C-JUN overexpressing CAR-T cells in acute myeloid leukemia: preclinical characterization and phase I trial.

Chimeric antigen receptor (CAR) T cells show suboptimal efficacy in acute myeloid leukemia (AML). We find that CAR T cells exposed to myeloid leukemia show impaired activation and cytolytic function, accompanied by impaired antigen receptor downstream calcium, ZAP70, ERK, and C-JUN signaling, compared to those exposed to B-cell leukemia. These defects are caused in part by the high expression of CD155 by AML. Overexpressing C-JUN, but not other antigen receptor downstream components, maximally restores anti-tumor function. C-JUN overexpression increases costimulatory molecules and cytokines through reinvigoration of ERK or transcriptional activation, independent of anti-exhaustion. We conduct an open-label, non-randomized, single-arm, phase I trial of C-JUN-overexpressing CAR-T in AML (NCT04835519) with safety and efficacy as primary and secondary endpoints, respectively. Of the four patients treated, one has grade 4 (dose-limiting toxicity) and three have grade 1-2 cytokine release syndrome. Two patients have no detectable bone marrow blasts and one patient has blast reduction after treatment. Thus, overexpressing C-JUN endows CAR-T efficacy in AML.

In Situ Transformable Pro-nanotheranostic Platform for Activable Photoacoustic Imaging and Synergistic Photothermal/Chemodynamic Cancer Therapy.

Nanotheranostic platforms integrated with diagnostic and therapeutic functions have been widely developed for tumor medicine. However, the "always-on" nanotheranostic platforms suffer from poor tumor specificity, which may largely restrict therapeutic efficacy and prevent precise theranostics. Here, we develop an in situ transformable pro-nanotheranostic platform (ZnS/Cu2O@ZIF-8@PVP) by encapsulating ZnS and Cu2O nanoparticles in a metal-organic framework (MOF) nanomaterial of ZIF-8 that allows activable photoacoustic (PA) imaging and synergistic photothermal/chemodynamic therapy (PTT/CDT) of tumors in vivo. It is shown that the pro-nanotheranostic platform gradually decomposes and releases ZnS nanoparticles and Cu+ ions in acidic conditions, which spontaneously trigger a cation exchange reaction and synthesize Cu2S nanodots in situ with activated PA signals and PTT effects. Moreover, the excessive Cu+ ions function as Fenton-like catalysts and catalyze the production of highly reactive hydroxyl radicals (•OH) for CDT using elevated levels of H2O2 in tumor microenvironments (TMEs). In vivo studies demonstrate that the in situ transformable pro-nanotheranostic platform can specifically image tumors via PA and photothermal imaging and efficiently ablate tumors through synergistic CDT/PTT. Our in situ transformable pro-nanotheranostic platform could provide a new arsenal for precise theranostics in cancer therapy.

FOLR1-induced folate deficiency reduces viral replication via modulating APOBEC3 family expression.

Folate receptor alpha (FOLR1) is vital for cells ingesting folate (FA). FA plays an indispensable role in cell proliferation and survival. However, it is not clear whether the axis of FOLR1/FA has a similar function in viral replication. In this study, we used vesicular stomatitis virus (VSV) to investigate the relationship between FOLR1-mediated FA deficiency and viral replication, as well as the underlying mechanisms. We discovered that FOLR1 upregulation led to the deficiency of FA in HeLa cells and mice. Meanwhile, VSV replication was notably suppressed by FOLR1 overexpression, and this antiviral activity was related to FA deficiency. Mechanistically, FA deficiency mainly upregulated apolipoprotein B mRNA editing enzyme catalytic subunit 3B (APOBEC3B) expression, which suppressed VSV replication in vitro and in vivo. In addition, methotrexate (MTX), an FA metabolism inhibitor, effectively inhibited VSV replication by enhancing the expression of APOBEC3B in vitro and in vivo. Overall, our present study provided a new perspective for the role of FA metabolism in viral infections and highlights the potential of MTX as a broad-spectrum antiviral agent against RNA viruses.

