[Observation of the efficacy of autologous mucosal transplantation to prevent esophageal stricture after near-circumferential endoscopic submucosal dissection for early esophageal cancer].

Objective: To investigate the efficacy of autologous mucosal transplantation to prevent esophageal stricture after near-circumferential endoscopic submucosal dissection (ESD) for early esophageal cancer. Methods: The case data of 33 patients, who underwent near-circumferential ESD for early esophageal cancer and were followed up regularly in the First Affiliated Hospital of Zhengzhou University from April 2017 to July 2022, were analyzed retrospectively, including 14 males and 19 females, aged (66.4±7.4) (47-77) years. According to the different treatment methods, they were divided into 4 groups: group A (6 cases) were treated with autologous mucosa transplantation and fully covered metal stent implantation, combined with oral, intravenous and local injection of hormone; Group B (8 cases) were treated with autologous mucosa transplantation and fully covered metal stent implantation; Group C (11 cases) were treated with fully covered metal stent implantation combined with oral or intravenous hormone; Group D (8 cases) were treated with fully covered metal stent implantation. After the operation, the growth of the transplanted mucosa, esophageal stricture and surgical complications were observed by endoscopy, so as to understand the efficacy of automucosa transplantation in preventing esophageal stricture after near-circumferential ESD for early esophageal cancer. Results: The gastroscopic operation was successful in 33 patients. The times of expansion in groups B, C and D were more than that in group A, and the times of expansion [M(Q1,Q3)] in group A were 0(0, 1.8) times, while the times of expansion in group B, C and D were 5.5(4.3, 6.8), 4.0(4.0, 7.0) and 5.5(3.5, 10.8) times, respectively, with statistical significance (all P<0.05). There was no significant difference in times of expansion among groups B, C and D (all P>0.05). The stent placement time [M(Q1,Q3)] in group B [7.5(6.3, 8.8) days] was shorter than that in group A [64.5(41.5, 75.5) days] (P=0.006). There was no significant difference in stent placement time between group C [38.0(28.0, 50.0) days] and group D [31.5(27.3, 66.3) days] and group A (both P>0.05). The stent placement time in group C was longer than that in group B (P<0.05).There was no significant difference in stent placement time between group B, C and D (all P>0.05). There was no significant difference in the incidence of complications among the groups (all P>0.05). Conclusions: Autologous mucosal transplantation is safe and effective in preventing stenosis after near-circumferential ESD for early esophageal cancer. The effect of autologous mucosal transplantation combined with fully covered metal stent placement, systemic and local steroid application in preventing esophageal stricture after near-circumferential ESD for early esophageal cancer is better than that of single application.

[Predictive value of serum Gal-13, GLP-1 and VEGF levels in adverse pregnancy outcomes of gestational diabetes mellitus].

To explore the application value of serum Gal-13, GLP-1 and VEGF in the prevention and guidance of adverse pregnancy outcomes in gestational diabetes (GDM). A retrospective study with case-control method was used to select 1 012 GDM patients from Haikou Maternal and Child Health Hospital from January 2019 to December 2022 as the study objects, and they were divided into poor pregnancy outcome group (n=342) and good pregnancy outcome group (n=670) according to whether they had adverse pregnancy outcomes. The medical records of 521 healthy women with normal glucose metabolism were selected as the control group. Serum Gal-13 and GLP-1 were detected by enzyme-linked immunosorbent assay and VEGF was determined by IAMMGE specific protein analyzer. After comparing the differences of the above factors among the three groups, multivariate logistic regression model was used to analyze the influencing factors of adverse pregnancy outcomes in GDM patients, and ROC curve was drawn to analyze the predictive value of serum Gal-13, GLP-1 and VEGF levels on adverse pregnancy outcomes in GDM patients. The results showed that Fasting blood glucose (FPG), glycosylated hemoglobin (HbA1c) and fasting insulin (FINS) in the adverse pregnancy outcome group were 5.92(4.98, 6.41) mmol/L, 5.32(4.96, 5.47)%, 62.56(49.21,99.50) pmol/L, VEGF was 495.47(389.14, 567.13) ng/L, TSH was 1.48(1.34, 1.58) mIU/L, right ventricular myocardial work index (Tei index) was 0.59(0.45, 0.67), 89 cases of elderly parturients; FPG was 4.45(4.16, 5.03) mmol/L, HbA1c was 5.04(4.86, 5.29)%, FINS was 57.41(46.90, 74.08) pmol/L, VEGF was 405.84(348.02, 462.68) ng/L, TSH was 1.42(1.25, 1.50) mIU/L, Tei index was 0.50(0.47, 0.64), there were 142 cases of old women. In the control group, FPG was 4.33(4.05, 4.75) mmol/L, HbA1c was 5.01(4.13, 5.18)%, FINS was 38.48(36.76, 41.72) pmol/L and VEGF was 302.45(283.14, 336.56) ng/L, TSH was 1.32(1.24, 1.47)mIU/L, Tei index was 0.48(0.39, 0.59), and there were 106 elderly parturiencies. The levels of FPG, HbA1c, FINS, VEGF, TSH and Tei index in the adverse pregnancy outcome group and the good pregnancy outcome group were higher than those in the control group, and the proportion of elderly parturients was higher than that in the control group, and the adverse pregnancy outcome group was higher than that in the good pregnancy outcome group. The differences were statistically significant (H=8.620, P<0.001, H=2.616, P=0.014, H=6.156, P<0.001, H=3.051, P<0.001, H=4.892, P=0.044, χ2=2.548, P=0.045). In the adverse pregnancy outcome group, Gal-13 was 15.27(8.35, 24.45)pg/ml, GLP-1 was 9.27(8.26, 12.35) pmol/L and FT4 was 11.59(9.67, 13.48) pmol/L. In the group with good pregnancy outcome, Gal-13 was 25.34(20.14, 29.73) pg/ml, GLP-1 was 12.38(10.25, 15.63) pmol/L and FT4 was 13.86(10.67, 15.10) pmol/L. In the control group, Gal-13 was 31.21(27.48, 34.45) pg/ml, GLP-1 was 11.34(10.40, 14.37) pmol/L and FT4 was 14.15(10.75, 15.43)pmol/L. The levels of Gal-13, GLP-1 and FT4 in the adverse pregnancy outcome group and the good pregnancy outcome group were significantly lower than those in the control group, and the adverse pregnancy outcome group was lower than that in the good pregnancy outcome group. The differences were statistically significant (H=6.458, P=0.011, H=8.445, P<0.001, H=5.694, P<0.001). The levels of Gal-13 and GLP-1 in normal blood glucose recovery group were higher than those in non-normal blood glucose recovery group, and the levels of VEGF were lower than those in non-normal blood glucose recovery group (P<0.05).In multivariate logistic regression analysis, Gal-13, GLP-1, VEGF, TSH, FT4 and Tei indexes were independent influencing factors for adverse pregnancy outcomes with GDM (P<0.05). ROC curve analysis showed that the AUC of Gal-13, GLP-1 and VEGF alone in predicting adverse pregnancy were 0.779, 0.761 and 0.615, respectively. The value of the combined diagnosis was the highest (AUC=0.912), the sensitivity was 90.1%, and the specificity was 80.0%. In conclusion, Gal-13, GLP-1 and VEGF may be independent influencing factors for adverse pregnancy outcomes in GDM patients, and the combined detection of the three may help to improve the auxiliary diagnostic efficacy for predicting adverse pregnancy outcomes.

