Engineered exosomes for targeted delivery of miR-187-3p suppress the viability of hemangioma stem cells by targeting Notch signaling.

Background: Infantile hemangioma (IH) is the most common benign vascular tumor of infancy and is proposed to arise from hemangioma stem cells (HemSCs). Therapies for IH include oral beta-blockers, surgery, and the delivery of novel therapeutic agents, such as bioactive microRNAs (miRNAs). However, in the extracellular environment, miRNA is easily hydrolyzed by RNase. miR-187-3p has previously been confirmed to promote or inhibit various malignancies, but its role in the development and progression of IH remains unclear. Methods: In this study, engineered exosomes (E-exos) were exploited to deliver miR-187-3p into HemSCs. The E-exos were generated by introducing miR-187-3p mimics into human adipose mesenchymal stem cell-derived exosomes (hAMSC-exos) via electroporation. The expression and secretion of miR-187-3p were examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Western blot analysis, transmission electron microscopy (TEM), and dynamic light scattering (DLS) were used to characterize the exosomes. The effects of the E-exos on HemSC viability were examined using the tube formation assay and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay. Western blot analysis was used to evaluate the effects of E-exos on Notch-1, Notch-4, and Jagged-1 expression in HemSCs. Results: E-exos did not differ significantly from hAMSC-exos in terms of morphology, particle size, or surface markers. E-exos could be internalized by HemSCs, and the course of cellular uptake of E-exos was time dependent. After 12 hours of treatment, E-exos significant inhibited tube formation. Notch signaling was also inhibited by miR-187-3p loading by E-exos. E-exos showed excellent inhibitory effects against HemSC proliferation via Notch signaling. Conclusions: This study provides a foundation for using hAMSC-exos to optimize current clinical options to facilitate IH treatment and deliver therapeutic agents in the future.

Exosome-derived miR-196b-5p facilitates intercellular interaction in infantile hemangioma via down-regulating CDKN1B.

BACKGROUND: Though infantile hemangioma (IH) is a common benign vascular tumor, its pathogenesis remains unclear. This study explored the function of hemangioma-derived stem cells (HemSCs) derived exosomes, which exerted an intercellular effect on hemangioma-derived endothelial cells (HemECs). METHODS: First, HemSCs and HemECs were extracted and cultured. HemSCs derived exosomes (HemSCs-exos) were harvested. miRNA sequencing and target prediction were used to explore differentially expressed miRNAs and potential binding targets. After HemECs were co-cultured with HemSCs-exos, a series of in vitro assays were then performed including cell counting kit-8 (CCK-8) assay, cell apoptosis assay, cell cycle assay and tube formation assay to evaluate proliferation, angiogenesis abilities, etc. qRT-PCR and Western blot were conducted to detect the expression level of target genes and proteins. RESULTS: After co-culturing with HemSCs-exos, proliferation, and angiogenesis abilities of HemECs were enhanced, while apoptosis and cell cycle arrest rate were decreased. MiR-196b-5p was observed to be significantly highly expressed in HemSCs-exos. CDKN1B was identified as the binding target of miR-196b-5p. HemECs' proliferation and angiogenesis abilities were elevated when co-cultured with exosomes from HemSCs transfected with miR-196b-5p mimic. In addition, apoptosis rate declined, and lower cells were arrested in G0/G1 phases. Cyclin E, bcl-2 were significantly highly expressed, whereas p27, Bax expression were significantly down-regulated. The positive effect of miR-196b-5p in HemSCs-exos was dramatically reversed when HemECs were transfected with oe-CDKN1B. CONCLUSIONS: The current study found a novel intercellular interaction between IH cells. Briefly, exosome-derived miRNA-196b-5p in HemSCs could facilitate proliferation and angiogenesis abilities, and attenuate apoptosis and cell cycle repression rate of HemECs by directly binding with CDKN1B.

Oral atenolol treatment for infantile hemangiomas: clinical analysis of 133 consecutive patients.