Brominated flame retardants and heavy metals in common aquatic products from the pearl river delta, south china: Bioaccessibility assessment and human health implications.

Aquatic products are an important source of environmental pollutants to humans. This study was conducted to assess the bioaccessibility of selected brominated flame retardants and heavy metals in common aquatic products from the Pearl River Delta, South China, as well as associated human health risks. Based on a questionnaire survey, ten of the most consumed aquatic products were collected from local markets. The bioaccessibility of polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCDDs), and heavy metals was assessed using an in vitro gastrointestinal model. Bioaccessibility of heavy metals (33.0-84.0%) and HBCDDs (38.5-68.4%) was significantly higher than that of PBDEs (13.4-65.4%). Total non-carcinogenic and carcinogenic risks from heavy metal consumption were much higher than the threshold values due to excessive abundances of arsenic in shellfish (HQ = 2.45, CR = 1.1 ×10-3). Furthermore, middle-aged populations and females were subjected to greater health risks due to different intakes of aquatic products among age and gender groups. Significant difference in bioaccessibility among analytes indicated that bioaccessibility of pollutants is non-negligible in health risk assessment. This is the first study systematically investigating health risks of aquatic products consumption and concludes that shellfish is a great cause for concern for the PRD residents.

Engineering H2O2 Self-Supplying Nanotheranostic Platform for Targeted and Imaging-Guided Chemodynamic Therapy.

Developing highly efficient chemodynamic therapy (CDT)-based theranostic technology for cancer treatment is highly desired but still challenging. A novel nanotheranostic platform is constructed for enhanced CDT by engineering hybrid CaO2 and Fe3O4 nanoparticles with a hyaluronate acid (HA) stabilizer and NIR fluorophore label. This design not only enables the nanotheranostic agent to afford highly efficient CDT against tumor cells but also confers NIR fluorescence (NIRF) and magnetic resonance (MR) bimodal imaging for in vivo visualization of CDT. Moreover, the use of the HA stabilizer allows for the facile synthesis of the nanotheranostic agent with excellent biocompatibility and active targetability. The nanotheranaostic agent possesses a high capacity of self-supplying H2O2 and producing •OH in acidic conditions, while retaining the desired stability under physiological conditions. It also demonstrates high selectivity to tumor cells via CDT with minimized toxicity to normal cells. In vivo studies reveal that our nanotheranaostic agent exhibits efficacious tumor growth inhibition via a CDT mechanism with favorable biosafety. Moreover, in vivo visualization of the CDT progress via NIRF and MR bimodal imaging demonstrates specific targeting and treatment of tumors. The developed H2O2 self-supplying, active targeting, and bimodal imaging nanotheranostic platform holds the potential as a highly efficient strategy for CDT of cancer.

Association Study Between Methylation in the Promoter Regions of cGAS, MAVS, and TRAF3 Genes and the Risk of Cervical Precancerous Lesions and Cervical Cancer in a Southern Chinese Population.

