[Comparison of ultrathin bronchoscopy with conventional bronchoscopy for the diagnostic value of peripheral pulmonary lesions].

Objective: To assess and compare the diagnostic efficacy of next-generation ultrathin bronchoscopy (UTB) and conventional bronchoscopy (CB), both combined with radial endobronchial ultrasound (r-EBUS), in the evaluation of peripheral pulmonary lesions (PPL). Methods: A cohort of 39 patients with PPL who underwent multimodal bronchoscopy at Dushu Lake Hospital, Soochow University, from June 1, 2021 to May 31, 2023 was consecutively enrolled. A single bronchoscopist performed multimodal bronchoscopies using CB (external diameter 4.9 mm or 5.9 mm, working channel diameter 2 or 3 mm, CB group) for transbronchial biopsy under r-EBUS guidance (rEBUS-TBLB), followed by UTB (external diameter 3 mm, working channel diameter 1.7 mm, UTB group) for transbronchial biopsy under r-EBUS guidance. Pathological findings and a 6-month clinical follow-up were used as the gold standard to compare the diagnostic yield of biopsy specimens, ultrasound characteristics, and localization rates of the two bronchoscope types. The aim was to evaluate the clinical application value of UTB combined with r-EBUS. Binary variables were analysed using the McNemar test for paired data. Continuous variables or ranked data were analysed using the Wilcoxon signed-rank test for paired data. Results: The diagnostic yields for UTB and CB groups were 66.67% (26/39) and 30.77% (12/39), respectively, with the UTB group significantly surpassing the CB group (χ2=10.56, P=0.001, 1-ß=0.968). r-EBUS with CB exhibited no visible lesion in 13 cases, adjacent to the lesion in 19 cases, and within the lesion in 7 cases.Substitution of UTB resulted in r-EBUS images changing from no visible lesion to adjacent to the lesion in 7 cases, from no visible lesion to within the lesion in 3 cases, and from adjacent to the lesion to within the lesion in 12 cases. The positioning of the r-EBUS probe in relation to the lesions improved significantly with UTB usage (Z=-4.46, P<0.001). Localization rates (number of patients with "within" or "adjacent to" the image/total number of patients) for UTB and CB were 92.30% (36/39) and 66.67% (26/39), respectively (χ2=8.10, P=0.002). UTB improved r-EBUS probe localization rates. The diagnostic yields of UTB were higher than CB for solid lesions, lesions>30 mm in diameter, non-upper lobar location, benign or malignant lesions and lesions with or without a bronchus sign. Conclusion: The UTB group demonstrated a significantly higher diagnostic yield than the CB group, providing superior r-EBUS probe images, and a significant diagnostic advantage for PPL.

Effects of dezocine combined with dexmedetomidine on adverse reactions and inflammatory factors in patients undergoing HIPEC after intestinal surgery and its protective effect on the heart in the perioperative period.

