Effects of dietary supplementation with N-carbamylglutamate on maternal endometrium and fetal development during early pregnancy in Inner Mongolia white cashmere goats.

This study investigated the effects of dietary supplementation with N-carbamylglutamate (NCG) on maternal endometrium and fetal development during early pregnancy of Inner Mongolia white cashmere goats. Forty-eight pregnant Inner Mongolia white cashmere goats (average age 3 years old, average lactation parity 2, and average body weight 43.81 ± 2.66 kg) were randomly allocated to three groups: a basal diet (control group, n = 16), a basal diet plus 0.30-g NCG/d (NCG1 group, n = 16), and a basal diet plus 0.40-g NCG/d (NCG2 group, n = 16). All of the does were housed in individual pens and the NCG treatment was conducted from Days 0 to 90 of pregnancy. At Days 17 and 90 of pregnancy, six representative pregnant does in each group were slaughtered. The current study results demonstrated that maternal NCG administration during early pregnancy effectively increased the arginine family of amino acids and the glucogenic amino acids concentrations and promoted the mRNA expression of osteopontin (OPN), αv and ß3 integrins, and endometrial development of Inner Mongolia white cashmere goats. The supplementation improved the fetal brown adipose tissue (BAT) stores and the mRNA expression of UCP-1 and BMP7, thereby helping to the fetal early development.

[Response and plasticity of functional traits in Lycium ruthenicum to N and P addition.] / é»‘æžœæž¸æžåŠŸèƒ½æ€§çŠ¶å¯¹æ°®ç£·æ·»åŠ çš„å“åº”åŠå ¶å¯å¡‘æ€§.

Analyzing the effects of nutrient addition on the functional traits of desert plants is important for revealing the responses of desert plant species to environmental changes. In this study, we examined the responses of whole plant, root, stem, leaf and fruit traits of Lycium ruthenicum to the addition of N and P, with an experiment with three (low, medium and high) N and P addition levels and three N/P ratios (5:1, 15:1 and 45:1). The results showed that functional traits of L. ruthenicum had divergent responses to NP addition level and N/P ratio. With the increases of NP addition level, the biomass and specific leaf area were increased, while the root-shoot ratio, leaf dry matter content, root tissue density and specific root length were decreased. Belowground biomass, specific root length and net photosynthetic rate increased with the increases of N/P ratio. The coefficient of variation of 17 functional traits was 7.3%-69.1%. The biomass, root-shoot ratio and speci-fic root length were sensitive traits to NP [plastic index (PI)>0.5], with greater variability (49.4%-69.1%), whereas the leaf length-width ratio, leaf thickness, leaf tissue density, and leaf stem dry matter content were conservative traits (PI<0.20). The results of principal component analysis (PCA) showed that the position of L. ruthenicum in the multivariate feature space exhibited lateral migration with the changes of NP addition levels, with a tendency of higher aboveground and belowground biomass and a lower root-shoot ratio. Leaf tissue density was negatively related to leaf thickness and specific leaf area. Leaf dry matter content was negatively correlated with leaf thickness and specific leaf area but positively associated with leaf tissue density. Biomass had a positive correlation with specific leaf area and a negative relation to specific root length. The results of stepwise regression analysis showed that specific root length, specific leaf area and leaf net photosynthetic rate were major functional traits affecting the biomass of L. ruthenicum. L. ruthenicum adapted to the fluctuations of soil nutrient environment through changing resource utilization strategy, altering root carbon allocation, and also the trade-off and covariance among traits and inconsistent response.

[Ginger-partitioned moxibustion in the prevention of nausea and vomiting induced by chemotherapy in lung cancer：a randomized controlled trial].

