUNEL were adopted for the evaluation of the viability, proliferation, migration, invasion, inflammatory response, and apoptosis of fibroblast-like synoviocyte (FLS). In addition, the interaction of SPTBN1 and PIK3R2 was testified by applying immunoprecipitation (IP) and western blot was utilized for the assessment of migration-, apoptosis-, and PI3K/AKT signal-related proteins., Results: It was discovered that SPTBN1 declined in RA synovial cells and its overexpression repressed the proliferation, migration, invasion, and inflammation of RA-FLSs but promoted apoptosis. IP confirmed that SPTBN1 could bind to PIK3R2 in FLSs. To further figure out the hidden mechanism of SPTBN1 in RA, a series of functional experiments were carried out and the results demonstrated that the reduced expressions of MMP2, MMP9, IL-8, IL-1β, IL-6, and Bcl2 as well as increased levels of Bax and cleaved caspase3 in SPTBN1-overexpressed RA-FLSs were reversed by PIK3R2 depletion, revealing that SPTBN1 repressed the migration and inflammation and promoted the apoptosis of RA-FLSs via binding to PIK3R2. Results obtained from western blot also revealed that PIK3R2 interference ascended the contents of p-PI3K and p-AKT in SPTBN1-overexpressed RA-FLSs, implying that SPTBN1 repressed PI3K/AKT signal in RA via PIK3R2., Discussion: SPTBN1 alleviated the proliferation, migration, invasion, and inflammation in RA via interacting with PIK3R2., (© 2022 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

A new iridoid glycoside, cornushmf A(1) and nine known iridoids(2-10) were isolated from the water extract of the wine-processed Corni Fructus by various column chromatographies. Their chemical structures were identified by comprehensive spectroscopic methods as 7β-O-(2″-formylfuran-5″-methylene)-morroniside(1), 7-dehydrologanin(2), sweroside(3), 7β-O-methylmorroniside(4), 7α-O-methylmorroniside(5), 7β-O-ethylmorroniside(6), 7α-O-ethylmorroniside(7), cornuside(8), sarracenin(9), and loganin(10).

In view of the current inadequate standards for Gleditsiae Spina in the Chinese Pharmacopoeia, this study put forward some new items of the quality standards of Gleditsiae Spina. Thin-layer chromatography(TLC) was performed for identification with the reference substance of taxifolin and the reference material of Gleditsiae Spina as the control. According to the general principles of the Chinese Pharmacopoeia(2020 edition, Vol. 4), the moisture, total ash content, and alcohol-soluble extract of medicinal materials and decoction pieces of Gleditsiae Spina were determined. The content determination method for medicinal materials and decoction pieces of Gleditsiae Spina was established using high-performance liquid chromatography(HPLC), with taxifolin as the quality control index. Based on the determination results of 30 batches of samples of Gleditsiae Spina from different habitats, the draft quality standards of Gleditsiae Spina were developed, which provided suggestions for the revision of the quality standards of Gleditsiae Spina in the Chinese Pharmacopoeia.

Objective: To evaluate the cost-effectiveness of anti-tumor associated antigen autoantibody (TAAb) for hepatocellular carcinoma (HCC) screening in cirrhosis population with chronic hepatitis B (CHB). Methods: A simulated cohort of 40-year-old patients with CHB cirrhosis was established with a sample size of 10 000. Using TAAb screening alone or TAAb and AFP screening in parallel (TAAb + AFP) as the research strategy, and liver ultrasound and AFP screening in parallel (liver ultrasound + AFP) as the control strategy, the decision analysis Markov model was constructed and the model validity was evaluated. The 6-month cycle was simulated using TreeAge Pro 2020 software. Cost and quality-adjusted life years (QALY) were calculated. Incremental cost-effectiveness ratio (ICER) was used to compare the two strategies, and sensitivity analysis was used to evaluate the uncertainty of results. Results: The Markov model had a total of 11 outcomes, of which 7 were natural outcomes and 4 wereclinical intervention outcomes, and the goodness of fit was 0.969. The lifetime screening cost of TAAb+AFP strategy for HCC screening was 249 612 yuan/case, and the QALY per capita was 7.704 years. Compared with liver ultrasound +AFP strategy (247 805 yuan/case), the total health cost increased by 1 807 yuan/case, and the QALY obtained was 0.014. The ICER was 127 635 yuan /QALY. When the TAAb screening fee was higher than 889.552 yuan, or the discount rate was higher than 0.068, or the antiviral treatment compliance was lower than 45.1%, ICER > 212 676 yuan /QALY. When the single TAAb screening fee was 400-600 yuan, the TAAB+AFP strategy had cost effective value. When the willingness to pay was 70 892, 141 784 and 212 676 yuan /QALY, the probability of cost-effectiveness of TAAb+AFP strategy was 70.6%, 75.3% and 77.8%, respectively. Conclusion: It is cost-effective to use TAAb+AFP for early screening of liver cancer in Chinese population with CHB cirrhosis.