BACKGROUND: Infantile hemangiomas (IHs) are the most frequently occurring pediatric lesions. Oral propranolol has been shown to be safe and effective in infants with IHs. Side effects such as sleep disturbances have been associated with propranolol. Atenolol is a hydrophilic, selective ß1-blocker and therefore may be not associated with side effects attributable to ß2-adrenergic receptor blockade and lipophilicity. However, the efficacy of atenolol in the treatment of IHs is poorly understood. The aim of this study was to evaluate the efficacy of atenolol in the treatment of proliferating IHs in a clinical cohort including 133 consecutive patients. METHODS: In this study, we enrolled 133 patients diagnosed as proliferating IHs from the routine clinical and referral practices of the authors. The procedures followed were in accordance with the ethical standards of the Institute Review Board of Shanghai Ninth People's Hospital and Helsinki Declaration. Clinical characteristics, including demographic data and clinical morphology, were collated. Responses to oral atenolol therapy were graded as: excellent, good, fair and poor. According to the reaction to atenolol treatment, additional medications or therapy were used for IH patients to achieve satisfactory clinical results. RESULTS: In this study, 128 (96.2%) of 133 IH patients responded to oral atenolol, and the response rate (RR) was significantly different for different ages of patients (P<0.05), with the youngest patients having the highest RR. The mean time of treatment was 4.9 months. Forty-one patients who exhibited residual hyperpigmentation or telangiectasia were further treated with timolol maleate cream (n=32) or pulsed dye laser (n=9). All the 41 patients showed positive response. No life-threatening complications were noted during and after oral atenolol. Only 4 (3.0%) of 133 patients developed minor complications including diarrhea. No agitation and bronchospasm were noted in our study. CONCLUSIONS: This study demonstrated that atenolol was effective in the treatment of IHs. Compared to propranolol, atenolol seems to have a similar effect on IHs. Furthermore, atenolol seems to be less frequently associated with potentially life-threatening side effects.

A survey on the application of oral propranolol and atenolol for the management of infantile hemangiomas in mainland China: Survey on propranolol atenolol hemangiomas.

ABSTRACT: Since 2008, oral propranolol has evolved as the first-line therapy for infantile hemangiomas (IHs). Meanwhile, oral atenolol gradually shows comparative effectiveness versus oral propranolol with few side effects. Here, we conducted a mobile internal survey among a group of Chinese clinicians about how they choose the dosage, dose regimen, and dose escalation methods of propranolol and atenolol for the treatment of IH.A mobile-ready internal survey on the application of oral propranolol and oral atenolol for IH in mainland China was performed and distributed to 333 potential clinicians from different levels of healthcare institutions in mainland China. Eighty-one doctors responded to the survey. All the respondents had the experience of treating IH with oral propranolol and 32 had the experience with oral atenolol.Most of the doctors from tertiary hospitals chose 2 mg/kg/d twice daily, while most of those with the experience of propranolol from private hospitals chose 1 mg/kg/d once daily. More doctors from tertiary hospitals had the experience of atenolol than those from private hospitals.Oral atenolol has become another medication intervention option for IH in mainland China. This survey is helpful to standardize and develop a guideline of oral atenolol therapy for IH.

An experimental model of the epithelial to mesenchymal transition and pro-fibrogenesis in urothelial cells related to bladder pain syndrome/interstitial cystitis.