[The mid-term effect of corneal collagen cross-linking for progressive keratoconus and the changes in rigid gas permeable contact lens fitting parameters].

Objective: To investigate the effect of corneal collagen cross-linking (CXL) for progressive keratoconus and to evaluate changes in the parameters of rigid gas permeable contact lens (RGPCL) fitting after surgery. Methods: It was a prospective cohort study. Fifty-three eyes of 41 keratoconus patients received accelerated CXL in Qingdao Eye Hospital of Shandong First Medical University from May to December 2018. There were 31 males and 10 females, aged (20.46±4.15) years. According to the corneal thickness, de-epithelial CXL (33 eyes) or trans-epithelial CXL (20 eyes) was performed. The best spectacle-corrected visual acuity, refractive power and the thinnest corneal thickness at baseline and at 6 weeks were compared. Corneal topography was performed at baseline and at 6 weeks, 3, 6 and 12 months postoperatively. Rose K RGPCLs were used before and 6 weeks after surgery, and the fitting status was monitored until 12 months after surgery. The t test was performed to analyze the difference before and after the operation. Results: The best spectacle-corrected visual acuity, refractive power, and the thinnest corneal thickness were not significantly changed over 6 weeks of follow-up, but the Kf, Ks and Kmax values were significantly increased in all patients (all P<0.05). In the de-epithelial group, the Kmax values before the operation, at 3, 6 and 12 months after the operation were (55.00±5.51) diopters (D), (54.73±5.34) D, (54.58±6.15) D and (54.20±5.49) D, respectively, and the decrease at 12 months was significant [(0.80±2.05) D; t=2.25, P=0.001]. In the trans-epithelial group, the Kmax values were (59.43±8.98) D, (57.97±8.79) D, (58.19±8.37) D and (56.94±7.19) D at the four time points, respectively, and the decreases at 3, 6 and 12 months were all significant [(1.46±2.09) D, (1.25±1.82) D, (2.49±3.64) D; t=3.12, 3.06, 3.50; P=0.006, 0.006, 0.007]. The best RGPCL-corrected visual acuity, the diameter and the average diopters of RGPCLs showed no significant change in both groups. The RGPCL base curve decreased by 0.07 mm in the de-epithelial group and by 0.13 mm in the trans-epithelial group (both P<0.05). The design of edge lifting was used in 10 eyes postoperatively in the de-epithelial group compared with 8 eyes preoperatively, and in 4 eyes postopratively in the trans-epithelial group compared with 7 eyes preoperatively. The number of eyes using the toric peripheral design of the lens was increased to 3 compared with 2 preoperatively in the de-epithelial group and from 1 to 4 in the trans-epithelial group. The acceptance rate of RGPCL fitting in both groups increased at 6 and 12 months after surgery compared to 6 weeks after surgery. Conclusions: The corneal curvature became steep slightly at 6 weeks after CXL and gradually recovered and flattened. The Kmax in the trans-epithelial group decreased earlier and more than that in the de-epithelial group. The base curve of the RGPCLs was slightly reduced after 6 weeks, and the toric peripheral design was increasingly needed, but the requirement for the design of the lifted edge was different between the two groups. A good RGPCL fitting can be achieved within 1 year after CXL.

