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• Two new CPs based on a semi-rigid tricarboxylate, 5-(3,4-dicarboxylphenoxy) nicotic acid (H3L) have been isolated under hydrothermal conditions. • CP 1 shows 2-D 4-connected uninodal (44ˑ62) layer. • CP 2 exhibits a 3-connected uninodal hcb 2-D layer structure. • The solid-state photoluminescence analysis indicated that both compounds emit blue light. Coordination polymers (CPs), particularly rich conjugate π-electron ligands derived CPs, have been excessively studied for their photophysical properties and promising applications as fluorescence-emitting materials. Two novel coordination polymers (CPs) based on a semi-rigid multifunctionaltricarboxylate, namely,5-(3,4-dicarboxylphenoxy) nicotic acid (H 3 L) have been solvothermallysynthesized: [Cu(H 2 L) 2 (H 2 O) 2 1 , [Cu(HL)(2,2′-bpy)] (2,2′-bpy = 2,2′-bipyridine) 2. The structures, CHN analysis, IR analysis, UV–vis absorption spectra,thermal stability of bothCPs were researched. Single-crystal X-ray diffraction analysis indicates that CP 1 exhibits the individual 2-D layer structure with a 4-connected uninodal (44ˑ62) topology, which self-assembles into a final3-D supramolecular network. For CP 2 , the introduced ancillary N-donor ligand2.2′-bpy only acts as a decorative part, thus 2 also takes a 2-D layer structure. Note that the 2-D layer with 3-connected uninodal hcb topology of CP 2 is very distinct from that of CP 1. Additionally, the solid-state photoluminescence analysis indicated that both compounds emit blue light. [ABSTRACT FROM AUTHOR]

Abstract: An alternative low cost method was proposed for the low temperature (600°C) preparation of CdTiO3 nanoplates, using low-melting-point Cd(NO3)2 ·4H2O and high-reactive-activity TiO2 nanocrystals as the reactants. The structure, composition, specific surface area, thermal stability and optical properties of the as-synthesized products were characterized by X-ray diffraction, energy dispersive X-ray spectroscopy, field emission scanning electron microscopy, Brunauer–Emmett–Teller surface area analysis, UV–vis absorption and room temperature photoluminescence spectra. The as-synthesized CdTiO3 nanoplates were thermally stable at temperatures ≤900°C, and their phase changed from ilmenite to perovskite when heated in air at 1000°C for 2h. Besides, they exhibited a strong and broad visible light emission in the range of about 470–750nm upon laser excitation at 325nm, enabling their use as a luminescent material. [Copyright &y& Elsevier]

Long noncoding RNAs play important roles in various biological processes. However, not much is known about their roles in inflammatory response. Mast cells, involved in innate and adaptive immunity, are one of the major effector cells in allergic inflammatory reactions and contribute to the pathogenesis of disorders, including asthma. In the present study, we aimed to verify and elucidate the function and possible role of a novel lncRNA, called lncRNA-AK149641, in the mechanism of lipopolysaccharide (LPS)-induced inflammatory response in P815 mast cells. The results showed that downregulating lncRNA-AK149641 decreased secretion of tumor necrosis factor-α into the supernatants of LPS-stimulated mast cells. Mechanistically, the activity of nuclear factor-kappa B (NF-κB) decreased after downregulating lncRNA-AK149641, as shown by western blot and electrophoretic mobility shift assays. Moreover, RNA binding protein immunoprecipitation (RIP) verified that lncRNA-AK149641 was able to bind to NF-κB in the nucleus. In conclusion, we demonstrated that lncRNA-AK149641 regulated LPS-induced inflammatory response in mast cells through the NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Propolis is one functional supplement with hundreds of years of usage. However, it's rarely consumed directly for its resinous property. Herein, a pre-treated process which can remove the impurity while preserve its bioactivities is needed to maximise its therapeutic opportunities. In the present study, a membrane-based ultrafiltration process was developed on a KM1812-NF experimental instrument. Using Brazilian green propolis as testing material, all experimental steps and parameters were sequentially optimized. In addition, a mathematical model was developed to fit the process. As a result, the optimum solvent was 60 % ethanol adjusted to pH 8-9, while the optimum MWCO (molecular weight cut-off) value of membrane was 30 KDa. The membrane filtration dynamic model fitted with the function y=(ax+b)/(1+cx+dx 2 ). The resulting propolis ultrafiltrate from Brazilian green propolis, termed P30K, contains the similar profile of flavonoids and phenolic acids as raw propolis. Meanwhile, the ORAC (oxygen radical absorbance capacity) value of P30K is 11429.45±1557.58 μM TE/g and the IC 50 value of inhibition of fluorescent AGEs (advanced glycation end products) formation is 0.064 mg/mL. Our work provides an innovative alternative process for extraction of active compounds from propolis and reveals P30K as an efficient therapeutic antioxidant., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

A one-pot step-economic tandem process involving (5 + 2)-cycloaddition and Nazarov cyclization reactions has been reported for the facile synthesis of indanone-fused benzo[ cd ]azulenes from ( E )-2-arylidene-3-hydroxyindanones and conjugated eneynes. This highly regio- and stereoselective bisannulation reaction is enabled by dual silver and Brønsted acid catalysis and opens up a new avenue for the construction of important bicyclo[5.3.0]decane skeletons.