OBJECTIVE: The aim of this study was to explore the effects of dezocine combined with dexmedetomidine on adverse reactions and inflammatory factors in patients undergoing hyperthermic intraperitoneal chemotherapy (HIPEC) after intestinal surgery and its protective effect on the heart in the perioperative period. PATIENTS AND METHODS: A total of 80 patients treated with HIPEC after intestinal surgery in our hospital from September 2018 to December 2019 were enrolled as research subjects. All patients were evenly divided into two groups using a random number table. As to analgesia and sedation during treatment, dezocine was injected intramuscularly at 30 min before treatment in the control group. Meanwhile, dezocine combined with dexmedetomidine was given in the same way in the observation group. Adverse reactions and changes in numeric rating scale (NRS) pain score during intervention were compared between the two groups. The changes in the levels of inflammatory and myocardial injury-related factors, and vascular endothelial function and regeneration ability among cardiovascular indicators at 12 h after intervention were compared as well. Additionally, the correlations of left ventricular mass index (LVMI) with the changes in the levels of inflammatory factor high-sensitivity C-reactive protein (hs-CRP), myocardial injury-related factor lactic dehydrogenase (LDH), vascular endothelial function indicator endothelin-1 (ET-1) and cardiovascular regeneration ability index vascular endothelial growth factor (VEGF) were analyzed. RESULTS: Compared with control group, the total prevalence rate of severe pain, respiratory depression, nausea and vomiting, diarrhea, and muscle rigidity during intervention was significantly reduced in the observation group (p<0.05). NRS pain score at 1, 4, 8 and 12 h after intervention decreased remarkably in the observation group compared with the control group (p<0.05). Meanwhile, the levels of inflammatory factors tumor necrosis factor-α (TNF-α) and hs-CRP, and myocardial injury-related factors LDH and creatine kinase MB (CKMB) as well as ET-1 at 12 h after intervention declined remarkably in observation group compared with control group (p<0.05). However, the levels of nitric oxide (NO), VEGF and basic fibroblast growth factor (bFGF) rose significantly in the observation group (p<0.05). Besides, LVMI was positively correlated with hs-CRP and LDH, whereas was negatively associated with ET-1 and VEGF (p<0.05). CONCLUSIONS: In HIPEC, dezocine combined with dexmedetomidine used for sedation and analgesia is able to effectively reduce adverse reactions and relieve inflammatory responses in vivo, exerting a cardio-protective effect.

[Diagnosis and treatment status of perioperative anemia in patients with gastrointestinal neoplasms: a multi-center study in Hubei Province].

Objective: To investigate the incidence and treatment of perioperative anemia in patients with gastrointestinal neoplasms in Hubei Province. Methods: The clinicopathological data of 7 474 patients with gastrointestinal neoplasms in 62 hospitals in 15 cities (state) of Hubei Province in 2019 were collected in the form of network database. There were 4 749 males and 2 725 females. The median age of the patients was 62 years (range: 17 to 96 years). The hemoglobin value of the first time in hospital and the first day after operation was used as the criterion of preoperative anemia and postoperative anemia. Anemia was defined as male hemoglobin <120 g/L and female hemoglobin <110.0 g/L, mild anemia as 90 to normal, moderate anemia as 60 to <90 g/L, severe anemia as <60 g/L. The t test and χ2 test were used for inter-group comparison. Results: The overall incidence of preoperative anemia was 38.60%(2 885/7 474), and the incidences of mild anemia, moderate anemia and severe anemia were 25.09%(1 875/7 474), 11.37%(850/7 474) and 2.14%(160/7 474), respectively. The overall incidence of postoperative anemia was 61.40%(4 589/7 474). The incidence of mild anemia, moderate anemia and severe anemia were 48.73%(3 642/7 474), 12.20%(912/7 474) and 0.47%(35/7 474), respectively. The proportion of preoperative anemia patients receiving treatment was 26.86% (775/2 885), and the proportion of postoperative anemia patients receiving treatment was 14.93% (685/4 589). The proportions of preoperative anemia patients in grade ⅢA, grade ⅢB, and grade ⅡA hospitals receiving treatment were 26.12% (649/2 485), 32.32% (85/263), and 29.93% (41/137), and the proportions of postoperative anemia patients receiving treatment were 14.61% (592/4 052), 22.05% (73/331), and 9.71% (20/206). The proportion of intraoperative blood transfusion (16.74% (483/2 885) vs. 3.05% (140/4 589), χ²=434.555, P<0.01) and the incidence of postoperative complications (17.78% (513/2 885) vs. 14.08% (646/4 589), χ²=18.553, P<0.01) in the preoperative anemia group were higher than those in the non-anemia group, and the postoperative hospital stay in the preoperative anemia group was longer than that in the non-anemia group ((14.1±7.3) days vs. (13.3±6.2) days, t=5.202, P<0.01). Conclusions: The incidence of perioperative anemia in patients with gastrointestinal neoplasms is high. Preoperative anemia can increase the demand for intraoperative blood transfusion and affect the short-term prognosis of patients. At present, the concept of standardized treatment of perioperative anemia among gastrointestinal surgeons in Hubei Province needs to be improved.