BACKGROUND: Suitable in vitro models are needed to investigate urothelial epithelial to mesenchymal transition (EMT) and pro-fibrogenesis phenotype in bladder pain syndrome/interstitial cystitis (BPS/IC). This study is to establish a novel experimental BPS/IC cell model and explore how different concentrations of tumor necrosis factor (TNF)-α influence the EMT and pro-fibrogenesis phenotype of urothelial cells. METHODS: SV-HUC-1 urothelial cells were cultured with 2, 10, or 50 ng/mL TNF-α to mimic chronic inflammatory stimulation. The EMT and pro-fibrogenesis phenotype, including production of collagen I and pro-fibrosis cytokines, were estimated after 72 h of culture. RESULTS: The bladder urothelial cells of BPS/IC exhibited upregulated vimentin, TNF-α and TNF receptor, downregulated E-cadherin, and increased collagen I. Higher concentrations of TNF-α (10 and 50 ng/mL) produced an obvious mesenchymal morphology, enhanced invasion and migratory capacity, increased expression of vimentin, and decreased expression of E-cadherin. Collagen I was increased in cells treated with 2 and 10 ng/mL TNF-α after 72 h. Secretion of interleukin (IL)-6 and IL-8 was promoted with 10 and 50 ng/mL TNF-α, while that of IL-1ß or transforming growth factor-ß was unaffected. Slug and Smad2 were upregulated by TNF-α after 72 h. The Smad pathway was activated most strongly with 10 ng/mL TNF-α and Slug pathway activation was positively correlated with the concentration of TNF-α. CONCLUSIONS: Sustained 10 ng/mL TNF-α stimulation induced the EMT and pro-fibrogenesis phenotype resembling BPS/IC in SV-HUC-1 cells. Minor inflammatory stimulation induced the pro-fibrogenesis phenotype while severe inflammatory stimulation was more likely to produce significant EMT changes. Different degrees of activation of the Slug and Smad pathways may underlie this phenomenon.

[Progress on medication-related osteonecrosis of the jaw].

Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication of bisphosphonates (BPs) or other targeted agent therapies. MRONJ appears as exposed bone, pus, and swelling in the oral and maxillofacial regions. However, neither surgery nor conservative therapy can eliminate symptoms thoroughly. In addition to BPs, several antiresorptive and antiangiogenic agents, such as denosumab and bevacizumab, as well as targeted agents, such as sunitinib and temsirolimus, can cause osteonecrosis of  the  jaw according to the literature. This review aims to summarize the research progress on these new drugs.

Early neurological deterioration in acute ischemic stroke: A propensity score analysis.

BACKGROUND: To investigate whether endovascular therapy (EVT) was one of the factors influencing the incidence of early neurological deterioration (END) in patients with acute ischemic stroke (AIS) as compared with intravenous thrombolysis alone. METHODS: This study was based on our single-center's database that included information on stroke patients hospitalised between January 2012 and September 2015. A total of 220 patients who underwent EVT after IV rt-PA, EVT or IV rt-PA alone. To reduce the lack of randomization, we conducted a propensity score analysis using the SPSS custom dialog. After matching was completed, the 2 groups (with END versus non-END) were compared between matched groups. Variables with a p value ≤ 0.1 by univariate analysis were candidates for inclusion in logistic regression analysis. RESULTS: Of 220 acute ischemic strokes attended, 213 patients were included (62.0%, 23.0% and 15.0% with circulation occlusion in the anterior, posterior and both branches, respectively). END was detected in 68 patients (31.9%). Multivariable analysis showed that END was positively associated with glucose level (OR, 1.40; 95%CI, 1.10-1.79; p = 0.007), uric acid level (OR, 1.01; 95% CI, 1.00-1.02; p = 0.026) and treatment methods (EVT: OR, 3.87; 95% CI, 1.32-11.35; p = 0.014). However, there was significant difference in baseline data (NIHSS and INR) between EVT group and non-EVT group. CONCLUSION: Our findings suggest that hyperglycemia, hyperuricemia and EVT may be independently associated with END in AIS, even after controlling for possible confound factors. Further studies are warranted to confirm these results.

[Risk factors for recurrence of large atherosclerotic cerebral infarction].

