[Buzhong Yiqi Decoction ameliorates spleen deficiency syndrome by regulating gut microbiota].

This study aims to decipher the mechanism of Buzhong Yiqi Decoction(BZYQD) in the treatment of spleen deficiency syndrome via gut microbiota. The mouse models of spleen deficiency syndrome were established by fecal microbiota transplantation(FMT, from patients with spleen deficiency syndrome) and administration of Sennae Folium(SF, 10 g·kg~(-1)), respectively, and treated with BZYQD for 5 d. The pseudosterile mice(administrated with large doses of antibiotics) and the mice transplanted with fecal bacteria from healthy human were taken as the controls. The levels of IgA, interleukin(IL)-2, IL-1ß, interferon(IFN)-γ, tumor necrosis factor-alpha(TNF-α), and 5-hydroxytryptamine(5-HT) in the intestinal tissue of two models were measured by enzyme-linked immunosorbent assay, and the CD8~+/CD3~+ ratio was determined by flow cytometry. The composition and changes of the gut microbiota were determined by 16S rRNA high-throughput sequencing and qPCR. Furthermore, the correlation analysis was performed to study the mediating role of gut microbiota in the treatment. The results showed that BZYQD elevated the IgA level, lowered the IL-1ß, TNF-α, and 5-HT levels, and decreased the CD8~+/CD3~+ ratio in the intestinal tissue of the two models. Moreover, BZYQD had two-way regulatory effects on the levels of IL-2 and IFN-γ. BZYQD inhibited the overgrowth and reduced the richness of gut microbiota in the SF model, and improved the gut microbiota structure in the two models. Algoriphagus, Mycobacterium, and CL500＿29＿marine＿group were the common differential genera in the two models compared with the control. Acinetobacter, Parabacteroides, and Ruminococcus were the differential genera unique to the FMT model, and Sphingorhabdus, Lactobacillus, and Anaeroplasma were the unique differential genera in the SF model. BZYQD was capable of regulating all these genera. The qPCR results showed that BZYQD increased the relative abundance of Akkermansia muciniphila and decreased that of Bacteroides uniformis in the two models. The correlation analysis revealed that the levels of above intestinal cytokines were significantly correlated with characteristic gut microorganisms in different mo-dels. The IL-1ß level had a significantly positive correlation with Acinetobacter and CL500＿29＿marine＿group in the two models, while the different levels of IL-2 and IFN-γ in the two models may be related to its different gut microbiota structures. In conclusion, BZYQD could regulate the disordered gut microbiota structure in different animal models of spleen deficiency syndrome to improve the intestinal immune status, which might be one of the mechanisms of BZYQD in treating spleen deficiency syndrome.

Thermally Induced Orderly Alignment of Porphyrin Photoactive Motifs in Metal-Organic Frameworks for Boosting Photocatalytic CO2 Reduction.

Efficient transfer of charge carriers through a fast transport pathway is crucial to excellent photocatalytic reduction performance in solar-driven CO2 reduction, but it is still challenging to effectively modulate the electronic transport pathway between photoactive motifs by feasible chemical means. In this work, we propose a thermally induced strategy to precisely modulate the fast electron transport pathway formed between the photoactive motifs of a porphyrin metal-organic framework using thorium ion with large ionic radius and high coordination number as the coordination-labile metal node. As a result, the stacking pattern of porphyrin molecules in the framework before and after the crystal transformations has changed dramatically, which leads to significant differences in the separation efficiency of photogenerated carriers in MOFs. The rate of photocatalytic reduction of CO2 to CO by IHEP-22(Co) reaches 350.9 µmol·h-1·g-1, which is 3.60 times that of IHEP-21(Co) and 1.46 times that of IHEP-23(Co). Photoelectrochemical characterizations and theoretical calculations suggest that the electron transport channels formed between porphyrin molecules inhibit the recombination of photogenerated carriers, resulting in high performance for photocatalytic CO2 reduction. The interaction mechanism of CO2 with IHEP-22(Co) was clarified by using in-situ electron paramagnetic resonance, in-situ diffuse reflectance infrared Fourier transform spectroscopy, in-situ extended X-ray absorption fine structure spectroscopy, and theoretical calculations. These results provide a new method to regulate the efficient separation and migration of charge carriers in CO2 reduction photocatalysts and will be helpful to guide the design and synthesis of photocatalysts with superior performance for the production of solar fuels.