Reverse prediction and molecular docking techniques were employed to evaluate the feasibility of reniformin A(RA) as an anti-tumor leading compound. Based on the reverse prediction, network pharmacology was used to construct a &quot;disease-compound-target-pathway&quot; network. Thirty-nine tumor-related targets of RA were predicted, which participated in the regulation of multiple cellular activities such as apoptosis, cell cycle, and tumor metastasis, and regulated estrogen signal transduction and inflammatory response. Discovery Studio 2020 was adopted for molecular docking and toxicity prediction(TOPKAT). As revealed by the results, the binding affinity of RA with the tumor-related targets ABL1, ESR1, SRC and BCL-XL was stronger than that of oridonin(OD), while its mutagenicity, rodent carcinogenesis, and oral LD&#95;(50) in rats were all inferior to that of OD. Furthermore, in vitro experiments were performed to confirm the anti-tumor activity of RA, and the mechanism was preliminarily discussed. The results demonstrated that RA was superior to OD in cytotoxicity, inhibition of cell colony formation, and induction of apoptosis. RA, possessing potent anti-tumor activity, is expected to be a new anti-tumor leading compound.

Over-expression of the pathway specific positive regulator gene is an effective way to activate silent gene cluster. In the curret study, the SARP family regulatory gene, vasR2, was over-expressed in strain Verrucosispora sp. NS0172 and the cryptic gene cluster responsible for the biosynthesis of pentaketide ansamycin was partially activated. Two tetraketides (1 and 2) and a triketide (3) ansamycins, together with five known compounds (4-8), were isolated and elucidated from strain NS0172OEvasR2. Their NMR data were completely assigned by analysis of their HR-ESI-MS and 1 H, 13 C NMR, HMQC, HMBC and 1 H- 1 H COSY spectra., (Copyright © 2021 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

One new ent -Kaurane diterpenoid ( 1 ) was isolated from the ethyl acetate fraction of Isodon henryi . Along with ten diterpenoids ( 2-11 ) were isolated from this plant for the first time, including six 7,20-epoxy diterpenoids, three enmenol-type diterpenoids and one 6,7-seco- ent -kaurene diterpenoid. Their structures were elucidated by 1 D and 2 D NMR, confirmed by HRESIMS and electronic circular dichroism analyses. Furthermore, the cytotoxicities of twelve compounds were investigated in five human cancer cell lines, including A2780, BGC-823, HCT-116, HepG2 and HeLa. And the IC 50 values of these diterpenoids ranged from 2.1 to 88.8 μM in the tested cell lines. Based on the molecular structures of 12 compounds and the bioassay results, it suggests that α , β -unsaturated pentanone is the cytotoxic active site of 7,20 epoxy ent -kaurane diterpenoid, but it does not contribute much to enmenol-type diterpenoid.Supplemental data for this article can be accessed at https://doi.org/10.1080/14786419.2019.1675067.

Four new gallate derivatives-ornusgallate A, ent -cornusgallate A, cornusgallate B and C (1a, 1b, 2, 3)-were isolated from the wine-processed fruit of Cornus officinalis . Among them, 1a and 1b are new natural compounds with novel skeletons. Their chemical structures were elucidated by comprehensive spectroscopy methods including NMR, IR, HRESIMS, UV, ECD spectra and single-crystal X-ray diffraction analysis. The in vitro anti-inflammatory activities of all compounds were assayed in RAW 264.7 cells by assessing LPS-induced NO production. As the result, all compounds exhibited anti-inflammatory activities at attested concentrations. Among the tested compounds, compound 2 exhibited the strongest anti- inflammatory activity.

Constitutively expression of the pathway-specific activators is an effective method to activate silent gene clusters and improve natural product production. In this study, nine shunt products of aminoansamycins (1-9) were identified from a recombinant mutant strain S35-LAL by overexpressed the large-ATP-binding regulator of the LuxR family (LAL) gene aas1 in Streptomyces sp. S35. All the compounds showed no anti-microbial, anti-T3SS and cytotoxic activities., (Copyright © 2020 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

One new bisesquiterpenoid, biepiasreorlid II (1), three new sesquiterpene lactones 8α-methoxy-epiasterolid (4), 3β-acetoxyl-8-epiasterolid (5), and 3β-acetoxyl-atractylenolide I (6), along with five known analogues (2-3 and 7-9), were obtained from rhizome of Atractylodes macrocephala Koidz. All structures were assigned on the basis of detailed spectroscopic analyses. The absolute configuration of 1 was established by the analysis of single-crystal X-ray diffraction with Ga Kα radiation, and 4-6 were elucidated by TDDFT-ECD calculations. The CREB agonistic activity was investigated in HEK293T cells using dual luciferase reporter assay. Compounds 1, 2, 5, and 7-9 exhibited strong to agonistic activities on CREB., (Copyright © 2020. Published by Elsevier B.V.)

Discovering anticancer drugs that do not have adverse side effects has been a developing research field worldwide in recent decades. In this work, four previously undescribed cytotoxic diterpenoids were isolated from the aerial parts of Isodon excisoides. Interestingly, these four diterpenoids were two pairs of tautomers that were first reported in plants. Their structures were further elucidated using various spectroscopic methods. The tautomerization phenomenon and mechanism for these two pairs of tautomers were emphatically described. The theoretical simulation results indicated that the diterpene tautomerization is greatly related to certain factors, including the existence of a transition state, the change of bond length and the level of conversion energy; the tautomerization for the two pairs of tautomers is mainly caused by proton transfer. For bioassays, the cytotoxicities of the tautomers against five human cancer cell lines were also investigated. The results indicated that each of the four diterpenoids showed significant cytotoxicity in at least three cell lines and could serve as potential anticancer agents for further investigation.

