CD39 expression defines exhausted CD4+ T cells associated with poor survival and immune evasion in human gastric cancer.

Objectives: CD4+ T cell helper and regulatory function in human cancers has been well characterised. However, the definition of tumor-infiltrating CD4+ T cell exhaustion and how it contributes to the immune response and disease progression in human gastric cancer (GC) remain largely unknown. Methods: A total of 128 GC patients were enrolled in the study. The expression of CD39 and PD-1 on CD4+ T cells in the different samples was analysed by flow cytometry. GC-infiltrating CD4+ T cell subpopulations based on CD39 expression were phenotypically and functionally assessed. The role of CD39 in the immune response of GC-infiltrating T cells was investigated by inhibiting CD39 enzymatic activity. Results: In comparison with CD4+ T cells from the non-tumor tissues, significantly more GC-infiltrating CD4+ T cells expressed CD39. Most GC-infiltrating CD39+CD4+ T cells exhibited CD45RA-CCR7- effector-memory phenotype expressing more exhaustion-associated inhibitory molecules and transcription factors and produced less TNF-α, IFN-γ and cytolytic molecules than their CD39-CD4+ counterparts. Moreover, ex vivo inhibition of CD39 enzymatic activity enhanced their functional potential reflected by TNF-α and IFN-γ production. Finally, increased percentages of GC-infiltrating CD39+CD4+ T cells were positively associated with disease progression and patients' poorer overall survival. Conclusion: Our study demonstrates that CD39 expression defines GC-infiltrating CD4+ T cell exhaustion and their immunosuppressive function. Targeting CD39 may be a promising therapeutic strategy for treating GC patients.

Artificial intelligence aided precise detection of local recurrence on MRI for nasopharyngeal carcinoma: a multicenter cohort study.

Background: MRI is the routine examination to surveil the recurrence of nasopharyngeal carcinoma, but it has relatively lower sensitivity than PET/CT. We aimed to find if artificial intelligence (AI) could be competent pre-inspector for MRI radiologists and whether AI-aided MRI could perform better or even equal to PET/CT. Methods: This multicenter study enrolled 6916 patients from five hospitals between September 2009 and October 2020. A 2.5D convolutional neural network diagnostic model and a nnU-Net contouring model were developed in the training and test cohorts and used to independently predict and visualize the recurrence of patients in the internal and external validation cohorts. We evaluated the area under the ROC curve (AUC) of AI and compared AI with MRI and PET/CT in sensitivity and specificity using the McNemar test. The prospective cohort was randomized into the AI and non-AI groups, and their sensitivity and specificity were compared using the Chi-square test. Findings: The AI model achieved AUCs of 0.92 and 0.88 in the internal and external validation cohorts, corresponding to the sensitivity of 79.5% and 74.3% and specificity of 91.0% and 92.8%. It had comparable sensitivity to MRI (e.g., 74.3% vs. 74.7%, P = 0.89) but lower sensitivity than PET/CT (77.9% vs. 92.0%, P < 0.0001) at the same individual-specificities. The AI model achieved moderate precision with a median dice similarity coefficient of 0.67. AI-aided MRI improved specificity (92.5% vs. 85.0%, P = 0.034), equaled PET/CT in the internal validation subcohort, and increased sensitivity (81.9% vs. 70.8%, P = 0.021) in the external validation subcohort. In the prospective cohort of 1248 patients, the AI group had higher sensitivity than the non-AI group (78.6% vs. 67.3%, P = 0.23), albeit nonsignificant. In future randomized controlled trials, a sample size of 3943 patients in each arm would be required to demonstrate the statistically significant difference. Interpretation: The AI model equaled MRI by expert radiologists, and AI-aided MRI by expert radiologists equaled PET/CT. A larger randomized controlled trial is warranted to demonstrate the AI's benefit sufficiently. Funding: The Sun Yat-sen University Clinical Research 5010 Program (2015020), Guangdong Basic and Applied Basic Research Foundation (2022A1515110356), and Guangzhou Science and Technology Program (2023A04J1788).

LncRNA OTUD6B-AS1 promotes paclitaxel resistance in triple negative breast cancer by regulation of miR-26a-5p/MTDH pathway-mediated autophagy and genomic instability.