Personalized radiomics signature to screen for KIT-11 mutation genotypes among patients with gastrointestinal stromal tumors: a retrospective multicenter study.

OBJECTIVES: Gastrointestinal stromal tumors (GISTs) carrying different KIT exon 11 (KIT-11) mutations exhibit varying prognoses and responses to Imatinib. Herein, we aimed to determine whether computed tomography (CT) radiomics can accurately stratify KIT-11 mutation genotypes to benefit Imatinib therapy and GISTs monitoring. METHODS: Overall, 1143 GISTs from 3 independent centers were separated into a training cohort (TC) or validation cohort (VC). In addition, the KIT-11 mutation genotype was classified into 4 categories: no KIT-11 mutation (K11-NM), point mutations or duplications (K11-PM/D), KIT-11 557/558 deletions (K11-557/558D), and KIT-11 deletion without codons 557/558 involvement (K11-D). Subsequently, radiomic signatures (RS) were generated based on the arterial phase of contrast CT, which were then developed as KIT-11 mutation predictors using 1408 quantitative image features and LASSO regression analysis, with further evaluation of its predictive capability. RESULTS: The TC AUCs for K11-NM, K11-PM/D, K11-557/558D, and K11-D ranged from 0.848 (95% CI 0.812-0.884), 0.759 (95% CI 0.722-0.797), 0.956 (95% CI 0.938-0.974), and 0.876 (95% CI 0.844-0.908), whereas the VC AUCs ranged from 0.723 (95% CI 0.660-0.786), 0.688 (95% CI 0.643-0.732), 0.870 (95% CI 0.824-0.918), and 0.830 (95% CI 0.780-0.878). Macro-weighted AUCs for the KIT-11 mutant genotype ranged from 0.838 (95% CI 0.820-0.855) in the TC to 0.758 (95% CI 0.758-0.784) in VC. TC had an overall accuracy of 0.694 (95%CI 0.660-0.729) for RS-based predictions of the KIT-11 mutant genotype, whereas VC had an accuracy of 0.637 (95%CI 0.595-0.679). CONCLUSIONS: CT radiomics signature exhibited good predictive performance in estimating the KIT-11 mutation genotype, especially in prediction of K11-557/558D genotype. RS-based classification of K11-NM, K11-557/558D, and K11-D patients may be an indication for choice of Imatinib therapy.

Insights into the Reduction Mechanisms of Np(VI) to Np(V) by Carbohydrazide.

An efficient approach to Np separation in the Plutonium Uranium Reduction EXtraction (PUREX) process is to adjust Np(VI) to Np(V) by free-salt reductants, such as hydrazine and its derivatives. Recently, carbohydrazide (CO(N2H3)2), a derivative of hydrazine and urea, has received much attention, which can reduce Np(VI) to Np(V) in the extraction reprocessing of spent nuclear fuel. Herein, according to the experimental observations, we examine the reduction mechanism of four Np(VI) by one carbohydrazide molecule using multiple theoretical calculations. The fourth Np(VI) reduction with a 22.26 kcal mol-1 energy barrier is the rate-determining step, which is in accordance with the experimental observations (20.54 ± 1.20 kcal mol-1). The results of spin density reflect that the reduction of the first and third Np(VI) ion is an outer-sphere electron transfer, while that of the second and fourth Np(VI) ion is the hydrogen transfer. Localized molecular orbitals (LMOs) uncover that the breaking of the N-H bond and formation of the Oyl-H bond are accompanied by the reaction from initial complexes (ICs) to intermediates (INTs). This work offers basic perspectives for the reduction mechanism of Np(VI) to Np(V) by CO(N2H3)2, which is also expected to design excellent free-salt Np(VI) reductants for the separation of Np in the advanced PUREX process.

Unveiling the Reduction Mechanism of Pu(IV) by Acetaldoxime.