OBJECTIVE: To explore the risk factors for recurrence of large atherosclerotic cerebral infarction in first?episode patients. METHODS: The consecutive patients with acute cerebral infarction diagnosed in the Department of Neurology were screened for large atherosclerotic cerebral infarction by CTA/MRA examination, and all the confirmed patients were followed up for 1 year. The patients were divided into recurrent ischemic stroke group and non?recurrent group according to occurrence of cerebrovascular events during the follow?up. RESULTS: A total of 256 eligible patients were included in this study, and all of them completed the follow?up. During the 1?year follow?up, 30 (11.7%) patients had ischemic cerebrovascular stroke events. Univariate analysis showed significant differences in alcohol drinking (P=0.028), smoking (P=0.007), high?density lipoprotein cholesterol (HDL; P=0.045), ischemic heart disease (P=0.002), antihypertensive agents (P=0.036) and statin use (P=0.016) between the recurrent group and non?recurrent group. Cox regression analysis showed that irregular use of statins (RR=0.410, P=0.043), smoking (RR=2.253, P=0.043), HDL (RR=0.327, P=0.029), and ischemic heart disease (RR=8.566, P<0.001) were correlated with recurrent ischemic stroke. CONCLUSION: The first?episode patients with irregular use of statins, low HDL levels, smoking and ischemic heart disease are at higher risks for having ischemic stroke recurrence.

Therapeutic effect of carotid artery stenting versus endarterectomy for patients with high-risk carotid stenosis.

OBJECTIVE: To investigate therapeutic effect of carotid artery stenting versus endarterectomy for patients with high-risk carotid stenosis. METHODS: A total of 130 carotid stenosis patients at high-risk of stroke were randomly divided into stenting group and endarterectomy group, including 65 patients in each group. The patients in the endarterectomy group underwent endarterectomy and those in the stenting group received carotid artery stenting for treatment. RESULTS: After operation, carotid intima-media thickness (IMT), plague areas and carotid artery resistance indexes in both groups decreased significantly, and the carotid artery peak blood flow velocities increased significantly and had significant differences with that before operation (P < 0.05). After operation, total cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL) values in two groups all significantly decreased, and intragroup and intergroup differences were statistically significant (P < 0.05). Postoperative three months of followed-up found that the mortality rate in stenting group was 1.5% and that in the endarterectomy group was 9.2%; the mortality rate in the stenting group was significantly lower than the endarterectomy group (P < 0.05). CONCLUSION: Compared with carotid endarterectomy, application of carotid artery stenting can effectively promote patency of blood flow in the carotid artery, and exertion of its effect is related to lowering lipid and lowering inflammatory factor expression.

[Plasma homocysteine levels in ischemic stroke patients with obstructive sleep apnea].

OBJECTIVE: To investigate the association of plasma homocysteine and OSA (obstructive sleep apnea) syndrome in ischemic stroke (IS). METHODS: A total of 92 male IS patients were classified by apnea hypopnea index (AHI) into 2 groups: non-OSA group (AHI < 5/h) and OSA group (AHI > or = 5). All patients were tested for plasma homocysteine when polysomnography was finished at (14 +/- 2) d after the onset of IS. RESULTS: The mean level of homocysteine was significantly higher in the OSA group than that in the non-OSA group (17 +/- 5 vs 11 +/- 3 micromol/L, P < 0.01). Pearson correlation analysis revealed a positive correlation between the homocysteine level and the severity of AHI (r = 0.482, P < 0.01). Further multiple linear regression analysis showed that AHI and folate were independent predictors of homocysteine level (R2 = 0.553, P < 0.01, beta for AHI = 0.671, beta for folate = -0.256). CONCLUSION: The severity of OSA is significantly associated with an elevated level of homocysteine in IS patients. And this association is independent of other causative factors of an elevated level of homocysteine.

[Antireflux anastomosis following resection of esophageal cancer].