Genomic instability (GIN) is pivotal in regulating tumor drug resistance, which blocked the treatment of triple negative breast cancer (TNBC). Although recent studies implied that non-coding RNA (ncRNA)-mediated autophagy abolishment promoted tumorigenesis by up-regulation of GIN, autophagy was known as a risk factor in tumor drug resistance. However, previous study also pointed that up-regulation of autophagy promoted GIN. Therefore, the relationship between autophagy and GIN is not clear, and more work is needed. And, if an ncRNA is identified to be a co-regulator of autophagy and GIN, it will be a potential therapy target of chemotherapy resistance in TNBC. In our study, we recognized both autophagy-GIN-associated microRNA (mi-26a-5p) by big data analysis, which was prognosis-correlated in breast cancer. Next, we identified the up-stream regulators (long non-coding RNA, lncRNA) and down-stream targets of miR-26a-5p by bioinformatics analysis (online public databases). Finally, we established lncRNA OTUD6B-AS1/miR-26a-5p/MTDH signaling pathway, and verified their functions by cytological, molecular biological and zoological experiments. In general, our study found (1) miR-26a-5p was a protective factor of breast cancer, while OTUD6B-AS1 and MTDH were risk factors; (2) OTUD6B-AS1 was the up-stream regulator of miR-26a-5p verified by luciferase; (3) up-regulation of miR-26a-5p and down-regulation of MTDH promoted cellular cytotoxicity of paclitaxel (PTX) in vitro and in vivo. (4) down-regulation of miR-26a-5p, overexpression of MTDH and OTUD6B-AS1 promoted autophagy and DNA damage; (5) up-regulation of OTUD6B-AS1 and MTDH inhibited DNA damage response (DDR) by inhibiting the phosphorylated activation of RAD51, ATR and ATM.

Activation of potassium released from soil by root-secreted organic acids in different varieties of tobacco (Nicotiana tabacum).

Organic acids secreted from the roots of plants play important roles in nutrient acquisition and metal detoxification; however, the precise underlying mechanisms of these processes remain poorly understood. In the present study we examined the content of organic acids exuded from roots and the effects of these organic acids on the activation of slowly available potassium (K) at different K levels, including normal K supply and K-deficient conditions. In addition, the study system also comprised a high-K tobacco variety (ND202) and two common ones (K326 and NC89). Our results showed that high-K varieties exhibited significantly higher contents of organic acids in its root exudates and available K in both rhizosphere and non-rhizosphere soils than the other varieties. This research also suggested that a cyclic process in which soil was acidified after being complexed by organic acids was involved in the release of slowly available K, and that this process primarily depended on the soil pH at high organic acids concentrations, but the complexation of organic ligands became dominant at low concentrations. In conclusion, tobacco roots secrete organic acids to increase available K content and improve the utilisation rate of soil K. High-K varieties probably enhance slowly available K activation by secreting relatively high amounts of organic acids, thus leading to more available K in soil for absorption by plants.

Upexpression of BHLHE40 in gastric epithelial cells increases CXCL12 production through interaction with p-STAT3 in Helicobacter pylori-associated gastritis.

BHLHE40, a member of the basic helix-loop-helix transcription factor family, has been reported to play an important role in inflammatory diseases. However, the regulation and function of BHLHE40 in Helicobacter pylori (H pylori)-associated gastritis is unknown. We observed that gastric BHLHE40 was significantly elevated in patients and mice with H pylori infection. Then, we demonstrate that H pylori-infected GECs express BHLHE40 via cagA-ERK pathway. BHLHE40 translocates to cell nucleus, and then binds to cagA protein-activated p-STAT3 (Tyr705). The complex increases chemotactic factor CXCL12 expression (production). Release of CXCL12 from GECs fosters CD4+ T cell infiltration in the gastric mucosa. Our results identify the cagA-BHLHE40-CXCL12 axis that contributes to inflammatory response in gastric mucosa during H pylori infection.

Reduction in MnSOD promotes the migration and invasion of squamous carcinoma cells.

