Effect of an artificial intelligence-assisted system on endoscopic diagnosis of superficial oesophageal squamous cell carcinoma and precancerous lesions: a multicentre, tandem, double-blind, randomised controlled trial.

BACKGROUND: Despite the usefulness of white light endoscopy (WLE) and non-magnified narrow-band imaging (NBI) for screening for superficial oesophageal squamous cell carcinoma and precancerous lesions, these lesions might be missed due to their subtle features and interpretation variations among endoscopists. Our team has developed an artificial intelligence (AI) system to detect superficial oesophageal squamous cell carcinoma and precancerous lesions using WLE and non-magnified NBI. We aimed to evaluate the auxiliary diagnostic performance of the AI system in a real clinical setting. METHODS: We did a multicentre, tandem, double-blind, randomised controlled trial at 12 hospitals in China. Eligible patients were aged 18 years or older and underwent sedated upper gastrointestinal endoscopy for screening, investigation of gastrointestinal symptoms, or surveillance. Patients were randomly assigned (1:1) to either the AI-first group or the routine-first group using a computerised random number generator. Patients, pathologists, and statistical analysts were masked to group assignment, whereas endoscopists and research assistants were not. The same endoscopist at each centre did tandem upper gastrointestinal endoscopy for each eligible patient on the same day. In the AI-first group, the endoscopist did the first examination with the assistance of the AI system and the second examination without it. In the routine-first group, the order of examinations was reversed. The primary outcome was the miss rate of superficial oesophageal squamous cell carcinoma and precancerous lesions, calculated on a per-lesion and per-patient basis. All analyses were done on a per-protocol basis. This trial is registered with the Chinese Clinical Trial Registry (ChiCTR2100052116) and is completed. FINDINGS: Between Oct 19, 2021, and June 8, 2022, 5934 patients were randomly assigned to the AI-first group and 5912 to the routine-first group, of whom 5865 and 5850 were eligible for analysis. Per-lesion miss rates were 1·7% (2/118; 95% CI 0·0-4·0) in the AI-first group versus 6·7% (6/90; 1·5-11·8) in the routine-first group (risk ratio 0·25, 95% CI 0·06-1·08; p=0·079). Per-patient miss rates were 1·9% (2/106; 0·0-4·5) in AI-first group versus 5·1% (4/79; 0·2-9·9) in the routine-first group (0·37, 0·08-1·71; p=0·40). Bleeding after biopsy of oesophageal lesions was observed in 13 (0·2%) patients in the AI-first group and 11 (0·2%) patients in the routine-first group. No serious adverse events were reported by patients in either group. INTERPRETATION: The observed effect of AI-assisted endoscopy on the per-lesion and per-patient miss rates of superficial oesophageal squamous cell carcinoma and precancerous lesions under WLE and non-magnified NBI was consistent with substantial benefit through to a neutral or small negative effect. The effectiveness and cost-benefit of this AI system in real-world clinical settings remain to be further assessed. FUNDING: National Natural Science Foundation of China, 1·3·5 project for disciplines of excellence, West China Hospital, Sichuan University, and Chengdu Science and Technology Project. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Small bowel perforation caused by thermal injury during colonic polypectomy: A case report and literature review.

RATIONALE: Iatrogenic gastrointestinal perforation is a known uncommon complication of colonoscopy. The perforation usually occurs in the colon itself. Rarely, colonoscopic procedures can also cause the perforations of the small intestine. PATIENT CONCERNS AND DIAGNOSES: We describe the case of a 70-year-old man who experienced abdominal pain several hours after electrical polypectomy in the transverse colon. Urgent abdominal computed tomography scans showed a few bubbles on the frontal surface around the liver and a little extraluminal free air in the upper abdomen. Urgent exploratory laparotomy revealed a round perforation with a diameter of approximately 5 mm in the ileum 80 cm proximal to the ileocecal valve, accompanied by the outflow of intestinal contents. A small bowel perforation by thermal injury was diagnosed during colonic polypectomy. INTERVENTIONS AND OUTCOMES: The ileal perforation was repaired primarily after debridement of the perforation site and abdominal cavity. The patient recovered well after surgery. Histopathological examination of the perforation site demonstrated inflammatory necrosis and infiltration of inflammatory cells. LESSONS: Small bowel perforation should be considered after colonoscopic procedures although the incidence is exceedingly rare. Urgent exploratory laparotomy is warranted when a visceral perforation is identified after colonoscopy.