Clinical significance of perioperative EMT-CTC in rectal cancer patients receiving open/laparoscopic surgery.

The objective of this study was to explore the clinical significance of perioperative CTCs (circulating tumor cells) counts and EMT-CTCs (epithelial-mesenchymal transition-CTCs) in rectal cancer patients. A total of 30 patients with rectal cancer who underwent radical resection of rectal cancer at the Guangxi Zhuang Autonomous Region People's hospital were enrolled. Five ml peripheral blood was withdrawn from 30 patients with rectal cancer before the operation and seven days after the operation and at the corresponding time also from 20 healthy volunteers. CanPatrol™ CTC detection technique was used to enrich and identify CTCs and IER3 expression simultaneously. We found out that the preoperative total CTCs were correlated with lymph node metastasis (p=0.008) and tumor size, and mixed CTCs were closely correlated with lymph node metastasis (p=0.009). The number of IER3-positive total CTCs and mesenchymal CTCs were statistically associated with tumor size, p=0.034 and 0.043, respectively. The number of CTCs varied significantly before and after the operation in all patients (p=0.049). There were significant differences in CTCs variations between the open operation group and the laparoscopic operation group. In the laparoscopic operation group, the average number of single-cell CTCs was 6.9 before operation and 3.5 after the operation (p=0.013). In the open operation group, the average number of single-cell CTCs was 5.9 before operation and 4.2 after the operation. To conclude, surgery is associated with a decrease of CTCs in rectal cancer patients, especially in patients receiving laparoscopic surgery. The number of CTCs before the operation in rectal cancer patients is related to the size of tumors and regional lymph node metastasis. CTCs detection and characterization may be useful for clinical staging and lymph node dissection during operation.

Dietary threonine prevented stress-related mucosal diseases in rats.

Stress-related mucosal disease (SRMD), or stress ulceration, is a group of conditions ranging from stress-related superficial gastric mucosal damage to deep gastric ulcers that are primarily correlated with mucosal ischemia, and pharmacologic interventions that optimize tissue perfusion or preserve defensive mucus aim to decrease the occurrence of conditions, such as gastric acidity, or enhance gastric defenses. However, the identification of multifactorial pathogenesis may be effective in preventing SMRD, and the use of stress prophylaxis is generally preferred. Since threonine is a component in the polymerization and synthesis of gastric mucin and possibly enhanced defense actions and lignin may provide structural support for defense and antioxidative function, we hypothesized that dietary intake of threonine and/or lignin can enhance defense against SRMD. The water immersion-restraint stress (WIRS) was used in rats and additional groups were pretreated with threonine alone or the combination of threonine and lignin. Based on gross and microscopic evaluations, threonine alone or the combination of threonine and lignin, a natural antioxidant, significantly reduced the development of SRMD (P < 0.05). According to molecular explorations, the levels of inflammatory mediators, such as interleukin (IL)-8, IL-6, IL-1ß, inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ), all of which are mediators that play a significant role in controlling WIRS, significantly decreased in the groups pretreated with either threonine alone or the combination of threonine and lignin (P < 0.01). WIRS significantly increased apoptosis in the stomach. However, the apoptotic index significantly decreased with threonine pretreatment. According to periodic acid Schiff staining results, the expression of gastric mucin was significantly preserved in groups pretreated with threonine but remarkedly decreased in the WIRS group. The gastric heme oxygenase-1 levels significantly increased in the group treated with threonine. In conclusion, the dietary intake of threonine or the combination of threonine and lignin is effective in preventing SRMD.

Effect of miR-29b on rats with gestational diabetes mellitus by targeting PI3K/Akt signal.

OBJECTIVE: To investigate the role of micro-ribonucleic acid-29b (miR-29b) in rats with gestational diabetes mellitus (GDM) through the phosphatidylinositol 3-kinase (PI3K)/serine/threonine kinase (Akt) signal and its mechanism by establishing rat models of GDM. MATERIALS AND METHODS: Rat models of GDM were constructed, and then the expression levels of miR-29b, total PI3K, phosphorylated PI3K (p-PI3K), total Akt and phosphorylated Akt (p-Akt) in the model group and control group were measured via Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Western blotting assays, and the association between miR-29b expression and total PI3K expression was analyzed. In addition, miR-29b mimics and inhibitors were used to further explore the regulatory pathway, and the influences of miR-29b mimics and inhibitors on PI3K and Akt phosphorylation in GDM rats, characteristic indicators of oxidative stress such as superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) in liver tissues of GDM rats, and fasting blood glucose in GDM rats were studied. RESULTS: Compared with those in the control group, miR-29b expression was lowered in rat models of GDM, while PI3K/Akt signal expression was increased. In rats with GDM, miR-29b expression was prominently negatively correlated with total PI3K expression (r=-0.777, p=0.007, p<0.01). MiR-29b mimics could reduce PI3K and Akt phosphorylation, increase SOD and CAT expression levels and decrease MDA content (p<0.05). Moreover, miR-29b mimics significantly lowered the blood glucose level in rats with GDM (p<0.05). CONCLUSIONS: MiR-29b mimics can alleviate oxidative stress and reduce blood glucose by inhibiting the PI3K/Akt signal transduction.