OBJECTIVE: To observe the effect of ginger-partitioned moxibustion intervention on gastrointestinal reaction, the quality of life, the counts of blood platelet (PLT) and white blood cells (WBC) after chemotherapy in lung cancer patients. METHODS: The lung cancer patients treated with chemotherapy were randomized into observation group (30 cases) and control group (30 cases). In the control group, the intravenous injection with Tropisetron(5 mg) was given 1 h before chemotherapy. In the observation group, in addition to the same treatment as the control group, 2 hours after chemotherapy, ginger-partitioned moxibustion was applied to bilateral Zusanli (ST36), bilateral Neiguan (PC6) and bilateral Tianshu (ST25) for 20 min each time. The treatments were conducted once daily for 3 days. Separately, 2 days before chemotherapy, 24 h and 7 days after chemotherapy, the gastrointestinal reaction score and the score of the quality of life, the PLT and WBC counts were observed in the two groups. RESULTS: The effective rate of the gastrointestinal reaction degree in the observation group were higher than those in the control group 24 h and 7 days after chemotherapy (P<0.05). Twenty-four hours after chemotherapy, the score of the quality of life, the PLT and WBC counts were lower as compared with those before the treatment in both groups respectively(P<0.05). Seven days after chemotherapy, the score of the quality of life, the PLT and WBC counts in the observation group were higher than those in the control group (P<0.05). CONCLUSION: The ginger-partitioned moxibustion achieves the definite clinical effect of the prevention of nausea and vomiting induced by chemotherapy in lung cancer. This therapy is simple in operation, high in safety, absent in obvious adverse reactions and high in patient's compliance.

[Effect of acupuncture in different time on nausea and vomiting induced by chemotherapy of lung cancer].

OBJECTIVE: To observe the effect of acupuncture in different time on nausea and vomiting induced by chemotherapy of lung cancer. METHODS: A total of 150 patients with chemotherapy for lung cancer were randomized into a No.1 observation group, a No.2 observation group and a control group, 50 cases in each one. Excluded the dropped-off cases, finally, there were 49 cases in the No.1 observation group, 44 cases in the No.2 observation group and 47 cases in the control group. In the control group, 30 min before chemotherapy, the slow intravenous injection with tropisetron hydrochloride was used, 5 mg each time, once a day for 3 days. In the No.1 observation group, 30 min before chemotherapy, the slow intravenous injection with tropisetron hydrochloride was given combined with acupuncture. The acupoints selected were Zusanli (ST 36), Zhongwan (CV 12) and Neiguan (PC 6). The needles were retained for 30 min. The treatment was given once a day for 3 days totally. In the No.2 observation group, 30 min before chemotherapy, the slow intravenous injection with tropisetron hydrochloride was used, and 30 min after chemotherapy, acupuncture treatment was exerted. The acupoints and needling method were same as those in the No.1 observation group. Before and after treatment, the digestive reaction score, Karnofsky performance status scale (KPS) score and white blood cell count were all observed in the three groups. Additionally, the therapeutic effect and adverse reaction were observed and the therapeutic effect was compared among the treatment with acupuncture in different time. RESULTS: On the 2nd day of chemotherapy, the effective rates were 85.7% (42/49) and 75.0% (33/44) in the No.1 observation group and the No.2 observation group respectively, both higher obviously than 68.1% (32/47) in the control group (P<0.05), and the effective rate in the No.1 observation group was higher obviously than the No.2 observation group (P<0.05). On the 3rd day of chemotherapy, the effective rates were 81.6% (40/49) and 61.4% (27/44) in the No.1 observation group and the No.2 observation group respectively, both higher obviously than 57.5% (27/47) in the control group (P<0.05), and the effective rate in the No.1 observation group was higher obviously than the No.2 observation group (P<0.05). Compared before treatment, the KPS scores after treatment were obviously lower in the three groups (P<0.05), and the decreased value of KPS score in the No.1 observation group was much lower than the control group and the No.2 observation group (P<0.05). After 3-day chemotherapy, the white blood cell count was all reduced in each group, but the decreased value was not different statistically among the groups (P>0.05). CONCLUSION: Acupuncture combined with the slow intravenous injection with tropisetron hydrochloride achieve the satisfactory effect of prevention and treatment for vomiting induced by chemotherapy of lung cancer. The acupuncture intervention before chemotherapy greatly improves the effect on the nausea and vomiting induced by chemotherapy of lung cancer.

[Effect of "Tiaoshen Acupuncture" on postpartum low back pain: a randomized controlled trial].