[The application status of optimal medical therapy after percutaneous coronary intervention and its influence on prognosis].

Objective: To investigate the application status of optimal medical therapy (OMT) in patients with coronary heart disease after percutaneous coronary intervention (PCI) and its influence on the 1-year prognosis of patients after surgery. Methods: Data of 3 812 patients diagnosed with coronary heart disease by coronary angiography and successfully completed PCI in the Department of Cardiology, TEDA International Cardiovascular Hospital from October 2016 to September 2017 were prospectively collected. The OMT status and the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) during the hospitalization and 1, 6, and 12 months after discharge were recorded. Patients were divided into OMT group (n=1 299) and non-OMT group (n=2 289) according to their adherence to OMT after PCI. Chi-square test was used to compare the differences of MACCE between groups, and to screen for significant differences and clinically significant variables between groups. Cox regression model was used to analyze the influencing factors of MACCE after PCI. Results: Among 3 588 patients (224 cases lost to follow-up), 58.8% (2 110/3 588) used OMT during hospitalization after PCI, and 36.0% (1 293/3 588) still adhered to OMT after 12 months of follow-up. The utilization rates of OMT showed a decreasing trend, among which till the 12th month, ß-blockers and ACEI/ARB showed the greatest decreasing degree, from 75.3%(2 701/3 588) and 75.1%(2 692/3 588) to 59.1%(2 122/3 588) and 53.0%(1 903/3 588). Pearson χ2 analysis showed that elderly patients, the number of amalgamative diseases, history of PCI, history of chronic myocardial infarction, history of chronic renal insufficiency, the lesion counts, lesion type, the Gensini score, adhere to the OMT and smoking during the follow-up were related to postoperative MACCE, the difference was statistically significant (P<0.05). Cox regression model showed that OMT adherence after PCI was an independent protective factor for postoperative MACCE events (HR=0.471,95%CI: 0.300-0.734, P=0.001). Conclusion: The application of OMT after PCI was suboptimal, and the application rate decreased with the lengthening of the discharge time, among which the use of ACEI/ARB and ß-blockers deserved more attention. Adherence to OMT after PCI was an independent protective factor, which could reduce the incidence of postoperative MACCE and improve the prognosis of patients.

Effect of ulinastatin on myocardial ischemia-reperfusion injury through JNK and P38 MAPK signaling pathways.

OBJECTIVE: The aim of this study was to investigate the effect of ulinastatin (UTI) on myocardial ischemia-reperfusion injury (MIRI) through the c-Jun N-terminal kinase (JNK) signaling pathway and p38 mitogen-activated protein kinase (MAPK) signaling pathway. MATERIALS AND METHODS: Healthy adult male Sprague-Dawley (SD) rats were randomly divided into 5 groups, including the sham group (n=10), MIRI group (model group, n=10), UTI group (n=10), UTI + JNK inhibitor SP600125 (UTI+SP600125 group, n=10) and UTI + p38 MAPK inhibitor SB203580 (UTI+SB203580 group, n=10). Hemodynamics, myocardial infarction and the messenger ribonucleic acid (mRNA) expressions of p38 MAPK, JNK, superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP) were compared among groups. The protein levels of p38 MAPK and JNK in serum were detected via Western blotting. Furthermore, the correlations of serum p38 MAPK and JNK with TNF-α were analyzed. RESULTS: In the UTI group, the left ventricular systolic pressure (LVSP), the left ventricular end-diastolic pressure (LVEDP) and maximal rate of increase of the left ventricular pressure (+dp/dtmax) were significantly higher than those of the model group. However, the maximal rate of the decrease of the left ventricular pressure (-dp/dtmax), infarction area and ischemia area were significantly smaller than those of the model group. LVSP, LVEDP and +dp/dtmax in UTI+SP600125 group and UTI+SB203580 group were markedly higher than those of the UTI group. Meanwhile, the mRNA expressions of p38 MAPK and JNK in the UTI group were significantly lower than those of the model group. However, the mRNA expression levels of p38 MAPK and JNK in UTI+SP600125 group and UTI+SB203580 group were remarkably higher than the UTI group. Besides, the UTI group showed a markedly higher level of SOD and significantly lower levels of MDA, NO, TNF-α, IL-6 and hs-CRP than the model group. Furthermore, UTI+SP600125 group and UTI+SB203580 group showed significantly higher levels of MDA, NO, TNF-α, IL-6 and hs-CRP than the UTI group. The protein levels p38 MAPK and JNK were remarkably lower in the UTI group than those of the model group. However, they were remarkably higher in UTI+SP600125 group and UTI+SB203580 group than the UTI group. In addition, both p38 MAPK and JNK proteins were positively correlated with TNF-α (r=0.983 and 0.892, p=0.043 and p=0.033). CONCLUSIONS: UTI may inhibit MIRI caused by p38 MAPK signaling pathway and JNK signaling pathway by down-regulating TNF-α expression, thereby protecting and improving MIR.