The separation of plutonium (Pu) from spent nuclear fuel was achieved by effectively adjusting the oxidation state of Pu from +IV to +III in the plutonium uranium reduction extraction (PUREX) process. Acetaldoxime (CH3CHNOH) as a free salt reductant can rapidly reduce Pu(IV), but the reduction mechanism remains indistinct. Herein, we explore the reduction mechanism of two Pu(IV) ions by one CH3CHNOH molecule, where the second Pu(IV) reduction is the rate-determining step with the energy barrier of 19.24 kcal mol-1, which is in line with the experimental activation energy (20.95 ± 2.34 kcal mol-1). Additionally, the results of structure and spin density analyses demonstrate that the first and second Pu(IV) reduction is attributed to hydrogen atom transfer and hydroxyl ligand transfer, respectively. Analysis of localized molecular orbitals unveils that the reduction process is accompanied by the breaking of the Pu-OOH bond and the formation of the OOH-H and C-OOH bonds. The reaction energies confirm that the reduction of Pu(IV) by acetaldoxime is both thermodynamically and kinetically accessible. In this work, we elucidate the reduction mechanism of Pu(IV) with CH3CHNOH, which provides a theoretical understanding of the rapid reduction of Pu(IV).

Influence of early colorectal cancer component on the positive margins after endoscopic resection: a retrospective study.

BACKGROUND: Endoscopic treatment methods for early colorectal cancer (ECRC) mainly depend on the size and morphology. It is unclear whether different endoscopic resection methods could achieve curative resection for ECRC confined in the mucosa. The study was designed to compare the rate of positive vertical margin (VM) of ECRC with advanced adenomas (AAs) including adenoma > 1 cm, villous adenoma, high-grade intraepithelial neoplasia/dysplasia stratified by different endoscopic resection methods. METHODS: Rate of positive VM for 489 ECRCs including Intramucosal (pTis) and superficial submucosal invasion (pT1) carcinomas were compared with those of 753 AAs stratified by different endoscopic resection methods using Chi-squared test. Multivariate logistic model was performed to investigate the risk factors of positive VM for different endoscopic resection methods. RESULTS: The pTis ECRC exhibited a similar rate of positive VM as that of AAs for en bloc hot snare polypectomy (HSP, 0% Vs. 0.85%, P = 0.617), endoscopic mucosal resection (EMR, 0.81% vs. 0.25%, P = 0.375) and endoscopic submucosal dissection (ESD, 1.82% Vs. 1.02%, P = 0.659). The pTis carcinoma was not found to be a risk factor for positive VM by en bloc EMR (P = 0.349) or ESD (P = 0.368). The en bloc resection achieved for pT1a carcinomas exhibited similar to positive VM achieved through ESD (2.06% Vs. 1.02%, P = 1.000) for AAs. Nonetheless, EMR resulted in higher risk of positive VM (5.41% Vs. 0.25%, P < 0.001) for pT1a carcinomas as compared to AAs. The pT1a invasion was identified as a risk factor for positive VM in polyps with en bloc EMR (odds ratio = 23.90, P = 0.005) but not ESD (OR = 2.96, P = 0.396). CONCLUSION: Collectively, the pTis carcinoma was not found to be a risk factor for positive VM resected by en bloc HSP, EMR or ESD. Additionally, ESD may be preferred over EMR for pT1a carcinomas with lower rate of positive VM.

Reduction of Np(VI) with hydrazinopropionitrile via water-mediated proton transfer.

Effectively adjusting and controlling the valence state of neptunium (Np) is essential in its separation during spent fuel reprocessing. Hydrazine and its derivatives as free-salts can selectively reduce Np(VI) to Np(V). Reduction mechanisms of Np(VI) with hydrazine and four derivatives have been explored using multiple theoretical methods in our previous works. Herein, we examine the reduction mechanism of Np(VI) with hydrazinopropionitrile (NCCH2N2H3) which exhibits faster kinetics than most other hydrazine derivatives probably due to its σ-π hyperconjugation effect. Free radical ion pathways I, II and III involving the three types of hydrazine H atoms were found that correspond to the experimentally established mechanism of reduction of two Np(VI) via initial oxidation to [NCCH2N2H3]+˙, followed by conversion to NCCH2N2H (+2H3O+) and ultimately to CH3CN + N2. Potential energy profiles suggest that the second redox stage is rate-determining for all three pathways. Pathway I with water-mediated proton transfer is energetically preferred for hydrazinopropionitrile. Analyses using the approaches of localized molecular orbitals (LMOs), quantum theory of atoms in molecules (QTAIM), and intrinsic reaction coordinate (IRC) elucidate the bonding evolution for the structures on the reaction pathways. The results of the spin density reveal that the reduction of the first Np(VI) ion is the outer-sphere electron transfer, while that of the second Np(VI) ion is the hydrogen transfer. This work offers new insights into the nature of reduction of Np(VI) by hydrazinopropionitrile via water-mediated proton transfer, and provides a basis for designing free-salt reductants for Np separations.