A case-control study was used to explore the association between the methylation status in the promoter regions of the cGAS, MAVS, and TRAF3 genes and the diseases of cervical precancerous lesions (CPL) and cervical cancer (CC) in a Southern Chinese population, and to further explore their interaction effects with high-risk human papillomavirus (hrHPV) infection and environmental factors in these diseases. The study protocol was approved by the ethics committee of The First Affiliated Hospital of Jinan University, and this study was performed in 97 healthy controls, 75 patients with CPL and 33 patients with CC, while each participant has read and signed the informed consent forms before enrolment. The promoter methylation status genes were detected from the bisulfite-treated DNA by the bisulfite sequencing PCR (BSP) technique, which was carried out using MethPrimer. The cGAS, MAVS, and TRAF3 promoter methylation levels in CPL (CPL cGAS = 35.40%, CPL MAVS = 24.26%, and CPL TRAF3 = 96.76%) were significantly higher than those in the control (Control cGAS = 31.87%, Control MAVS = 21.16%, and Control TRAF3 = 96.26%, PcGAS < 0.001, PMAVS < 0.001, and PTRAF3 = 0.001); however, there was no significant differences between the CC and control. In the logistic regression model with adjusted covariates, compared with the individuals whose cGAS methylation levels were less than or equal to 31.87%, the women with the levels more than 31.87% increased the risk of CPL by 2.49 times (ORa = 2.49, 95% CI = 1.31-4.75, P a = 0.006). The women with MAVS methylation levels above 21.16% were 1.97 times more likely to have CPL than the those with the levels less than 21.16% (ORa = 1.97, 95% CI = 1.06-3.69, P a = 0.033). A synergistic interaction was found between hrHPV and gene promoter methylation levels of cGAS and MAVS in CPL; however, no potential interaction was observed in CC. The promoter methylation levels in cGAS, MAVS, and TRAF3 genes are higher in CPL than in control, indicating that hypermethylation might be an early event in the progression of cervical intraepithelial neoplasia (CIN). The interaction between the promoter methylation levels in cGAS and MAVS genes and hrHPV infection might play a role in the development of CPL.

Silica nanoparticles as an enhancer in the IL-1ß-induced inflammation cycle of A549 cells.

Objective: The industrial production and combustion of coal can produce silica nanoparticles (nano-SiO2). It enters the human body mainly through the respiratory tract and exerts a toxic effect. However, whether nano-SiO2 can increase the IL-1ß-induced inflammatory expression in A549 cells has not been tested. Therefore, the synergistic toxicity of nano-SiO2 and IL-1ß to A549 was observed in our study. Materials and methods: We exposed A549 cells to nano-SiO2 (0, 100, 500, and 1000 µg/ml) for 12 and 24 h. The effect of nano-SiO2 on the viability of A549 cells was observed by the CCK-8 method. The A549 cells were exposed to nano-SiO2 (1 mg/mL) and cytokine IL-1ß (10 ng/mL) for 4 h, and we detected the expression of IL-1ß and IL-6 cytokines by real time quantitative polymerase chain (RT-qPCR) and enzyme linked immunosorbent assay (ELISA). The expression of ß-Actin, I-κB, phospho-ERK1/2 (P-ERK1/2), total-ERK1/2 (T-ERK1/2), phospho-JNK (P-JNK), total-JNK (T-JNK), phospho-P38 (P-P38), and total-P38 (T-P38) in A549 cells was detected by the Western Blot method. Results: The nano-SiO2 treatment resulted in a time-dependent decrease in the viability of A549 cells. The synergistic effect of nano-SiO2 and IL-1ß was observed on the new production of IL-1ß and IL-6 in A549 cells. The Western blot results showed that nano-SiO2 can increase the expression of IL-1ß and IL-6 by promoting the phosphorylation of ERK1/2 and elevating the phosphorylation of I-κB by IL-1ß. IL-1ß and IL-6 were induced by nano-SiO2, and the IL-1ß treatment with 20 µM of I-κBα phosphorylation inhibitor (PD98059) and 20 µM of ERK1/2 inhibitor (BAY11-7082) for 1 h was significantly lower than that of the control group in A549 cells. Discussion and conclusion: These results indicated that nano-SiO2 had a toxic effect on A549 cells, and this effect could increase IL-1ß on the A549 cell-induced inflammatory response. The results suggested that the release of IL-1ß and IL-6 in A549 was enhanced by the synergistic IL-1ß-induced phosphorylation of ERK1/2 and I-κB. This process is similar to a snowball, and it is possible that IL-1ß is continuously produced and repeatedly superimposed in A549 cells to produce an inflammatory effect; then, a vicious circle occurs, and an inflammatory storm is accelerated.

Coordination Nanosheets of Phthalocyanine as Multifunctional Platform for Imaging-Guided Synergistic Therapy of Cancer.