Objective: Pancreatic cancer (PC) is one of the most common malignant tumors of the digestive system with a high degree of malignancy. Currently, there have been many studies on exosomal microRNAs (miRNAs) discovery in pancreatic cancer. This systematic review aimed to give an overview about known exosomal miRNAs and discuss their diagnostic performance, as well as prognostic value in PC., Materials and Methods: PubMed and Web of Science were used for systematic literature research for this review. This literature research was mainly to identify studies that performed plasmatic and serological testing for exosomal miRNAs in pancreatic cancer patients and controls. Two independent reviewers separately extracted data on study characteristics and results., Results: In total, nine prior studies were included in this review. Of which, eleven different single exosomal miRNAs and three exosomal miRNA panels were reported., Conclusions: When single exosomal miRNA was used as a diagnostic tool, the specificity is generally high, but the sensitivity is commonly low. When multiple of exosomal miRNAs were used simultaneously, higher sensitivities can be obtained at relatively reasonable specificity levels with certain miRNA combinations. Developing a combination of miRNA markers may be a promising approach for early detection of pancreatic cancer.

In this study, we investigated the expression of RhoC in the multiple myeloma (MM) cell line RPMI- 8226, as well as the effects of silencing RhoC on the growth of tumor xenografts and tumor-induced angiogenesis in nude mice with MM. For this purpose, we transduced RPMI-8226 cells with lentiviral particles overexpressing short hairpin RNAs (shRNA) targeting RhoC. Tumor xenografts were generated by subcutaneously injecting nude mice with RPMI-8226 cells overexpressing control shRNA [negative control (NC) group] or the RhoC shRNA [the experimental (S) group], respectively. RhoC protein and mRNA levels in the tumor xenografts were measured. Nude mice were also subcutaneously inoculated with Matrigel mixed with vascular endothelial growth factor, and CD31 and KI67 levels in the tumor xenografts were measured by immunohistochemistry. Similarly, we assessed tumor xenograft growth and angiogenesis in Matrigel implants in the mice of both groups. We found that RhoC levels, microvessel density, and CD31 labeling index were more reduced in the S group than in the NC group. However, there was no significant difference in the size of tumor xenografts between the 2 groups. The number of new vessels and the neovascular length in the Matrigel implants were significantly lower in the S group than in the NC group. Therefore, we concluded that RhoC expression in myeloma xenografts has important effects on the induction of angiogenesis.

The association between coffee consumption and pancreatic cancer risk has been extensively studied; however, there is no consistent conclusion. Therefore, this meta-analysis study sought to evaluate dose-response relationship between them. A search was conducted using the PubMed and Web of Science databases. Thirteen high-quality cohort studies were identified, involving in 959,992 study participants and 3831 pancreatic cancer cases. Comparing the highest with lowest categories of coffee intake, the pooled relative risk (RR) was 1.08 (95% CI 0.94-1.25). For dose-response analysis, no evidence of a nonlinear dose-response association between coffee consumption and pancreatic cancer ( p for nonlinearity =0.171) was found. The risk of pancreatic cancer was increased by 5.87% (RR =1.06, 95% CI 1.05-1.07) with the increment of one cup/day. Coffee consumption was identified to be related with the increasing risk of pancreatic cancer in a dose-response manner. Nevertheless, further mechanistic studies are needed to clarify the concerned issues.

To obtain diterpene glycosides from an aqueous extract of the aerial parts of Isodon henryi and further investigate their cytotoxicities, in this study, a total of seven compounds were isolated, including six ent -kaurane diterpene glycosides ( 1 - 6 ) and one diterpene aglycon (7). Among the seven ent -kaurane diterpenes obtained, four were novel compounds, including ent-7,20-epoxy- kaur-16-en-1α,6β,7β,15β-tetrahydroxyl-11-O-β-d-glucopyranoside ( 1 ), ent -7,20-epoxy-kaur-16-en- 6 β ,7 β ,14 β ,15 β -tetrahydroxyl-1- O - β -d-glucopyranoside ( 2 ), ent -7,20-epoxy-kaur-16-en-6 β ,7 β ,15 β - trihydroxyl-1- O - β -d-glucopyranoside ( 3 ), and ent -7,20-epoxy-kaur-16-en-7 β ,11 β ,14α,15 β -tetrahydr- oxyl-6- O - β -d-glucopyranoside ( 4 ), and three were isolated from this plant for the first time ( 5 -7). Their structures were elucidated by utilizing spectroscopic methods and electronic circular dichroism analyses. Furthermore, the cytotoxicities of all seven compounds were investigated in four human cancer cell lines, including A2780, BGC-823, HCT-116, and HepG2. The IC 50 values of these diterpenes ranged from 0.18 to 2.44 mM in the tested cell lines. In addition, the structure-cytotoxicity relationship of diterpene glycosides was also evaluated to study the effect of glycosylation on the cytotoxicity of diterpene compounds., Competing Interests: There are no conflicts of interest to declare.

The chemical constituents of the water extraction of the aerial parts of Isodon henryi were investigated by various chromatographic methods including D-101 macroporous adsorptive resins,silica gel,sephadex LH-20,and semi-preparative HPLC. As a result,ten compounds were separated and purified. By analyses of the UV,IR,MS,NMR spectra,their structures were determined as rabdosinate( 1),lasiokaurin( 2),epinodosinol( 3),rabdosichuanin C( 4),epinodosin( 5),hebeirubescensin k( 6),rubescensin C( 7),enmenol( 8),oridonin( 9),and enmenol-1-β-glucoside( 10). Compounds 1-8 and 10 were isolated from I. henryi for the first time. Compounds 2 and 9 showed inhibitory effects against four tumor cells,with IC50 values of 2. 25-9. 32 μmol·L-1.