OBJECTIVE: To investigate the antireflux effects of a modified Nissen fundoplication following esophagectomy for cancer. METHODS: From March 2006 to March 2007, 70 patients with esophageal cancer were divided into two groups randomly. Esophagogastrostomy with a stapler only was perform in 35 patients as controls (group C), and a modified Nissen fundoplication was added after esophagogastrostomy with stapler in the other 35 patients as observed group (group O). There were 48 male and 22 female, ranging in age from 47 to 77 years (mean 60.1 years). The operative morbidity and mortality were recorded. Fourty-nine patients were followed at 3 months after surgery, and the questionnaire of life quality (EORTC QLQ C-30) was conducted in 24 patients in group C and 25 patients in group O. Thirty patients were examined with esophageal manometry, 24 h pH monitoring and gastroscopy. There were 16 patients in group C and 14 patients in group O. RESULTS: There was no significant difference in postoperative morbidity between the two groups (P > 0.05). However, the scores of heart burn and regurgitation in the group O were less than in group C (P = 0.041 and 0.034 respectively), but there was no difference in scores of dysphagia between the two groups (P = 0.677). The pressure at the anastomotic site was higher than that in the stomach in group O (P = 0.032), but not in group C (P = 0.448). DeMeester score in group O was 53 ± 46, compared to 140 ± 103 in group C (P = 0.043). The score of esophagitis was 0.9 ± 0.8 in group O, which was lower than 1.6 ± 1.0 in group C (P = 0.041). CONCLUSIONS: Addition of modified Nissen fundoplication after esophagectomy and esophagogastrostomy for cancer significantly increases the pressure at the anastomotic site, thus reduces the extent of gastroesophageal reflux, which leads to the reduction of the extent of reflux esophagitis and the improvement of the quality of life.

Biochemical pathways in the antiatherosclerotic effect of berberine.

BACKGROUND: This study investigated the inhibitory effect of berberine (BBR) on lipopolysaccharide (LPS) induced cyclooxygenase-2 (COX-2) expression via the mitogen activated protein kinase (MAPK) signalling cascade pathways in human peripheral blood monocytes (PBMC). METHODS: PBMC from whole blood were isolated and cultured for up to 24 hours after division into 5 groups treated with LPS, LPS + BBR 25 micromol/L, LPS + BBR 50 micromol/L or LPS + BBR 100 micromol/L and untreated. Monocytes were extracted for RT-PCR and Western blot analyses to examine COX-2 mRNA and protein activated expression of p38 mitogen activated protein kinase (p38MAPK), Jun N-terminal kinase (JNK) and extracellular regulated kinases 1/2 (ERK1/2) signalling pathways. RESULTS: COX-2 mRNA and protein expression decreased to a minimum at 12 hours after BBR treatment (P < 0.05). With the increasing concentration of BBR treatment, the COX-2 expression decreased progressively (P < 0.01). With BBR treatment for 6, 12 or 24 hours at three doses, ERK1/2 protein expression was significantly inhibited. For the JNK pathway, only with the treatment of BBR at the concentration of 100 micromol/L was JNK protein expression inhibited compared with the LPS stimulation group (P < 0.01). Irrespective of the BBR concentration, no difference was shown between the BBR group and the LPS group for p38MAPK protein expression. Human monocytes COX-2 mRNA, by RT-PCR, and protein expression, by Western blot analysis, were inhibited when incubated with PD98059, SP600125 and SB203580 (P < 0.05). CONCLUSIONS: Berberine inhibits COX-2 expression via the ERK1/2 signalling pathway and, possibly, at a high dosage via the JNK pathway. P38MAPK may have no relationship with the effect of BBR in PBMC. Berberine inhibited COX-2 mRNA and protein expression in a dose dependent manner and suppressed COX-2 expression to a minimal level after 12 hours of berberine treatment.

Responses of human sling and clasp fibers to cholecystokinin (CCK) and gastrin through CCK receptors.