Objective: To observe the effect of electroacupuncture (EA) at "Zhongliao" (BL33) and "Xialiao" (BL34) on the 5-hydroxytryptamine (5-HT) signaling system in colon tissue and short-chain fatty acids in feces of rats with slow transit constipation (STC), so as to explore the underlying mechanisms of EA in the treatment of STC., Methods: A total of 32 SD rats were randomly divided into normal, model, drug control and EA groups, with 8 rats in each group. The STC model was established by intragastric administration of loperamide for 14 days. The EA stimulation (2 Hz/15 Hz) was performed at bilateral BL33 and BL34 for 30 min, once a day for 14 days. The first black stool de-fecation time and fecal water content were detected after treatment. The expressions of 5-hydroxytryptamine 4 receptor (5-HT4R), tryptophan hydroxylase 1 (TPH1) and 5-HT transporter (SERT) in colon tissues were detected by Western blot. The contents of substance P (SP) and vasoactive intestinal peptide (VIP) in serum were detected by ELISA. The contents of 5-HT in colon tissue and short chain fatty acid (SCFA) in feces were detected by mass spectrometry., Results: Compared with the normal group, the fecal water content, the expressions of 5-HT, 5-HT4R, TPH1 and SERT in colon tissue, the content of serum SP were significantly decreased ( P <0.05), the first black stool de-fecation time, and the content of serum VIP was significantly increased ( P <0.05), the contents of SCFA in feces were significantly decreased except isobutyric acid ( P <0.05) in the model group. Compared with the model group, the fecal water content, the expressions of 5-HT, 5-HT4R, TPH1 and SERT in colon tissues, the contents of acetic acid and butyrate in feces were significantly increased ( P <0.05) in the EA and drug control groups, the first black stool defecation time was decreased ( P <0.05) in the EA and drug control groups, and the content of serum SP was increased and the content of serum VIP was decreased ( P <0.05) in the EA group. Compared with the drug control group, the content of serum VIP was significantly decreased ( P <0.05), and the expressions of TPH1 and SERT in colon tissue were significantly increased ( P <0.05) in the EA group., Conclusion: EA at BL33 and BL34 can promote intestinal motility by intervening multiple links of 5-HT signaling system in treating STC.

Background: No large-scale epidemiological survey on the prevalence of gastroesophageal reflux disease (GERD) in China has been conducted. China has a large population and a complex geographical environment. It is important to understand the prevalence and spatial distribution of GERD in China., Aim: To explore the prevalence and the spatial, temporal, and population distributions of GERD in the natural Chinese population., Methods: We searched Chinese and English databases for literature on the prevalence of GERD in the natural Chinese population. The prevalence of GERD was pooled using a random-effects meta-analysis model. Subgroup analysis was performed according to time, region, and population. We used ArcGIS software to draw statistical maps and trend analysis charts. Spatial autocorrelation analysis was carried out using Geoda software. Spearman correlation analysis was used to assess the spatial distribution relationship between GERD and upper digestive tract tumours., Results: Altogether, 70 studies involving 276014 individuals from 24 provinces of China were included. The overall pooled prevalence of GERD was 8.7% (95%CI: 7.5%-9.9%) in mainland China. Over the past two decades, the prevalence of GERD in China has increased from 6.0% to 10.6%. GERD was more common in people aged 40-60, with body mass index ≥ 24, and of Uygur ethnicity. The prevalence was higher in the west and east than in the centre, and there may be a local spatial autocorrelation between the Qinghai-Tibet Plateau and the southeast. GERD was correlated with gastric ( r = 0.421, P = 0.041) and oesophageal tumours ( r = 0.511, P = 0.011) in spatial distribution., Conclusion: GERD is becoming common in China. The prevalence differs by region and population. The development of appropriate strategies for the prevention and treatment of GERD is needed., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Alternative lengthening of telomeres (ALT), a telomerase-independent process maintaining telomeres, is mediated by break-induced replication (BIR). RAD52 promotes ALT by facilitating D-loop formation, but ALT also occurs through a RAD52-independent BIR pathway. Here, we show that the telomere non-coding RNA TERRA forms dynamic telomeric R-loops and contributes to ALT activity in RAD52 knockout cells. TERRA forms R-loops in vitro and at telomeres in a RAD51AP1-dependent manner. The formation of R-loops by TERRA increases G-quadruplexes (G4s) at telomeres. G4 stabilization enhances ALT even when TERRA is depleted, suggesting that G4s act downstream of R-loops to promote BIR. In vitro, the telomeric R-loops assembled by TERRA and RAD51AP1 generate G4s, which persist after R-loop resolution and allow formation of telomeric D-loops without RAD52. Thus, the dynamic telomeric R-loops formed by TERRA and RAD51AP1 enable the RAD52-independent ALT pathway, and G4s orchestrate an R- to D-loop switch at telomeres to stimulate BIR., Competing Interests: Declaration of interests L.Z. is a member of the advisory board of Molecular Cell., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Rabbit meat is a good edible meat source with high nutritional values. Cooking has a significant impact on the edible properties, nutritional qualities and flavor characteristics of meat. Studying the effect of cooking methods on rabbit meat qualities could encourage more understanding and acceptance of rabbit meat by consumers, and could also provide some reference for rabbit meat processing. Therefore, the effects of boiling, sous-vide cooking, steaming, microwaving, roasting, frying and pressure cooking on the edible, nutritive and volatile qualities of rabbit meat were investigated., Results: The sous-vide cooked rabbit meat sample showed higher moisture content, water-holding capacity and lower cooking losses than other samples, but the results of roasted rabbit meat sample were the opposite, and scanning electron microscopy observations also verified the results. There was no significant difference in 2-thiobarbituric acid reactive substance (TBARS) value in the cooked samples except for roasting. Microwaving, roasting and frying exhibited stronger antioxidant activity than the other cooked samples after in vitro digestion. A total of 38 volatiles were identified in the cooked meat samples, and the samples were well divided into four groups by principal component analysis, and 13 volatiles were considered discriminatory variables for the cooked rabbit meat., Conclusion: The physicochemical characteristics of cooked meat differed significantly between the processing methods. Roasted meat showed lower TBARS value and stronger antioxidant activity after simulated digestion compared to the other meats. However, pressure cooked meat detected the most volatile components while roasting the least. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