OBJECTIVE: To observe the effect of "Tiaoshen Acupuncture" on postpartum low back pain. METHODS: A total of 98 cases of postpartum low back pain were randomly divided into a control group (45 cases, 4 cases dropping) and a treatment group (47 cases, 2 cases dropping). Conventional acupuncture was treated in the control group, and "Tiaoshen Acupuncture" was added in the treatment group on the basis treatment in the control group, acupuncture was applied at Baihui (GV 20), Neiguan (PC 6), Taichong (LR 3). The treatment was given 30 minutes each time, 5 times a week, 10 times for a total course of treatment. Before and after treatment, pain was assessed by the short-form of McGill pain questionnaire (SF-MPQ), dysfunction was assessed by Oswestry disability index (ODI), and depression was assessed by the Edinburgh postnatal depression scale (EPDS). And the changes of various indexs were observed before and after treatment. RESULTS: After treatment, the pain grade index (PRI) score, visual analog scale (VAS) score and present pain intensity (PPI) score in SF-MPQ of the control group and the treatment group were significantly lower than those before treatment (all P<0.001). The ODI score and EPDS score were also significantly lower than those before treatment (all P<0.001). The decline scores of the treatment group before and after treatment were significantly higher than those in the control group (P<0.001, P<0.01). CONCLUSION: "Tiaoshen Acupuncture" combined with conventional acupuncture and conventional acupuncture can effectively improve the symptoms of pain, dysfunction and depression in patients with postpartum low back pain, and the former is significantly better than the latter.

Manganese-Catalyzed Intermolecular Oxidative Annulation of Alkynes with γ-Vinyl Aldehydes: An Entry to Bridged Carbocyclic Systems.

Manganese-catalyzed intermolecular oxidative annulation of alkynes with γ-vinyl aldehydes involving acylation and alkylation is described, thus providing a scenario for the divergent synthesis of bridged carbocyclic systems. By means of this manganese-catalyzed alkyne dicarbofunctionalization strategy, three chemical bonds, including two C-C bonds and one C-H bond, are formed via an aldehyde C(sp2)-H oxidative functionalization/[4 + 2] annulation/protonation cascade.

Downregulation and subcellular distribution of HER2 involved in MDA-MB-453 breast cancer cell apoptosis induced by lapatinib/celastrol combination.

PURPOSE: To investigate the effect and related molecular mechanisms of lapatinib/celastrol combination or single-agent treatment in HER2/neu-overexpressing MDA-MB-453 breast cancer cells. METHODS: The effects of treatment with lapatinib, celastrol or their combination on cell growth were determined using MTT assay. Drug synergy was determined using the combination index (CI) methods derived from Chou-Talalay equations using CalcuSyn software. Apoptotic morphology was observed by fluorescence microscope with Hoechst 33258 staining. Changes of apoptotic and growth pathways-related proteins were analysed by Western blot. The expression of HER2 of cell surface was performed by flow cytometry. Subcellular distribution of HER2 was observed by immunofluorescence study. RESULTS: Combination celastrol and lapatinib produced strong synergy in growth inhibition and apoptosis in comparison to single-agent treatment in HER2/neu-overexpressing MDA-MB-453 cells. Interestingly, compared with celastrol treatment alone, lapatinib/celastrol combination induced more HER2 membrane protein downregulation and ectopic to cytoplasm and nucleus in MDA-MB-453 cells. CONCLUSION: The combination of celastrol and lapatinib could be used as a novel combination regimen which provides a strong anticancer synergy in the treatment of HER2/neu-overexpressing cancer cells.

Protective effects of total flavonoids of Astragalus against adjuvant-induced arthritis in rats by regulating OPG/RANKL/NF-κB pathway.