Cytotoxic diterpenoids were enriched and orientation prepared from the aerial parts of Isodon excisoides target-guided by UPLC-LTQ-Orbitrap-MS. Four diterpenoids were obtained, including a novel compound: 1α-acetoxy-7α, 14β, 20α-trihydroxy-ent-kaur-16-en-15-one (1); together with three known compounds kamebakaurin (2), lasiokaurin (3), enmenol-1-β-glucoside (4). Their structures were elucidated on the basis of spectroscopic methods in conjunction with published data for their analogues. All compounds were tested for their cytotoxic effects against five human cancer cell lines HCT-116, HepG2, A2780, NCI-H1650 and BGC-823, respectively. Compounds 1 and 2 showed obviously cytotoxic activity against the five cancer cell lines with IC 50 ranging from 1.06 to 3.60 μM. Compounds 3 and 4 showed selective cytotoxic activity.

The Warburg effect is a dominant phenotype of most tumor cells. Recent reports have shown that the Warburg effect can be reprogrammed by the tumor microenvironment. Lactic acidosis and glucose deprivation are the common adverse microenvironments in solid tumor. The metabolic reprogramming induced by lactic acid and glucose deprivation remains to be elucidated in glioblastoma. Here, we show that, under glucose deprivation, lactic acid can preserve high ATP levels and resist cell death in U251 cells. At the same time, we find that MCT1 and MCT4 are significantly highly expressed. The metabolic regulation factor HIF-1α decreased and C-MYC increased. Nuclear respiratory factor 1 (NRF1) and oxidative phosphorylation (OXPHOS)-related proteins (NDUFB8, ND1) are all distinctly increased. Therefore, lactic acid can induce lactate transport and convert the dominant Warburg effect to OXPHOS. Through bioinformatics analysis, the high expression of HIF-1α, MCT1 or MCT4 indicate a poor prognosis in glioblastoma. In addition, in glioblastoma tissue, HIF-1α, MCT4 and LDH are highly expressed in the interior region, and their expression is decreased in the lateral region. MCT1 can not be detected in the interior region and is highly expressed in the lateral region. Hence, different regions of glioblastoma have diverse energy metabolic pathways. Glycolysis occurs mainly in the interior region and OXPHOS in the lateral region. In general, lactic acid can induce regional energy metabolic reprogramming and assist tumor cells to adapt and resist adverse microenvironments. This study provides new ideas for furthering understanding of the metabolic features of glioblastoma. It may promote the development of new therapeutic strategies in GBM., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Two new phenolic glycoside, 2-methoxy-4-hydroxylphenyl-1-O-α-L-rhamnopyranosyl- (1″ → 6')-β-D-glucopyranoside. (1) and threo-3-methoxy-5-hydroxy-phenylpropanetriol-8-O-β-D-glucopyranoside (2), were isolated from the stems of Zanthoxylum armatum. The compounds 1 and 2 showed weak scavenging activity in DPPH free radical assay with IC 50 values of 323 and 114 mM, respectively.

We evaluated autoantibodies against nine tumor-associated antigens, including p62, p16, Koc, p53, Cyclin B1, Cyclin E, Survivin, HCC1, and RalA as serological markers in lung cancer. Enzyme-linked immunosorbent assay (ELISA) was used to detect autoantibodies in sera from 50 lung cancer patients and 42 normal controls. Then, four tumor-associated antigens of higher values were selected and validated in sera from validation group. Western blot and serum absorption test were used to confirm positive findings from ELISA. When cutoff values were set as mean optical density values plus 3 standard deviation of normal controls, the positive rate of autoantibodies against four tumor-associated antigens (Survivin, Cyclin B1, HCC1, and p53) reached 32%, 20%, 22%, and 18%, with area under the curve values of 0.653, 0.767, 0.622, and 0.623 in sera from 50 lung cancer, respectively (all p < 0.05). Results from the validation group confirmed the results. When lung cancer patients were divided by their clinicopathological characteristics into different subgroups, we have found that serum anti-Cyclin B1 and anti-HCC1 autoantibodies increased in stages 1, 2, and 3 lung cancer; anti-Survivin autoantibodies increased in stages 2 and 3 lung cancer; and anti-p53 autoantibody only increased in stage 1 when compared with their corresponding levels in controls (all p < 0.05). Serum anti-Cyclin B1 and anti-Survivin autoantibodies increased with disease histological grade 2 and 3 (both p < 0.05). And higher serum level of anti-p53 autoantibodies is positively associated with tumor size. Parallel utilization of these four anti-tumor-associated antigens (any positive) can increase sensitivity to 65.0% at 100% specificity with area under the curve of 0.908 ( p < 0.001) in lung cancer detection in validation group. Our results suggest that autoantibodies against these four tumor-associated antigens have higher values in lung cancer detection, and serum anti-Cyclin-B1 has the potential to serve as novel non-invasive biomarkers in early-stage lung cancer.