[Factor analysis of diagnosis and surgical treatment of local regional recurrence in breast cancer patients].

Objective: To analyze the association between clinicopathological factors and clinical diagnosis, treatment and surgery of local regional recurrence (LRR) in breast cancer. Methods: A retrospective study was done to evaluate consecutive 7 823 breast cancer LRR cases between January 2009 and August 2018 at Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine. A total of 108 LRR patients were enrolled: 35 cases (32.4%) with ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery, 40 cases (37.0%) of chest wall recurrence (CR), and 33 cases (30.6%) with regional lymph node recurrence (LNR). All patients were female, aged from 26 to 83 years with a mean of 49 years. Clinicopathological factor and its relationship with different sites of LRR and following surgical choice were analyzed by χ(2) test, rank-sum test and Logistic regression. Survival analysis were performed between different LRR patterns and whether undergoing second surgery. Kaplan-Meier survival curves and Log-rank tests demonstrated the distribution of overall survival. Results: Both univariate analysis and multivariate analysis found that axillary lymph nodes (ALN) status (OR=7.27, 95% CI: 1.30 to 40.53, P=0.042) and disease-free interval (OR=0.18, 95% CI: 0.06 to 0.60, P=0.013) were related to different site of LRR. Compared with patients with IBTR, LNR and CR patients had a higher rate of ALN metastasis and a shorter disease-free interval. A total of 36 LRR patients underwent following surgery. In univariate analysis, initial ALN surgery (χ(2)=16.705, P=0.001), pathological type (χ(2)=7.047, P=0.03), ALN status (χ(2)=10.812, P=0.002), disease-free interval (χ(2)=6.118, P=0.023) and LRR site(χ(2)=19.328, P=0.000) were associated with surgical treatment for LRR patients. Multivariate analysis demonstrated that only site of LRR was independently associated with surgery (OR=0.17, 95% CI: 0.05 to 0.65, P=0.024). The 5-year overall survival was 100% and 60.1% (P=0.018) for LRR patients treated with surgery or not. Furthermore, CR patients had significantly worse overall survival than LNR and IBTR patients, with 5-year overall survival 53.1%, 73.5%, and 100% respectively (P=0.021). Conclusions: Initial lymph nodes metastasis and disease-free interval are associated with different site of LRR. LRR site significantly influenced following surgery choice after LRR, which are both related with overall survival after LRR.

Investigation on the properties of borate bonding agents: Ti6Al4V-porcelain bonding, chemical durability and preliminary cytotoxicity.