Oligonol prevented the relapse of dextran sulfate sodium-ulcerative colitis through enhancing NRF2-mediated antioxidative defense mechanism.

Repeated bouts of ulcerative colitis featured troublesome course of inflammatory bowel disease leading to fatal colitis-associated cancer, which is strongly associated with oxidative stress and sustained inflammation. Since oligonol, low molecular weighted polyphenol extracted from fruit lychee, showed antioxidative and anti-inflammatory actions, we hypothesized that oligonolcan prevent relapse of colitis. We compared oligonol with current gold standard therapeutics, sulfasalazine in preventive efficacy of relapse. First, dextran sulfate sodium (DSS)-induced colitis were made following pretreatment with oligonol, 10, 50, and 100 mg/kg for 7 days to measure therapeutic effect of oligonol and relapse model via repeated DSS administration was made following with either 50 mg/kg oligonol or 30 mg/kg sulfasalazine to explore relapse preventing action of oligonol in C57BL/6 mice. Detailed changes in colon were measured to explain molecular mechanisms. Pretreatment of 10, 50, 100 mg/kg oligonol (p.o.), significantly reduced DSS-induced colitis; total pathologic scores, colon length, and clinical symptom scores (P < 0.05). Oligonol pretreatment significantly decreased the levels of interleukin (IL)-1, IL-6, and tumor necrosis factor-α (TNF-α) as well as nuclear factor-κB (NF-κB), c-Fos, and c-Jun in affected colon tissues, but the expression of heme oxygenase-1 (HO-1) and NADH: quinone oxidoreductase-1(NQO-1) as well as total antioxidant concentration (P < 0.005) was significantly increased with oligonol. A relapse model established with repeated DSS administration led to high mortality. However, oligonol significantly ameliorated exacerbations of colitis, while sulfasalazine did not (P < 0.01). Significantly decreased expressions of cyclooxygenase-2 (COX-2), TNF-α, and macrophages inhibition were relapse preventing actions of oligonal, but significant action of oligonol relevant to relapse prevention was either significantly increased expressions of NQO-1 or significantly preserved mucin (P < 0.05). Concerted anti-inflammatory, antioxidative, and host defense enhancing actions of oligonol can be applied during maintenance therapy of IBD to prevent relapse of IBD.

[The relationship between vimentin protein expression in endothelial cells and contrast-enhanced ultrasound characters in VETC (+ ) hepatocellular carcinoma].

Objective: To detect the possible molecular mechanisms of the formation of vessels that encapsulated tumor clusters (VETC) and identify the relationship between vimentin protein expression in endothelial cells and contrast-enhanced ultrasound characters in VETC (+ ) hepatocellular carcinoma (HCC). Methods: A total of 64 paraffin embedded HCC tissue samples were collected, all of which the tumor diameters were between 2 cm and 5 cm measured by the preoperative ultrasound. Immunohistochemistry staining for CD34 was used to detect the formation of VETC and the expressions of angiopoietin-2 (Ang-2) and vimentin were also determined. Human umbilical vein endothelial cells (HUVECs) were treated with 150 ng/ml recombinant human Ang-2 protein (rhAng-2) at various times and the protein expression of vimentin was detected by western blot assay. The contrast-enhanced ultrasound characters were also analyzed in both VETC (+ ) and VETC (-) HCC. Results: Tumor clusters encapsulated by vessels to form cobweb-like networks, which were identified as VETC phenotype, were observed in 27 HCC tissues (42.18%). In VETC (+ ) HCC tissues, Ang-2 was overexpressed in tumor cells and endothelial cells while vimentin was only upregulated in endothelial cells. With the treatment of 150 ng/ml rhAng-2 protein, the expression of vimentin in HUVECs was 0.878±0.102 and 0.918±0.092 at 12 h and 36 h, significantly upregulated when compared to the 0.322±0.061 at 6 h (P<0.01). In contrast-enhanced ultrasound, a crack and tendon-like filling character was observed in VETC (+ ) HCC during the arterial-phase, while the large scale and diffuse-like filling character was observed in VETC (-) HCC. The filling time of unit diameter in VETC (+ ) HCC was (3.95±0.22)s, significantly longer than (2.28±0.27)s of VETC (-) HCC (P<0.01). Conclusions: The overexpressions of Ang-2 and vimentin are positively correlated with the formation of VETC and considered as potential therapeutic targets of VETC (+ ) HCC. The crack and tendon-like filling characters in arterial-phase of contrast-enhanced ultrasound indicates the VETC (+ ) HCC.

Host nuclear factor erythroid 2-related factor-2 defense system determines the outcome of dextran sulfate sodium-induced colitis in mice.

