Helicobacter pylori Infection as a Predictor of Treatment Outcomes of Gastric Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Helicobacter pylori infection is strongly associated with gastric cancer. However, there is currently no consensus on the association between H. pylori and gastric cancer prognosis. METHODS: A systematic search was conducted on studies in PubMed, EMBASE, and Web of Science up to March 10, 2022. The quality of all included studies was assessed using the Newcastle-Ottawa Scale. The hazard ratio (HR) and its 95% confidence interval (95% CI) were extracted to analyze the association between H. pylori infection and prognosis of gastric cancer. In addition, subgroup analysis and publication bias were performed. RESULTS: A total of 21 studies were involved. The pooled HR was 0.67 (95% CI, 0.56-0.79) for overall survival (OS) in H. pylori-positive patients, with the control (HR = 1) being the H. pylori-negative group. In the subgroup analysis, the pooled HR was 0.38 (95% CI, 0.24-0.59) for OS in H. pylori-positive patients who received surgery combined with chemotherapy. The pooled HR for disease-free survival was 0.74 (95% CI, 0.63-0.8) and 0.41 (95% CI, 0.26-0.65) in patients who received surgery combined with chemotherapy. CONCLUSION: H. pylori-positive gastric cancer patients have a better overall prognosis than H. pylori-negative patients. H. pylori infection has improved the prognosis of patients undergoing surgery or chemotherapy, among which the improvement was most obvious in patients undergoing surgery combined with chemotherapy.

Endoscopic Therapy of Small Bowel Polyps by Single-Balloon Enteroscopy in Patients with Peutz-Jeghers Syndrome.

Background: Little is known about the efficacy and safety of single-balloon enteroscopy (SBE) in patients with Peutz-Jeghers syndrome (PJS). The aim of this study was to assess the efficacy and safety of SBE for the treatment of small bowel polyps in patients with PJS. Methods: We conducted a single-center observational study, which included all patients diagnosed with PJS who underwent SBE for polypectomy between January 2018 and March 2021. Complete treatment was defined as the absence of polyps ≥10 mm after SBE resection. The clinical records were retrospectively reviewed. Results: 102 patients (including 40 men and 62 women) with a mean age of 28.7 years (range 13-55 y) were enrolled in our study. The intubation depth via the oral approach of patients with a history of laparotomy was significantly shorter than that of the patients without a history of laparotomy ([241.6 ± 64.2] cm vs [280.9 ± 40.2] cm, P=0.008). The maximum size of the resected polyps via anus during the second hospitalization was significantly smaller than that during the first hospitalization ([2.25 ± 1.29] cm vs [4.26 ± 3.51] cm, P=0.032). For patients with total enteroscopy, the complete treatment rate was 98% (49/50). For patients without total enteroscopy, all polyps larger than 10 mm in the examined segment of small bowel were resected successfully. Complications occurred in 10 of 129 hospitalizations (delayed bleeding in 4, perforation in 3, and acute pancreatitis in 3). Conclusions: SBE is effective and safe for resection of small bowel polyps in patients with PJS.

Identification of three immune subtypes characterized by distinct tumor immune microenvironment and therapeutic response in stomach adenocarcinoma.