Reactive oxygen species (ROS) homeostasis is maintained at a higher level in cancer cells, which promotes tumorigenesis. Oxidative stress induced by anticancer drugs may further increase ROS to promote apoptosis, but can also enhance the metastasis of cancer cells. The effects of ROS homeostasis on cancer cells remain to be fully elucidated. In the present study, the effect of a reduction in manganese superoxide dismutase (MnSOD) on the migration and invasion of A431 cells was investigated. Our previous micro­assay data revealed that the mRNA expression of MnSOD was higher in the invasive A431­III cell line compared with that in the parental A431 cell line (A431­P). In the present study, high protein levels of MnSOD and H2O2 production were observed in A431­III cells; however, catalase protein levels were significantly lower in A431­III cells compared with those in the A431­P cell line. The knockdown of MnSOD increased H2O2 levels, enzyme activity, the mRNA levels of matrix metalloproteinase­1, ­2 and ­9, and the migratory and invasive abilities of the cells. Inducing a reduction in H2O2 using diphenyleneiodonium (DPI) and N­acetyl­l­cysteine decreased the migratory abilities of the cell lines, and DPI attenuated the migratory ability that had been increased by MnSOD small interfering RNA knockdown. Luteolin (Lu) and quercetin (Qu) increased the expression of catalase and reduced H2O2 levels, but without an observed change in the protein levels of MnSOD. Taken together, these data suggest that reduced MnSOD may induce ROS imbalance in cells and promote the metastatic ability of cancer cells. Lu and Qu may attenuate these processes and may be promising potential anticancer agents.

Modulation of CD8+ memory stem T cell activity and glycogen synthase kinase 3ß inhibition enhances anti-tumoral immunity in gastric cancer.

The potential contributions of CD8+ memory stem T cells to anti-tumor immunity and immunotherapy responses in gastric cancer has not been demonstrated. We found that CD8+ memory stem T cell frequencies were increased in the peripheral blood of gastric cancer patients compared to healthy donors and declined in frequency with disease progression. Despite minimal in vitro cytotoxic activity, the adoptive transfer of CD8+ memory stem T cells into Rag1-/- tumor bearing mice enhanced tumor regression compared to CD8+ central or effector memory T cell counterparts. This effect was associated with an increase in splenic, draining lymph node and tumor infiltrating CD8+ T cell numbers and the development of an altered CD8+ T cell phenotype not seen during homeostasis. GSK-3ß inhibition is known to promote memory stem T cell accumulation by arresting effector T cell differentiation in vivo. Surprisingly however, GSK-3ß inhibition conversely increased the cytotoxic capacity of CD8+ memory stem T cells in vitro, and this was associated with the induction of effector T cell-associated effector proteins including FasL. Finally, FasL neutralization following GSK-3ß inhibition directly attenuated the anti-tumoral capacity of CD8+ memory stem T cells both in vitro and in vivo. Altogether, our findings identify the therapeutic potential of modulating CD8+ memory stem T cells for improved anti-tumoral responses against gastric cancer.

Percutaneous Sacroiliac Screw Placement: A Prospective Randomized Comparison of Robot-assisted Navigation Procedures with a Conventional Technique.