Efficacy of international web-based educational intervention in the detection of high-risk flat and depressed colorectal lesions higher (CATCH project) with a video: Randomized trial.

OBJECTIVES: Three subcategories of high-risk flat and depressed lesions (FDLs), laterally spreading tumors non-granular type (LST-NG), depressed lesions, and large sessile serrated lesions (SSLs), are highly attributable to post-colonoscopy colorectal cancer (CRC). Efficient and organized educational programs on detecting high-risk FDLs are lacking. We aimed to explore whether a web-based educational intervention with training on FIND clues (fold deformation, intensive stool/mucus attachment, no vessel visibility, and demarcated reddish area) may improve the ability to detect high-risk FDLs. METHODS: This was an international web-based randomized control trial that enrolled non-expert endoscopists in 13 Asian countries. The participants were randomized into either education or non-education group. All participants took the pre-test and post-test to read 60 endoscopic images (40 high-risk FDLs, five polypoid, 15 no lesions) and answered whether there was a lesion. Only the education group received a self-education program (video and training questions and answers) between the tests. The primary outcome was a detection rate of high-risk FDLs. RESULTS: In total, 284 participants were randomized. After excluding non-responders, the final data analyses were based on 139 participants in the education group and 130 in the non-education group. The detection rate of high-risk FDLs in the education group significantly improved by 14.7% (66.6-81.3%) compared with -0.8% (70.8-70.0%) in the non-education group. Similarly, the detection rate of LST-NG, depressed lesions, and large SSLs significantly increased only in the education group by 12.7%, 12.0%, and 21.6%, respectively. CONCLUSION: Short self-education focusing on detecting high-risk FDLs was effective for Asian non-expert endoscopists. (UMIN000042348).

[Establishment and verification of quality evaluation method of Jizhi Syrup based on quantitative analysis of multi-components by single marker].

A quantitative analysis of multi-components by single marker(QAMS) method was established for the simultaneous determination of ephedrine hydrochloride, protocatechuic acid, 5-caffeoylquinic acid, 4-hydroxybenzoic acid, naringin, neohesperidin, glycyrrhizic acid, and praeruptorin A in Jizhi Syrup by high performance liquid chromatography(HPLC) with ultraviolet multi-wavelength detection system, and its feasibility in quality evaluation of Jizhi syrup was verified. With naringin as the internal reference substance, the relative correction factors and chromatographic peak localization methods of other seven components were respectively established at 210, 254, 280, and 320 nm. The method reproducibility was validated, and the result of QAMS were compared with those obtained by the external standard method(ESM) to verify the accuracy and feasibility of the method. The relative correction factors of ephedrine hydrochloride, protocatechuic acid, 5-caffeoylquinic acid, 4-hydroxybenzoic acid, neohesperidin, glycyrrhizic acid, and praeruptorin A with naringin as reference were 0.846, 0.582, 0.608, 0.293, 0.913, 2.207, and 0.940, respectively, which presented excellent reproducibility under different experimental conditions. Furthermore, QAMS and ESM showed no significant difference in the results for 15 batches of samples. Except protocatechuic acid and 5-caffeoylquinic acid, other six compounds were the exclusive components of single medicinal materials. In addition, glycyrrhizic acid and praeruptorin A were identified in the Jizhi Syrup for the first time, filling up the blank of no component detected in Glycyrrhizae Radix et Rhizoma and Peucedani Radix. The method established in this study is convenient, efficient, specific, accurate, and reliable, which can comprehensively and effectively evaluate the quality of Jizhi Syrup to ensure the safety and efficacy of this drug in clinical application.

[Active constituents of Urtica fissa in inhibition of benign prostatic hyperplasia].