Alternative lengthening of telomeres (ALT) is a telomerase-independent but recombination-dependent pathway that maintains telomeres. Here, we describe a protocol to stimulate the formation of ALT-associated PML bodies (APBs) and ALT activity by tethering PML-IV to telomeres in human U2OS cells. Through immunofluorescence, in situ hybridization, and microscopy, we analyze dynamics of telomere clustering, visualize recruitment of DNA repair proteins to APBs, and measure telomere DNA synthesis during ALT. This protocol provides a unique approach to delineate the ALT pathway. For complete details on the use and execution of this protocol, please refer to Zhang et al. (2021)., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

Background: The spatial-temporal distribution of Helicobacter pylori infection in China is poorly understood. We aimed to study the spatial-temporal distribution of H. pylori infection in Chinese mainland and to explore its influencing factors., Materials and Methods: We searched the relevant literature from 2001 to 2021 and applied meta-analysis to obtain the pooled prevalence estimates of all studies and subgroups. Then, we used the pooled prevalence as the dependent variable for the following analysis, including time series analysis, statistical mapping, spatial autocorrelation analysis, and influencing factor analysis based on generalized additive model and panel data model., Results: A total of 726 articles and 3,407,392 people were included. The pooled prevalence was 43.7% (95% confidence interval: 42.7%-44.8%). The prevalence decreased in the past 20 years, with high in the eastern and western regions and low in the central region. Qinghai Tibet Plateau and Guizhou Plateau were the high incidence areas of this disease. The intake of vegetable oil, aquatic products, meat, milk, per capita gross domestic product, and annual average humidity were significantly correlated with H. pylori., Conclusions: The prevalence of H. pylori is decreasing in Chinese mainland, but still high in underdeveloped areas. Appropriate strategies for the prevention need greater attention., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Homologous recombination (HR) repairs DNA double-strand breaks (DSBs) in the S and G2 phases of the cell cycle 1-3 . Several HR proteins are preferentially recruited to DSBs at transcriptionally active loci 4-10 , but how transcription promotes HR is poorly understood. Here we develop an assay to assess the effect of local transcription on HR. Using this assay, we find that transcription stimulates HR to a substantial extent. Tethering RNA transcripts to the vicinity of DSBs recapitulates the effects of local transcription, which suggests that transcription enhances HR through RNA transcripts. Tethered RNA transcripts stimulate HR in a sequence- and orientation-dependent manner, indicating that they function by forming DNA-RNA hybrids. In contrast to most HR proteins, RAD51-associated protein 1 (RAD51AP1) only promotes HR when local transcription is active. RAD51AP1 drives the formation of R-loops in vitro and is required for tethered RNAs to stimulate HR in cells. Notably, RAD51AP1 is necessary for the DSB-induced formation of DNA-RNA hybrids in donor DNA, linking R-loops to D-loops. In vitro, RAD51AP1-generated R-loops enhance the RAD51-mediated formation of D-loops locally and give rise to intermediates that we term 'DR-loops', which contain both DNA-DNA and DNA-RNA hybrids and favour RAD51 function. Thus, at DSBs in transcribed regions, RAD51AP1 promotes the invasion of RNA transcripts into donor DNA, and stimulates HR through the formation of DR-loops.

Alternative lengthening of telomeres (ALT) is mediated by break-induced replication (BIR), but how BIR is regulated at telomeres is poorly understood. Here, we show that telomeric BIR is a self-perpetuating process. By tethering PML-IV to telomeres, we induced telomere clustering in ALT-associated PML bodies (APBs) and a POLD3-dependent ATR response at telomeres, showing that BIR generates replication stress. Ablation of BLM helicase activity in APBs abolishes telomere synthesis but causes multiple chromosome bridges between telomeres, revealing a function of BLM in processing inter-telomere BIR intermediates. Interestingly, the accumulation of BLM in APBs requires its own helicase activity and POLD3, suggesting that BIR triggers a feedforward loop to further recruit BLM. Enhancing BIR induces PIAS4-mediated TRF2 SUMOylation, and PIAS4 loss deprives APBs of repair proteins and compromises ALT telomere synthesis. Thus, a BLM-driven and PIAS4-mediated feedforward loop operates in APBs to perpetuate BIR, providing a critical mechanism to extend ALT telomeres., Competing Interests: Declaration of interests The authors declare no competing interests. L.Z. is a member of the Advisory Board of Molecular Cell., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The traditional strategy to improve the efficiency of an entire coupled enzyme system relies on separate direction of the evolution of enzymes involved in their respective enzymatic reactions. This strategy can lead to enhanced single-enzyme catalytic efficiency but may also lead to loss of coordination among enzymes. This study aimed to overcome such shortcomings by executing a directed evolution strategy on multiple enzymes in one combined group that catalyzes the asymmetric biosynthesis of l -phosphinothricin. The genes of a glutamate dehydrogenase from Pseudomonas moorei ( Pm GluDH) and a glucose dehydrogenase from Exiguobacterium sibiricum ( Es GDH), along with other gene parts (promoters, ribosomal binding sites (RBSs), and terminators) were simultaneously evolved. The catalytic efficiency of PmGluDH was boosted by introducing the beneficial mutation A164G (from 1.29 s -1 mM -1 to 183.52 s -1 mM -1 ), and the Es GDH expression level was improved by optimizing the linker length between the RBS and the start codon of gdh. The total turnover numbers of the bioreaction increased from 115 (GluDH WT NADPH ) to 5846 (A164G NADPH coupled with low expression of Es GDH), and to 33950 (A164G NADPH coupled with high expression of Es GDH). The coupling efficiency was increased from ∼30% (GluDH&#95;WT with low expression of GDH) to 83.3% (GluDH&#95;A164G with high expression of GDH). In the batch production of l -phosphinothricin utilizing whole-cell catalysis, the strongest biocatalytic reaction exhibited a high space-time yield (6410 g·L -1 ·d -1 ) with strict stereoselectivity (>99% enantiomeric excess). Importance: The traditional strategy to improve multienzyme-catalyzed reaction efficiency may lead to enhanced single-enzyme catalytic efficiency but may also result in loss of coordination among enzymes. We describe a directed evolution strategy of an entire coupled enzyme system to simultaneously enhance enzyme coordination and catalytic efficiency. The simultaneous evolution strategy was applied to a multienzyme-catalyzed reaction for the asymmetric synthesis of l -phosphinothricin, which not only enhanced the catalytic efficiency of GluDH but also improved the coordination between GluDH and GDH. Since this strategy is enzyme-independent, it may be applicable to other coupled enzyme systems for chiral chemical synthesis., (Copyright © 2020 American Society for Microbiology.)