BACKGROUND: Sacroiliac (SI) screw fixation is a demanding technique, with a high rate of screw malposition due to the complex pelvic anatomy. TiRobot™ is an orthopedic surgery robot which can be used for SI screw fixation. This study aimed to evaluate the accuracy of robot-assisted placement of SI screws compared with a freehand technique. METHODS: Thirty patients requiring posterior pelvic ring stabilization were randomized to receive freehand or robot-assisted SI screw fixation, between January 2016 and June 2016 at Beijing Jishuitan Hospital. Forty-five screws were placed at levels S1 and S2. In both methods, the primary end point screw position was assessed and classified using postoperative computed tomography. Fisher's exact probability test was used to analyze the screws' positions. Secondary end points, such as duration of trajectory planning, surgical time after reduction of the pelvis, insertion time for guide wire, number of guide wire attempts, and radiation exposure without pelvic reduction, were also assessed. RESULTS: Twenty-three screws were placed in the robot-assisted group and 22 screws in the freehand group; no postoperative complications or revisions were reported. The excellent and good rate of screw placement was 100% in the robot-assisted group and 95% in the freehand group. The P value (0.009) showed the same superiority in screw distribution. The fluoroscopy time after pelvic reduction in the robot-assisted group was significantly shorter than that in the freehand group (median [Q1, Q3]: 6.0 [6.0, 9.0] s vs. median [Q1, Q3]: 36.0 [21.5, 48.0] s; χ2 = 13.590, respectively, P < 0.001); no difference in operation time after reduction of the pelvis was noted (χ2 = 1.990, P = 0.158). Time for guide wire insertion was significantly shorter for the robot-assisted group than that for the freehand group (median [Q1, Q3]: 2.0 [2.0, 2.7] min vs. median [Q1, Q3]: 19.0 [15.5, 45.0] min; χ2 = 20.952, respectively, P < 0.001). The number of guide wire attempts in the robot-assisted group was significantly less than that in the freehand group (median [Q1, Q3]: 1.0 [1.0,1.0] time vs. median [Q1, Q3]: 7.0 [1.0, 9.0] times; χ2 = 15.771, respectively, P < 0.001). The instrumented SI levels did not differ between both groups (from S1 to S2, χ2 = 4.760, P = 0.093). CONCLUSIONS: Accuracy of the robot-assisted technique was superior to that of the freehand technique. Robot-assisted navigation is safe for unstable posterior pelvic ring stabilization, especially in S1, but also in S2. SI screw insertion with robot-assisted navigation is clinically feasible.

Helicobacter pylori CagA Protein Negatively Regulates Autophagy and Promotes Inflammatory Response via c-Met-PI3K/Akt-mTOR Signaling Pathway.

Cytotoxin-associated-gene A (CagA) of Helicobacter pylori (H. pylori) is a virulence factor that plays critical roles in H. pylori-induced gastric inflammation. In the present study, gastric biopsies were used for genotyping cagA and vacA genes, determining the autophagic activity, and the severity of gastric inflammation response. It was revealed that autophagy in gastric mucosal tissues infected with cagA+H. pylori strains was lower than the levels produced by cagA-H. pylori strains, accompanied with accumulation of SQSTM1 and decreased LAMP1 expression. In vitro, deletion mutant of cagA gene resulted in increased autophagic activity, and decreased expression of SQSTM1 and cytokines, whereas over-expression of CagA down-regulated the starvation-induced autophagy, and induced more production of the cytokines. Moreover, the production of the cytokines was increased by inhibition of autophagy, but decreased by enhancement of autophagy. Deletion of CagA decreased the ability to activate Akt kinase at Ser-473 site and increased autophagy. c-Met siRNA significantly affected CagA-mediated autophagy, and decreased the level of p-Akt, p-mTOR, and p-S6. Both c-Met siRNA and MK-2206 could reverse inflammatory response. H. pylori CagA protein negatively regulates autophagy and promotes the inflammation in H. pylori infection, which is regulated by c-Met-PI3K/Akt-mTOR signaling pathway activation.

Type 2 Diabetic Mellitus Is a Risk Factor for Nasopharyngeal Carcinoma: A 1:2 Matched Case-Control Study.

BACKGROUND: Diabetes has been identified as an adverse prognostic variable which associated with an increased mortality in various cancers, including colorectal, lung, and breast cancers. However, previous studies provided inconsistent results on the association between diabetes and nasopharyngeal carcinoma (NPC). The main aim of this study was to investigate the associations between diabetes mellitus and the survival of NPC patients. METHODS: This study was designed as a 1:2 matched case-control study. Cases were patients who met the criteria for the diagnosis of type 2 diabetic mellitus (DM) below. Controls, matched 1:2, were patients who were normoglycemic (NDM). The survival rates were assessed by Kaplan-Meier analysis, and the survival curves were compared using a log-rank test. Multivariate analysis was conducted using the Cox proportional hazard regression model. RESULTS: Both locoregional relapse-free survival (LRRFS) and disease-free survival (DFS) in the NDM group were higher than that in the DM group (p = 0.001 and p = 0.033). Additionally, subset analyses revealed that the differences in OS, LRRFS, and DFS were all significant between the two groups in the N0-N1 subset (p = 0.007, p =.000 and p = 0.002). The LRRFS was higher in the NDM group in the III-IV, T3-T4 and N0-N1 subsets (p = 0.004, p = 0.002 and p =.000). In T3-T4 subset, the NDM group experienced higher DFS than the DM group (p = 0.039). In multivariate analysis, T stage and N stage were found to be independent predictors for OS, DMFS and DFS; chemotherapy was a significant prognostic factor for DMFS and DFS, age for OS, and diabetes for LRRFS and DFS. CONCLUSIONS: Type 2 diabetic mellitus is associated with poorer prognosis among patients with NPC.