MiR-92a promotes stem cell-like properties by activating Wnt/ß-catenin signaling in colorectal cancer.

We previously reported the oncogenic function of miR-92a in colorectal cancer. This study identified that miR-92a was upregulated in chemoresistant colorectal cancer cells and tissues. Ectopic expression of miR-92a conferred resistance to 5-fluorouracil-induced apoptosis in vitro, while antagomiR-92a significantly enhanced chemosensitivity in vivo. Moreover, Overexpression of miR-92a promoted the tumor sphere formation and the expression of stem cell markers. MiR-92a overexpression also displayed higher tumourigenesis in vivo. Furthermore, we demonstrated that miR-92a upregulates the Wnt/ß-catenin signaling activity via directly targeting KLF4, GSK3ß and DKK3, which are multiple level negative regulators of the Wnt/ß-catenin signaling cascade. In addition, our results indicate IL-6/STAT3 pathway increases miR-92a expression by directly targeting its promoter, resulting in Wnt/ß-catenin signaling activation and consequent promotion of stem-like phenotypes of colorectal cancer cells. Our present results suggest the essential role of IL-6/STAT3/miR-92a/Wnt/ß-catenin pathway in regulating the stem cell-like traits of colorectal cancer cells and provide a potential target for colorectal cancer therapy.

Synthesis of a novel adamantyl nitroxide derivative with potent anti-hepatoma activity in vitro and in vivo.

In this study, a novel adamantyl nitroxide derivative was synthesized and its antitumor activities in vitro and in vivo were investigated. The adamantyl nitroxide derivative 4 displayed a potent anticancer activity against all the tested human hepatoma cells, especially with IC50 of 68.1 µM in Bel-7404 cells, compared to the positive control 5-FU (IC50=607.7 µM). The significant inhibition of cell growth was also observed in xenograft mouse model, with low toxicity. Compound 4 suppressed the cell migration and invasion, induced the G2/M phase arrest. Further mechanistic studies revealed that compound 4 induced cell death, which was accompanied with damaging mitochondria, increasing the generation of intracellular reactive oxygen species, cleavages of caspase-9 and caspase-3, as well as activations of Bax and Bcl-2. These results confirmed that adamantyl nitroxide derivative exhibited selective antitumor activities via mitochondrial apoptosis pathway in Bel-7404 cells, and would be a potential anticancer agent for liver cancer.

Post-transcriptional up-regulation of PDGF-C by HuR in advanced and stressed breast cancer.

Breast cancer is a heterogeneous disease characterized by multiple genetic alterations leading to the activation of growth factor signaling pathways that promote cell proliferation. Platelet-derived growth factor-C (PDGF-C) is overexpressed in various malignancies; however, the involvement of PDGF-C in breast cancers and the mechanisms underlying PDGF-C deregulation remain unclear. Here, we show that PDGF-C is overexpressed in clinical breast cancers and correlates with poor prognosis. PDGF-C up-regulation was mediated by the human embryonic lethal abnormal vision-like protein HuR, which stabilizes the PDGF-C transcript by binding to two predicted AU-rich elements (AREs) in the 3'-untranslated region (3'-UTR). HuR is up-regulated in hydrogen peroxide-treated or ultraviolet-irradiated breast cancer cells. Clinically, HuR levels are correlated with PDGF-C expression and histological grade or pathological tumor-node-metastasis (pTNM) stage. Our findings reveal a novel mechanism underlying HuR-mediated breast cancer progression, and suggest that HuR and PDGF-C are potential molecular candidates for targeted therapy of breast cancers.

HuR: a promising therapeutic target for angiogenesis.