The exploration of localized surface plasmon resonance (LSPR) beyond the usual visible waveband, for example within the ultraviolet (UV) or deep-ultraviolet (D-UV) regions, is of great significance due to its unique applications in secret communications and optics. However, it is still challenging to universally synthesize the corresponding metal nanostructures due to their high activity. Herein, we report a universal, eco-friendly, facile and rapid synthesis of various nano-metals encapsulated by ultrathin carbon shells, significantly with a remarkable deep-UV LSPR characteristic, via a liquid-phase laser fabrication method. Firstly, a new generation of the laser ablation in liquid (LAL) method has been developed with an emphasis on the elaborate selection of solvents to generate ultrathin carbon shells, and hence to stabilize the formed metal nanocrystals. As a result, a series of metal@carbon nanoparticles (NPs), including Cr@C, Ti@C, Fe@C, V@C, Al@C, Sn@C, Mn@C and Pd@C, can be fabricated by this modified LAL method. Interestingly, these NPs exhibit LSPR peaks in the range of 200-330 nm, which are very rare for localized surface plasmon resonance. Consequently, the UV plasmonic effects of these metal@carbon NPs were demonstrated both by the observed enhancement in UV photoluminescence (PL) from the carbon nanoshells and by the improvement of the photo-responsivity of UV GaN photodetectors. This work could provide a universal method for carbon shelled metal NPs and expand plasmonics into the D-UV waveband.

In this study, enzyme-linked immunosorbent assay has been used to examine the frequencies of serum autoantibodies against two candidate tumor-associated antigens intensively selected from the Human Protein Atlas database, in combination with 13 tumor-associated antigens available from our lab in sera from 44 OC patients and 50 normal healthy controls. Conventional evaluation (mean + 3SD as the cutoff value to determine a positive reactivity), receiver operating characteristic curve analyses, and classification tree analysis were further used to evaluate the diagnostic performance of autoantibodies against these tumor-associated antigens (anti-tumor-associated antigens) in ovarian cancer. For single anti-tumor-associated antigen, when the cutoff values were set as mean + 3SD of normal healthy controls, NPM1, MDM2, PLAT, p53, and c-Myc could achieve sensitivity higher than 20% at 98% specificity. Combinational utilization of autoantibodies against MDM2, PLAT, NPM1, 14-3-3 Zeta, p53, and RalA achieved the optimal diagnostic performance with 72.7% sensitivity at 96% specificity. Receiver operating characteristic curve analysis showed that the area under the receiver operating characteristic curves of autoantibodies against c-Myc, NPM1, MDM2, p16, p53, and 14-3-3 Zeta were greater than 0.80. This indicated that these tumor-associated antigens held high potential to serve as diagnostic biomarkers in ovarian cancer detection. Decision tree analysis indicated that anti-c-Myc held high potential in the detection of ovarian cancer. Further studies are warranted to validate the diagnostic performance of these anti-tumor-associated antigens with high area under the receiver operating characteristic curve, including autoantibodies against c-Myc, MDM2, PLAT, NPM1, 14-3-3 Zeta, p53, and RalA.

The chemical constituents of the water extraction of the aerial parts of Isodon excisoides were investigated by various chromatographic methods including D-101 macroporous adsorptive resins, silica gel, Sephadex LH-20, MCI and semi-preparative HPLC. As a result, six compounds were separated and purified.By analyses of the HR-ESI-MS, 1D and 2D NMR spectra, their structures were determined as 3-O-β-D-allopyranosyl-1-octen-3-ol(1), blumenolA (2), lumichrome (3), loliolide(4), cirsiliol(5) and pedalitin(6). Compound 1 was a new compound, and compounds 2-4 were isolated from this plant for the first time., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Cervical cancer is a cause of cancer death, making it as the one of the most common cause for death among women globally. Though many studies before have explored a lot for cervical cancer prevention and treatment, there are still a lot far from to know based on the molecular mechanisms. Janus kinase 2 (JAK2) has been reported to play an essential role in the progression of apoptosis, autophagy and proliferation for cells. We loaded gold-quercetin into poly (dl-lactide-co-glycolide) nanoparticles to cervical cancer cells due to the propertities of quercetin in ameliorating cellular processes and the easier absorbance of nanoparticles. Here, in our study, quercetin nanoparticles (NQ) were administrated to cells to investigate the underlying mechanism by which the cervical cancer was regulated. First, JAK2-inhibited carvical cancer cell lines were involved for our experiments in vitro and in vivo. Western blotting, quantitative RT-PCR (qRT-PCR), ELISA, Immunohistochemistry, and flow-cytometric analysis were used to determine the key signaling pathway regulated by JAK2 for cervical cancer progression. And the role of quercetin nanoparticles was determined during the process. Data here indicated that JAK2, indeed, expressed highly in cancer cell lines compared to the normal cervical cells. And apoptosis and autophagy were found in JAK2-inhibited cancer cells through activating Caspase-3, and suppressing Cyclin-D1 and mTOR regulated by Signal Transducer and Activator of Transcription (STAT) 3/5 and phosphatidylinositide 3-kinase/protein kinases (PI3K/AKT) signaling pathway. The cervical cancer cells proliferation was inhibited. Further, tumor size and weight were reduced by inhibition of JAK2 in vivo experiments. Notably, administration with quercetin nanoparticles displayed similar role with JAK2 suppression, which could inhibit cervical cancer cells proliferation, invasion and migration. In addition, autophogy and apoptosis were induced, promoting cervical cancer cell death. To our knowledge, it was the first time to evaluate the role of quercetin nanoparticles in improving cervical cancer from apoptosis, autophagy and proliferation, which could be a potential target for future therapeutic approach clinically., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