Burkholderia pseudomallei survival in lung epithelial cells benefits from miRNA-mediated suppression of ATG10.

Burkholderia pseudomallei is the causative agent of melioidosis, a disease with high mortality, which is prevalent in tropical regions of the world. A recent study shows that B. pseudomallei can survive inside mammalian cells because of its ability to actively evade cell autophagy. However, the underlying mechanisms remain unclear. In the present study, based on microarray screening, we found that ATG10 was downregulated following B. pseudomallei infection in A549 human lung epithelial cells. Forced expression of ATG10 accelerated the elimination of intracellular B. pseudomallei by enhancing the process of autophagy. Moreover, MIR4458, MIR4667-5p, and MIR4668-5p were found, by microarray screening, to be upregulated in response to B. pseudomallei infection. These 3 novel miRNAs, MIR4458, MIR4667-5p, and MIR4668-5p, targeted to the 3'-untranslated region of ATG10 in different time-course and spatial manners. Upregulation of these miRNAs reduced the level of ATG10 and inhibited autophagy, leading to increasing survival rate of intracellular B. pseudomallei. Furthermore, the increase of these miRNAs was correlated with the reduced promoter methylation status in A549 cells in response to B. pseudomallei infection. Our results reveal that 3 novel miRNAs regulate autophagy-mediated elimination of B. pseudomallei by targeting ATG10, and provide potential targets for clinical treatment.

Efficacy, safety, and immunogenicity of an oral recombinant Helicobacter pylori vaccine in children in China: a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Helicobacter pylori is one of the most common gastric pathogens, affecting at least half the world's population, and is strongly associated with gastritis, peptic ulcer, gastric adenocarcinoma, and lymphoma. We aimed to assess the efficacy, safety, and immunogenicity of a three-dose oral recombinant H pylori vaccine in children in China. METHODS: We did this randomised, double-blind, placebo-controlled, phase 3 trial at one centre in Ganyu County, Jiangsu Province, China. Healthy children aged 6-15 years without past or present H pylori infection were randomly assigned (1:1), via computer-generated randomisation codes in blocks of ten, to receive the H pylori vaccine or placebo. Participants, their guardians, and study investigators were masked to treatment allocation. The primary efficacy endpoint was the occurrence of H pylori infection within 1 year after vaccination. We did analysis in the per-protocol population. This trial is registered with ClinicalTrials.gov, number NCT02302170. FINDINGS: Between Dec 2, 2004, and March 19, 2005, we randomly assigned 4464 participants to either the vaccine group (n=2232) or the placebo group (n=2232), of whom 4403 (99%) participants completed the three-dose vaccination schedule and were included in the per-protocol efficacy analysis. We extended follow-up to 3 years. We recorded 64 events of H pylori infection within the first year (14 events in 2074·3 person-years at risk in the vaccine group vs 50 events in 2089·6 person-years at risk in the placebo group), resulting in a vaccine efficacy of 71·8% (95% CI 48·2-85·6). 157 (7%) participants in the vaccine group and 161 (7%) participants in the placebo group reported at least one adverse reaction. Serious adverse events were reported in five (<1%) participants in the vaccine group and seven (<1%) participants in the placebo group, but none was considered to be vaccination related. INTERPRETATION: The oral recombinant H pylori vaccine was effective, safe, and immunogenic in H pylori-naive children. This vaccine could substantially reduce the incidence of H pylori infection; however, follow up over a longer period is needed to confirm the protection of the vaccine against H pylori-associated diseases. FUNDING: Chongqing Kangwei Biological Technology.

miR-30b, down-regulated in gastric cancer, promotes apoptosis and suppresses tumor growth by targeting plasminogen activator inhibitor-1.