To escape replicative senescence, cancer cells have to overcome telomere attrition during DNA replication. Most of cancers rely on telomerase to extend and maintain telomeres, but 4-11% of cancers use a homologous recombination-based pathway called alternative lengthening of telomeres (ALT). ALT is prevalent in cancers from the mesenchymal origin and usually associates with poor clinical outcome. Given its critical role in protecting telomeres and genomic integrity in tumor cells, ALT is an Achilles heel of tumors and an attractive target for cancer therapy. Here, we review the recent progress in the mechanistic studies of ALT, and discuss the emerging therapeutic strategies to target ALT-positive cancers., Competing Interests: Competing interestsThe authors declares that they have no competing interests., (© The Author(s) 2020.)

Impaired megakaryocyte (MK) maturation and reduced platelet production are important causes of immune thrombocytopenia (ITP). However, MK distribution and bone marrow (BM) niche alteration in ITP are unclear. To investigate the maturation and distribution of MKs in the BM niche and examine the components of BM niche regulation of MK migration, BM and peripheral blood were obtained from 30 ITP patients and 28 healthy donors. Nestin + mesenchymal stem cells (MSCs) and CD41 + MKs were sorted by fluorescence-activated cell sorting. The components of the BM niche and related signaling were analyzed via immunofluorescence, flow cytometry, enzyme-linked immunosorbent assay, reverse transcription polymerase chain reaction, and western blot analysis. The number of MKs in the BM vascular niche was reduced in ITP. Moreover, the concentrations of CXCL12 and CXCR4 + MKs in the BM were decreased in ITP. Further investigation demonstrated that nestin + MSCs and CXCL12 messenger RNA (mRNA) in nestin + MSCs were both reduced whereas the apoptosis of nestin + MSCs was significantly increased in ITP. Sympathetic nerves, Schwann cells, the proportion of β3-adrenoreceptor (β3-AR) + nestin + MSCs, and β3-AR mRNA in nestin + MSCs were all markedly reduced in ITP. Moreover, matrix metalloproteinase 9, vascular endothelial growth factor (VEGF), and VEGF receptor 1 were significantly reduced in ITP. Our data show that impaired MK distribution mediated by an abnormal CXCL12/CXCR4 axis is partially involved in reduced platelet production in ITP. Moreover, sympathetic neuropathy and nestin + MSC apoptosis may have an effect on the alterations of BM CXCL12 in ITP., (© 2019 by The American Society of Hematology.)

Numerous DNA repair and signaling proteins function at DNA damage sites to protect the genome. Here, we show that fusion of the promiscuous biotin ligase BirA R118G with RAD18 leads to localized protein biotinylation at DNA damage sites, allowing identification of ZPET (zinc finger protein proximal to RAD eighteen)/ZNF280C as a potential DNA damage response (DDR) protein. ZPET binds ssDNA and localizes to DNA double-strand breaks (DSBs) and stalled replication forks. In vitro, ZPET inhibits MRE11 binding to ssDNA. In cells, ZPET delays MRE11 binding to chromatin after DSB formation and slows DNA end resection through binding ssDNA. ZPET hinders resection independently of 53BP1 and HELB. Cells lacking ZPET displayed enhanced homologous recombination (HR), accelerated replication forks under stress, and increased resistance to DSBs and PARP inhibition. These results not only reveal ZPET as an HR repressor but also suggest that localized protein biotinylation at DNA damage sites is a useful strategy to identify DDR proteins., (© 2019 Moquin et al.; Published by Cold Spring Harbor Laboratory Press.)