Multiple angiogenic factors and inhibitors are becoming potential therapeutic targets for ischemia diseases and cancer. Posttranscriptional regulation through the untranslated region of mRNA is emerging as a critical regulating level in nearly all the biological processes. As a kind of RNA binding proteins, HuR plays important role in augmenting the hypoxic or inflammatory signal, stabilizing the resultant angiogenic factors and promoting the proliferation and migration of endothelial cells. These implicate HuR in the proangiogenic factors mediated angiogenesis in the hypoxia and inflammatory. We consider hypotheses that a more effective angiogenesis can be acquired through strengthened and prolonged effects of angiogenic factors, and that progresses in therapeutic angiogensis might also shed light on the implication of HuR in blocking tumor angiogensis. These considerations may help us to explain HuR as a promising therapeutic target for angiogenesis related disease. It may be a candidate in hypoxia therapy and cancer management.

Hyperglycemia promotes vasculogenesis in choroidal neovascularization in diabetic mice by stimulating VEGF and SDF-1 expression in retinal pigment epithelial cells.

To investigate the influence of hyperglycemia on the severity of choroidal neovascularization (CNV) in diabetic mice, especially the involvement of bone marrow-derived cells (BMCs) and underlying molecular mechanisms. The mice were randomly divided into control group, diabetes group and diabetes treated with insulin group, which were laser treated to induce CNV. The CNV severity was evaluated by fundus fluorescein angiography, HE staining and choroidal flatmount. The BMCs recruitment and differentiation in CNV were examined in GFP chimeric mice by choroidal flatmount and immunofluorescence. The bone marrow-derived mesenchymal stem cells (BMSCs) recruitment and migration were tested in vivo and in vitro. VEGF and SDF-1 production in vivo and in vitro were tested by realtime PCR and ELISA. The CNV severity and expression of VEGF and SDF-1 were enhanced in DM mice compared with control mice and that insulin treatment decreased CNV severity in DM mice. The DM mice demonstrated more BMCs and bone marrow-derived mesenchymal stem cells (BMSCs) recruited and incorporated into CNV, increased ratio of BMCs expressing endothelial cell marker or macrophage marker, and up-regulated expression of VEGF and SDF-1 in CNV. Human BMSCs migration and expression of VEGF and SDF-1 in retinal pigment epithelial (RPE) cells increased when cultured under high glucose. This study suggested that hyperglycemia enhanced the expression of VEGF and SDF-1 in RPE cells, and promoted recruitment and incorporation of BMCs and affected differentiation of BMCs in CNV, which led to more severe CNV in diabetic mice.

The mechanisms of 5-FU-PLA-O-CMC-NPS-mediated inhibition of the proliferation of colorectal cancer cell line SW480.

We aimed to investigate how 5-FU-PLA-O-CMC-NP (5-FPOCN) inhibits the proliferation of the SW480 colon cancer cell line. Following the treatment of cell line SW480 with 0.1, 1, 10 or 100 µg/ml 5-FPOCN or 5-fluorouracil (fluorouracil, 5-Fu) for 0, 24, 48, or 72, the rate of cell was tested by the tetrazolium assay (MTT). After the SW480 cells were treated with 5-FPOCN or 5-FU for 72 h, the growth rate and apoptosis were detected. After the SW480 cells were treated with 5-FPOCN or 5-FU for 24, 48, 72, or 120, flow cytometry (FCM) was used to determine the cell cycle distribution. The changes in the expression of P21, CyclinD1 and Rb were detected by Western blotting and real-time PCR. We found that different doses of 5-FPOCN can significantly inhibit the growth rate of SW480 cells, and this effect is dose and time dependent. However, there is no significant difference from 72 to 120 h (P>0.05). After 5-FPOCN treatment for 72 h, there is a negative correlation between the concentration of 5-FPOCN and the activity of SW480 cells and a positive correlation between the concentration of 5-FPOCN and SW480 cell apoptosis. G1 phase was significantly increased, and S phase was significantly decreased in 5-FPOCN-treated SW480 cells at 72 h compared to the control group (P<0.05); there was a positive correlation between the concentration of 5-FPOCN and the above changes. It was suggested that 5-FPOCN can delay G1/S phase and that this is a dose-dependent effect. The expression of P21 protein and messenger RNA (mRNA) and Rb protein and mRNA was significantly increased in 5-FPOCN-treated SW480 cells at 72 h compared to the control group, and this was a dose- and time-dependent effect. CyclinD1 protein and mRNA expression was reduced as the dose increased, and its expression was negatively associated with the increased expression of P21. We concluded that 5-FPOCN can significantly inhibit the growth of colon cancer SW480 cells. 5-FPOCN increased P21 expression and decreased cyclin family and pRb expression to promote cell cycle delay and apoptosis.