BACKGROUND: Gastric cancer is one of the most common malignant diseases worldwide. Emerging evidence has shown that microRNAs (miRNAs) are associated with tumor development and progression. Our previous studies have revealed that H. pylori infection was able to induce the altered expression of miR-30b in gastric epithelial cells. However, little is known about the potential role of miR-30b in gastric cancer. METHODS: We analyzed the expression of miR-30b in gastric cancer cell lines and human gastric cancer tissues. We examined the effect of miR-30b mimics on the apoptosis of gastric cancer cells in vitro by flow cytometry (FCM) and caspase-3/7 activity assays. Nude mouse xenograft model was used to determine whether miR-30b is involved in tumorigenesis of gastric cancer. The target of miR-30b was identified by bioinformatics analysis, luciferase assay and Western blot. Finally, we performed the correlation analysis between miR-30b and its target expression in gastric cancer. RESULTS: miR-30b was significantly down-regulated in gastric cancer cells and human gastric cancer tissues. Enforced expression of miR-30b promoted the apoptosis of gastric cancer cells in vitro, and miR-30b could significantly inhibit tumorigenicity of gastric cancer by increasing the apoptosis proportion of cancer cells in vivo. Moreover, plasminogen activator inhibitor-1 (PAI-1) was identified as the potential target of miR-30b, and miR-30b level was inversely correlated with PAI-1 expression in gastric cancer. In addition, silencing of PAI-1 was able to phenocopy the effect of miR-30b overexpression on apoptosis regulation of cancer cells, and overexpression of PAI-1 could suppressed the effect of promoting cell apoptosis by miR-30b, indicating PAI-1 is potentially involved in miR-30b-induced apoptosis on cancer cells. CONCLUSION: miR-30b may function as a novel tumor suppressor gene in gastric cancer by targeting PAI-1 and regulating the apoptosis of cancer cells. miR-30b could serve as a potential biomarker and therapeutic target against gastric cancer.

Theoretical studies on gas-phase reactions of sulfuric acid catalyzed hydrolysis of formaldehyde and formaldehyde with sulfuric acid and H2SO4···H2O complex.

The gas-phase reactions of sulfuric acid catalyzed hydrolysis of formaldehyde and formaldehyde with sulfuric acid and H2SO4···H2O complex are investigated employing the high-level quantum chemical calculations with M06-2X and CCSD(T) theoretical methods and the conventional transition state theory (CTST) with Eckart tunneling correction. The calculated results show that the energy barrier of hydrolysis of formaldehyde in gas phase is lowered to 6.09 kcal/mol from 38.04 kcal/mol, when the sulfuric acid is acted as a catalyst at the CCSD(T)/aug-cc-pv(T+d)z//M06-2X/6-311++G(3df,3pd) level of theory. Furthermore, the rate constant of the sulfuric acid catalyzed hydrolysis of formaldehyde combined with the concentrations of the species in the atmosphere demonstrates that the gas-phase hydrolysis of formaldehyde of sulfuric acid catalyst is feasible and could be of great importance for the sink of formaldehyde, which is in previously forbidden hydrolysis reaction. However, it is shown that the gas-phase reactions of formaldehyde with sulfuric acid and H2SO4···H2O complex lead to the formation of H2C(OH)OSO3H, which is of minor importance in the atmosphere.

CD8(+) T cells that produce interleukin-17 regulate myeloid-derived suppressor cells and are associated with survival time of patients with gastric cancer.