This study aims to investigate the clinical significance of serum autoantibodies against MDM2 and c-Myc and evaluate their feasibility in the immunodiagnosis of lung cancer. 50 sera samples with 43 available paired lung cancer tissue and adjacent normal tissue slides with follow up information and 44 sera from normal human controls (NHC) were used in the research group. Another 62 lung cancer sera and 43 NHC sera were used in the validation group. The results of IHC showed that MDM2 and c-Myc protein were overexpressed in lung cancer tissues compared to adjacent normal tissues (p < 0.001). Likewise, significantly higher levels of serum autoantibodies against MDM2 and c-Myc were found in lung cancer compared to NHC both in research and validation groups. Further analysis on IHC and ELISA results showed that serum level of autoantibodies against these two TAAs were positively associated with tissue staining scores (both p < 0.05). The area under curve (AUC) values of anti-MDM2 and anti-cMyc autoantibodies for discriminating lung cancers from NHC were 0.698 and 0.636 in research group, 0.777 and 0.815 in the validation group, respectively. Both anti-MDM2 and anti-c-Myc autoantibodies can discriminate stage I lung cancer patients from NHC with AUC values of 0.703 and 0.662. Kaplan-Meier analysis showed that higher level of serum anti-c-Myc autoantibodies was significantly related to shortened disease-free survival (DFS) (p = 0.041). In conclusion, our finding suggested that serum MDM2 and c-Myc autoantibodies may have the potential to serve as non-invasive diagnostic biomarkers in patients with lung cancer.

Background and Objectives: Vitamin D receptor (VDR) genetic polymorphisms are considered to be associated with type 2 diabetes mellitus (T2DM), but this is inconclusive. The aim of this study is to quantify the association between polymorphisms of BsmI and FokI in the VDR gene and T2DM risk through literature review., Methods and Study Design: Original articles published from 1999 to June 2014 were discovered through PubMed, ISI Web of Science, China National Knowledge Infrastructure, Chinese Wanfang Database, and the Chinese Biomedical Literature Database. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated with software STATA version 12.0., Results: Twenty-three articles containing 30 case-control studies were included. The association between the BsmI polymorphism and T2DM was weak in two genetic models (Bb vs bb and BB+Bb vs bb). The subgroup analysis showed that this association was only found in the studies with a small sample size (<200). A strong association between FokI polymorphism and T2DM indicated that this gene polymorphism was possibly a risk factor for T2DM (ff vs FF: OR=1.57, 95% CI: 1.28-1.93, p<0.001; Ff vs FF: OR=1.54, 95% CI: 1.31-1.81, p<0.001; ff+Ff vs FF: OR=1.57, 95% CI: 1.35-1.83, p<0.001), especially in Chinese populations., Conclusion: More reliable conclusions about associations between VDR genetic polymorphisms and T2DM will depend on studies with larger sample size and by ethnicity.

Recent studies have showed that RNAs regulate each other with microRNA (miRNA) response elements (MREs) and this mechanism is known as "competing endogenous RNA (ceRNA)" hypothesis. Long non-coding RNAs (lncRNAs) are supposed to play important roles in cancer. Compelling evidence suggests that lncRNAs can interact with miRNAs and regulate the expression of miRNAs as ceRNAs. Several lncRNAs such as H19, HOTAIR and MEG3 have been found to be associated with miRNAs in gastric cancer (GC), generating regulatory crosstalk across the transcriptome. These MRE sharing elements implicated in the ceRNA networks (ceRNETs) are able to regulate mRNA expression. The ceRNA regulatory networks including mRNAs, miRNAs, lncRNAs and circular RNAs may play critical roles in tumorigenesis, and the perturbations of ceRNETs may contribute to the pathogenesis of GC.

Three types of ent-kaurane diterpenoids were isolated from the aerial parts of Isodon excisoides, including three new diterpenoids, 1α,7α,14β-trihydroxy-20-acetoxy-ent-kaur-15-one (1); 1α,7α,14β,18-tetrahydroxy-20-acetoxy-ent-kaur-15-one (2); and 1α-acetoxy-14β-hydroxy-7α,20-epoxy-ent-kaur-16-en-15-one (3); together with six known diterpenes henryin (4); kamebanin (5); reniformin C (6); kamebacetal A (7); kamebacetal B (8); and oridonin (9). The structures of the isolated compounds were elucidated by means of nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry in conjunction with published data for their analogs, as well as their fragmentation patterns. Compounds 5 and 9 were isolated from Isodon excisoides for the first time. To explore the structure-activity relationships of the isolated compounds, they were tested for their cytotoxic effects against five human cancer cell lines: HCT-116, HepG2, A2780, NCI-H1650, and BGC-823. Most of the isolated compounds showed certain cytotoxic activity against the five cancer cell lines with IC50 values ranging from 1.09-8.53 µM. Among the tested compounds, compound 4 exhibited the strongest cytotoxic activity in the tested cell lines, with IC50 values ranging from 1.31-2.07 µM. Compounds 1, 6, and 7 exhibited selective cytotoxic activity.