Administration of dextran sulfate sodium (DSS) in drinking water led to significant bout of colitis simulating ulcerative colitis of human. However, colitis usually developed 5 - 7 days after DSS administration. Therefore, we hypothesized host defense system might protect colitis up to 5 days of DSS administration. 2.5% DSS-induced colitis were administered to C57BL/6 mice and sequential measurements of pathology, cyclooxygenase-2 (COX-2), nuclear factor-κB (NF-κB), heme oxygenase-1 (HO-1), NADPH quinone oxidoreductase-1 (NQO1), γ-glutamylcysteine synthetase (γ-GCS), nuclear factor erythroid 2-related factor-2 (Nrf2), and keap1 were done at 2, 6, 12, 24, 48, 96, 120, and 168 hour of DSS administration, respectively. DSS-induced colitis was repeated in either COX-2-/- or Nrf2-/- mice. On serial pathological analysis, significant colitis was noted after 120 h of DSS administration, during which both activations of COX-2/NF-κB and HO-1/Nrf2 were noted. Nrf2 activations after keap1 inactivation led to significant increases in HO-1 after 168 hours of DSS administration, when NF-κB nuclear translocation was noted. Significantly attenuated colitis was noted in DSS-challenged COX-2-/- mice, in which the levels of HO-1 were significantly decreased compared to DSS-challenged WT littermates (p < 0.01), while the levels of NQO1 were significantly increased. On DSS administration to Nrf2-/- mice, colitis was significantly aggravated (p < 0.01), in which the expressions of COX-2 as well as expressions of HO-1 and γ-GCS were significantly increased (p < 0.01). Reciprocal activations of inflammatory and antioxidative defense signaling after DSS administration might be prerequisite to make intestinal homeostasis and host defense Nrf2 system can determine colitis.

Clinical efficacy of gamma knife and surgery treatment of mesial temporal lobe epilepsy and their effects on EF-Tumt and EF-Tsmt expression.

OBJECTIVE: To study the clinical efficacy of gamma knife and surgery treatment of mesial temporal lobe epilepsy (MTLE) and their effects on EF-Tumt and EF-Tsmt expression. PATIENTS AND METHODS: The data of 78 cases of MTLE patients treated in our hospital from April 2011 to March 2013 were retrospectively analyzed. The patients were divided into two groups according to the treatment methods: the surgery group (including 41 cases) and the gamma knife group (including 37 cases). The clinical efficacy, the occurrence and recurrence of complications were evaluated, respectively; meanwhile, the expression of the EF-Tumt protein and EF-Tsmt protein in brain tissue were analyzed. RESULTS: The difference between the efficacy rate of the two groups showed no statistical significance (χ2=0.960, p>0.05). The complication rate of the gamma knife group was significantly lower than that of the control group (χ2=6.430, p<0.05). The recurrence rate of the patients in the gamma knife group was significantly lower than that of the patients in the surgery group (p>0.05). Within the two groups, the positive expression granum of EF-Tsmt protein and EF-Tumt protein of the two groups after treatment were significantly lower than that before treatment (p<0.05). After treatment, the positive expression granum of EF-Tsmt protein of the patients in the gamma knife group was obviously more than that of the patients in the surgery group (p<0.05). The difference between the positive expression granum of EF-Tumt protein of the two groups showed no statistical significance (p>0.05). Before and after treatment within the group, the positive cell of EF-Tsmt protein and EF-Tumt protein of the two groups of patients after treatment were significantly lower than that before treatment (p<0.05). After treatment, the difference between the EF-Tsmt protein positive cell and the EF-Tumt protein positive cell of the two groups of patients showed no statistical significance (p>0.05). CONCLUSIONS: Both surgery and gamma knife could treat MTLE effectively, and the efficacy may be related to the ability to reduce the expression of EF-Tsmt protein and EF-Tumt protein in brain tissue.

The expression of osteopontin in breast cancer tissue and its relationship with p21ras and CD44V6 expression.

OBJECTIVE: This study aimed to investigate the expression of osteopontin (OPN), p2lras, and CD44V6 in breast cancer tissues, and to analyze the relationships between their expression and a patient's clinicopathological characteristics and five-year survival rate. MATERIALS AND METHODS: Streptavidin-peroxidase immunohistochemistry was used to detect the expression of OPN, p2lras, and CD44V6 in tissue samples from 96 breast cancer patients, and the multivariate Cox proportional hazards model (mCOX-PHM) was used to analyze the factors that affect prognosis. RESULTS: Among the 96 breast cancer patients studied, positive staining for OPN, CD44V6, and p21ras was observed in 54.2%, 58.3%, and 43.8% of samples, respectively. The expression of OPN and CD44V6 were positively correlated (r = 0.58), and the expression of OPN and p21ras were also positively correlated (r = 0.25). Coexpression OPN, CD44V6, and p21ras was negatively correlated with a patient's five-year survival rate (p < 0.05). Kaplan-Meier analysis indicated that a patient without OPN, CD44V6, or p21ras expression had an improved survival (p < 0.05). Results from the mCOX-PHM analysis indicated that CD44V6 expression, the degree of tumor differentiation, and lymph node metastasis were all independent factors that indicate prognosis. The combined detection of OPN, CD44V6, and p21ras could contribute to a more accurate assessment of the biological behavior of breast cancers, and could help to indicate the prognosis of breast cancer patients.