"All-in-one" nanodrugs integrating various functionalities into one nanosystem are highly desired for cancer treatment. Coordination nanosheets as one type of two dimensional (2D) nanomaterials offer great opportunities, but there is lack of enough candidates. Here, a new kind of coordination nanosheets based on phthalocyanine are constructed. Manganese phthalocyanine (MnPc) tetracarboxylic acid is employed as photoactive ligand to form MnPc nanosheets; meanwhile, hyaluronic acid (HA) is coated on their surface. The obtained MnPc@HA nanosheets exhibit superior near-infrared (NIR) photothermal effect with photothermal conversion efficiency of 72.3%, much higher than those of the previously reported photothermal agents. Due to their 2D nanostructures, MnPc@HA nanosheets possess superhigh drug-loading capacity for chemotherapy drug curcumin. With HA as a targeting group, the nanosheets selectively accumulated in CD44 overexpressed tumors, followed by drug release under the control of NIR light. Moreover, MnPc@HA nanosheets with intrinsic paramagnetism can serve as T1 contrast agent for magnetic resonance imaging. The synergistic effect of phototherapy and chemotherapy endows curcumin-loaded MnPc@HA nanosheets with superior tumor-eradicating efficacy. Besides, MnPc@HA nanosheets are biocompatible and safe for biomedical applications. This work provides novel insight for developing new multifunctional platforms based on 2D coordination nanosheets to synergistically combat cancer.

Interaction Between Susceptibility Loci in MAVS and TRAF3 Genes, and High-risk HPV Infection on the Risk of Cervical Precancerous Lesions in Chinese Population.

Persistent high-risk HPV infection is considered as a major cause of cervical cancer. Nevertheless, only some infected individuals actually develop cervical cancer. The RIG-I pathway in innate immunity plays an important role in antivirus response. Here, we hypothesized that altered function of mitochondrial antiviral signaling protein (MAVS) and mitochondrial TNF receptor-associated factor 3(TRAF3), key molecules downstream of the viral sensors RIG-I, may impair their ability of clearing HPV and thereby influence the risk for cervical precancerous lesions. To investigate the effects of MAVS and TRAF3 polymorphisms on susceptibility to cervical precancerous lesions, 8 SNPs were analyzed in 164 cervical precancerous lesion cases and 428 controls. Gene-environment interactions were also calculated. We found that CA genotype of rs6052130 in MAVS gene were at 1.48 times higher risk of developing cervical precancerous lesion than individuals with CC genotype (CA vs. CC: ORadjusted = 1.48, 95% CI, 1.02-2.16). In addition, a significant synergetic interaction between high-risk HPV infection and rs6052130 was found on an additive scale. A significantly decreased risk of cervical precancerous lesions for the TC genotype of rs12435483 in the TRAF3 gene (ORadjusted = 0.67, 95% CI, 0.45-0.98) was also found. Moreover, MDR analysis identified a significant three-locus interaction model, involving high-risk HPV infection, TRAF3 rs12435483 and number of full-term pregnancies. Our results indicate that the MAVS rs6052130 and TRAF3 rs12435483 confer genetic susceptibility to cervical precancerous lesions. Moreover, MAVS rs6052130-mutant individuals have an increased vulnerability to high-risk HPV-induced cervical precancerous lesions.

Association of variants of miRNA processing genes with cervical precancerous lesion risk in a southern Chinese population.