BACKGROUND: Astragalus membranaceus Bunge is one of the oldest and most frequently used crude herbs in traditional Chinese medicine. The total flavonoids of Astragalus (TFA) are the main active components isolated from Astragalus membranaceus Bunge. Our recent study has shown its potential immunomodulatory and anti-inflammatory effects in vivo and in vitro. However, its anti-arthritic effects and mechanisms of action involved have not been elucidated. The aim of this study was to evaluate the protective effects and possible mechanisms of TFA on Freund's complete adjuvant (FCA)-induced arthritis in rats. METHODS: Wistar rats were intradermally injected FCA into the right hind metatarsal footpads to establish adjuvant-arthritic model. The rats were intragastrically administered daily with TFA at 25, 50 and 100mg/kg for 28days after FCA induction. Body weight, primary paw swelling, arthritis index, thymus and spleen indices were measured. The levels of serum tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, prostaglandin (PG)E2, osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) were determined using ELISA. Histopathological changes and scores in joint tissues were examined using hematoxylin and eosin (H&E). The expression of nuclear factor (NF)-κB p65 in synovial tissues was assayed using immunohistochemical method. RESULTS: TFA significantly increased body weight, attenuated primary paw swelling and arthritis index, decreased thymus and spleen indices of rats induced by FCA. Furthermore, TFA significantly inhibited serum TNF-α, IL-1ß, PGE2 and RANKL production, and promoted serum OPG production and OPG/RANKL ratio of rats induced by FCA. Histopathological examination indicated that TFA significantly attenuated inflammatory cell infiltration, synovial hyperplasia, pannus formation, and bone and cartilage damage. Immunohistochemical assay indicated that TFA inhibited NF-κB p65 expression in synovial tissues of rats induced by FCA. CONCLUSIONS: These results suggest that TFA exerts potential protective effects against FCA-induced arthritis in rats by regulating OPG/RANKL/NF-κB pathway.

[Effects of Volatile Oils from Different Preparations of Angelica sinensis Root on Acute Inflammation Induced by LPS in Rats].

Objective: To compare the intervention effects of volatile oils from different preparations of Angelica sinensis root on acute inflammation induced by lipopolysaccharide in rats. Methods: Acute inflammation model was induced by intraperitoneal injection of lipopolysaccharide( 100 µg/kg) in rats. Blood and serum inflammatory mediators and cytokines were detected, combining with the pathological histological observation of lung and liver to evaluate the anti-inflammatory activities of volatile oils from parching Angelica sinensis root with wine( J-VOAS),volatile oils from charred Angelica sinensis root( C-VOAS) and Angelica sinensis root( S-VOAS). Results: Compared with control group, the WBC count, the percentage of NE and PLT count in acute inflammation model group significantly increased ( P < 0. 05),and the percentage of LY significantly decreased( P < 0. 05); the content of IL-1ß,IL-6,NO and TNF-α significantly increased( P < 0. 001) and content of IL-10 significantly decreased( P < 0. 05) in model group; after J-VOAS,C-VOAS and S-VOAS intervention, the blood routine index and serum inflammatory mediators and cytokines significantly reversed( P < 0. 05). The pathological histological study showed that expanded alveoli, massive inflammatory cells infiltration in alveoli and pulmonary interstitium, the liver leaflets diffuse necrosis, hepatic cord derangement, and some of the liver cells degeneration and edema in model group; after J-VOAS intervention, their pathological changes significantly reduced. Conclusion: All volatile oils from different preparations of Angelica sinensis root had intervention on acute inflammation induced by LPS. And J-VOAS had the best effect, followed by C-VOAS and S-VOAS.

[Effect of different processed volatile oils from Angelica sinensis on urinary metabolomics rats].

Different processed volatile oils from AS on urine metabolites of normal rats were analyzed to reveal the possible metabolic pathways. Totally 50 male Waster rats were randomly divided into normal control group, C-ASVO group, J-ASVO group, T-ASVO group and Y-ASVO group, with 10 rats in each group. The normal group was given isovolumetric 0.5% polyoxyethylene sorbitan fatty acid ester（Tween-80）, while the other groups were given 0.176 mL•kg⁻¹ different processed volatile oils from AS. Drugs were given for 3 successive days. The urine was collected at 48 h with metabolic cages. GC-MS was employed to detect the metabolic fingerprint of rat urine in different times. Principal component analysis(PCA) and orthogonal partial least-squares discriminant analysis(OPLS-DA) were adopted for a multivariate statistical analysis. Metabolites with potential differences were selected based on the results of variable importance in the projection(VIP) and t test. The metabolic pathway analysis(MetPA) database was built for different metabolites' metabolic pathways. The results showed that compared with the normal group, 31 kinds of endogenous metabolites in the different processed volatile oils from AS groups change significantly(P<0.05). And there were differences in normal rat urine metabolites among the different processed volatile oils from AS, of which the influence degree of J-ASVO was slightly stronger than C-ASVO, T-ASVO, and Y-ASVO. Therefore, the metabolism effect may be focused on energy metabolism, amino acid metabolism, fatty acid metabolism and glucose metabolism. This study focused on metabolism and mechanism of different processed volatile oils from AS, and provided new ideas for pharmacological actions of traditional Chinese medicines.