[Effects of nuclear factor of activated T cells on the promoter activity of constitutively activated SV40].

AIM: To check if the common used constitutively promoters, such as CMV, TK and SV40 could be responded to the nuclear factor of activated T cell (NFAT), and to explore the strategies to choose rational internal control in the dual luciferase reporter assay. METHODS: pCMV-luc vector, in which luciferase activity is driven by CMV promoter, was cloned by amplifying the CMV promoter fragment from the pCDNA3.1 vector and then inserting the CMV promoter region into the pGL3-basic vector using the standard protocol. pTK-Luc reporter was similarly constructed, with the TK promoter from the pRL-TK vector. The constructed pCMV-Luc or pTK-Luc was co-transfected with pBIND or pRL-TK respectively, together with NFAT or constitutively active form named NFATCA. Relative luciferase activity was calculated as instructed by the manual instruction. RESULTS: Both pCMV-Luc and pTK-Luc vectors were successfully constructed. Luciferase activity assay revealed that SV40 promoter responded to active NFAT. CONCLUSION: The common used internal control promoter SV40 could respond to active NFAT, which should be kept in mind for selection of the rational internal control vector in the dual luciferase reporter assay. In addition, our study here also provides a practical strategy for rational selection of the internal control.

A novel late embryogenesis abundant like protein associated with chilling stress in Nicotiana tabacum cv. bright yellow-2 cell suspension culture.

Low temperature is one of the major abiotic stresses limiting the productivity and geographical distribution of many important crops. To identify proteins associated with chilling stress in Nicotiana tabacum cv. bright yellow-2 (BY-2) cell suspension culture, we utilized a proteomic approach with two-dimensional electrophoresis to compare proteins from samples of treated with or without chilling treatment at 4 °C. One protein specifically more abundant in chilling treated sample was identified and designated as NtLEA7-3. Rapid amplification of cDNA ends gave rise to a full-length NtLEA7-3 cDNA with a complete open reading frame of 1267 bp, encoding a 322 amino acid polypeptide. Homology search and sequence multi-alignment demonstrated that the deduced NtLEA7-3 protein sequence shared a high identity with LEA-like proteins from other plants. Subcellular localization analysis indicated that the NtLEA7-3 was localized exclusively in the nucleus. When the gene was overexpressed in bright yellow-2 cells, the transgenic bright yellow-2 cells show more resistant to chilling stress than the wild-type cells. In addition, transgenic Arabidopsis plants overexpressing the NtLEA7-3 are much more resistant to cold, drought, and salt stresses. Interestingly, the expression of NtLEA7-3 in tobacco was not tissue-specific and induced by chilling, drought and salt stresses. All of these, taken together, suggest that NtLEA7-3 is worthwhile to elucidate the contribution of the proteins to the tolerance mechanism to chilling stress, and can be considered as a potential target for crop genetic improvement in the future.

Glycyrrhizin treatment is associated with attenuation of lipopolysaccharide-induced acute lung injury by inhibiting cyclooxygenase-2 and inducible nitric oxide synthase expression.

Glycyrrhizin (GL), a major active constituent of licorice root, has been attributed numerous pharmacologic effects, including anti-inflammatory, anti-viral, anti-tumor, and hepatoprotective activities. In this study, we investigated the anti-inflammatory effect of GL on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. ALI was induced in Balb/c mice by intratracheal instillation of LPS (1 mg/kg). Before 1 h of LPS administration, the mice received intraperitoneal injection of GL at varied doses (10, 25, and 50 mg/kg). The severity of pulmonary injury was evaluated 12 h after LPS administration. GL pretreatment led to significant attenuation of LPS induced evident lung histopathologic changes, alveolar hemorrhage, and neutrophil infiltration with evidence of reduced myeloperoxidase (MPO) activity. The lung wet/dry weight ratios, as an index of lung edema, were markedly reduced by GL pretreatment. The concentrations of pro-inflammatory cytokines interleukin (IL)-1ß and tumor necrosis factor (TNF)-α were elevated in bronchoalveolar lavage fluid (BALF) after LPS administration, which were significantly inhibited by GL pretreatment. GL pretreatment also reduced the concentrations of nitric oxide (NO) in lung tissues. Furthermore, the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) was suppressed by GL pretreatment. In conclusion, GL potently protected against LPS-induced ALI, and the protective effects of GL may attribute partly to the suppression of COX-2 and iNOS expression.