Reconstruction of atmospheric soot history in inland regions from lake sediments over the past 150 years.

Historical reconstruction of atmospheric black carbon (BC, in the form of char and soot) is still constrained for inland areas. Here we determined and compared the past 150-yr records of BC and polycyclic aromatic compounds (PACs) in sediments from two representative lakes, Huguangyan (HGY) and Chaohu (CH), in eastern China. HGY only receives atmospheric deposition while CH is influenced by riverine input. BC, char, and soot have similar vertical concentration profiles as PACs in both lakes. Abrupt increases in concentrations and mass accumulation rates (MARs) of soot have mainly occurred since ~1950, the establishment of the People's Republic of China, when energy usage changed to more fossil fuel contributions reflected by the variations in the concentration ratios of char/soot and individual PACs. In HGY, soot MARs increased by ~7.7 times in the period 1980-2012 relative to the period 1850-1950. Similar increases (~6.7 times) were observed in CH. The increase in soot MARs is also in line with the emission inventory records in the literature and the fact that the submicrometer-sized soot particles can be dispersed regionally. The study provides an alternative method to reconstruct the atmospheric soot history in populated inland areas.

Role of proton pump inhibitors in preventing hypergastrinemia-associated carcinogenesis and in antagonizing the trophic effect of gastrin.

Gastrin is the main hormone stimulating gastric acid secretion, but it exerts proliferative and anti-apoptotic actions on various cancer cell types, in addition to its well-known trophic effect on enterochromaffin-like cells. As treatment with proton pump inhibitors (PPIs) increases the biosynthesis and secretion of gastrin, it has been postulated that treatment with PPIs could increase the risk of cancer, especially in Barrett's esophagus, gastric carcinoids, and colorectal cancer (CRC). Some tumors produce gastrin of their own, which can act in an autocrine manner to promote tumor growth. In addition, gastrin is known to foster the tumor microenvironment. However, in spite of these potentially increased cancer risks due to PPI-induced hypergastrinemia, prospective, large-scale cohort studies did not show an increase in CRC prevalence. The question as to why the long-term use of PPIs was not associated with an increased cancer risk of CRC might be answered by the fact that the PPIs antagonized the trophic effects of hypergastrinemia. Furthermore, the blockade of proton pumps or potassium channels in cancer cells could limit the abnormal glycolytic energy metabolism of cancer cells. Apart from their suppressive effect on gastric acids, PPIs exert an anti-tumor effect through the selective induction of apoptosis as well as an anti-inflammatory effect, and they protect cells from developing chemo- or radiotherapeutic resistance. Moreover, the anti-carcinogenic actions of PPIs were augmented with PPI-induced hypergastrinemia. Together with their potential targeted killing of cancer stem cells, these effects demonstrate their potential anti-cancer actions.

Elemental carbon and polycyclic aromatic compounds in a 150-year sediment core from Lake Qinghai, Tibetan Plateau, China: influence of regional and local sources and transport pathways.

Elemental carbon (EC) and polycyclic aromatic compounds (PACs) are potential proxies for the reconstruction of change in human activities and the origin of air masses in historic times. In this study, the historic deposition of char and soot (the two subtypes of EC) and PACs in a 150-year sediment core from different topographic subbasins of Lake Qinghai on the Qinghai Tibetan Plateau (QTP) were reconstructed. The objective was to explore how the variations in the concentrations of EC and PACs, in the ratios of char to soot and of oxygenated polycyclic aromatic hydrocarbons (OPAHs) to parent PAHs, and in the composition of the PAC mixtures reflect historical changes in climate and human activity and the origin of air masses arriving at the QTP. The deposition fluxes of soot in the different subbasins were similar, averaging 0.18 (range of 0.15-0.25) and 0.16 (0.13-0.23) g m(-2) year(-1), respectively, but they varied for char (averaging 0.11 and 0.22 g m(-2) year(-1), respectively), suggesting ubiquitous atmospheric deposition of soot and local river inputs of char. The different vertical distributions of the char/soot ratios in the different subbasins can be interpreted in terms of the different transport mechanisms of char and soot. An abrupt increase in soot concentrations since 1980 coincides with results from the QTP ice cores that were interpreted to be indicative of soot transport from South Asia. Similar concentration patterns of PAHs with soot and 9,10-anthraquinone/anthracene (9,10-AQ/ANT) ratios all >2.0 suggest regional PAC sources. Increasing PAH/soot ratios and decreasing 9,10-AQ/ANT ratios since the beginning of the 1970s indicate increasing local emissions. The historical trends of these diagnostic ratios indicate an increase in the fossil-fuel contribution since the beginning of the 1970s. The increase of perylene concentrations with increasing core depth and the ratio of perylene to its penta-aromatic isomers indicate that perylene originates mainly from in situ biogenic diagenesis. We demonstrate that the concentrations of EC, char, soot, and PACs in sediments can be used to reconstruct local, regional, and remote sources and transport pathways of pollutants to the QTP.

Stronger association of polycyclic aromatic hydrocarbons with soot than with char in soils and sediments.