The miRNA processing genes play essential roles in the biosynthesis of mammalian miRNAs, and their genetic variants are involved in the development of various cancers. Our study aimed to determine the potential association between miRNA processing gene polymorphisms and cervical precancerous lesions. Five single nucleotide polymorphisms (SNPs), including Ran-GTP (RAN) rs14035, exportin-5 (XPO5) rs11077, DICER1 rs3742330, DICER1 rs13078, and TARBP2 rs784567, were genotyped in a case-control study to estimate risk factors of cervical precancerous lesions. The gene-environment interactions and haplotype association were estimated. We identified a 27% decreased risk of cervical precancerous lesions for individuals with minor G allele in DICER1 rs3742330 (odds ratio (OR) = 0.73, 95% confidence interval (95% CI) = 0.58-0.92, P = 0.009). The AG and AG/GG genotypes in DICER1 rs3742330 were also found to decrease the risk of cervical precancerous lesions (AG compared with AA: OR = 0.51, 95% CI = 0.35-0.73, P <0.001; AG/GG compared with AA: OR = 0.54, 95% CI = 0.39-0.77, P = 0.001). The GT haplotype in DICER1 had a risk effect on cervical precancerous lesions compared with the AT haplotype (OR = 1.36, 95% CI = 1.08-1.73, P = 0.010). A two-factor (DICER1 rs3742330 and human papillomavirus (HPV) infection) and two three-factor (model 1: rs3742330, passive smoking, and HPV infection; model 2: rs3742330, abortion history, and HPV infection) interaction models for cervical precancerous lesions were identified. In conclusion, the genetic variants in the miRNA processing genes and interactions with certain environmental factors might contribute to the risk of cervical precancerous lesions in southern Chinese women.

Biomimetic nanothylakoids for efficient imaging-guided photodynamic therapy for cancer.

Biomimetic nanothylakoids, which are constructed from the thylakoid membrane of vegetable leaves, show high efficiency in tumor microenvironment modulation and photodynamic antitumor therapy under near infrared fluorescence guidance. Furthermore, their outstanding biosafety, facile preparation and low cost make nanothylakoids suitable for further clinical applications.

Dual Roles of Protein as a Template and a Sulfur Provider: A General Approach to Metal Sulfides for Efficient Photothermal Therapy of Cancer.

Fabrication of clinically translatable nanoparticles (NPs) as photothermal therapy (PTT) agents against cancer is becoming increasingly desirable, but still challenging, especially in facile and controllable synthesis of biocompatible NPs with high photothermal efficiency. A new strategy which uses protein as both a template and a sulfur provider is proposed for facile, cost-effective, and large-scale construction of biocompatible metal sulfide NPs with controlled structure and high photothermal efficiency. Upon mixing proteins and metal ions under alkaline conditions, the metal ions can be rapidly coordinated via a biuret-reaction like process. In the presence of alkali, the inert disulfide bonds of S-rich proteins can be activated to react with metal ions and generate metal sulfide NPs under gentle conditions. As a template, the protein can confine and regulate the nucleation and growth of the metal sulfide NPs within the protein formed cavities. Thus, the obtained metal sulfides such as Ag2 S, Bi2 S3 , CdS, and CuS NPs are all with small size and coated with proteins, affording them biocompatible surfaces. As a model material, CuS NPs are evaluated as a PTT agent for cancer treatment. They exhibit high photothermal efficiency, high stability, water solubility, and good biocompatibility, making them an excellent PTT agent against tumors. This work paves a new avenue toward the synthesis of structure-controlled and biocompatible metal sulfide NPs, which can find wide applications in biomedical fields.

The effects of TLR3, TRIF and TRAF3 SNPs and interactions with environmental factors on type 2 diabetes mellitus and vascular complications in a Han Chinese population.

Toll-like receptor 3 (TLR3) is involved in type I interferon-ß (IFN-ß) via TIR-domain-containing adapter-inducing interferon-ß (TRIF) and Tumor necrosis factor receptor-associated factor 3 (TRAF3), culminating in inflammation and immunity reactions. TLR3 is implicated in insulin resistance and type 2 diabetes mellitus (T2DM). Eight SNPs of these genes were detected in 552 T2DM patients and 552 matched healthy control subjects. Gene-gene and gene-environment interactions and haplotype associations were also evaluated. We identified a 21% increased risk of T2DM for the T allele of rs12435483 in the TRAF3 gene (OR: 1.21; 95% CI: 1.01-1.44; P=0.036). The GA genotype and GA+AA genotype of TRAF3 rs12147254 were found to increase the risk of coronary heart disease (CHD) among T2DM patients (GA vs. GG: OR=4.17, 95% CI: 1.04-16.79, P=0.045; GA+AA vs. GG: OR=3.97, 95% CI: 1.02-15.48, P=0.047). However, the GACGAC haplotype in TRAF3 had a protective effect on T2DM micro-macrovascular complications (OR=0.33, 95% CI: 0.13-0.85, P=0.017). Two-factor (TRAF3 rs12435483 and LDL) and three-factor (TRAF3 rs12435483, BMI and HDL) interactions of the risk of T2DM were identified. In conclusion, the genetic variants in the TLR3-TRIF-TRAF3-INF-ß signaling pathway and interactions with some particular environmental factors (LDL, BMI and HDL) may contribute to susceptibility to T2DM and vascular complications in the Han Chinese population.