BACKGROUND AND AIM: Cholecystokinin (CCK) and gastrin exert their influences via CCK receptors. This research was conducted to look at the responses of the sling and clasp fibers forming the human lower esophageal sphincter (LES) to CCK and gastrin, and the role of CCK receptors in the responses. METHODS: Muscle strips of sling and clasp fibers from the LES were obtained from patients undergoing subtotal esophagectomy. Isometric tension responses of the strips to CCK-8 and gastrin-17 were studied, and the maximum effect (E(max)) for each agonist was derived. CCK-A receptor antagonist, CR1409 and CCK-B antagonist, CR2945 were applied to sling and clasp fibers and their pK(B) values were calculated. RESULTS: Sling fibers produced significant contractions following exposure to CCK-8 and gastrin-17, while clasp fibers had less responses to the two agents. CR1409 and CR2945 inhibited responses of sling to CCK-8 in a concentration-dependent fashion. The inhibition effects of the two antagonists on clasp fibers were not measurable because there was a mild contraction of the fiber in response to CCK-8. CONCLUSION: The contractions generated by sling fibers following exposure to CCK and gastrin are greater than that produced by clasp fibers. CCK-A receptors are more important for the generation of contractions by the sling fibers, whereas both CCK-A and CCK-B receptors are involved in the functional regulation of the clasp fibers. [Corrections added after online publication 28 April 2008: in the Background and Aims section of the preceding abstract, all instances of 'CKK' were corrected to 'CCK'. In the final sentence of the abstract 'CCKA'was corrected to 'CCK-A'. In the article title '(CKK)' was corrected to '(CCK)'.].

Effects of aspirin on atherosclerosis and the cyclooxygenase-2 expression in atherosclerotic rabbits.

BACKGROUND: Atherosclerosis is a complex vascular inflammatory disease. Aspirin is a mainstay in the prevention of vascular complications of atherosclerosis. In this study, the effectiveness of aspirin in suppressing atherosclerosis and the inflammation process was evaluated in rabbits fed with a high fat diet. METHODS: Eighteen male New Zealand rabbits were randomly divided into 3 groups: control group, untreated cholesterol-fed group, aspirin treated cholesterol-fed group, which were fed for 12 weeks. After 12 weeks, the aorta was harvested for pathologic morphology observation. Immunohistochemical analysis of cyclooxygenase-2 (COX-2), macrophage and vascular smooth muscle cell (VSMC) was performed. The statistical analysis was performed by the statistical program SPSS10.0. RESULTS: The aorta plaque/intima size (P/I) by pathologic morphology observation was 0%, (59.6 +/- 13.7)% and (36.3 +/- 16.5)% in the control, untreated cholesterol-fed group and aspirin treated group, respectively. The maximum plaque thickness, the degree of artery stenosis and the proportion of the intimal circumference occupied by atheroma of the 3 groups were significantly different from each other (P < 0.01). The expression of COX-2 and macrophage in plaque of the aspirin treated group were decreased compared with that in untreated cholesterol-fed group. However, no difference was found in the expression of VSMC between the aspirin treated and the untreated cholesterol-fed group. CONCLUSION: The mechanism of atherosclerosis suppression by aspirin in cholesterol-fed rabbits is related to the inhibition of COX-2 expression together with the reduced inflammation followed by, but not related to the hypolipidemic effects.

[Mechanism of relaxation mediated by nitric oxide on human lower esophageal sphincter].