The gadolinium-based contrast agent Omniscan® promotes in vitro fibroblast survival through in situ precipitation.

The current study aims to explore how the gadolinium (Gd)-based contrast agent (GBCA) Omniscan® enhanced cell viability of murine fibroblasts. The results of scanning electron microscopy showed that Omniscan® can precipitate in cell culture media and deposit on cell membranes. Energy-dispersive X-ray analysis and Fourier-transform infrared spectroscopy demonstrated the presence of Gd and phosphates in the agglomerated particles. By filtering the Omniscan®-containing medium through a 220 nm filter, it can be clearly found that the increased cell viability should be mainly attributed to the insoluble species of gadolinium rather than to chelated gadolinium. Moreover, the effects of other gadolinium-based contrast agents, Magnevist® and Dotarem®, were compared with that of Omniscan®. It is noted that the three contrast agents differed in their ability to induce cell viability, which is possibly ascribed to the different chemical stabilities of gadolinium chelates as demonstrated by the attenuation in cell growth upon the addition of excess ligands to the compounds. The results of flow cytometry analysis also showed that Omniscan® can promote cell growth via an increase in the S-phase cell population as evidenced by the elevated levels of cell cycle associated proteins cyclin D, cyclin A and the phosphorylated Rb protein. Furthermore, our results revealed that integrin-mediated signaling may play an important role in both Omniscan® and Magnevist®-enhanced focal adhesion formation since the blockade of integrins decreased the level of ERK phosphorylation induced by the two GBCAs. Taken together, these data suggested that in situ gadolinium phosphate precipitation formation mediated Omniscan®-promoted fibroblast survival, which is similar to that of gadolinium chloride. It was demonstrated that the application of GBCAs with more stable thermodynamic stability may cause less dissociation of the gadolinium ion and thus resulted in less precipitation, finally leading to lower occurrence of nephrogenic systemic fibrosis. The obtained results would also be helpful for the development of safe gadolinium-based contrast agents.

Metabolomics study of hematopoietic function of Angelica sinensis on blood deficiency mice model.

ETHNOPHARMACOLOGICAL RELEVANCE: Angelica sinensis (AS) has been used in traditional Chinese medicine for thousands of years to enrich and invigorate blood. In this study, the aim is to investigate the influence of AS on metabolism of blood deficiency mice model and to explore its anti-blood deficiency mechanism. MATERIALS AND METHODS: The blood deficiency mice model was induced by being hypodermically injected with N-acetyl phenylhydrazine (APH) and being intraperitoneally injected with cyclophosphamide (CTX). Gas chromatography-mass spectrometry (GC-MS), principle component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were used to identify potential biomarkers in plasma and splenic tissue. RESULTS: The levels of white blood cell (WBC), red blood cell (RBC), hemoglobin (HGB) and platelet (PLT) showed a trend to return to control group after administrating with AS, while the dose of 10g/kg showed the best effect. Potential metabolite biomarkers (nine in the plasma and nine in the spleen homogenates) were identified in this study. These biomarkers were mainly related to five metabolic pathways, such as arachidonic acid metabolism, valine, leucine and isoleucine biosynthesis, glycine, serine and threonine metabolism, arginine and proline metabolism and TCA cycle. CONCLUSION: Metabolomics was used to reflect an organism׳s physiological and metabolic state comprehensively, indicating that metabolomics was a potentially powerful tool to reveal the anti-blood deficiency mechanism of AS.

Metabonomic analysis of the anti-inflammatory effects of volatile oils of Angelica sinensis on rat model of acute inflammation.