BACKGROUND: In primary stomach adenocarcinoma (STAD), the tumor immune microenvironment (TIME) is important for cancer occurrence and progression; however, its clinical significance remains unclear. This study investigated the association between patient survival, TIME, and therapeutic response to STAD. METHODS: Gene expression profiles of STAD cases were collected from the Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus. Molecular subtypes were explored with consistent clustering methods according to 119 immune signatures and the infiltrating scores of 22 immune cells using the Multi-Omics Immuno-Oncology Biological Research algorithm. We determined IFNγ scores and immune cytolytic activity (CYT) scores on the basis of corresponding gene signatures via single-sample Gene Set Enrichment Analysis. Comparisons of survival, TIME, 10 immunity-related oncogenic pathways, immune checkpoint expression, and therapeutic response were conducted among the three subtypes. We further applied linear discriminant analysis to construct a characteristic index to classify the subtypes, and the Pearson correlation coefficient for the relationship between the index and immune checkpoint genes. Weighted Correlation Network Analysis (WGCNA) was used to mine the associated modules and specific genes. RESULTS: We collected gene expression profiles from 352 STAD cases in the TCGA database, 300 in GSE62254, and 344 in GSE84437. Three STAD subtypes (IS1-IS3) were established according to the TIME signatures. The IS3 subtype had the highest immune score and the best prognosis, as well as markedly increased immune T-cell CYT, Th1/IFNγ scores, and immune checkpoint gene expression, compared to the other two subtypes. It was highly similar to the PD-1 response group in the previous study samples of GSE91061. The established TIME classification index performed well in classifying subtypes and was directly proportional to immune checkpoint-related gene expression levels. WGCNA explored 6 modules and 14 genes, namely DYSF, MAN1C1, HTRA3, EMCN, RFLNB, KANK3, MAGEH1, CD93, PCAT19, FUT11, BMP1, FOSB, DCHS1, and TCF3, which were associated with the established TIME classification index and STAD patient prognosis. CONCLUSION: TIME phenotypes of STAD patients could be divided into three different molecular subtypes, which displayed different prognoses, immune features, and therapeutic responses. Our results shed new light on predicting patient outcomes and the discovery of new anti-STAD therapeutic strategies according to the TIME.

Comparison of the Effectiveness and Safety of Different Methods of Colorectal Endoscopic Submucosal Dissection: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Traditional endoscopic submucosal dissection (ESD) has developed different methods, such as pocket method (P-ESD), traction-assisted method (T-ESD), and hybrid method (H-ESD). In this meta-analysis, the benefits and drawbacks of different ESD methods were discussed and ranked. STUDY DESIGN: Studies comparing different methods of colorectal ESD were searched by using PubMed, EMBASE, and Cochrane Library databases. The study was conducted for five endpoints: en bloc resection rate, R0 resection rate, operation time, dissection speed, and adverse events rate. Pairwise and network meta-analyses were performed through Rev Man 5.4 and Stata 16.0. The quality of all included studies was assessed using the Cochrane Risk of Bias Tool and the Newcastle-Ottawa Scale. RESULTS: Twenty-six studies met the inclusion criteria, including 7 RCTs and 19 non-RCTs, with a total of 3,002 patients. The pooled analysis showed that the en bloc resection rate of H-ESD was significantly lower than that of C-ESD, P-ESD, and T-ESD (RR = 0.28, 95% CI [0.12, 0.65]; RR = 0.11, 95% CI [0.03, 0.44]; RR = 8.28, 95% CI [2.50, 27.42]). Compared with C-ESD, the operation time of H-ESD and T-ESD was significantly shorter (MD = -21.83, 95% CI [-34.76, -8.90]; MD = -23.8, 95% CI [-32.55, -15.06]). Meanwhile, the operation time of T-ESD was also significantly shorter than that of P-ESD (MD = -18.74, 95% CI [-31.93, -5.54]). The dissection speed of T-ESD was significantly faster than that of C-ESD (MD = 6.26, 95% CI [2.29, 10.23]). CONCLUSION: P-ESD and T-ESD are probably the two best methods of colorectal ESD at present. The advantages of P-ESD are high en bloc resection rate and low incidence of adverse events. The advantages of T-ESD are rapid dissection and short operation time.

Risk of esophageal adenocarcinoma in patients with Barrett's esophagus using proton pump inhibitors: a systematic review with meta-analysis and sequential trial analysis.

BACKGROUND: Proton pump inhibitors (PPIs) have been used to treat Barrett's esophagus (BE), but there seems to be insufficient evidence that PPIs can prevent esophageal adenocarcinoma (EAC) and high grade dysplasia (HGD). This study aimed to evaluate the effects of PPIs in BE patients. METHODS: PubMed and EMBASE were systematically searched. Stata13 and trial sequential analysis (TSA) software were used to carry out related statistics. Pooled odds ratio (OR) with 95% confidence intervals (CIs) were calculated. RESULTS: Using PPIs to reduce the incidence of EAC and HGD has not been confirmed (OR, 0.61; 95% CI, 0.29-1.26). The pooled results of three cohort studies reported that PPIs use was protective (OR 0.48; 95% CI, 0.33-0.70). But the pooled results of five case-control study indicating PPIs use does not prove this protective effect (OR 0.73; 95% CI, 0.21-2.48). On pooled analysis of 4 US studies 2 Netherlands, protective effect on development of EAC and HGD was noted (OR, 0.59; 95% CI, 0.43-0.80) and (OR, 0.16; 95% CI, 0.03-0.75). CONCLUSIONS: According to the Meta analysis and TSA of existing studies, the protective effect of PPIs on the progression of BE patients to EAC and/or HGD has not been confirmed. TSA shows that more patients are needed before a clear conclusion can be reached.