OBJECTIVE: To explore the mechanism of relaxation mediated by nitric oxide on the human lower esophageal sphincter (LES), and compare the difference in relaxation response between clasp fibers and sling fibers. METHODS: 32 LES specimens were obtained from 32 patients with high-positioned carcinoma of the mid-esophagus, 12 males and 16 females, aged 55.9 +/- 9.3, during operation. The clasp fibers and sling fibers were isolated and suspended in perfusion tough. Electric field stimulation (EFS) was applied to the clasp and sling fibers in vitro. Nitric oxide synthase (NOS) inhibitor L-NNA, NOS substrate L-arginine, neurotoxin tetrodotoxin (TTX), and atropine were added respectively to observe their effects on the clasp and sling fibers under EFS. Sodium nitroprusside was added on the two kinds of smooth muscle stripes to observe its influence as well. RESULTS: EFS induced frequency-dependent relaxation to clasp fibers and some of sling fibers, which was inhibited by L-NNA in a concentration-dependent manner and was reversed by L-arginine partially. Maximal relaxation in clasp fibers and sling fibers was observed at 512 Hz and 16 Hz respectively. The higher amplitude relaxation was induced in the sling fibers at lower stimulus frequencies (< 32 Hz). Conversely, the same response was induced in the clasp fibers at higher stimulus frequencies (> 64 Hz). Meanwhile, off-contraction was induced by EFS in some sling fibers and clasp fibers. In some sling fibers, contraction was induced by EFS which was inhibited by atropine. Maximal contraction in these fibers was observed at 128 Hz. TTX abolished the effect of EFS on both clasp and sling fibers, which was considered neurogenic. Sodium nitroprusside elicited the similar response to EFS. CONCLUSIONS: Relaxation of clasp and sling fibers is related to L-NNA, TTX, and sodium nitroprusside, and can be mediated by nitric oxide. Lower stimulus frequencies induce higher amplitude relaxation to sling fibers, and conversely, higher stimulus frequencies induce higher amplitude relaxation to clasp fibers. EFS induces contraction response in some sling fibers.

[Long-term outcome of antireflux surgery for gastroesophageal reflux disease].

OBJECTIVE: To investigate the long-term outcomes of various antireflux procedures for gastroesophageal reflux disease (GERD). METHODS: Between November 1988 and January 2004, 129 patients with GERD underwent antireflux procedures. Six kinds of antireflux procedures were performed including Nissen fundoplication, cardiac oblique invagination (COI) procedure, Belsey Mark IV, Toupet, Thal and Dor procedures. One hundred and sixteen patients were followed up. Esophageal manometry study was carried out in 95 patients preoperatively and 51 postoperatively. 24-hour esophageal pH monitoring were carried out in 56 patients preoperatively and 35 postoperatively. Esophagoscopy were performed in all patients before operation and 48 cases after operation. RESULTS: Clinical symptom scores reduced significantly from 4.1 +/- 0.4 before surgery to 1.1 +/- 1.0 after surgery (t = 27.21, P < 0.01). The outcome of surgery showed excellent in 42 cases (36.2%), good in 60 (51.7%), fair in 7 (6.0%), poor in 7 (6.0%). The long-term follow-up showed excellent or good results in 87.9% of patients. There was no significant difference in Nissen fundoplication, COI procedure and Belsey Mark IV. CONCLUSIONS: There are significant differences in symptom score, esophageal manometry, 24-hour esophageal pH monitoring and esophagoscopy pre- and post-operatively. There is no significant difference in Nissen fundoplication, COI procedure and Belsey Mark IV.

Meta-analysis of defibrase in treatment of acute cerebral infarction.

BACKGROUND: Fibrinogen-depleting agents are promising in the treatment of cerebral ischemic disease. They were studied by many trials, and the outcomes were different because of different regimens and different doses. In this study, we assessed the efficacy and safety of defibrase on acute cerebral infarction in China. METHODS: A search using Chinese hospital knowledge database (CHKD) and MEDLINE database for randomized controlled trials was carried out. A CHKD (1994 June 2005) search was performed with the keyword "defibrase", then a second search for the keyword "acute cerebral infarction"; a MEDLINE search (1950 June 2005) was performed with the following keywords: [(cerebral ischemia), OR (acute cerebral infarction), OR (stroke)], AND [defibrase]. Meta-analysis was performed with RevMan software 4.2. RESULTS: Included were 14 studies comparing the efficiency and safety of defibrase with other drugs in the treatment of acute cerebral infarction. Patients' records were pooled (total 646 patients; defibrase, n = 328, no defibrase n = 318). Neurological deficit score (NDS) before treatment showed weighted mean differences (WMD) = 0.95, 95% confidence interval (CI) = (-0.60, 2.50), P = 0.23; NDS after treatment showed WMD = -2.20, 95% CI = (-4.21, -0.18), P = 0.03; Barthel index at 3 months showed WMD = 4.45, 95% CI = (-0.13, 9.03), P = 0.06; the plasma fibrinogen level before treatment showed WMD = 0.02, 95% CI = (-0.16, 0.19), P = 0.86; plasma fibrinogen level after treatment showed WMD = -1.51, 95% CI = (-1.88, -1.15), P < 0.00 001. CONCLUSIONS: With the given dose and regimen of defibrase in China, defibrase may play a role of anticoagulation. It might inhibit the progression of stroke and prevent the recurrence of stroke.