The knowledge of the association of polycyclic aromatic hydrocarbons (PAHs) with organic matter and carbonaceous materials is critical for a better understanding of their environmental transport, fate, and toxicological effects. Extensive studies have been done with regard to the relationship of PAHs with total organic carbon (TOC) and elemental carbon (EC) in different environmental matrices. The relationship between PAHs and the two subtypes of EC, char (combustion residues) and soot (produced via gas-to-particle conversion) also has been tested in field and laboratory experiments using reference materials. However, a direct comparison of associations of PAHs between with char and with soot in real environmental matrices has to our knowledge not yet been reported because of a lack of methodology to differentiate them. In this study, char and soot were measured using the IMPROVE method to test their associations with 12 EPA priority PAHs measured in topsoil samples (N=22, top 10 cm) collected from the Guanzhong Plain and in surface sediment samples (N=32, top 5 cm) from the Wei River (central China). In both soils and sediments, ∑12PAHs were more strongly associated with soot than with char, mainly due to the fact that soot and PAHs were produced in the same gas phase during combustion, had a strong affinity for each other, and were transported and deposited together, while char, the combustion residue, was transported differently to PAHs due to its large particle size. Stronger correlations between PAHs and the different carbon fractions (TOC, soot, and char) in sediments than in soils were observed, which is associated with the redistribution of PAHs among the organic matter pools in water because of the processes during soil erosion and sedimentation in the river.

Gastrin promotes intestinal polyposis through cholecystokinin-B receptor-mediated proliferative signaling and fostering tumor microenvironment.

Increased serum gastrin concentrations in patients with colorectal cancer suggested the tumorigenic trophic effect of gastrin. Detailed and global molecular mechanisms explaining trophic effect of gastrin had not been revealed. In the current study, intestinal polyposis of APC(Min/⁺) mice was compared between phosphate buffered saline (PBS) injected and gastrin (10 µg/kg, thrice per week) injected group. Total number of intestinal polyposis was counted and immunohistochemical staining with F4/80 and CD3 was done. MTT assay, cell cycle analysis, and Western blot for cyclin D1, CDK4, and ß-catenin were performed in Raw 264.7 and HCT116 cells before and after gastrin administration. Experiments were repeated with YM022 or transfection with si-cholecystokinin-B receptor (CCK-B-R). Intraperitoneal gastrin significantly increased intestinal polyposis in APC(Min/⁺) mice (P<0.005), in which significant increases in macrophage were noted on F4/80 immunohistochemical staining (Plt;0.05) as well as Ki-67 staining (Plt;0.05) after gastrin. On comparative cytokine array, gastrin increased interleukin-1ß (IL-1ß), interleukin 3Rß (IL-3Rß), stromal cell-derived factor-1α (SDF-1α), thymus and activation-regulated chemokine (TARC), and thymus-derived chemotactic agent 3 (TCA-3) in macrophage cells, which was further confirmed with real time polymerase chain reaction (RT-PCR) analysis (P<0.05). In addition to increased inflammatory cytokines, gastrin increased macrophage proliferation accompanied with increased cyclin D1 and CDK4. Targeted for HCT116 cells, gastrin significantly increased proliferation as well as increases in synthetic phase of cell cycle. YM022 as gastrin antagonist significantly abolished the trophic actions of gastrin (P<0.05). HCT116 cells transfected with siCCK-B-R, gastrin did not increase either cell cycle or ß-catenin in spite of gastrin administration. Conclusively, gastrin promoted intestinal polyposis through either direct gastrin receptor-mediated proliferative signaling or fostering tumor microenvironment such as macrophage activation.

Nonsteroidal anti-inflammatory drugs (NSAID) sparing effects of glucosamine hydrochloride through N-glycosylation inhibition; strategy to rescue stomach from NSAID damage.

Gastrointestinal or cardiovascular complications limit nonsteroidal anti-inflammatory drugs (NSAID) prescription. Glucosamine hydrochloride (GS-HCl) alternatively chosen, but debates still exist in its clinical efficiency. COX-2 instability through inhibiting COX-2 N-glycosylation of GS-HCl raised the possibility of NSAID sparing effect. Study was done to determine whether combination treatment of glucosamine and NSAID contributes to gastric safety through NSAID sparing effect. IEC-6 cells were stimulated with TNF-α and compared the expressions of inflammatory mediators after indomethacin alone or combination of indomethacin and GS-HCl by Western blotting and RT-PCR. C57BL/6 mice injected with type II collagen to induce arthritis were treated with indomethacin alone or combination of reduced dose of indomethacin and GS-HCl after 3 weeks. TNF-α increased the expression of COX-2, iNOS and inflammatory cytokines, but GS-HCl significantly attenuated TNF-α-induced COX-2 expression. Decreased COX-2 after GS-HCl was caused by N-glycosylation inhibition as much as tunicamycin. Combination of reduced dose of indomethacin and GS-HCl significantly reduced the expressions of ICAM-1, VCAM-1, IL-8, IL-1ß, MMP-2, MMP-7, MMP-9, and MMP-11 mRNA as well as NF-κB activation better than high dose indomethacin alone. These NSAID sparing effect of GS-HCl was further proven in collagen-induced arthritis model. Combination of GS-HCl and 2.5 mg/kg indomethacin showed significant protection from gastric damages as well as efficacious anti-arthritic effect. Taken together, COX-2 N-glycosylation inhibition by GS-HCl led to indomethacin sparing effects, based on which combination of GS-HCl and reduced dose of NSAID can provide the strategy to secure stomach from NSAID-induced gastric damage as well as excellent anti-arthritic effects.