Metabonomics based on GC-MS was used to study the possible anti-inflammatory mechanisms of volatile oils of Angelica sinensis (VOAS) in rats with acute inflammation. Acute inflammation was induced by subcutaneous injection of carrageenan in rats. The levels of prostaglandin E2 (PGE2 ), histamine (HIS) and 5-hydroxytryptamine (5-HT) in the inflammatory fluid were detected. Principal component analysis and orthogonal partial least squares-discriminant analysis models were performed for pattern recognition analysis. After the administration of VOAS, the levels of PGE2 , HIS, and 5-HT returned to levels observed in normal group. According to GC-MS analysis, the intervention of VOAS in rats with acute inflammation induced substantial and characteristic changes in their metabolic profiles. Fourteen metabolite biomarkers, namely, lactic acid, malic acid, citric acid, trans-dehydroandrosterone, aldosterone, linoleic acid, hexadecanoic acid, pregnenolone, octadecenoic acid, myristic acid, l-histidine, octadecanoic acid, arachidonic acid (AA) and l-tryptophan, were detected in the inflammatory fluid. The levels of all biomarkers either increased or decreased significantly in model groups. VOAS possibly intervened in the metabolic process of inflammation by altering histidine metabolism, tryptophan metabolism, AA metabolism, steroid hormone biosynthesis, fatty acid metabolism and energy metabolism. Metabonomics was used to reflect an organism's physiological and metabolic state comprehensively, and it is a potentially powerful tool that reveals the anti-acute-inflammatory mechanism of VOAS.

[Comparative metabonomics study on urine in rat treated by Angelica sinensis volatile oil].

Metabonomics was employed to investigate the effect of Angelica sinensis volatile oil (ASVO) to the endogenous metabolites of normal rats, and to reveal the possible ways of metabolism in rats caused by ASVO. The fifty male Waster rats were randomly divided into five groups (each consists of 10 rats), such as control group, high dose group of ASVO, middle dose group of ASVO, low dose group of ASVO, and Aspirin group. They were given 0.9% saline, 0.352 mL x kg(-1) ASVO, 0.176 mL x kg(-1) ASVO, 0.088 mL x kg(-1) ASVO and ASP respectively with the equal volume of 0.2 mL. Drugs and vehicle were given for 3 successive days. The urine was collected at 12, 24, 36, 48 h after modeling with metabolic cages. Rat urine metabolic fingerprint in different stages was analyzed using GC-MS, based on which the principal component analysis (PCA)and orthogonal partial least-squares discriminant analysis (OPLS-DA) models were established for metabonomic analysis. Potential biomarkers were screened by using variable importance in the projection (VIP) and T test. It was revealed that the middle dose of ASVO at 36 h induces a substantial change in rat urine. Compared with control group, seven kinds of endogenous metabolites in ASP group and ASVO group change significantly (P < 0.05), among which aconitic acid, succinic acid, citric acid, alpha-ketone glutaric acid, glycine and malic acid content had an upward trend (P < 0.05) and prostaglandin content had a downward trend (P < 0.01). The mechanism of ASVO and ASP have the similarity. It is likely that ASVO intervenes the metabolic process by affecting the energy, amino acid and lipid metabolism. Our work also indicates that rats administrated with ASVO can increase the energy metabolism of the body, induce the production of inflammatory substances and strengthen the body's immune ability. The result has also provide a proof for futher interpret ASVO pharmacological effects.

[Investigation of current infection with Helicobacter pylori in children with gastrointestinal symptoms].

OBJECTIVE: To investigate current infection with Helicobacter pylori (H. pylori) and related risk factors in children with gastrointestinal symptoms. METHODS: A total of 376 children with upper gastrointestinal symptoms were examined by gastroscopy. Three pieces of gastric mucosa were sampled for rapid urease test and pathohistological examination. Some children received 13C-urea breath test. Children with two or more positive results were diagnosed with H. pylori infection. A questionnaire on living environment, family economic status, parents' education level and family history of gastrointestinal diseases was completed for all children. RESULTS: The H. pylori infection rate was 44.9% (169/376) in children with upper gastrointestinal symptoms. There was no statistical difference in the infection rate between males and females (P>0.05). The H. pylori infection rates in the 3 to 7-year old, 8 to 12-year old and 13 to 16-year-old children were 39.5% (47/119), 41.0% (55/134), and 54.5% (67/123) respectively, with significant differences between different age groups (χ2=6.76, P<0.05). The H. pylori positive rate was significantly higher in children who were in full-time nursery or collective living and dining than in those who were not (53.6% vs 40.6%; P<0.05). The H. pylori positive rate in high-income families was lower than that in middle to low-income families (36.9% vs 48.3%; P<0.05). In addition, the H. pylori positive rate in children with well-educated parents was lower than in those with parents who had not received higher education (39.5% vs 50.8%; P<0.05). The H. pylori infection rate in children with a family history of digestive disease was significantly higher than in those without family history of gastrointestinal diseases (52.9% vs 41.2%; P<0.05). CONCLUSIONS: The infection rate increases with age and is higher in children who are in collective living and dining, come from low income family, have parents who have not received higher education and have a family history of upper gastrointestinal diseases.