Our understanding of the pathogenesis of immune thrombocytopenia (ITP) remains limited due to the complexity and heterogeneity of the disease. Recently, we observed that bone marrow mesenchymal stem cells (MSCs) derived from ITP patients exhibited growth defects and functional abnormalities that might be involved in the breakdown of self-tolerance. However, the underlying mechanism remains unclear. In this study, we profiled the expression of both mRNAs and miRNAs by utilizing the microarray technique and deciphered the mechanism underlying the impairment of MSCs derived from ITP patients (MSC-ITP). In total, we identified 740 genes and 32 miRNAs that were differentially expressed between ITP patients and controls. A compromised unfolded protein response (UPR) and decreased DNA transcription were shown to be significantly related to MSC-ITP. The interaction of miRNA with mRNA suggested that the cellular stress response, the UPR, and DNA transcription may be involved in the defects observed in MSC-ITP. Key differentially expressed genes were further validated by RT-PCR. Our results highlight that defects in the cellular stress response, as shown by a compromised UPR and differential DNA transcription, play key roles in causing the abnormalities observed in MSC-ITP. These data might contribute to a better understanding of the abnormal bone marrow niche and provide new insights into the pathogenesis of ITP.

Immune thrombocytopenia (ITP) is an autoimmune disease. Mesenchymal stem cells (MSCs) play important roles in the physiology and homeostasis of the haematopoietic system, including supporting megakaryocytic differentiation from CD34 + haematopoietic progenitor cells. Tumour necrosis factor alpha-induced protein 3 (TNFAIP3, also termed A20) plays a key role in terminating NF-κB signalling. Human genetic studies showed that the polymorphisms of the TNFAIP3 gene may contribute to ITP susceptibility. In this study, we showed a significant decrease in TNFAIP3 and increase in NF-κB/SMAD7 in ITP-MSCs. In co-cultures with CD34 + cells, NF-κB was overexpressed in MSCs from healthy controls (HC-MSCs) after transfection with NFKBIA (IκB)-specific short hairpin (sh)RNAs, resulting in MSC deficiency and a reduction in megakaryocytic differentiation and thrombopoiesis. Knockdown of TNFAIP3 expression using TNFAIP3-specific shRNAs in HC-MSCs affected megakaryocytopoiesis. However, IKBKB knockdown corrected megakaryocytopoiesis inhibition in the ITP-MSCs by decreasing NF-κB expression. Amplified TNFAIP3 expression in ITP-MSCs by TNFAIP3 cDNA can facilitate megakaryocyte differentiation. shRNA-mediated knockdown of SMAD7 expression rescued the impaired MSC function in ITP patients. Therefore, we demonstrate that a pathological reduction in TNFAIP3 levels induced NF-κB/SMAD7 pathway activation, causing a deficiency in MSCs in ITP patients. The ability of ITP-MSCs to support megakaryocytic differentiation and thrombopoiesis of CD34 + cells was impaired., (© 2018 John Wiley & Sons Ltd.)

Objectives: To explore the possible risk factors for the occurrence and mortality of thrombotic microangiopathy (TMA) with concomitant acute graft-vs-host disease (aGVHD) and to investigate outcomes and treatments of this disorder after allo-HSCT., Methods: Fifty cases diagnosed with TMA with concomitant aGVHD and 150 controls were identified from a cohort composed of 3992 patients who underwent allo-HSCT from 2008 to 2016., Results: Grade III-IV aGVHD (P = .000), acute kidney injury (AKI) (P = .033), and hypertension (P = .028) were significant independent risk factors associated with the occurrence of TMA with concomitant aGVHD. A haptoglobin level below normal (P = .013), a maximum volume of diarrhea >2500 mL/d (P = .015), and bloody diarrhea (P = .049) were significant markers for death in both univariate and multivariate analyses. Patients diagnosed with TMA with concomitant aGVHD had a lower overall survival (OS), a higher non-relapse mortality (NRM), but a lower risk of relapse., Conclusions: Thrombotic microangiopathy with concomitant aGVHD is a significant complication after allo-HSCT, with a worse outcome, including significantly lower OS and higher NRM. There are specific risk factors associated with occurrence and mortality of this complication., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Primary immune thrombocytopenia is a severe bleeding disorder. About 50-85% of patients achieve initial remission from first-line therapies, but optimal second-line treatment remains a challenge. All-trans retinoic acid (ATRA) has an immunomodulatory effect on haemopoiesis, making it a possible treatment option. We aimed to evaluate the efficacy and safety of ATRA plus danazol versus danazol in non-splenectomised patients with corticosteroid-resistant or relapsed primary immune thrombocytopenia., Methods: We did a multicentre, randomised, open-label, phase 2 study of adult patients (≥18 years) with primary immune thrombocytopenia from five different tertiary medical centres in China. Those eligible were non-splenectomised, resistant to corticosteroid treatment or relapsed, and had a platelet count less than 30 × 10 9 per L. Masked statisticians used simple randomisation to assign patients (1:1) to receive oral ATRA (10 mg twice daily) plus oral danazol (200 mg twice daily) or oral danazol monotherapy (200 mg twice daily) for 16 weeks. Neither clinicians nor patients were masked to group assignments. All patients were assessed every week during the first 8 weeks of treatment, and at 2-week intervals thereafter. The primary endpoint was 12-month sustained response defined as platelet count of 30 × 10 9 per L or more and at least a doubling of baseline platelet count (partial response), or a platelet count of 100 × 10 9 per L or more (complete response) and the absence of bleeding without rescue medication at the 12-month follow-up. All randomly allocated patients, except for those who withdrew consent, were included in the modified intention-to-treat population and efficacy assessment, and all patients who received at least one dose of the study agents were included in the safety analysis. Study enrolment was stopped early because the trial results crossed the interim analysis efficacy boundary for sustained response. This trial is registered with ClinicalTrials.gov, number NCT01667263., Findings: From June 1, 2012, to July 1, 2016, we screened 130 patients for eligibility; 34 were excluded and 96 were randomly assigned. 93 patients were included in the modified intention-to-treat analysis: 45 in the ATRA plus danazol group and 48 in the danazol group. At the 12-month follow-up, sustained response was achieved more frequently in patients receiving ATRA plus danazol than in those receiving danazol monotherapy (28 [62%] of 45 vs 12 [25%] of 48; odds ratio 4·94, 95% CI 2·03-12·02, p=0·00037). Only two grade 3 adverse events were reported: one (2%) patient receiving ATRA plus danazol with dry skin, and one (2%) patient receiving danazol monotherapy with liver injury. There was no grade 4 or worse adverse event or treatment-related death in either group., Interpretation: Patients with primary immune thrombocytopenia given ATRA plus danazol had a rapid and sustained response compared with danazol monotherapy. This finding suggests that ATRA represents a promising candidate for patients with corticosteroid-resistant or relapsed primary immune thrombocytopenia., Funding: National Natural Science Foundation of China, Beijing Natural Science Foundation, Beijing Municipal Science and Technology Commission, and the National Key Research and Development Program of China., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Acute graft-versus-host disease (aGVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our previous study found that the novel anti-inflammatory cytokine IL-35 could suppress aGVHD in patients after allo-HSCT. In this study, we used C57BL/6 (B6, H-2b) mice as donors and (B6×DBA/2) F1 (BDF1, H-2b×d) mice as recipients to create a model of aGVHD and explore the relationship between IL-35 and aGVHD. The mice receiving IL-35 survived longer than did the control mice. We observed that treatment with IL-35 and RAPA could reduce the incidence of aGVHD. Additionally, this treatment inhibited intestinal and thymic epithelial cell apoptosis and liver infiltration by the donor T-cells, thereby ameliorating the enteropathy and liver injury caused by aGVHD. We found that IL-35 and RAPA also markedly suppressed TNF-α and IL-17A expression and enhanced IFN-γ expression in the intestine and liver. We measured Tregs in spleen and found that IL-35 and RAPA treatment expanded the number of Tregs in spleen. We found that the phosphorylation of STAT1 and STAT4 were inhibited in mice with aGVHD. In contrast, STAT1 and STAT4 were phosphorylated when the mice were treated with IL-35. IL-35 may have therapeutic potential in the treatment of aGVHD after allo-HSCT., (Copyright © 2015. Published by Elsevier B.V.)