Diagnostic efficacy of gadoxetic acid-enhanced MRI for the detection and characterisation of liver metastases: comparison with multidetector-row CT.

OBJECTIVES: We compared the diagnostic performance of gadoxetic acid-enhanced MRI and 16-slice multidetector CT (MDCT) with respect to their abilities to detect hepatic metastases and differentiate hepatic metastases from hepatic cysts and haemangiomas. METHODS: 67 patients with 110 liver metastases (size 0.3-2.5 cm), 33 haemangiomas (size 0.5-1.5 cm) and 17 cysts (size 0.3-1.0 cm) underwent 4-phase MDCT and gadoxetic acid-enhanced MRI, including early dynamic phases, post-contrast T(2) weighted turbo spin echo sequences and 20 min hepatocyte-selective phases. Two observers independently analysed each image in random order. Sensitivity and diagnostic accuracy for lesion detection and differentiation for MDCT and gadoxetic acid-enhanced MRI were calculated using receiver operating characteristic analysis. RESULTS: For both observers, the Az values of gadoxetic acid-enhanced MRI (mean, 0.982 and 0.981) were significantly higher than the Az values of MDCT (mean, 0.839 and 0.892) (p<0.05) for the detection of metastases and for the differentiation of metastases from haemangiomas and cysts. Sensitivities of gadoxetic acid-enhanced MRI with regard to the detection and characterisation of liver metastases (mean, 96.9% and 96.0%) were significantly higher than those of MDCT (mean, 78.7% and 75.0%) (p<0.05). CONCLUSION: Gadoxetic acid-enhanced MRI showed higher diagnostic accuracy and sensitivity than did MDCT for the detection of hepatic metastases and for the differentiation between hepatic metastases and hepatic haemangiomas or cysts.

Comparison of elemental carbon in lake sediments measured by three different methods and 150-year pollution history in Eastern China.

Concentrations of elemental carbon (EC) were measured in a 150 yr sediment record collected from Lake Chaohu in Anhui Province, eastern China, using three different thermal analytical methods: IMPROVE_A thermal optical reflectance (TOR), STN_thermal optical transmittance (TOT), and chemothermal oxidation (CTO). Distribution patterns for EC concentrations are different among the three methods, most likely due to the operational definition of EC and different temperature treatments prescribed for each method. However, similar profiles were found for high-temperature EC fractions among different methods. Historical soot(TOR) (high-temperature EC fractions measured by the IMPROVE_A TOR method) from Lake Chaohu exhibited stable low concentrations prior to the late 1970s and a sharp increase thereafter, corresponding well with the rapid industrialization of China in the last three decades. This may suggest that high-temperature thermal protocols are suitable for differentiating between soot and other carbon fractions. A similar soot(TOR) record was also obtained from Lake Taihu (~200 km away), suggesting a regional source of soot. The ratio of char(TOR) (low-temperature EC fraction measured by the IMPROVE_A TOR method, after correction for pyrolysis) to soot(TOR) in Lake Chaohu shows an overall decreasing trend, consistent with gradual changes in fuel use from wood burning to increasing fossil fuel combustions. Average higher char(TOR)/soot(TOR) was observed in Lake Taihu than in Lake Chaohu in the past 150 years, consistent with the longer and more extensive industrialization around the Taihu region.

CT and MRI findings of cirrhosis-related benign nodules with ischaemia or infarction after variceal bleeding.

AIM: To present computed tomography (CT) and magnetic resonance imaging (MRI) findings of cirrhosis-related benign nodules with ischaemia or infarction. MATERIALS AND METHODS: Sixteen consecutive patients (14 men and two women) who had been diagnosed with cirrhosis-related benign nodules with ischaemia or infarction after variceal bleeding based on the results of dynamic CT (n=15) and MRI (n=8) were included in this study. Five patients had histopathological confirmation via liver transplantation (n=2) and percutaneous biopsy (n=3). Images were analyzed for the enhancement pattern, signal intensities, location, and configuration of the lesions. RESULTS: Most of the lesions were depicted as multifocal discrete or clustered nodules with some irregular patchy areas (size range 3-28 mm). They were predominantly found in subcapsular area or caudate lobe. Most nodular lesions were seen as hypoattenuating (hypointense) nodules with rim enhancement during dynamic CT or MRI. On T2-weighted images, nodular lesions were predominantly seen as target appearing hyperintense nodules. On follow-up images (range 2-24 months), most of the lesions disappeared or decreased in size. CONCLUSION: CT and MRI can be used to demonstrate characteristic findings of cirrhosis-related benign nodules with ischaemia or infarction. Rapid resolution of the nodules at follow-up imaging can also be helpful for diagnosing these lesions.