The present study investigated the material basis of Urtica fissa for the inhibition of benign prostatic hyperplasia(BPH). The active fractions were screened, and the extracts of dichloromethane and ethyl acetate exhibited significantly inhibitory activities against 5α-reductase in vitro and BPH in model rats. The chemical constituents in the active fractions were systematically investigated, and 28 compounds were obtained, which were identified as lobechine methyl ester(1), dibutyl-O-phthalate(2), 1-monolinolein(3), epipinoresinol(4), 5-hydroxy-3,4-dimethyl-5-pentanyl-2(5H)-furanone(5), E-7,9-diene-11-methenyl palmitic acid(6), evofolin B(7), ficusal(8), threo-2,3-bis-(4-hydroxy-3-methoxyphenyl)-3-ethoxypropan-1-ol(9), α-viniferin(10),(9R,7E)-9-hydroxy-5,7-mengatigmadien-4-one-9-O-ß-D-glucopyranoside(11), indole-3-carboxaldehyde(12), p-hydroxy ethyl cinnamate(13), benzyl alcohol-O-ß-D-glucoside(14), L-methionine(15), 4-methoxyaniline(16), 6-aminopurine(17), 8'-acetyl oilvil(18), 4-methoxyl-8'-acetyl oilvil(19), vanillic acid(20), ß-hydroxypropiovanillone(21), 7-hydroxy-6-methoxycoumarin(22), p-hydroxybenzaldehyde(23), pinoresinol(24), erythro-1,2-bis-(4-hydroxy-3-methoxyphenyl)-1,3-propanediol(25), urticol(26), urticol-7-O-ß-D-glucopyranoside(27), and lobechine(28). Compounds 1-17 were isolated from U. fissa for the first time. Meanwhile, compound 1 was a new natural product. Compounds 10, 11, 19, 21, and 27 exhibited significant inhibitory effects on 5α-reductase.

[Chemical constituents from Urtica dioica fruits].

The chemical constituents in Urtica dioica fruits were investigated by silica gel chromatography, preparative HPLC, NMR, and HR-MS for the first time. As a result, 21 compounds were isolated from the fruits of U. dioica and identified 7R,8S,8'R-olivil(1), oleic acid(2), α-linoleic acid(3), palmic acid(4), methyl palmitate(5), α-linolenic acid(6), α-linolenic acid methyl ester(7), 5-O-caffeoyl-shikimic acid(8), vanillic acid(9), p-coumaric acid(10), 5-O-p-coumaroylshikimic acid(11), cinnamic acid(12), quinic acid(13), shikimic acid(14), ethyl caffeate(15), coniferyl ferulate(16), ferulic acid(17), caffeic acid(18), chlorogenic acid(19), pinoresinol(20), and quercetin(21). Compound 1 was a new compound and compounds 2-16 were isolated from U. dioica for the first time.

Neo-adjuvant radiation therapy provides a survival advantage in T3-T4 nodal positive gastric and gastroesophageal junction adenocarcinoma: a SEER database analysis.

BACKGROUND: Due to negative results in clinical trials of postoperative chemoradiation for gastric cancer, at present, there is a tendency to move chemoradiation therapy forward in gastric and gastroesophageal junction (GEJ) adenocarcinoma. Several randomized controlled trials (RCTs) are currently recruiting subjects to investigate the effect of neo-adjuvant radiotherapy (NRT) in gastric and GEJ cancer. Large retrospective studies may be beneficial in clarifying the potential benefit of NRT, providing implications for RCTs. METHODS: We retrieved the clinicopathological and treatment data of gastric and GEJ adenocarcinoma patients who underwent surgical resection and chemotherapy between 2004 and 2015 from Surveillance, Epidemiology, and End Results (SEER) database. We compared survival between NRT and non-NRT patients among four clinical subgroups (T1-2N-, T1-2N+, T3-4N-, and T3-4N+). RESULTS: Overall, 5272 patients were identified, among which 1984 patients received NRT. After adjusting confounding variables, significantly improved survival between patients with and without NRT was only observed in T3-4N+ subgroup [hazard ratio (HR) 0.79, 95% confidence interval (CI): 0.66-0.95; P = 0.01]. Besides, Kaplan-Meier plots showed significant cause-specific survival advantage of NRT in intestinal type (P <  0.001), but not in diffuse type (P = 0.11) for T3-4N+ patients. In the multivariate competing risk model, NRT still showed survival advantage only in T3-4 N+ patients (subdistribution HR: 0.77; 95% CI: 0.64-0.93; P = 0.006), but not in other subgroups. CONCLUSIONS: NRT might benefit resectable gastric and GEJ cancer patients of T3-4 stages with positive lymph nodes, particularly for intestinal-type. Nevertheless, these results should be interpreted with caution, and more data from ongoing RCTs are warranted.

Theoretical Insights into the Reduction Mechanism of Np(VI) with Phenylhydrazine.