[Monitoring leaf nitrogen concentration and nitrogen accumulation of double cropping rice based on crop growth monitoring and diagnosis apparatus]. / 基于作物生长监测诊断仪的双季稻叶片氮含量和氮积累量监测.

To verify the accuracy and adaptability of crop growth monitoring and diagnosis apparatus (CGMD) in monitoring nitrogen nutrition index of double cropping rice, we established a monitoring model of leaf nitrogen concentration (LNC) and leaf nitrogen accumulation (LNA) for double cropping rice based on CGMD. Eight early and late rice cultivars were selected and four nitrogen application rates were set up. The differential vegetation index (DVI), normalized difference vegetation index (NDVI) and ratio vegetation index (RVI) were collected using CGMD. Meanwhile, ASD FH2 high spectrometer was used to collect canopy spectral reflectance and calculated DVI, NDVI, and RVI. To verify the accuracy of CGMD, we compared the canopy vegetation indices change characteristics collected by CGMD and ASD FH2. The CGMD-based monitoring models of LNC and LNA were established, which was tested with independent field data. The results showed that LNC, LNA, DVI, NDVI and RVI of early and late rice increased with increasing nitrogen application rate, and increased first and then decreased with the advance of growth progress. The determination coefficient (R2) of fitting for DVI, NDVI and RVI from CGMD and ASD FH2 were 0.9350, 0.9436 and 0.9433, respectively. This result indicated that the measurement accuracy of CGMD was high, and that the CGMD could be used to replace ASD FH2 to measure canopy vegetation indices of early and late rice. Compared with the three canopy vegetation indices based on CGMD, the correlation between NDVICGMD and LNC and that between RVICGMD and LNA was the highest. The exponential model based on NDVICGMD could be used to accurate estimate LNC with the R2 in the range of 0.8581-0.9318, and the root mean square error (RMSE), relation root mean square error (RRMSE) and correlation coefficient (r) of model validation in the range of 0.1%-0.2%, 4.0%-8.5%, and 0.9041-0.9854, respectively. The power function model based on RVICGMD could be used to estimate LNA with the R2 in the range of 0.8684-0.9577, and the RMSE, RRMSE and r of model validation in the range of 0.37-0.89 g·m-2, 6.7%-20.4% and 0.9191-0.9851, respectively. Compared with the chemical testing method, using the CGMD could conveniently and accurately measure LNC and LNA of early and late rice, which had a potential to be widely applied for high yield and high efficiency cultivation and precise management of nitrogen fertilizer in double cropping rice production.

Nuclear Factor κB/MicroRNA-155 Upregulates the Expression Pattern of Cytokines in Regulating the Relapse of Chronic Sinusitis with Nasal Polyps and the Underlying Mechanism of Glucocorticoid.