Protective effect of nicotine on lipopolysaccharide-induced acute lung injury in mice.

BACKGROUND: Recently, nicotine administration has been shown to be a potent inhibitor of a variety of innate immune responses, including endotoxin-induced sepsis. OBJECTIVE: It was the aim of this study to evaluate the effect of nicotine on attenuating lung injury and improving the survival in mice with lipopolysaccharide (LPS)-induced acute lung injury (ALI). METHODS: ALI was induced in mice by intratracheal instillation of LPS (3 mg/ml). The mice received intratracheal instillation of nicotine (50, 250 and 500 µg/kg) before or after LPS administration. Pulmonary histological changes were evaluated by hematoxylin-eosin stain, and lung wet/dry weight ratios were observed. Concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and high mobility group box (HMGB)-1, as well as myeloperoxidase (MPO) activity were measured by enzyme-linked immunosorbent assay. The mortality rate was recorded and analyzed by the Kaplan-Meier method. RESULTS: Nicotine pretreatment significantly attenuated the severity of lung injury and inhibited the production of TNF-α, IL-1ß and HMGB-1 in mice with ALI. After LPS administration, the lung wet/dry weight ratios, as an index of lung edema, and MPO activity were also markedly reduced by nicotine pretreatment. Early treatment with a high dose of nicotine (500 µg/kg) after LPS administration decreased the mortality in mice with ALI, even when treatment was started 24 h after LPS administration. CONCLUSION: Nicotine attenuated the lung injury and reduced mortality in mice with LPS-induced ALI.

NtKTI1, a Kunitz trypsin inhibitor with antifungal activity from Nicotiana tabacum, plays an important role in tobacco's defense response.

A cDNA library from tobacco inoculated with Rhizoctonia solani was constructed, and several cDNA fragments were identified by differential hybridization screening. One cDNA clone that was dramatically repressed, NtKTI1, was confirmed as a member of the Kunitz plant proteinase inhibitor family. RT-PCR analysis revealed that NtKTI1 was constitutively expressed throughout the whole plant and preferentially expressed in the roots and stems. Furthermore, RT-PCR analysis showed that NtKTI1 expression was repressed after R. solani inoculation, mechanical wounding and salicylic acid treatment, but was unaffected by methyl jasmonate, abscisic acid and NaCl treatment. In vitro assays showed that NtKTI1 exerted prominent antifungal activity towards R. solani and moderate antifungal activity against Rhizopus nigricans and Phytophthora parasitica var. nicotianae. Bioassays of transgenic tobacco demonstrated that overexpression of NtKTI1 enhanced significantly the resistance of tobacco against R. solani, and the antisense lines exhibited higher susceptibility than control lines towards the phytopathogen. Taken together, these studies suggest that NtKTI1 may be a functional Kunitz trypsin inhibitor with antifungal activity against several important phytopathogens in the tobacco defense response.

Simvastatin inhibits angiotensin II-induced cardiac cell hypertrophy: role of Homer 1a.