Association of LPP and TAGAP Polymorphisms with Celiac Disease Risk: A Meta-Analysis.

Background: Lipoma preferred partner (LPP) and T-cell activation Rho GTPase activating protein (TAGAP) polymorphisms might influence the susceptibility to celiac disease. Therefore, we performed a meta-analysis by identifying relevant studies to estimate the risks of these polymorphisms on celiac disease. Methods: The PubMed, Web of Science and Embase databases were searched (up to October 2016) for LPP rs1464510 and TAGAP rs1738074 polymorphisms. Results: This meta-analysis included the same 7 studies for LPP rs1464510 and TAGAP rs1738074. The minor risk A allele at both rs1464510 and rs1738074 carried risks (odds ratios) of 1.26 (95% CI: 1.22-1.30) and 1.17 (95% CI: 1.14-1.21), respectively, which contributed to increased risks in all celiac disease patients by 10.72% and 6.59%, respectively. The estimated lambdas were 0.512 and 0.496, respectively, suggesting that a co-dominant model would be suitable for both gene effects. Conclusions: This meta-analysis provides robust estimates that polymorphisms in LPP and TAGAP genes are potential risk factors for celiac disease in European and American. Prospective studies and more genome-wide association studies (GWAS) are needed to confirm these findings, and some corresponding molecular biology experiments should be carried out to clarify the pathogenic mechanisms of celiac disease.

Black Phosphorus Nanosheet-Based Drug Delivery System for Synergistic Photodynamic/Photothermal/Chemotherapy of Cancer.

A black phosphorus (BP)-based drug delivery system for synergistic photodynamic/photothermal/chemotherapy of cancer is constructed. As a 2D nanosheet, BP shows super high drug loading capacity and pH-/photoresponsive drug release. The intrinsic photothermal and photodynamic effects of BP enhance the antitumor activities. The synergistic photodynamic/photothermal/chemotherapy makes BP-based drug delivery system a multifunctional nanomedicine platform.

Rational Tuning of the Electrocatalytic Nanobiointerface for a "Turn-Off" Biofuel-Cell-Based Self-Powered Biosensor for p53 Protein.

Herein, a novel tunable electrocatalytic nanobiointerface for the construction of a high-sensitivity and high-selectivity biofuel-cell (BFC)-based self-powered biosensor for the detection of transcription factor protein p53 is reported, in which bilirubin oxidase (BOD)/DNA supramolecular modified graphene/platinum nanoparticles hybrid nanosheet (GPNHN) works as a new enhanced material of biocathode to control the attachment of target, and thus tune the electron-transfer process of oxygen reduction for transducing signaling magnification. It is found that in the presence of p53, the strong interaction between the wild-type p53 and its consensus DNA sequence on the electrode surface can block the electron transfer from the BOD to the electrode, thus providing a good opportunity for reducing the electrocatalytic activity of oxygen reduction in the biocathode. This in combination with the glucose oxidation at the carbon nanotube/Meldola's blue/glucose dehydrogenase bioanode can result in a current/or power decrease of BFC in the presence of wild-type p53. The specially designed BFC-based self-powered p53 sensor shows a wide linear range from 1 pM to 1 µM with a detection limit of 1 pM for analyzing wild-type p53. Most importantly, our BFC-based self-powered sensors can detect the concentrations of wild-type p53 in normal and cancer cell lysates without any extensive sample pretreatment/separation or specialized instruments. The present BFC-based self-powered sensor can provide a simple, economical, sensitive, and rapid way for analyzing p53 protein in normal and cancer cells at clinical level, which shows great potential for creating the treatment modalities that capitalize on the concentration variation of the wild-type p53.