BACKGROUND The aim of this study was to explore the upregulated nuclear factor kappaB (NF-kappaB)/microRNA-155 (miR-155) in regulating inflammatory responses and relapse of chronic rhinosinusitis (CRS) with nasal polyps (NP), which underlies the molecular mechanism of glucocorticoid treatment. MATERIAL AND METHODS The study recruited 25 patients with eosinophilic (Eos) CRSwNP, 25 patients with Non-Eos CRSwNP, 25 patients with CRS without NP (CRSsNP) and 30 patients with nasal septum deviation (control group). The expression of NF-kappaB/miR-155 and inflammatory cytokines was detected in epithelial tissue specimens. Additionally, a mouse model of Eos CRSwNP was established, and the mice were treated by NF-kappaB inhibitor, miR-155 antagomir, or dexamethasone (DEX) to explore the role of NF-kB/miR-155 and the anti-inflammatory effects of glucocorticoid treatment. RESULTS Results showed that the expression level of NF-kappaB/miR-155 was significantly elevated in the Eos CRSwNP group, accompanied by the upregulation of cytokines: tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-4, IL-5 (P<0.05) compared with the control group, the CRSsNP group or the Non-Eos CRSwNP group. The upregulation of NF-kappaB/miR-155 increased inflammatory mediator cyclooxygenase2 (COX2) while decreasing anti-inflammatory mediator Src homology-2 domain-containing inositol 5-phosphatase 1 (SOCS1), which resulted in the aberrant expression pattern of cytokines in the mice model. DEX treatment inhibited the expression of cytokines and decreased the relapse rate of Eos CRSwNP via inhibiting NF-kappaB/miR-155 (P<0.05). CONCLUSIONS The upregulation of NF-kappaB/miR-155 was crucial in mediating the aberrant expression of inflammatory cytokines in Eos CRSwNP. This molecular mechanism is a concern with the high relapse rate of Eos CRSwNP. However, glucocorticoid treatment inhibited the relapse of CRSwNP via downregulation of NF-kappaB/miR-155.

[Model construction and application for nitrogen nutrition monitoring and diagnosis in double-cropping rice of Jiangxi Province, China]. / æ±Ÿè¥¿åŒå­£ç¨»æ°®ç´ ç›‘æµ‹è¯Šæ–­æ¨¡åž‹çš„å»ºç«‹ä¸Žåº”ç”¨.

The spectrometer-based nitrogen (N) nutrition monitoring and diagnosis models for double-cropping rice in Jiangxi is important for recommending precise N topdressing rate, achieving high yield, improving grain quality and increasing economic efficiency. Field experiments were conducted in Jiangxi in 2016 and 2017, involving different early rice and late rice cultivars and N application rates. Plant N accumulation (PNA) and canopy spectral vegetation indices (VIs) were measured at tillering and jointing stages with two spectrometers, i.e., GreenSeeker (an active multispectral sensor containing 780 and 660 nm wavelengths) and crop growth monitoring and diagnosis apparatus (CGMD, a passive multispectral sensor containing 810 and 720 nm wavelengths). The VI-based models of PNA were established from a experimental dataset and then validated using an independent dataset. The N topdressing rates for tillering and jointing stages were calculated using the newly developed N spectral diagnosis model and higher yield cultivation experience of double-cropping rice. The results showed that the VIs from two spectrometers were strongly positively correlated with PNA at both growth stages, with the model performance for tillering or jointing stages was better than that for the early growth stages. The exponential equation of normalized difference vegetation index (NDVI(780,660)) from GreenSeeker could be used to estimate PNA with a determination coefficient (R2) in the range of 0.92-0.94, the root mean square error (RMSE), relative root mean square error (RRMSE) and correlation coefficient (r) of model validation in the range of 3.09-5.96 kg·hm-2, 5.8%-18.5% and 0.92-0.98, respectively. The linear equation of difference vegetation index (DVI(810,720)) from CGMD could be used to estimate PNA with a R2 in the range of 0.90-0.93, the RMSE, RRMSE and r of model validation in the range of 3.71-6.33 kg·hm-2, 11.7%-14.3% and 0.93-0.96, respectively. The recommended N topdressing rate with CGMD was higher than that with GreenSeeker. Compared with conventional farmer's plan, the precision N application plan reduced N fertilizer application rate by 5.5 kg·hm-2, while N agronomic efficiency and net income was improved by 0.8% and 128 yuan·hm-2, respectively. Application of the spectral monitoring and diagnosis method to guiding fertilization could reduce cost and increase grain yield and net income, and thus had great potential for guiding double-cropping rice production.

Dexamethasone protects against arsanilic acid­induced rat vestibular dysfunction through the BDNF and JNK 1/2 signaling pathways.