1. The scaffolding protein Homer 1a is constitutively expressed in the myocardium, although its function in cardiomyocytes remains poorly understood. The aim of the present study was to investigate Homer 1a expression in hypertrophic cardiac cells and its role in angiotensin (Ang) II-induced cardiac hypertrophy. 2. After serum starvation for 24 h, cells were treated with 1 micromol/L simvastatin, 100 nmol/L angiotensin (Ang) II or their combination added to Dulbecco's modified Eagle's medium containing 0.5% serum. For combination treatment with AngII plus simvastatin, cells were exposed to simvastatin 12 h before the addition of AngII to the medium and cells were then incubated in the presence of both drugs for a further 24 h. Western blotting was used to determine Homer 1a protein expression. Hypertrophy was evaluated by determining the protein content per cell. 3. Homer 1a protein levels were upregulated following AngII-induced hypertrophy in H9C2 cells and neonatal rat cardiomyocytes, and these increases were augmented by simvastatin pretreatment. Concomitantly, simvastatin pretreatment inhibited extracellular signal-regulated kinase (ERK) 1/2 phosphorylation and AngII-induced hypertrophy. 4. The inhibitory effects of simvastatin against AngII-induced hypertrophy were attenuated by Homer 1a silencing, suggesting that simvastatin suppresses cardiac hypertrophy in a Homer 1a-dependent manner. Furthermore, AngII-induced hypertrophy and ERK1/2 phosphorylation in neonatal rat cardiomyocytes were significantly inhibited following the overexpression of Homer 1a using an adenovirus. 5. These results suggest a possible role for Homer 1a in inhibiting cardiac hypertrophy perhaps in part through inhibition of ERK1/2 activation.

GhZFP1, a novel CCCH-type zinc finger protein from cotton, enhances salt stress tolerance and fungal disease resistance in transgenic tobacco by interacting with GZIRD21A and GZIPR5.

* Zinc finger proteins are a superfamily involved in many aspects of plant growth and development. However, CCCH-type zinc finger proteins involved in plant stress tolerance are poorly understood. * A cDNA clone designated Gossypium hirsutum zinc finger protein 1 (GhZFP1), which encodes a novel CCCH-type zinc finger protein, was isolated from a salt-induced cotton (G. hirsutum) cDNA library using differential hybridization screening and further studied in transgenic tobacco Nicotiana tabacum cv. NC89. Using yeast two-hybrid screening (Y2H), proteins GZIRD21A (GhZFP1 interacting and responsive to dehydration protein 21A) and GZIPR5 (GhZFP1 interacting and pathogenesis-related protein 5), which interacted with GhZFP1, were isolated. * GhZFP1 contains two typical zinc finger motifs (Cx8Cx5Cx3H and Cx5Cx4Cx3H), a putative nuclear export sequence (NES) and a potential nuclear localization signal (NLS). Transient expression analysis using a GhZFP1::GFP fusion gene in onion epidermal cells indicated a nuclear localization for GhZFP1. RNA blot analysis showed that the GhZFP1 transcript was induced by salt (NaCl), drought and salicylic acid (SA). The regions in GhZFP1 that interact with GZIRD21A and GZIPR5 were identified using truncation mutations. * Overexpression of GhZFP1 in transgenic tobacco enhanced tolerance to salt stress and resistance to Rhizoctonia solani. Therefore, it appears that GhZFP1 might be involved as an important regulator in plant responses to abiotic and biotic stresses.

Tissue-specific expression of the PNZIP promoter is mediated by combinatorial interaction of different cis-elements and a novel transcriptional factor.

Recent studies demonstrated that PNZIP and its homologs encode a special cyclase and play an important role in chlorophyll biosynthesis in higher plants. To investigate the molecular mechanism governing the PNZIP gene, the PNZIP promoter was isolated and analyzed. Deletion analysis indicated that G-box is an important element in the regulation of the reporter gene expression. Further mutation assay demonstrated that G-box and GATACT elements are necessary and sufficient for the high and tissue-specific expression of the GUS gene. Using yeast one-hybrid screening, we have isolated a novel tobacco bZIP protein, NtbZIP, which can specifically recognize the G-box of the PNZIP promoter. The NtbZIP protein shares a limited amino acid homology to Arabidopsis ABI5 and AtAREB1 and very low homology to other bZIP proteins. Northern blot analysis showed that the NtbZIP gene is not induced by exogenous ABA and is expressed in different tobacco organs. Cotransformation assays showed that the NtbZIP protein could activate the transcription of the GUS gene driven by the PNZIP promoter. Transgenic tobaccos analysis demonstrated that constitutively expressing antisense NtbZIP gene resulted in a lower NTZIP synthesis and reduced chlorophyll levels. We suggest that NTZIP is a target gene of NtbZIP, which is involved in the regulation of chlorophyll biosynthesis.

[Celecoxib induces apoptosis and inhibits angiogenesis in gastric cancer].