The purpose of this study was to investigate the properties of the borate bonding agents (BBAS) including chemical durability, biocompatibility and bonding characteristics of porcelain to Ti6Al4V. The bond strength was performed by the three-point bending test. And the chemical durability and ion release of BBAS were tested by chemical soaking and inductively coupled plasma optical emission spectrometry (ICP-OES), respectively. Moreover, cytotoxicity was evaluated by cell viability assay and cell adhesion using human osteosarcoma cells (MG-63) and cell counter kit-8 (CCK-8) assay. To investigate the influences of composition and microstructure changes on all the properties mentioned above, the 11B and 27Al spectra and infrared spectra of BBAS were measured by solid-state nuclear magnetic resonance (SSNMR) and Fourier transform infrared spectroscopy (FTIR), respectively. Combined with all these properties of BBAS, the optimal addition proportion of Al2O3 into BBAS is 20 mol%. The relative contents of [BO3], [BO4], [AlO4], [AlO5] and [AlO6] have great influences on these properties of BBAS. BBAS, possessing excellent chemical durability, good biocompatibility and low ion release and being an effective way to improve the Ti6Al4V-porcelain bond strength, have significant clinical potentials in porcelain fused to metal restorations.

[Relationship between epicardial adipose tissue and clinical prognosis of patients with coronary heart disease after percutaneous coronary intervention].

Objective: To further evaluate the clinical value of epicardial adipose tissue volume (EATV) in predicting the prognosis of coronary heart disease (CHD) after percutaneous coronary intervention (PCI). Methods: From July 2013 to July 2016 in TEDA International Cardiovascular Disease Hospital, a total of 474 patients diagnosed with CHD were included in this study.According to the result of EATV, patients were divided into three groups, group A (EATV≤75 ml), group B (75 ml120.39 ml can be used as an independent risk factor for predicting the occurrence of MACE. Conclusion: The level of EATV is closely related to the occurrence of MACE events, and EATV>120.39 ml is an independent risk factor for MACE in patients with CHD after PCI.

[Detection and clinical significance of circulating tumor cells in osteosarcoma using immunofluorescence combined with in situ hybridization].

Objective: To investigate the clinical significance of detection of circulating tumor cells (CTCs) in peripheral blood from patients with osteosarcoma (OS) using the iFISH (immunofluorescence and fluorescence in situ hybridization) method. Methods: The live cells recovery rate of immune-magnetic beads was evaluated by live-cell fluorescent tracer technology. The expression of CD45 and CK18 on the cell surface of HOS and HepG2 cells was measured by flow cytometry. And the chromosome aneuploidy was detected by centromeric FISH probe CEP8. Subsequently, 23 OS patients were enrolled and divided into two groups, relapse or metastasis group and primary group. And the prognostic significance of CTCs numbers was analyzed. Results: The live cells recovery rate of immune-magnetic beads was higher than 90%. The flow cytometry results showed that HOS cells were double negative for the surface biomarkers of CD45 and CK18. In addition, the FISH-CEP8 signal abnormality rate were 96.5% in HOS cells. Thus, CTC was identified using the criteria as follows: the cells with CEP8-positive signal >2 accounted for more than 96.5% of the total cells, of which the cells with >3 positive signal were more than 65.0%. Among the enrolled patients, 19 patients had detectable CTCs in the peripheral blood. The CTCs numbers in the relapse or metastasis group and primary group were 2.846±1.281 and 1.400±1.506, respectively. The results showed that the CTCs in patients with recurrence or metastasis were significantly higher than those in primary patients (P=0.021). Conclusions: To our knowledge, this is the first evidence of existence of CTCs in OS patients. The CTCs numbers were positively associated with disease progression and poor prognosis. These results may provide a potential prognostic tool for monitoring metastasis and recurrence in OS patients. Trial registration: Chinese Clinical Trial Registry, ChiCTR-OOC-15005925.

[Clinical efficacy of ladder neoadjuvant therapy in treatment of advanced mid-low rectal cancer].