BACKGROUND & AIMS: CD8(+) T cells that produce interleukin (IL)-17 (Tc17 cells) promote inflammation and have been identified in tumors. We investigated their role in the pathogenesis of gastric cancer. METHODS: We used flow cytometry analyses to determine levels and phenotype of Tc17 cells in blood and tumor samples from 103 patients with gastric cancer. We performed multivariate analysis to identify factors associated with overall survival using the Cox proportional hazards model. CD8(+) T cells and monocytes were isolated and cocultured in an assay for induction of Tc17 cells. Tumor cells and myeloid-derived suppressor cells (MDSCs) were isolated and used in assays of Tc17 cell function. RESULTS: Tc17 cells with distinct cytokine and functional profiles were found in gastric tumor samples from patients. The percentage of Tc17 cells increased with tumor progression and was associated with overall survival time. Tumor-activated monocytes secreted IL-6, IL-1ß, and IL-23, which promoted development of Tc17 cell populations. Supernatants from cultured Tc17 cells induced production of the chemokine CXCL12 by tumor cells; this promoted CXCR4-dependent migration of MDSCs and impaired functions of anti-tumor CD8(+) cytotoxic T cells via a cell contact-dependent mechanism. CONCLUSIONS: Percentages of Tc17 cells in gastric tumors are associated with survival times of patients. These cells promote chemotaxis of MDSCs, which might promote tumor progression.

Formic acid catalyzed gas-phase reaction of H2O with SO3 and the reverse reaction: a theoretical study.

The formic acid catalyzed gas-phase reaction between H(2)O and SO(3) and its reverse reaction are respectively investigated by means of quantum chemical calculations at the CCSD(T)//B3LYP/cc-pv(T+d)z and CCSD(T)//MP2/aug-cc-pv(T+d)z levels of theory. Remarkably, the activation energy relative to the reactants for the reaction of H(2)O with SO(3) is lowered through formic acid catalysis from 15.97 kcal mol(-1) to -15.12 and -14.83 kcal mol(-1) for the formed H(2)O⋅⋅⋅SO(3) complex plus HCOOH and the formed H(2)O⋅⋅⋅HCOOH complex plus SO(3), respectively, at the CCSD(T)//MP2/aug-cc-pv(T+d)z level. For the reverse reaction, the energy barrier for decomposition of sulfuric acid is reduced to -3.07 kcal mol(-1) from 35.82 kcal mol(-1) with the aid of formic acid. The results show that formic acid plays a strong catalytic role in facilitating the formation and decomposition of sulfuric acid. The rate constant of the SO(3)+H(2)O reaction with formic acid is 10(5) times greater than that of the corresponding reaction with water dimer. The calculated rate constant for the HCOOH+H(2)SO(4) reaction is about 10(-13) cm(3) molecule(-1) s(-1) in the temperature range 200-280 K. The results of the present investigation show that formic acid plays a crucial role in the cycle between SO(3) and H(2)SO(4) in atmospheric chemistry.

Comparision of high sensitivity C-reactive protein and matrix metalloproteinase 9 in patients with unstable angina between with and without significant coronary artery plaques.

BACKGROUND: Inflammation within vulnerable coronary plaques may cause unstable angina by promoting rupture and erosion. C-reactive protein (CRP) is the most reliable and accessible test method for clinical use for identifying coronary artery disease event. Matrix metalloproteinase 9 (MMP-9) is highly over-expressed in the vulnerable regions of a plaque. Our aim was to evaluate the plasma levels of MMP-9 and hsCRP in subjects with both unstable angina and coronary plaques, as well as in those with unstable angina without coronary plaques. METHODS: Patients with newly diagnosed unstable angina pectoris from clinical presentation and ECG, who were undergoing coronary angiography from April 2007 to April 2009, were included in this study. A total of 170 subjects were enrolled in the study. Before angiography, the baseline clinical data (mainly including conventional risk factors) was collected. These patients were divided into two groups, a non-plaque group (G1) which included 55 patients with no significant stenosis or less than 20% stenosis in at least one of the major coronary artery branches, and a plaque group (G2) which included 115 patients with at least one of the major coronary artery branches unstable angina pectoris with at least 50% stenosis of one major coronary artery. The patients presenting with calcified nodules of a major coronary artery were excluded from this study. We examined the serum levels of MMP-9 for all cases by multi-effect enzyme-linked immunosorbent assay. RESULTS: There was a significant difference in the serum levels of MMP-9 between the two groups (P < 0.001). The percentage of patients with hypertension, diabetes and current smokers were significantly different between the two groups (P = 0.034, P = 0.031, and P = 0.044 respectively). The univariate Logistic regression analyses of risk factors showed that smoking was the main risk factor for angina in the non-plaque group with the OR being 1.95 (95%CI 1.02 - 3.75). Hypertension, diabetes mellitus were negatively related with the occurrence of angina in the non-plaque group with the ORs being 0.50, and 0.36, respectively (95%CI 0.26 - 0.96 and 0.14 - 0.94). The MMP-9 level was negatively related to the occurrence of angina in the non-plaque group with an OR of 0.59 (95%CI 0.47 - 0.81). CONCLUSIONS: There is a significantly difference in MMP-9 levels between the plaque and non-plaque groups. Current smoking has a significant influence on unstable angina patients without documented plaques. The serum MMP-9 level may be a significant biomarker which can help differentiate patients with unstable angina with plaques from those with unstable angina but without plaques.