Effectively adjusting and controlling the valence state of neptunium from the spent fuel reprocessing process is essential to separating neptunium. Hydrazine and its derivatives as free-salt reductants have been experimentally demonstrated to effectively reduce Np(VI) to Np(V). We have theoretically investigated the reduction mechanisms of Np(VI) with hydrazine and three derivatives (HOC2H4N2H3, CH3N2H3, and CHON2H3) in previous works. Herein, we further explored the reduction reaction of Np(VI) with phenylhydrazine (C6H5N2H3) including the free radical ion mechanism and the free radical mechanism. Potential energy profiles (PEPs) indicate that the rate-determining step of both mechanisms is the first stage. Moreover, for the free radical ion mechanism, phenylhydrazine possesses better reduction ability to Np(VI) compared to HOC2H4N2H3, CH3N2H3, and CHON2H3, which falls completely in line with the experimental results. Additionally, the analyses of the quantum theory of atoms in molecules (QTAIM), natural bond orbitals (NBOs), electron localization function (ELF), and localized molecular orbitals (LMOs) have been put forward to elucidate the bonding evolution for the structures of the reaction pathways. This work offers insights into the reduction mechanism of Np(VI) with phenylhydrazine from the theory point of view and contributes to design more high-efficiency reductants for the separation of U/Np and Np/Pu in spent fuel reprocessing.

Poorly differentiated is more significant than signet ring cell component for lymph node metastasis in mixed-type early gastric cancer: a retrospective study from a large-volume hospital.

OBJECTIVE: The purpose of this study was to explore the role of different undifferentiated components in the lymph node metastasis (LNM) of early mixed gastric cancer. METHODS: A total of 1596 patients with EGC who underwent gastrectomy were divided into four types: pure differentiated (PD), pure poorly differentiated (Poorly D), pure signet ring cell carcinoma (SRC), and mixed. Mixed type was classified into four subtypes: differentiated-predominant type mixed with poorly differentiated component (MD-P), poorly differentiated-predominant type mixed with differentiated component (MP-D), differentiated-predominant type mixed with SRC component (MD-S), and poorly differentiated-predominant type mixed with SRC component (MP-S). We analyzed the clinicopathological differences between all types and the rates of LNM of patients fulfilling endoscopic submucosal dissection (ESD) criteria. RESULTS: LNM was more common in mixed (21.9%) than in PD (7.5%, P < 0.001) or SRC (11.3%, P < 0.001). When analyzed the subgroups of mixed type, LNM was more frequent in MD-P (15.4%) than in PD (7.5%, P = 0.003). LNM in MD-S (7.4%, P = 1.000) was not higher than in PD. MP-S (24.5%) showed a higher rate of LNM than SRC (11.3%, P < 0.001) rather than Poorly-D (22.7%, P = 0.681). For lesions satisfying ESD criteria, MD-S (0%, P = 1.000), and MD-P (5.9%, P = 0.12) did not have higher rates of LNM than PD (1.4%). CONCLUSION: The presence of poorly differentiated component but not SRC increases the LNM rate of mixed type. ESD is recommended for the treatment of MD-S and MD-P consistent with ESD criteria.

Association between positivity of serum autoantibodies and liver disease severity in patients with biopsy-proven NAFLD.

BACKGROUND AND AIMS: Some previous studies reported serum autoantibody positivity in patients with nonalcoholic fatty liver disease (NAFLD). The clinical significance of these findings remains uncertain. We aimed to investigate the association between the presence of serum autoantibodies and liver disease severity in NAFLD. METHODS AND RESULTS: A total of 388 consecutive patients with biopsy-proven NAFLD were included in the study. Various serum autoantibodies (including also anti-nuclear antibodies [ANA]) were detected by indirect immunofluorescent or immunoblotting assays. Overall, 84 (21.6%) patients with biopsy-confirmed NAFLD had positivity for at least one of the measured serum autoantibodies. ANA positivity was present in 50 (12.9%) patients, whereas anti-U1RNP or pANCA antibodies were detectable in 9 (2.3%) and 6 (1.5%) patients, respectively. Multivariate logistic regression analysis showed that ANA positivity (adjusted-odds ratio: 4.51, 95%CI: 1.77-11.5; P = 0.002) or positivity of any serum autoantibodies (adjusted-odds ratio: 3.14, 95%CI: 1.30-7.62; P = 0.01) were independently associated with advanced liver fibrosis (stages F3-F4). In serum autoantibody/ANA-positive patients, the proportion of those with advanced fibrosis was also greater among carriers of PNPLA3 rs738409 GG or CG than among those carrying PNPLA3 rs738409 CC genotype. CONCLUSIONS: Serum autoantibody positivity was independently associated with advanced liver fibrosis in patients with biopsy-proven NAFLD. The presence of serum autoantibodies in patients with advanced fibrosis occurred more frequently amongst those carrying PNPLA3 rs738409 GG or CG genotypes.