NIR light controlled release of caged hydrogen sulfide based on upconversion nanoparticles.

A NIR light induced H2S release platform based on UCNPs was constructed. Under NIR light excitation, UCNPs can emit UV light which triggers H2S release in a spatial and temporal pattern. The platform was also employed to real-time monitor the delivery process in vivo, which may provide a new way for the use of H2S-based therapeutics for a variety of diseases.

[Relationship between intestinal mucosal inflammation and mental disorders in patients with irritable bowel syndrome].

OBJECTIVE: To examine the relationship between inflammation and the comorbidity of mental disorders with irritable bowel syndrome (IBS) by comparing intestinal mucosa inflammatory biomarkers in patients with and without mental disorders. METHODS: A total of 43 consecutive IBS patients fulfilling the Rome III criteria and 15 volunteers serving as controls without digestive symptoms were recruited and interviewed with Composite International Diagnostic Interview (CIDI) by the well-trained staff and thus classified as with or without mental disorders. All subjects underwent colonoscopy and biopsies were acquired from the mucosa of distal ileum and colon. CD3(+) lymphocytes, mast cells, 5-HT positive cells and (indoleamine 2,3-dioxygenase) IDO positive cells were identified immunohistologically in mucosa biopsies in volunteers (n = 13), IBS patients without mental disorder (n = 24) and IBS patients with mental disorder (n = 19). RESULTS: The incidence of mental disorders in IBS patients was significantly higher than that in the volunteers (19/43 vs 2/15, P = 0.012), including 9 patients with anxiety disorders and 8 with mood disorders. (1) The number of mast cells in IBS patients with mental disorder and that in IBS patients without mental disorder has no statistical significance ((16.7 ± 3.6)/HP vs (15.4 ± 3.1)/HP in distal ileum, (12.8 ± 2.2)/HP vs (12.3 ± 2.5)/HP in sigmoid, both P > 0.05). Similar results were seen in 5-HT positive cells ((3.7 ± 0.9)/HP vs (3.4 ± 0.8)/HP in distal ileum, (6.1 ± 1.8)/HP vs (5.2 ± 1.8)/HP in sigmoid, both P > 0.05). In distal ileum, the number of CD3(+) cells in IBS patients with mental disorder has no statistical significance with that in the IBS patients without mental disorder ((62 ± 16)/HP vs (55 ± 22)/HP, P > 0.05). Similar results were seen in IDO positive cells (6(2, 8)/HP vs 2(1, 5)/HP, P > 0.05). (2) The number of IDO positive cells from distal ileum in IBS patients with anxiety disorder was significantly higher than that in the IBS patients without mental disorder (6 (4,8) vs 2 (1,5), P = 0.018). The number of mast cells from distal ileum in the IBS patients with mood disorder were significantly higher than that in those without mental disorders ((18.3 ± 3.2)/HP vs (15.4 ± 3.1)/HP, P = 0.032). CONCLUSIONS: Mental disorders in the IBS patients may be associated with intestinal mucosal inflammation. The activation of IDO may cause the comorbidity of IBS with anxiety disorder while the activation of mast cells probably leads to the comorbidity of IBS with mood disorder.

[A case report of collagenous gastritis in a young Chinese woman and literatures review].