The brain­derived neurotrophic factor (BDNF) and c­Jun NH 2­terminal kinase (JNK) signaling pathways are therapeutic targets to prevent degeneration in the central nervous system. Dexamethasone (DXMS), a glucocorticoid, protects against vestibular brain injury, however, the molecular mechanisms have yet to be fully elucidated. To investigate whether the BDNF and JNK signaling pathways are involved in the protective effects of DXMS in rats with vestibular dysfunction, a rat model of severe vestibular deficits was established by middle ear injection of arsanilic acid (AA; 100 mg/ml; 0.05 ml). After 3 days, rat symptoms and behavior scores with vestibular disorders were detected. In brain tissues, histopathological alterations, cell apoptosis, expression levels and patterns of BDNF signaling pathway­associated BDNF, tyrosine receptor kinase B (TrKB) and K+/Cl­ cotransporter isoform 2 (KCC2), and the expression of apoptosis­related cleaved­caspase 3 and the JNK signaling pathway were detected. It was identified that DXMS relieved AA­induced vestibular dysfunction, leading to improvement in rat behavior scores to normal levels, minimizing brain damage at the histopatholojnnkngical level, reducing cell apoptosis, enhancing the expression of BDNF, TrKB and KCC2, and downregulating cleaved­caspase 3 and phosphorylated­JNK1/2 in brain tissues. Together, these findings indicated the protective effect of DXMS on AA­induced rat vestibular dysfunction, and that activating BDNF and inhibiting JNK singling pathways were the underlying mechanisms. In addition, with additional treatment of mifepristone (RU486), a specific glucocorticoid agonist, all the events elicited by DXMS mentioned above in the AA­treated rat rats were reversed. In conclusion, DXMS was identified as a therapeutic agent targeting the BDNF and JNK singling pathways for AA­induced rat vestibular dysfunction.

[The changes of microRNA in nasal mucosa after the specific immunotherapy for allergic rhinitis in mice].

OBJECTIVE: To explore the changes of microRNAs in nasal mucosa after the specific immunotherapy (SIT) for allergic rhinitis (AR) in mice. METHOD: Female BALB/c mice, 6-8 weeks of age, were randomly divided into control group, model group and treatment group. AR model were established by intraperitoneal injection and intranasal challenge of ovalbumin and SIT was performed by inguinal subcutaneous injections. AR symptom scores were documented. The eosinophils (EOS) in the nasal mucosa were measured. Ovalbumin-specific IgE (OVA-sIgE) in the serum and expression of interferon-γ and interleukin-4 in the nasal lavage were measured by enzyme-linked immunosorbent assay meanwhile the ratio of interferon-γ and interleukin-4 was calculated. The microRNAs in the nasal mucosa were preliminary screened by microRNA gene microarray. Comparing with model group, the Fold changes of microRNA of the treatment group were ≥ 2.0 and the P < 0.05. MicroRNA target genes were predicted with GeneSpring 12.5 software. We took the intersection between genes in the signal pathway which associated with immune response,inflammation and target genes. The MEV-4-6-0 and Cytoscape_v2. 8. 2. software was applied to perform the cluster analysis and target gene regulatory networks maps. RESULT: The model of AR in mice and its SIT were successful. Comparing with the model group, the Fold changes of 15 microRNAs, of which 9 microRNAs were up-regulated and 6 microRNAs were down-regulated, were ≥ 2.0 in treatment group (P < 0.05). Cluste analysis showed clearly that microRNAs in the treatment group and model group respectively aggregated in two branches. The 15 microRNAs had 5302 target genes, of which, 451 genes were related more with SIT by the intersection. One microRNA can regulate many target genes, and one gene can also be affected by many microRNAs. Their synergistic effects may be involved in the mechanism of SIT. CONCLUSION: The expressions of microRNAs are changed in nasal mucosa after SIT for AR in mice and we can speculate that microRNAs are involved in the process of SIT for AR. Bioinformatics methods can diminish the scope of target genes of microRNAs, which will help us studying the effect of changed microRNA on its relative target genes after SIT, and make us better understanding the mechanism of the disease and its SIT.

[Effects of simultaneous multi-level surgery intervention on the changes of the oxidative stress and the cognitive function in young and middle-aged patients with Moderate-severe obstructive sleep apnea hypopnea syndrome].