Purpose: To determine the role of autoantibodies to PARP1 and BRCA1/BRCA2 which were involved in the synthetic lethal interaction in cancer., Methods: Enzyme-Linked Immunosorbent Assay (ELISA) was used to detect autoantibodies to PARP1 and BRCA1/BRCA2 in 618 serum samples including 131 from breast cancer, 94 from lung cancer, 34 from ovarian cancer, 107 from prostate cancer, 76 from liver cancer, 41 from pancreatic cancer and 135 from normal individuals. The positive sera with ELISA were confirmed by Western blot. Immunohistochemistry was used to examine the expression of PARP1 and BRCA1/BRCA2 in breast cancer., Results: Autoantibody frequency to PARP1, BRCA1, and BRCA2 in cancer varied from 0% to 50%. When the sera from cancer patients were tested for the presence of autoantibodies to PARP1 and BRCA1/BRCA2, the autoantibody responses slightly decreased and the positive autoantibody reactions varied from 0% to 50.0%. This was significantly higher autoantibody responses to PARP1 and BRCA1/BRCA2 (especially to PARP1 and BRCA1) in ovarian cancer and breast cancer compared to normal control sera (P < 0.001 and P < 0.01). Immunohistochemistry indicated that Pathology Grade at diagnosis to PARP1 expression in breast cancer was different (P < 0.05)., Conclusions: Different cancers have different profiles of autoantibodies. The autoantibodies to proteins involving the synthetic lethal interactions would be novel serological biomarker in some selective cancers.

Objectives: To investigate the association between three single nucleotide polymorphisms (SNPs) in the X-ray repair cross complementing 1 gene (XRCC1) and the risk of esophageal squamous cell carcinoma (ESCC) in Chinese population., Methods: A case-control study including 381 primary ESCC patients recruited from hospital and 432 normal controls matched with patients by age and gender from Chinese Han population was conducted. The genotypes of three XRCC1 polymorphisms at -77T>C (T-77C), codon 194 (Arg194Trp), and codon 399 (Arg399Gln) were studied by means of polymerase chain reaction-restriction fragment length polymorphism techniques (PCR-RFLP). Unconditional logistic regression model and haplotype analysis were used to estimate associations of these three SNPs in XRCC1 gene with ESCC risk., Results: Polymorphisms at these three sites in XRCC1 gene were not found to be associated with risk for developing ESCC; however the haplotype C(codon 194)G(codon 399)C(-77T>C) was significantly associated with reduced risk of ESCC (OR: 0.62, 95% CI: 0.40-0.96) upon haplotype analysis., Conclusion: These results suggested that the gene-gene interactions might play vital roles in the progression on esophageal cancer in Chinese Han population and it would be necessary to confirm these findings in a large and multiethnic population.

The liposome delivery system has been intensively explored as novel drug delivery system (DDS) for antitumor drugs, due to its safety, selective cytotoxicity, long circulation and slow elimination in blood, which is favorable for cancer therapy. The liposome-based chemotherapeutics are used to treat a variety of cancers to enhance the therapeutic index of antitumor drugs. Here, the author reviewed the important targets for cancer therapy and the pharmacokinetic behavior of liposomal drugs in vivo, as well as the application of the targeting liposomal system in cancer therapy. Considering further application for clinical use, the great challenges of the liposome-based delivery system were also proposed as follows: 1) prepare stealth liposome with steric stabilization and further enhance the therapeutic effects and safety; 2) explore more safe clinical targets and complementary or different types of targeting liposome; 3) thirdly, more investment is needed on the research of pharmacokinetics of the elements such as the ligands (antibody), PEG and lipids of liposome delivery system as well as safety evaluation. Considering the complex process of the liposomal encapsulation drugs in vivo, the author inferred that there are maybe different forms of the encapsulation drug to be internalized by the tumor tissues at the same time and space, although there are little reports on it.

Sera of cancer patients may contain antibodies that react with a unique group of autologous cellular antigens called tumor-associated antigens (TAAs). The present study aimed to determine whether a mini-array of multiple TAAs would enhance antibody detection and be a useful approach in esophageal cancer detection and diagnosis. Our mini-array of multiple TAAs consisted of eleven antigens, p53, pl6, Impl, CyclinB1, C-myc, RalA, p62, Survivin, Koc, CyclinD1 and CyclinE full-length recombinant proteins. Enzyme-linked immunosorbent assays (ELISA) were used to detect autoantibodies against eleven selected TAAs in 174 sera from patients with esophageal cancer, as well as 242 sera from normal individuals. In addition, positive results of ELISA were confirmed by Western blotting. In a parallel screening trial, with the successive addition of antigen to a final total of eleven TAAs, there was a stepwise increase in positive antibody reactions. The eleven TAAs were the best parallel combination, and the sensitivity and specificity in diagnosing esophageal cancer was 75.3% and 81.0%, respectively. The positive and negative predictive values were 74.0% and 82.0%, respectively, indicating that the parallel assay of eleven TAAs raised the diagnostic precision significantly. In addition, the levels of antibodies to seven antigens, comprising p53, Impl, C-myc, RalA, p62, Survivin, and CyclinD1, were significantly different in various stages of esophageal cancer, which showed that autoantibodies may be involved in the pathogenesis and progression of esophageal cancer. All in all, this study further supports our previous hypothesis that a combination of antibodies might acquire higher sensitivity for the diagnosis of certain types of cancer. A customized mini-array of multiple carefully-selected TAAs is able to enhance autoantibody detection in the immunodiagnosis of esophageal cancer and autoantibodies to TAAs might be reference indicators of clinical stage.