Background/aims: To compare the postoperative results of duodenum-preserving pancreatic head resection (DPPHR) techniques with those of conventional pancreatoduodenectomy (PD)., Methodology: We retrospectively reviewed the records of 58 patients who underwent DPPHR or PD at Jinhua central hospital between May 1998 and May 2011., Results: Eighteen patients underwent DPPHR (Group 1) and 40 conventional PD (Group 2). They were followed up for more than 6 months. Operation time in Group 1 was longer (290±18 min vs 269±14 min, p=0.001). Estimated blood loss in Group 1 was more (633±88 mL vs. 495±131 mL, p=0.003). Intraoperative transfusion in Group 1 was more (533±88 mL vs. 335±218 mL, p=0,001). However, postoperative transfusion was Iess (141±162 mL vs. 440±193 mL, p=0.000). Group 1 had a lower short-term complication rate (16.67% vs. 50.0%, p=0.0 16) and long-term complication rate (11.11% vs. 45.0%, p=0.012). Hospital mortality of both groups were 0., Conclusions: DPPHR for benign or premalignant lesions is a difficult procedure, but with a lower complication rate than conventional PD. Preserving the entire duodenum and a normal biliary tree allows better short-term and long-term results. DPPHR will be suitable for only a small group of patients and should be performed by experienced surgeons.

Background: Pancreatic carcinoma possesses one of the highest lethality rates, highest drug-resistance, and highest incidence rates. The objective of this research was to enhance the efficacy and drug-resistance for pancreatic carcinoma by using inhibition of SIRT1 combined with gemcitabine therapy methods., Methods: Three pancreatic carcinoma cells (PANC-1 cells, BxPC-3 cells, and SW1990 cells) received treatment with physiological saline, inhibition of SIRT1, gemcitabine, and combination therapy with inhibition of SIRT1 and gemcitabine in vitro; then BxPC-3 pancreatic cancer xenogeneic mice also received treatment with physiological saline, inhibition of SIRT1, gemcitabine, and combination therapy with inhibition of SIRT1 and gemcitabine in vivo., Results: The cleaved poly ADP ribose polymerase (PARP)-1 effect of drug in pancreatic carcinoma cells was significantly different (P < 0.05) and the efficacy in descending order was the combination therapy with inhibition of SIRT1 and gemcitabine, inhibition of SIRT1, and gemcitabine. The BxPC-3 pancreatic cancer xenogeneic mice model received treatment with physiological saline, inhibition of SIRT1, gemcitabine, and combination therapy with inhibition of SIRT1 and gemcitabine in vivo and the results showed that the tumor volumes decreased and the survival rate within 45 days increased according to the order of the given drugs and the difference was significant (P < 0.05)., Conclusion: Combination therapy with inhibition of SIRT1 and gemcitabine could improve efficacy and survival time in a BxPC-3 pancreatic cancer xenogeneic mice model, compared with single inhibition of SIRT1, or single gemcitabine therapy. The combination therapy method is a potential treatment method for pancreatic carcinoma.