OBJECTIVE: To explore the effects of simultaneous multi-level surgery intervention on the changes of the oxidative stress and the cognitive function in young and middle-aged patients with moderate-severe OSAHS. METHOD: One hundred and sixteen young and middle-aged patients with moderate-severe OSAHS received simultaneous multi-level surgery. PSG,malondialdehyde (MDA), advanced oxidation protein products (AOPP) and 8-isoprostaneF2α (8-iso-PGF2α) were tested, together with the evaluation of the questionnaires of Montreal cognitive assessment (MoCA), mini-mental state examination (MMSE) and Epworth sleepiness scale (ESS) before and 6 months after surgery. RESULT: (1) The AHI, TS90% and LSaO2 were all improved significantly 6 months after operation. No severe complications were observed in any patient. (2) The preoperative MoCA and MMSE scores were (23.52 ± 2.64) and (26.54 ± 1.07) respectively. The cognitive impairment were detected in OSAHS patients. MoCA was negatively correlated with AHI, TS90%, MDA, AOPP and 8-iso-PGF2a, while positively correlated with LSaO2 (P < 0.05, r = -0.233, -0.190, -0.256, -0.247, -0.221 and 0.215, respectively). Cognitive impairment was mainly manifested as disorder in the visual space and execu- tive function, memory and delayed recall (mainly short-term memory). (3) MoCA and MMSE scores were both increased (P < 0.05) after the operation. MoCA showed negative correlations with MDA, AOPP, 8-iso-PGF2α, AHI and TS90%, and positive correlation with LSaO2 (P < 0.05, r = -0.495, -0.463, -0.397, -0.332, -0.292 and 0.336, respectively). CONCLUSION: Oxidative stress and cognitive dysfunction are closely related in young and middle-aged patients with Moderate-severe OSAHS. Oxidative stress may play an important role in cognitive function of young and middle-aged patients with Moderate-severe OSAHS. Multi-level surgery can improve oxidative stress so that to improve cognitive impairment.

[Effects of staphylococcal enterotoxin of different concentrations on the expression of GATA-3 and Th1/Th2 cytokines in the maxillary sinus mucosa of rabbits].

OBJECTIVE: The aim of this study was to determine the expression of GATA-3 and the level of Th1 and Th2 cytokines upon repeated exposure to staphylococcal enterotoxin B(SEB) of different concentrations in the maxillary sinus mucosa of rabbits. METHOD: The rabbits were randomly divided into 2 groups (24 rabbits per group): low-dose SEB group and high-dose SEB group. The low-dose SEB group and high-dose SEB group received daily injections of 0.6 ng of SEB (2 ml) and 60 ng of SEB (2 ml) into the left maxillary sinus of rabbits for 28 days, respectively. Concurrent treatment of the right maxillary sinus with normal saline was used as a control. Six rabbits chosen randomly in two groups were killed on days 3, 7, 14, and 28, and to obtain the sinus mucosa from the two-side maxillary sinuses for measurement. Mucosal levels of IL-2, IL-4, IL-5, and IFN-γ were measured using ABC-ELISA. Tissue expression of GATA-3 were examined using Real-time PCR and immunohistochemistry. RESULT: IFN-γ and IL-2 levels were significantly elevated in the high-dose SEB group compared with the low-dose SEB and control groups on days 7, 14, and 28 (P < 0.05). However, IL-4 and IL-5 levels were markedly enhanced in the low-dose SEB group compared with the high-dose SEB and control groups on days 14 and 28 (P < 0.05). Real-time PCR showed that the expression of GATA-3 mRNA in the low-dose SEB group was markedly enhanced, and immunohistochemical staining illustrated that the number of GATA-3 positive cells was markedly increased in the low-dose SEB group as compared with the high-dose SEB group (P < 0.05). No significant differences were observed in GATA-3 expression between the high-dose SEB and the control groups (P > 0.05). CONCLUSION: SEB promoted Th1 cytokines production at high concentrations, and enhanced Th2 cytokines expression and Th2 immune response at low concentrations.

Staphylococcal enterotoxin burden determines the type of T helper cell response and pathology of the maxillary sinus mucosa in rabbits.