[Lignans with inhibitory effect on 5α-reductase from Urtica cannabina].

The lignans in Urtica cannabina were isolated by preparative HPLC, silica, and ODS column chromatographies, and identified by NMR and HR-MS. The inhibitory activities on 5α-reductase were evaluated in vitro. As a result, ten secolignans,(2R,4S)-2,4-bis(3-methoxyl-4-hydroxyphenyl)-3-butoxypropanol(1), 3,4-trans-3-hydroxymethyl-4-[bis(3,4-dimethoxyphenyl)methyl] butyrolactone(2), 3,4-trans-3-hydroxymethyl-4-[(3,4-dimethoxyphenyl)(3-methoxyl-4-hydroxyphenyl)methyl] butyrolactone(3), 3,4-trans-3-hydroxymethyl-4-[bis(3-methoxyl-4-hydroxyphenyl)methyl] butyrolactone(trans urticol, 4), 3,4-trans-3-hydroxymethyl-4-[bis(3,4-dimethoxyphenyl)methyl] butyrolactone-3-O-ß-D-glucopyranoside(5), 3,4-trans-3-hydroxymethyl-4-[(3,4-dimethoxyphenyl)(3-methoxyl-4-hydroxyphenyl)methyl]butyrolactone-3-O-ß-D-glucopyranoside(6), 3,4-trans-3-hydroxymethyl-4-[bis(3-methoxyl-4-hydroxyphenyl)methyl]butyrolactone-3-O-ß-D-glucopyranoside(trans-urticol-7-O-ß-D-glucopyranoside, 7), cycloolivil-4-O-ß-D-glucopyranoside(8), isolariciresinol-4'-O-ß-D-glucopyranoside(9), and olivil-4'-O-ß-D-glucopyranoside(10), together with a polyphenol [α-viniferin(11)], were isolated from U. cannabina for the first time. Compound 1 was a new lignan. Compound 7 was potent in inhibiting 5α-reductase.

Identification and validation of tumour microenvironment-based immune molecular subgroups for gastric cancer: immunotherapeutic implications.

BACKGROUND: Immunotherapy could trigger durable response in advanced gastric cancer, but it only benefits a minority of patients. We aimed to propose a robust molecular classification of gastric cancer microenvironment to identify ideal candidates for tailoring effective immunotherapy. METHODS: A training cohort of 375 gastric cancer samples with RNA sequencing data was analysed. We virtually microdissected tumour, stromal, and immune cell gene expression patterns employing a non-negative matrix factorization algorithm. These expression patterns were annotated using immune- and stromal-related gene signatures. Validation of immunogenomic classification was performed across six microarray datasets of 1406 samples. RESULTS: We found approximately half of gastric cancer samples to have higher immune cell infiltrates, PD-L1 expression, markers of cytolytic activity, and fewer copy number aberrations (all P < 0.05). We termed this group of tumours the Immune Class, which incorporated two components, namely Immune Activation and Immunosuppressive Subtype, according to immunosuppressive or activated microenvironment. Immune Activation Subtype was associated with improved survival in multivariate survival analysis and shared similar genomic characteristics with responders of anti-PD-1 therapy. Immunosuppressive Subtype featured high immune infiltration, stromal enrichment, and transforming growth factor (TGF)-ß signalling pathway activation and correlated with non-responsiveness signature of checkpoint blockade therapy, which might be suitable for anti-PD-L1 and anti-TGF-ß combined therapy. CONCLUSIONS: We proposed and independently validated three reproducible immune molecular subtypes of gastric cancer, which may provide implications for patient selection of immunotherapy.

Marital status, an independent predictor for survival of gastric neuroendocrine neoplasm patients: a SEER database analysis.