Polymorphisms in miRNA binding sites have been shown to affect miRNA binding to target genes, resulting in differential mRNA and protein expression and susceptibility to common diseases. Our purpose was to predict SNPs (single nucleotide polymorphisms) within miRNA binding sites of inflammatory genes in relation to gastric cancer. A complete list of SNPs in the 3'UTR regions of all inflammatory genes associated with gastric cancer was obtained from Pubmed. miRNA target prediction databases (MirSNP, Targetscan Human 6.2, PolymiRTS 3.0, miRNASNP 2.0, and Patrocles) were used to predict miRNA target sites. There were 99 SNPs with MAF>0.05 within the miRNA binding sites of 41 genes among 72 inflammation-related genes associated with gastric cancer. NF-κB and JAK-STAT are the two most important signaling pathways. 47 SNPs of 25 genes with 95 miRNAs were predicted. CCL2 and IL1F5 were found to be the shared target genes of hsa-miRNA-624-3p. Bioinformatic methods could identify a set of SNPs within miRNA binding sites of inflammatory genes, and provide data and direction for subsequent functional verification research.

The purpose of this study was to evaluate the associations of CYP1A1 genetic polymorphisms with the risk of developing esophageal cancer (EC). A case-control study was carried out in a Chinese population in which 157 hospital based EC cases and 157 population based healthy controls with 1:1 match by age and sex were included. PCR based restriction fragment length polymorphisms (PCR-RFLP) were used to detect genotypes in case and control groups. For the CYP1A1 Ile/Val polymorphism, comparing with wild genotype Ile/Ile, both the heterozygote genotype Ile/Val and the combined variant genotype Ile/Val+Val/Val increased the risk of esophageal cancer (OR: 2.05, 95%CI: 1.19-3.54, OR: 1.86, 95%CI: 1.11-3.12). No significant association was found between the CYP1A1 MspI polymorphism and EC. According to analysis of combined genotypes, the TC/AG combined genotype which contained both variant alleles of these two polymorphisms increased the risk of developing EC (OR: 2.12, 95%CI: 1.16-3.85). Our results suggested that genetic polymorphisms of CYP1A1 may increase the susceptibility to EC.

Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide. Although new therapeutic strategies have been continuously developed and applied to clinical treatment for HCC, the prognosis is still very poor. Thus, early detection of HCC may enhance effective and curative management. In this study, autoantibody responses to MDM2 protein in HCC patient's serum were evaluated by enzyme-linked immunosorbent assay (ELISA) and part sera were evaluated by Western blotting and indirect immunofluorescence assay. Immunohistochemistry (IHC) over tissue array slides was also performed to analyze protein expression of MDM2 in HCC and control tissues. The prevalence of autoantibodies against MDM2 was significantly higher than that in liver cirrhosis (LC), chronic hepatitis (CH), and normal human sera (NHS). The average titer of autoantibodies against MDM2 in HCC serum was higher compared to that in LC, CH, and NHS. A high titer of autoantibodies against MDM2 in ELISA could be observed in the serum in 6 to 9 months before the clinical diagnosis of HCC in the serum of several HCC patients with serial bleeding samples. Our preliminary data indicate that MDM2 and anti-MDM2 system may be a potential biomarker for early stage HCC screening and immunodiagnosis.

Objective: To investigate the clinical efficacy of noninvasive positive pressure ventilation (NPPV) in treatment of patients with arrhythmia complicated by sleep apnea syndrome (SAS)., Methods: One hundred and thirty-five arrhythmia patients with polysomnography diagnosed SAS were randomly divided into NPPV group (69 cases) and control group (66 cases), the NPPV group was treated with standard medications and NPPV, and the control group was treated with standard medications. SAS related parameters were compared between the groups after 3 months therapy., Results: (1) Epworth sleepiness scale (ESS) score, apnea-hypopnea index (AHI) and arousal index were significantly lower (8.25 ± 5.41 vs.4.08 ± 3.43, 39.95 ± 7.32 vs. 4.71 ± 1.80 and 39.69 ± 4.40 vs. 15.20 ± 2.05, P < 0.01) while not rapid eye movement (NREM) III and rapid eye movement stage of sleep time and lowest pulse oxygen saturation (LSaO2) were significantly higher in NPPV group than in control group [(4.53 ± 2.10)% vs. (16.78 ± 2.59)%,(8.37 ± 1.380)% vs. (15.25 ± 1.41)%, (77.15 ± 6.72)% vs. (93.35 ± 2.03)%, P < 0.01] after 3 months therapy. (2) Incidence of Sinus bradycardia, sinus tachycardia, sinus arrest, atrial premature beats, ventricular premature beats, paroxysmal atrial tachycardia, paroxysmal ventricular tachycardia, atrial fibrillation, II-III degree atrioventricular block, ST-T segment changes were reduced from 57.4%, 44.4%, 7.4%, 20.4%, 13.0%, 36.5%, 12.0%, 8.3%, 37.0%, 53.7% to 4.6%, 1.9%,0.0%, 3.7%, 2.8%, 7.0%, 0.9%, 0.0%, 1.9%, 4.6% (all P < 0.05) and the total number of arrhythmias happened at night were significantly lower (all P < 0.05) while the heart rate variability (HRV) were significantly higher (P < 0.01) in NPPV group than in control group; AHI was positively while LSaO2 was negatively correlated with the total night arrhythmia number (P < 0.01)., Conclusion: Noninvasive positive pressure ventilation is an effective therapy strategy for treating patients with arrhythmia complicated by sleep apnea syndrome.