Background: Hilar cholangiocarcinoma is one of the most difficult carcinomas to manage because of the location of the main tumor at the hepatic hilus and the complex anatomy of the biliary, arterial, and portal systems. To plan an operation, it is important to acquire accurate information about the relationship between hilar cholangiocarcinoma and adjacent vessels. This study aimed to evaluate the clinical value of cholangiography combined with spiral CT three-dimensional (3D) angiography for a preoperative assessment of hilar cholangiocarcinoma., Methods: From March 2007 to August 2009, cholangiography was performed in 13 patients with hilar cholangiocarcinoma. Meanwhile, contrast-enhanced abdominal scanning was performed using 16-slice spiral CT, and the 3D images of the hepatic artery and portal vein were acquired. The level and range of invasion of the hepatic artery, the portal vein, and the bile duct, the preoperative Bismuth classification, and T-staging were recorded and compared with those after surgical exploration., Results: The hepatic artery and portal vein were reconstructed successfully in all these patients. Percutaneous transhepatic cholangiography was performed in 9 patients, endoscopic retrograde cholangiopancreatography in 1, and magnetic resonance cholangiopancreatography in 3. The CT angiography records of invasion of the hepatic artery were consistent with the results of explorations in these patients. The data from 5 of the 13 patients were consistent with those on invasion of the portal vein. The results of the Bismuth classification and the T-staging system were consistent with those of surgical exploration in 12 of the 13 patients. Seven of 8 patients who were estimated to be suitable for operation based on images were curatively treated and 5 who were judged to be unsuitable for curative operation by cholangiography and CT angiography were confirmed intraoperatively and underwent palliative procedures., Conclusions: Cholangiography combined with multi-slice spiral 3D CT angiography can satisfactorily delineate the local invasion of hilar cholangiocarcinoma and accurately evaluate the resectability. This approach, therefore, contributes to the planning of safe operation.

Aim: To Construct Fab antibody against Rh antigen., Methods: The variable regions of light and heavy chains were amplified by RT-PCR from the PBMCs of volunteers with high titer (1:256-512 by inditect agglutation) antibody to Rh antigen. Meanwhile, the genes of constant regions of light and heavy chains were isolated from pComb3xTT and pComb3xlambda phagmid carrying the templates respectively. Vkappa light chain and Fd heavy chain were linked by the first splicing overlapping extension PCR (SOE), and a full-length Fab gene was created by the second SOE. The Fab gene was ligated to phagmid pComb3HxSS and transformed to E.coli XL1-Blue by electroporation. The obtained human Fab phage antibody library was panned using Rh(-)/Rh(+) RBC four times. the phage antibodies against Rh antigen were highly enriched. Indirect agglutation test, western blot analysis and sequencing analysis were performed to detect the specificity of Fab against Rh., Results: The repertoire of human phage display Fab library was 7.4 x 10(6);. After panning, A Fab clone which could bind to Rh antigen specifically was obtained., Conclusion: A Fab antibody that specifically aggulated Rh(+) RBC is obtained, this makes it possible to produce Rh antibody with high quantity and effection in our country.

Electrodes for the dopamine (DA) determination in biological samples have been developed with improved selectivity and sensitivity in an excess of ascorbic acid (AA). Negatively charged Ni(II) complex was synthesized and electropolymerized on the glassy carbon electrode to impart the surface with anionic characteristics that could act both as a catalyst and as a discriminating layer against AA based on the electrostatic interaction. Thus prepared electrodes enabled selective determination of DA even in a large excess of AA by differential pulse voltammetry at physiological pH. Linear response was found down to 1.0 x 10(-7) M with 5.0 x 10(-9) M of LOD (Limit of Detection). In a flow injection analysis performed in an amperometric mode, the detection limit was lowered by two orders of magnitude down to 1.0 x 10(-9) M with a linear range of 1.0 x 10(-9) to 1.0 x 10(-6) M. The relative standard deviation was found to be 3.36% from 25 independent measurements for 1.0 x 10(-5) M of DA. Stable oxidation current of DA was observed even after 30 days storage in air. The recoveries of DA in the 100-fold diluted human urine samples were 97.7% for 4 measurements. The rate constant for the DA oxidation was 1.3 x 10(-3) cm s(-1) from hydrodynamic experiments using a rotating disk electrode.

In the title compound, [V(4)O(8)(SeO(3))(2)(C(10)H(8)N(2))(4)], there are two distinct vanadium coordination environments. Alternating corner-shared VO(4)N(2) octahedra and SeO(3) pyramids result in eight-membered centrosymmetric V(2)Se(2)O(4) rings. In addition, pairs of V centres form centrosymmetric V(2)O(6)N(4) clusters via edge-sharing. These two kinds of secondary building units are linked in an ABABAB fashion to give an infinite chain whose nature is unprecedented in Se-V-O systems.

Objective: To explore the indications and effect of surgical resection for hepatic metastases from colorectal adenocarcinoma and to discuss the implications of clinicopathologic features on the prognosis., Methods: A retrospective study of 61 patients undergoing hepatectomy for metastatic tumors from colorectal adenocarcinoma from January 1991 to December 2000 in our hospital was performed retrospectively., Results: The 1-, 3- and 5-year survival rates after hepatic resection were 72.13%, 58.10% and 26.01% respectively. Complications occurred in 8 cases. Tumor pesudomembrance was found in 20 cases. Dukes stage, pathologic type,the number of hepatic metastases and tumor pesudomembrance were all significant factors for prognosis after surgery (P< 0.05). The 3-year survival rate of the patients with postoperative comprehensive treatment was higher than that with non-postoperative treatment (P< 0.05). The size of hepatic metastases and the resecting time didn't affect the prognosis (P > 0.05)., Conclusion: The hepatic metastases from colorectal cancer should be treated by a surgical approach. The earlier stage of clinical pathology,higher differentiation extent, metastases less than 3, the formation of pesudomembrance of the metastatic tumor and the postoperative comprehensive treatment predict a better survival.