Staphylococcal enterotoxin (SE) induces T lymphocyte activation along with nasal allergic inflammation during rhinosinusitis, but it is under debate on which types of T helper (Th) cells respond exclusively or whether they respond synergically. We hypothesize that their responses may vary based on dose of SE. To test this hypothesis, we initiated to determine the nature of the T cell response and pathological feature upon repeated exposure to staphylococcal enterotoxin A (SEA) at different doses in the maxillary sinus of rabbits. SEA (0.6 or 60 ng) was instilled daily into the left maxillary sinus of rabbits for 28 days. The right maxillary sinus receiving normal saline was used as control. Mucosal histological changes were examined by hematoxylin-eosin and toluidine blue staining. Tissue expression of myeloperoxidase (MPO), eosinophil cationic protein (ECP), T-box expressed in T cells (T-bet), and GATA binding protein 3 (GATA-3) were examined using immunohistochemistry. Mucosal levels of representative pro-inflammatory cytokines were measured using ELISA. SEA at 60 ng/day induced acute rhinosinusitis, as confirmed by CT scan. Histopathologic examination revealed epithelial disruption, subepithelial edema, and inflammatory cell infiltration. MPO and T-bet expression, as well as interleukin (IL)-2 and interferon (IFN)-γ levels, were up-regulated. However, 0.6 ng/day SEA did not cause discharge. Histological examination revealed prominent eosinophilic infiltration. ECP and GATA-3 expression, as well as IL-4 and IL-5 levels, were increased at this lower dose. In conclusion, SEA induces acute rhinosinusitis associated with a Th1-type immune response at high dose, and a predominantly Th2-biased allergic inflammation at low dose.

[The staphylococcal enterotoxin burden determines the ultrastructure of ciliated epithelia and inflammatory changes in maxillary sinus mucosa of rabbits].

OBJECTIVE: To investigate the ultrastructure of ciliated epithelia and inflammatory changes upon repeated exposure to staphylococcal enterotoxin A (SEA) of different concentrations in the maxillary sinus mucosa of rabbits. METHODS: The rabbits were randomly divided into 2 groups (24 rabbits per group): low-dose SEA group and high-dose SEA group. The low-dose SEA group and high-dose SEA group received daily injections of 0.6 ng of SEA (2 ml) and 60 ng of SEA (2 ml) into the left maxillary sinus of rabbits for 28 days, respectively. Concurrent treatment of the right maxillary sinus with normal saline was used as control. Six rabbits chosen randomly in two groups were examined by computed tomography (CT) scans and then sacrificed to obtain the sinus mucosa from the two-side of maxillary sinuses for histological assessment on days 3, 7, 14 and 28. To characterize the inflammatory changes of the sinus mucosa examined using light microscope, hematoxylin and eosin (HE) and toluidine blue staining was performed. Scanning and transmission electron microscopy were performed to observe ultrastructure of ciliated epithelia in the maxillary sinus mucosa. SPSS 13.0 software was used to analyze the data. RESULTS: On days 14 and 28, CT images showed opacification of the left maxillary sinus in the high-dose SEA group. The percentage of epithelial disruption was (22.73 ± 5.72) % and (30.79 ± 4.30)% in the high-dose SEA group respectively, and were significantly greater than those in the low-dose SEA group (5.12% ± 1.98% and 5.38% ± 1.64%, q value was 10.079 and 19.132) and control group (4.08% ± 1.29% and 4.81% ± 1.62%, q value was 11.016 and 19.592, respectively, all P < 0.01). The subepithelial thickness in the high-dose SEA group was (113.34 ± 14.81)µm and (120.86 ± 12.35) µm respectively, and were significantly different from those of the low-dose SEA group [(71.08 ± 10.39)µm and (81.63 ± 9.32)µm, q value was 8.090 and 8.782] and control group [(37.45 ± 7.67)µm and (38.79 ± 7.68)µm, q value was 15.759 and 19.541, all P < 0.01]. Viewed under the electron microscope, loss of cilia was observed, a few compound cilia and cytoplasmic protrusion were found, an obvious stretching of the endoplasmic reticulum and an obvious turgescence of the mitochondria was also observed. However, in the low-dose SEA group on days 14 and 28, CT scan of the left maxillary sinus showed transparency; light microscopy observations of the maxillary sinus mucosa showed the number of eosinophils was markedly increased as compared with the high-dose SEA and control groups, the differences were significant (q value was 5.871 and 6.766 on day 14, and q value was 7.572 and 8.970 on day 28, respectively, all P < 0.05). But no significant differences were observed in epithelial disruption between the low-dose SEA and the control groups on days 14 and 28 (q value was 1.512 and 0.859 respectively, all P > 0.05); inordinate array and adhesion of cilia was observed, but cilia loss, compound cilia, cytoplasmic protrusions, mitochondrial swelling and endoplasmic reticulum stretching were not found. CONCLUSIONS: SEA may induce allergic inflammation of the sinus mucosa without damaging the structure of ciliated epithelia at low concentration. Whereas SEA impairs the structure of mitochondria and endoplasmic reticulum in ciliated epithelial cells at high concentration, and results in cilia loss and epithelial disruption, which may be one of the main reasons to induce acute sinusitis.