Integrin-mediated signaling contributes to gadolinium-containing-particle-promoted cell survival and G1 to S phase cell cycle transition by enhancing focal adhesion formation.

We previously reported that Gd-containing particles formed under physiological conditions act as active entities to enhance cell survival and promote S phase entry via activation of both mitogen-activated protein kinase/extracellular-signal-regulated protein kinase (ERK) and phosphatidylinositol 3-kinase/Akt signaling pathways. However, how they transduce the extracellular signal inside the cell remains unclear. The present study demonstrates that Gd-containing particles can alleviate serum-deprivation-induced cell death and promote G1 to S phase cell cycle progression by enhancing cell adhesion to the extracellular matrix. As an indicator of adhesion, the vinculin distribution was detected by confocal laser scanning microscopy. The control cells exhibited fewer and less typical focal adhesions. After treatment with Gd-containing particles, a large number of vinculin-containing focal adhesions were maintained. In the presence of integrin antagonists, the percentage of S phase entry induced by Gd-containing particles was decreased and the enhancement of cell viability was also attenuated, along with a decrease in both cyclin D expression and ERK phosphorylation. In summary, the present results suggest that the integrin-mediated signaling pathway plays an important role in cell survival and G1 to S phase transition promoted by Gd-containing particles by enhancing focal adhesion formation. The results presented here provide novel evidence to advance knowledge leading to further understanding of the mechanisms of both cell proliferation and cell survival promoted by Gd and may be helpful for developing effective measures to prevent or treat nephrogenic systemic fibrosis.

Gadolinium-containing bioparticles as an active entity to promote cell cycle progression in mouse embryo fibroblast NIH3T3 cells.

In the present study, we demonstrated that gadolinium-containing particles formed in cell culture medium acted as a biologically active entity to mediate cell cycle progression in NIH3T3 cells. The particles were observed to accumulate at the cell surface by scanning electron microscopy. Energy-dispersive X-ray analysis was undertaken and confirmed that gadolinium was incorporated in the agglomerated particles. Moreover, the smaller gadolinium particles exhibited a stronger cell-cycle-promoting effect than the larger ones, but they shared the common signaling pathways. Both extracellular signal regulated kinase and phosphatidylinositol 3-kinase signaling pathways were activated by gadolinium-containing particles and may account for their proliferation-promoting effect on NIH3T3 cells. Furthermore, the study showed that the free gadolinium ion released from gadolinium-containing particles may be responsible for the proliferation effect. This study will be helpful to clarify the biological effect of the insoluble species formed from Gd(3+) as well as other multivalent metal ions under physiological conditions and will help to improve their medical applications.

[Early prediction of lamivudine response in e antigen-negative chronic hepatitis B patients].