BACKGROUND: Marital status proves to be an independent prognostic factor in a variety of cancers. However, its prognostic impact on gastric neuroendocrine neoplasms (G-NEN) has not been investigated. METHODS: We identified 3947 G-NEN patients from the Surveillance, Epidemiology, and End Results (SEER) database. Meanwhile, propensity scores for marital status were used to match 506 unmarried patients with 506 married patients. We used Kaplan-Meier method and multivariate Cox regression to analyse the association between marital status and the overall survival (OS) and G-NEN cause-specific survival (CSS) before matching and after matching. RESULTS: Married patients enjoyed better OS and CSS, compared with divorced/separated, single, and widowed patients. Multivariate Cox regression analysis indicated that unmarried status was associated with higher mortality hazards for both OS and CSS among G-NEN patients. Additionally, widowed individuals had the highest risks of overall (adjusted hazard ratio (HR): 1.56, 95% confidence interval (CI): 1.35-1.81, P < 0.001) and cancer-specific mortality (adjusted HR: 1.33, 95% CI: 1.05-1.68, P = 0.02) compared to other unmarried groups in both males and females. Furthermore, unmarried status remained an independent prognostic and risk factor for both OS (HR 1.51, 95% CI 1.19-1.90, P = 0.001) and CSS (HR 1.50, 95% CI 1.10-2.05, P = 0.01) in 1:1 propensity score-matched analysis. CONCLUSION: Marital status was an independent prognostic factor for G-NEN. Meanwhile, widowed patients with G-NEN had the highest risk of death compared with single, married, and divorced/separated patients.

Theoretical Study on the Reduction Mechanism of Np(VI) by Hydrazine Derivatives.

The key to effective separation of neptunium from the spent fuel reprocessing process is to adjust and control its valence state. Hydrazine and its derivatives have been experimentally confirmed to be effective salt-free reductants for reducing Np(VI) to Np(V). We theoretically studied the reduction reactions of Np(VI) with three hydrazine derivatives (2-hydroxyethyl hydrazine (HOC2H4N2H3), methyl hydrazine (CH3N2H3), and formyl hydrazide (CHON2H3)) and obtained the free radical ion mechanism and the free radical mechanism. Their potential energy profiles (PEPs) suggest that the free radical mechanism is the most probable reaction. Based on the energy barrier of the free radical ion mechanism, the trend of the reduction ability of the three hydrazine derivatives is HOC2H4N2H3 > CH3N2H3 > CHON2H3, which is in excellent agreement with the experimental results. Lastly, the analyses of natural bond orbitals (NBOs), quantum theory of atoms-in-molecules (QTAIM), and electron localization function (ELF) have been carried out to explore the bonding evolution of the structures along the reaction pathways. This work provides an insight into the reduction mechanism of Np(VI) with hydrazine derivatives from the theoretical perspective and helps to design more effective reductants for the separation of U/Np and Np/Pu in spent fuel reprocessing.

EGFL6 promotes cell proliferation in colorectal cancer via regulation of the WNT/ß-catenin pathway.

Epidermal growth factor-like protein 6 (EGFL6) serves as an exocrine protein promoting proliferation and migration during carcinogenesis in ovarian cancer. However, its function and mechanisms in colorectal cancer (CRC) have not been completely explored. To investigate the role of EGFL6 in CRC cell growth, in vitro CCK8, colony formation assays, flow cytometric analysis of the cell cycle and apoptosis, and an in vivo tumor xenograft model were utilized. Additionally, Western blotting and luciferase reporter assays were used to investigate the underlying mechanisms of EGFL6 function on the WNT/ß-catenin signaling pathway. Immunohistochemical staining showed that EGFL6 is overexpressed in CRCs and this overexpression was highly correlated with advanced T classification, N classification, distant metastasis, and poor survival. Knocking down EGFL6 in CRC cell lines induced the inhibition of cell growth, cell cycle arrest at the G0/G1 phase, and apoptosis. Further, knockdown of EGFL6 blocked WNT/ß-catenin signaling as measured by Western blotting and luciferase reporter assay. Results also showed that recombinant EGFL6 (rEGFL6) induced ß-catenin in a concentration- and time-dependent manner. Further experiments showed that administration of rEGFL6 to cell cultures with EGFL6 knocked down or treated with the WNT/ß-catenin inhibitor ICG-001 increased ß-catenin and its downstream protein CyclinD1. The CCK8 assay showed that EGFL6 promoted CRC cell growth partly by the promotion of TCF7L2 expression. These findings suggest that EGFL6 plays a crucial role in the progression of CRC by regulation of the WNT/ß-catenin signaling pathway.