OBJECTIVE: Collagenous gastritis is a rare entity, characterized by the deposition of a subepithelial collagen band with an inflammatory infiltrate in the mucosa. This report describes the first case of collagenous gastritis occurring in a young Chinese woman and reviews the literatures. METHODS: The patient underwent the gastroscopy screening, and the biopsy specimens were treated with HE staining, Masson staining, Congo red staining and Warthin-Starry staining.Patients' clinical data was discussed and followed up. RESULTS: A twenty-year-old girl had intermittent epigastric pain for 4 years, abdominal distention, hiccup and weight loss for two months. The gastric endoscopy revealed diffuse white nodular appearance of the mucosa in angular incisura and antrum. Pathologic examination of the gastric biopsies from the antrum and angular showed a subepithelial collagen deposition with moderate infiltrates of lymph plasma cells and eosinophils of the lamina propria. The collagen band measured up to 120.3 µm (mean 43.8 µm). Prednisone 20 mg/d for 4 weeks led to clinical remission and weight gain. CONCLUSION: There are about 40 cases in literatures to date, and the cause and pathogenesis of collagenous gastritis remain unknown. According to the clinical and pathological characteristics, the patient in this article is the subtype of collagenous gastritis that occurring in children and young adults. Specific therapy has not been established, the gluten-free diet and glucocorticosteroid may be helpful to relieve symptoms in collagenous gastritis patients.

[Role of peroxisome proliferators-activated receptor-gamma in the chemical prevention therapy of sulindac for precancerous lesions of rats].

OBJECTIVE: To understand whether peroxisome proliferators-activated receptor-gamma (PPAR-gamma) plays an important role in the chemopreventive effect of sulindac on precancerous lesions (aberrant crypt foci, ACF) of rats. METHODS: Male Sprague-Dawley rats were used in this study and raised in Special Pathogen Free room. Sulindac was the main research object. Carcinogenic agent, 1, 2-dimethylhydrazine (DMH), was used to induce colonic precancerous lesions. Pioglitazone was chosen as agonist of PPAR-gamma and GW9662 used as a specific complete antagonist of PPAR-gamma. ACFs were induced according to the protocol certified in prior experiments. There were 7 groups, named as Negative control group, DMH group, Sulindac group, Sulindac+GW9662 group, Pioglitazone group, Pioglitazone+GW9662 group and GW9662 group. The experiment period was 12 weeks. At the end of the experiment, all rats were sacrificed by euthanasia. Half of the colon including the rectum was taken and immersed in formalin at 4 degrees Celsius overnight, and then recorded the number and size of ACF with the help of anatomic microscope stained by methylene blue. RESULTS: (1) Sulindac and agonist of PPAR-gamma could significantly inhibit DMH-induced ACFs of rats from 137.8+/-59.4 to 73.9+/-32.1 and 96.4+/-32.6 with a decrease of 45.7% (P<0.01) and 30.0%(P<0.05) compared with DMH group. Antagonist of PPAR-gamma could counteract the chemopreventive effect of sulindac with an increase from 73.9+/-32.1 to 106.3+/-33.9; (2) The expression of PPAR-gamma in colorectal mucosa increased significantly during the DMH induction period compared with negative control group, the relative values of gray were 0.304+/-0.288 and 2.292+/-1.380 (P<0.01), sulindac and pioglitazone could decrease the expression of PPAR-gamma remarkably compared with DMH group, the relative values of gray were 1.023+/-1.115 and 0.352+/-0.187 (P<0.01), and the application of GW9662, antagonist of PPAR-gamma could promote the expression of PPAR-gamma in some degree, and the relative values of gray were 1.279+/-0.303 and 0.998+/-0.295 (P>0.05). CONCLUSION: The expression of PPAR-gamma had risen in DMH-induced ACFs of rats significantly. Sulindac and agonist of PPAR-Gamma (pioglitazone) could inhibit the formation of ACF, and followed by a decrease of PPAR-gamma. Antagonist of PPAR-gamma could interfere with the effect of sulindac. PPAR-gamma might play an important role in the chemopreventive effect of sulindac on colorectal pre-cancerous lesions of rats and activation of PPAR-gamma pathway could inhibit the initiation and evolvement of ACF induced by DMH.