OBJECTIVE: To evaluate the effects of ALT, HBsAg and HBV DNA at the baseline, 4 and 12 weeks after lamivudine treatment on the long term (104 weeks) response in e antigen-negative chronic hepatitis B patients. METHODS: 127 adult e antigen-negative chronic hepatitis B patients were enrolled in this study. All patients received treatment on LAM 100 mg/d for at least 104 weeks. The liver function, serum HBV markers and HBV viral load were regularly checked during the treatment. The effects of ALT, HBsAg and HBV DNA at the baseline, 4 and 12 weeks after lamivudine treatment on the response at 104 weeks were statistically analyzed. RESULTS: The proportion of patients with serum HBV DNA less than 1000 copies / ml at 104 weeks after LAM treatment was 50.0% and 86.8% in patients with baseline ALT less than 5 ULN and ALT is more than or equal to 5 ULN, respectively (P less than 0.01). In patients with baseline HBsAg less than 2000 COI and HBsAg is more than or equal to 2000 COI, the proportion of patients with serum HBsAg less than 500 COI at 104 weeks after LAM treatment was 19.1% and 17.5%, respectively (P more than 0.05). the HBsAg serological conversion rates were respectively 2.1% and 2.5% , respectively (P more than 0.05), the proportion of patients with serum HBV DNA less than 1000 copies/ml was 61.7% and 67.5%, respectively (P more than 0.05). In patients with baseline HBV DNA less than 10(6) copies/ml and HBV DNA is more than or equal to 10(6) copies/ml, the proportion of patients with HBV DNA less than 1000 copies/ml were statistically different at 4 weeks and 12 weeks after treatment, however, the proportion of patients with HBV DNA less than 1000 copies/ml at 104 weeks after LAM treatment was 62.7% and 67.1%, respectively (P more than 0.05). In patients with HBV DNA less than 1000 copies/ml and HBV DNA is more than or equal to 1000 copies/ml at 4 weeks after treatment, the proportion of patients with HBV DNA less than 1000 copies/ml at 104 weeks after LAM treatment was 70.7% and 60.9%, respectively (P more than 0.05). In patients with HBV DNA less than 1000 copies/ml and HBV DNA is more than or equal to 1000 copies/ml at 12 weeks after treatment, the proportion of patients with HBV DNA less than 1000 copies/ml at 104 weeks after treatment was 78.8% and 38.1%, respectively (P less than 0.01). CONCLUSION: e antigen negative chronic hepatitis B patients with baseline ALT is more than or equal to 5 ULN and HBV DNA less than 1000 copies/ml at 12 weeks after treatment have better virological response at 104 weeks after LAM treatment. The baseline HBsAg and HBV DNA load are associated with the virological response at 104 weeks after LAM treatment.

Gadolinium promoted proliferation and enhanced survival in human cervical carcinoma cells.

The effect of gadolinium chloride (Gd) on the proliferation of HeLa cells was investigated at lower concentration. The results obtained by MTT and cell cycle analysis showed that Gd promoted proliferation by inducing S phase entry in HeLa cells at the concentration less than 100 microM. It was further evidenced by both an increase in the levels of phosphorylation of retinoblastoma protein (pRb) and a remarkable increase in cyclin E expression. Moreover, the survival of cells, exposed to Gd up to 3-5 days, was increased compared with control. The attenuation of the serum deprivation-induced cell loss by Gd was associated with the sustained activation of FAK (PY(397)) and the delayed activation of JNKs pathway. Besides, it appeared that Gd promoted cell proliferation and survival in HeLa cells was not contributed to the ROS generation. Based on the present results, both positive and negative effects of the lanthanides as potential drugs or diagnostic agents are discussed.

Gadolinium-promoted cell cycle progression with enhanced S-phase entry via activation of both ERK and PI3K signaling pathways in NIH 3T3 cells.

The aim of this study was to investigate whether Gd is able to exert the proliferation-promoting effect and to explore its possible underlying mechanism. We showed that Gd promoted cell cycle progression with increased S-phase entry in a concentration- and time-dependent manner in NIH 3T3 cells. The effect was further evidenced by the expressions of key proteins in driving cells through the G(1)/S transition point of the cell cycle. In the presence of Gd, the protein levels of cyclins D, E, and A were dramatically increased and demonstrated a characteristically temporal pattern of sequential mitotic events. Additionally, the levels of phosphorylated retinoblastoma protein were also significantly increased at certain time periods. To further elucidate the underlying mechanism, extracellular signal-regulated kinase and phosphatidylinositol 3-kinase signaling pathways were assessed. Both pathways were activated by Gd. Moreover, the levels of cyclin D and cyclin A were evaluated after the addition of the pharmacological inhibitors at early and late G(1) phases, correspondingly, to reveal the contribution of the two pathways in the Gd-promoted G(1)/S transition. It showed that both pathways were needed for Gd-promoted cell cycle progression. The results presented here provide novel evidence to advance knowledge leading to further understanding of the mechanisms of both cell growth and death caused by Gd and may be helpful for more rational application of Gd-based compounds in the future.