OBJECTIVE: The aim of this study was to explore the effect of celecoxib, a cyclooxygenase-2 inhibitor, on induction of apoptosis and inhibition of angiogenesis in gastric cancer. METHODS: Fifty nine gastric cancer patients were randomly divided into 2 groups: celecoxib group (n = 37) and control group (n = 22). The patients in the celecoxib group were treated orally with celecoxib 200 mg twice daily for 7 days before resection. The patients in the control group received surgical resection alone. Another group of 20 healthy subjects were recruited as normal control. The number of apoptotic tumor cells was measured by terminal deoxynucleotidyl transferse-mediated dUTP nick end labeling (TUNEL). The expression of COX-2, VEGF and the microvessel density (MVD) were evaluated by immunohistochemistry. RESULTS: The TUNEL results showed an increase of apoptosis in the tumor cells after celecoxib treatment in comparison with that in the control group (7.1% +/- 1.0% vs. 6.2% +/- 0.9%, P < 0.05). The expression level of COX-2 and VEGF in the gastric cancer tissues was significantly decreased in the celecoxib group compared with those in the control group (P < 0.05). Furthermore, MVD was also significantly lower in the celecoxib group when compared with that in the control group (30.48 +/- 5.02 vs. 38.98 +/- 4.58, P < 0.05). CONCLUSION: Oral intake of celecoxib can induce apoptosis and suppress angiogenesis in gastric cancer. It may become an effective agent in the treatment of gastric cancer.

[Effect of electroacupuncture on drug-seeking behaviors induced by heroin priming and FosB expression in relevant brain regions].

OBJECTIVE: To explore the effect of electroacupuncture on heroin seeking behavior and FosB expression in relevant brain regions. METHODS: Rat model of heroin relapse behaviors was developed with progressive fixed ratio program,and model rats were randomly divided into 3 groups: a restraint group, a needle retention group, and a electroacupuncture group. The heroin seeking behavior was elicited by a small dose of heroin. FosB expression in relevnt brain region was assessed with immunohistochemical technique. RESULTS: Tests on reinstatement of drug seeking behavior induced by heroin priming showed that compared with the restraint group, active pokes in the electroacupuncture group decreased significantly(P<0.05). Compared with the restraint group, the expression of FosB positive nuclei in Acd, Pcg and CeA of rats brain both in the electroacupuncture group and the needle retention group (P<0.05) decreased significantly. In LC, the expression of FosB positive nuclei in the needle retention group decreased significantly compared with the restraint group (P<0.05). CONCLUSION: Continuous acupuncture and needle retention attentuate the reinstatement of heroin-seeking behaviors induced by heroin priming, and the inhibitory effect may be mediated partially by the expression of FosB in relevant regions which are involved in the process of heroin addiction.

Cotton GhDREB1 increases plant tolerance to low temperature and is negatively regulated by gibberellic acid.

The transcription factors C-repeat binding factors/dehydration-responsive element binding proteins (CBFs/DREBs) control the expression of many stress-inducible genes in Arabidopsis. A cDNA clone, designated GhDREB1, was isolated from cotton (Gossypium hirsutum) by cDNA library screening. Northern blot analysis indicated that mRNA accumulation of GhDREB1 was induced by low temperatures and salt stress, but was not induced by abscisic acid (ABA) or drought stress in cotton seedlings. Transgenic tobacco (Nicotiana tabacum) plants overexpressing GhDREB1 displayed stronger chilling tolerance than wild-type plants. Their leaf chlorophyll fluorescence, net photosynthetic rate and proline concentrations were higher than those of control plants during low-temperature treatment. However, under normal growth conditions, the transgenic tobacco plants exhibited retarded growth and delayed flowering. Interestingly, GhDREB1 transcripts in cotton seedlings were negatively regulated by gibberellic acid (GA(3)) treatment. Analysis of the promoter of the GhDREB1 gene revealed the presence of one low-temperature and four gibberellin-responsive elements. Green fluorescent protein (GFP) signal intensity or beta-glucuronidase (GUS) activity driven by the GhDREB1 promoter was clearly enhanced by low temperature but repressed by GA(3). These results suggest that GhDREB1 functions as a transcription factor and plays an important role in improving cold tolerance, and also affects plant growth and development via GA(3).