Background: Bile leakage remains a serious complication after biliary surgery. The aim of this study was to assess the etiology, diagnosis and treatment of postoperative biliary leakage., Methods: Thirty-eight patients with biliary leakage we treated in recent 8 years were analyzed retrospectively. Among them, 8 patients had bilioenterostomy leakage, 7 accessory bile duct leakage, 7 cholecyst bed leakage, 6 leakage after removal of T-tube, 5 leakage after laparoscopic cholecystectomy, 3 leakage around T-tube, and 2 leakage caused by choledochal damage. Drainage was performed in 17 patients, reoperation in 13, drainage plus percutaneous transhepatic cholangio drainage (PTCD), endoscopic retrograde cholangiography (ERCP), endoscopic nasobiliary drainage (ENBD) and endostenting in 5, and drainage plus growth hormone in 3., Results: In this series, 37 patients were cured, and 1 died of multiple organ dysfunction syndrome (MODS). These patients were hospitalized for 2 weeks to 8 weeks. The drainage group was hospitalized shorter than the undrainage group., Conclusions: A piece of white gauze can be used to touch surgical area in detecting biliary leakage intraoperatively. Mucous to mucous suture of the bile duct and appropriate time for removal of T-tube are recommended to prevent biliary leakage. Reoperation is essential to acute peritonitis. Drainage can be used if leakage don't diffuse or it occurs after pulling out T-tube. Drainage plus ERCP, ENBD, PTCD and drainage are effective.

Objective: This is a study on the allele composing of ABO, FUT1 and FUT2 gene loci of 10 para-Bombay individuals in China., Methods: Ten samples coming from different districts of China were suspected of para-Bombay phenotype by primary serology tests. Routine and absorb-elution tests were conducted to identify their ABO type, and duplex polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was applied to getting their ABO genotype. Most of them were submitted to a test of their Lewis type as well. Then through direct DNA sequencing with PCR products of FUT1 and FUT2 genes, the genotypes of their H and SE gene loci were analyzed., Results: It can be confirmed that the 10 samples are para-Bombay. All of their ABO genotypes are consistent with the serological absorb-elution results and the substances detected results in saliva. Seven out of 10 have recessive homozygous gene at their H locus. Each phenotype of h1h1 (nt547-552Deltaag), h2h2 (nt880-882Deltatt) and h4h4 (nt35 t-->c) are ascertained in 2 individuals; moreover, h3h3 (nt 658 c-->t) is identified in one individual. The rest are hh heterozygous individuals: one is h3/h(new-1); the other is h2/h(new-2); the last one is h1/h2. The h(new-1) (nt586 c-->t) allele has a point mutation at nt 586 C to T, which leads a nonsense mutation Gln(CAG) to stop (TAG).The second h (new-2) (nt328 g-->a) has an nt328 G to A missense mutation,which leads Ala (GCC),was replaced by Thr (ACC) at 110 amino acid position. All the 10 samples have Se (nt357 c-->t) synonymous mutation. One Bm(h) (B/O) individual with h4h4 phenotype has a Se(w)(nt357 c-->t; nt385 a-->t) allele, whose Lewis type is Le(a+b+). Moreover, the authors detected a (nt716 g-->a) mutation in two samples' Se gene., Conclusion: Four kinds of known h alleles (h1-h4), 2 kinds of novel non-functional FUT1 alleles, a Se(w) allele, and a novel SeG716A polymorphism in Chinese para-Bombay individuals were detected. At the same time, the authors noticed that all the 10 samples have the nt357 c-->t mutation in their FUT2 gene.

Objective: This is a study on some ABO subgroup samples which show discordant results of serological and molecular blood typing, the aim is to clarify their true ABO type by means of nucleotide analysis on exons 6 and 7 of their ABO gene., Methods: Absorb-elution test and family investigation were conducted to study 7 samples which were involved in ABO grouping discrepancies. Duplex polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) method was used to identify their ABO genotypes. PCR products of exons 6 and 7 were cloned and sequenced., Results: All the 7 ABO subgroup samples with the discordant results of serological and molecular blood typing were found to have the normal O gene. Four out of them were typed as ABsub by serology, they were all of the A*102/O genotype. Sequencing analysis found all their A gene having the nt467 (C-->T) and nt803 (G-->C) mutation by comparison with the A*101 allele, i.e. their real type should be CisAB/O. Three out of 7 were typed as AsubB by serology and as BO by genotype; and point mutation was detected in all of their B gene. One of them had the nt700 (C-->G) mutation, the other 2 unrelated individuals had the novel nt640 (A-->G) mutation in their B alleles., Conclusion: Through nucleotide analysis, 7 samples have been typed as AB subgroup in serology with the normal O gene, their real ABO type being CisAB in 4 cases and B(A) in 3 cases. At the same time, a kind of novel B (A)640 allele has been uncovered in this study.

In this paper, we determined the ratio of C13/C12 of methane in slurry gas from oil wells by the method of laser frequency modulation absorption spectroscopy that has many advantages such as high precision, high spectroscopic resolution and rapidly and simply dealing with samples. This technique provided us with a subsidiary method for oil-gas source exploration. The method of laser frequency modulation absorption spectroscopy is based on the method of laser frequency absorption spectroscopy and is more accurate. And this method can be expanded to apply to others aspects easily. We only need change other appropriate laser and select right absorption peak, then we can determined the ration and concentration of diverse gases.

Objective: To study the chemical constituents from the whole plant of Aster poliothamnus., Method: Separating the chemical constituents by means of chromatography and identifying ther structures on basis of chemical and spectral tecnology., Result and Conclusion: A new triterpene saponin was isolated and identified.