[Elemene in the treatment of the transplantable model of human laryngeal squamous carcinoma in nude mice].

OBJECTIVE: To investigate the inhibitory effect of elemene on the tumor growth of human laryngeal squamous carcinoma (LSCC) and to explore the possible mechanism of its inhibitory effect on LSCC. METHOD: Nude mice model engrafted with laryngocarcinoma was established by using human laryngeal squamous carcinoma cell line (Hep-2). When the transplantable tumor size is more than 10 mm, the mice were given elemene (120 mg/kg) in the treatment group or PBS in the control group, at the day of 1, 4, 7, 10, 13, 16, 19 and 22 respectively. The animals were killed three days after the last treatment. The tumor volume, tumor weight,mice net weight and tumor inhibition rate were measured. The expression of vascular endothelial growth factor-C (VEGF-C) and vascular endothelial growth factor receptor-3 (VEGFR-3) mRNA were quantitated by using reverse transcription and polymerase chain reaction technique. RESULT: Elemene could inhibit the tumor growth in vivo. The differences were statistically significant for the mice net weight, tumor weight, and tumor volume between the treatment group and the control group. The tumor inhibition percentage was 52.24%. The gene expression of VEGF-C and VEGFR-3 of the treatment group is lower than that of the control group and the differences were statistically significant (P < 0.01). CONCLUSION: Elemene could inhibit the subcutaneous plantation of human laryngeal carcinoma in nude mice and its mechanism may be associated with inhibited expression of VEGF-C and VEGFR-3.

[Expressions of immunoglobulin E, interleukin-5 and granulocyte-macrophage colony-stimulation factor in nasal polyps tissue].

OBJECTIVE: The study was designed to examine the suggested roles of Immunoglobulin E (IgE), Interleukin-5 (IL-5) and Granulocyte-macrophage colony-stimulation factor (GM-CSF) in the pathogenesis of eosinophil accumulation in nasal polyps (NP) and to understand the correlations between IgE and IL-5/GM-CSF in NP. METHOD: Nasal polyps (n=31) and healthy nasal mucosa samples (n=11) were taken during routine endonasal surgeries. The tissue-bound IgE was measured with a sequential two-step immunoenzymatic (Sandwich) assay (Access immunoassay system, Beckman, USA). IL-5 and GM-CSF concentrations were measured with ELISA technique in homogenized polyp tissue and in control mucosa, and the number of eosinophils was counted in the corresponding tissue with hematoxylin eosin staining. RESULT: The level of tissue-bound IgE, IL-5 and GM-CSF was significantly higher in NP compared with control specimens (P<0.01). There was significant correlation between tissue IgE/IL-5/GM-CSF and the number of eosinophils in the NP group (r=0.73, 0.54, 0.48, P<0.01). The correlation between concentration of IgE and IL-5/GM-CSF was also significant in nasal polyp group (r=0.65, 0.42, P<0.01 and P<0.05). CONCLUSION: This study demonstrated that the tissue-bound IgE, IL-5 and GM-CSF played an important role in the recruitment of eosinophils in NP. A local upregulation of the IgE synthesis in comparison with control group suggests that the immunologic pathway or local allergy involved in the recruitment of eosinophils in NP. A local upregulation of the IgE may play an important role in the upregulation of IL-5 and GM-CSF in NP.