[Functional study of the remnant esophagus and intrathoracic stomach in patients who underwent esophagectomy for cancer].

OBJECTIVE: To investigate pathophysiological changes of the remnant esophagus and gastric cardia in patients who underwent esophagectomy for cancer, and to provide objective evidences for the improvement of the postoperative quality of life. METHODS: The function of the remnant esophagus and intrathoracic stomach in patients who underwent esophagectomy for cancer were assessed objectively. The methods that we used were gastric scintigraphy, esophageal manometry, 24-hour esophageal pH monitoring, electronic gastroscopy, videofluoroscopy, and DeMeester scoring system for the assessment of heartburn. Findings were recorded and compared with normal controls. RESULTS: After esophagectomy for cancer, the emptying of intrathoracic stomach was delayed (t = 7.105, P < 0.01) and improved over time, but could not reach normal one year after surgery (t = 2.9, P = 0.016). In patients who had undergone esophagectomy for cancer, the contracting pressure of the upper esophageal sphincter and resting pressure of the remnant esophagus were higher than that in normal controls (t = 2.275, P = 0.03; t = 2.16, P = 0.039 respectively). 89.7% of patients who had undergone esophagectomy had gastroesophageal reflux measured with 24-hour pH monitoring. The extent of reflux was less severe when patients were in a semi-reclining position than in a prostration position (t = 3.074, P = 0.005). CONCLUSION: After esophagectomy for cancer, delayed emptying of the intrathoracic stomach is improved gradually over time, but it is inaccessible to normal level. Gastroesophageal reflux extensively exists in patients who underwent esophagectomy for cancer, but it can be lessened by taking semi-reclining position.

Aspirin induces apoptosis in oesophageal cancer cells by inhibiting the pathway of NF-kappaB downstream regulation of cyclooxygenase-2.

BACKGROUND: Aspirin has potential in the prevention or treatment of oesophageal cancer, the seventh most common cancer in the world, but its mechanism of action is still not certain. METHODS: The oesophageal squamous cell carcinoma cell line TE-13 was cultured with aspirin at different concentrations or for different times. Proliferation and apoptosis were measured by MTT reduction and flow cytometry. Expression of COX-2 mRNA was measured by RT-PCR and COX-2 protein levels with Western blot analysis. Nuclear NF-kappaB and cytoplasmic IkappaB protein levels were determined by electrophoretic mobility shift assay and Western blot, respectively. RESULTS: Aspirin significantly inhibited cell proliferation and induced apoptosis at concentrations of 1, 4, 8 mmol/L. Aspirin dose-dependently decreased the levels of COX-2 mRNA, COX-2 protein and nuclear NF-kappaB protein and increased the cytoplasmic IkappaB protein. CONCLUSION: We conclude that aspirin inhibits the proliferation of, and induced apoptosis in, the cultured TE-13 SCC cell line. These changes correlate with a reduction in COX-2 mRNA and protein expression, prostaglandin synthesis, an inhibition of NF-kappaB nuclear translocation, and an increase in cytoplasmic IkappaB. These results support the further investigation of the cyclooxygenase pathway in investigating the potential of aspirin and similar drugs in cancer prevention and therapy.