[Intensity-modulated or 3-D conformal radiotherapy combined with chemotherapy with docetaxel and cisplatin for locally advanced esophageal carcinoma].

OBJECTIVE: To evaluate the therapeutic effect and toxicity of intensity-modulated radiation therapy (IMRT) or three-dimensional conformal radiotherapy combined with chemotherapy (3-DCRT) with docetaxel and cisplatin in the treatment of locally advanced esophageal carcinoma. METHODS: Sixty patients with locally advanced esophageal carcinoma were randomly assigned in two equal groups to receive IMRT or 3-DCRT, both combined with the chemotherapy with docetaxel and cisplatin. The total dose of radiotherapy was 64 Gy, administered in 30 fractions in 6 weeks. RESULTS: The complete response rate (complete and partial remissions) of IMRT group was 90.0%, significantly higher than the rate of 80.0% in 3-DCRT group (P>0.05). The 1-, 2-, and 3-year survival rates of IMRT group were 86.7%, 70.0%, and 66.7%, as compared to 70.0%, 63.3%, and 63.3% in 3-DCRT group, respectively, showing no significant differences between the two groups (P>0.05). IMRT showed advantages over 3-DCRT in terms of the V20 and V30 parameters of the lung (P<0.05), and the incidences of radiation-induced esophagitis were comparable between the two groups (P>0.05). CONCLUSION: When combined with the chemotherapy with docetaxel and cisplatin, IMRT appears to be a more effective treatment than 3-DCRT for locally advanced esophageal cancer.

Theoretical study on the gas phase reaction of sulfuric acid with hydroxyl radical in the presence of water.

The reactions of H2SO4 with the OH radical without water and with water are investigated employing the quantum chemical calculations at the B3LYP/6-311+G(2df,2p) and MP2/aug-cc-pv(T+d)z levels of theory, respectively. The calculated results show that the reaction of H2SO4 with OH and H2O is a very complex mechanism because of the formation of the prereactive complex prior to the transition state and product. There are two prereactive complexes with stabilization energies being -20.28 and -20.67 kcal/mol, respectively. In addition, the single water can lower the energy barriers of the hydrogen abstraction and the proton transfer to 7.51 and 6.37 kcal/mol, respectively from 13.79 and 8.82 kcal/mol with respect to the corresponding prereactive complex. The computed rate constants indicate that the water-assisted reaction of sulfuric acid with OH radical is of greater importance than the reaction of the naked sulfuric acid with the OH radical because the rate constant of the water-assisted process is about 10(3) faster than that of the reaction sulfuric acid with OH. Therefore, the conclusion is obtained that the water-assisted process plays an important role in the sink for the gaseous sulfuric acid in the clean area.

[Research on vehicle-based remote sensing of natural gas pipeline leakage].

In the present paper the authors designed a vehicle-based remote sensing system using simulated platform and presented a new method of concentration calibration of natural gas pipeline leakage remote sensing. By investigating the performance of different distance, different material, different angle of topographic back scatter and different scan speed, a good coincidence was achieved between experimental results and theoretical results. The system can realize the remote detection of low-level methane concentration at a velocity of 53.3 km x h(-1), and the detecting distance is about 70 m with the minimum detectable sensitivity being 28.9 ppm x m. The research result shows the feasibility in the application.