Objective: To explore the clinical efficacy of ladder neoadjuvant therapy in treatment of advanced mid-low rectal cancer. Methods: We performed a retrospective study of one hundred and eighty mid and low rectal cancer patients who underwent ladder neoadjuvant therapy(neoadjuvant chemotherapy followed by surgery if neoadjuvant chemotherapy was effective; neoadjuvant chemotherapy followed by neoadjuvant chemoradiotherapy if neoadjuvant chemotherapy was ineffective)(n=90) or neoadjuvant chemoradiotherapy (n=90). Results: In the ladder neoadjuvant therapy group, the descent stage rate was 85.6% (77/90), the anastomosis rate was 50.0% (45/90), the pre-sacral infection rate was 4.4% (4/90), the pathological complete remission (pCR) was 13.3%(12/90), R0 resection rate was 85.6% (77/90), the 2-year disease control rate was 76.7% (69/90), and the 2-year survival rate was 90.0% (81/90). In the control group, the descent stage rate was 88.9% (80/90), The anastomosis rate was 45.6% (41/90), the rate of pre-sacral infection was 11.1% (10/90), pCR was 16.7% 15/90), R0 resection rate was 88.9% (80/90), the 2-year disease control rate was 78.9% (71/90), and the 2-year survival rate was 87.8% (79/90). The difference was not statistically significant (P>0.05). The ladder neoadjuvant therapy group had lower prophylactic transverse colostomyrate(10.0% vs 34.4%), lower radiation injury rate (6.7% vs 27.8%), and lower sexual dysfunction rate (38.9% vs 87.8)compared to the control group. Conclusions: The ladder neoadjuvant therapy might reduce side injury caused by radiotherapy, improve compliance of patients, and reduce treatment costs. Moreover, the RO resection rate, 2-year local control rate and 2-year survival rate of ladder neoadjuvant therapy group was comparable with neoadjuvant chemoradiotherapy.

[Cost-effectiveness analysis of octreotide long acting release and lanreotide slow release for the treatment of postoperative patients with active acromegaly in China].

Objective: To evaluate the cost-effectiveness of octreotide long acting release (LAR) vs lanreotide slow release (SR) for the treatment of postoperative acromegalic patients with elevated levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) in China. Methods: A decision tree model was constructed and the treatment impact was projected for one year in Chinese setting. The clinical efficacy measure used was the percentage of patients achieving normalization (control) of either IGF-1 or GH levels. Efficacy of octreotide LAR and lanreotide SR, incidence of comorbidities, impact of acromegaly on health-related quality of life, and drug-related side effects data were obtained from literature. The cost of medication was collected through a chart review from five hospitals in five cities of China. Clinical experts from these hospitals were requested to complete a questionnaire to document the utilization of medical resources, costs of comorbidities, side effects as well as cost of administration. One-way sensitivity analysis was performed to evaluate the robustness of the results. Results: Compared to lanreotied SR group, the percentage of patients achieving normalization of IGF-1 and GH levels of octreotide LAR group were 10% and 9% higher, respectively. When either IGF-1 or GH control were used as the efficacy measure, patients in the octreotide LAR group exhibit less comorbidities and need less continued treatment with a second operation and radiotherapy than those in lanreotide SR group. When IGF-1 was used as efficacy measure, octreotide LAR not only achieved better efficacy but resulted in overall cost-saving, with a total cost savings of ï¿¥ 3 792 per patient for one year, which demonstrated that octreotide LAR was a dominant cost-saving strategy. When GH control was used as the efficacy measure, octreotide LAR achieved a better overall clinical efficacy with a slightly higher total costs (ï¿¥ 4 121 higher per patient per year). Sensitivity analysis didn't change the conclusion that octreotide LAR remains dominant over lanreotide SR, indicating the robustness of this model. Conclusion: Octreotide LAR achieved better overall biochemical control compared with lanreotide SR which result in less comorbidity rate, second operation and radiotherapy as well as related costs.

Study to elucidate molecular mechanism behind zinc chemo-preventive role during lung carcinogenesis.

OBJECTIVE: The present planned to elucidate the mechanistic role zinc supplementation in the modulation of p53 post-translational acetylation, the activity of cyclooxygenase-2 (COX-2) along with other biophysical parameters during benzo(a)pyrene (BP) induced lung carcinogenesis in mice. MATERIALS AND METHODS: The mice were segregated into four groups viz., normal control, BP treated, BP + zinc and zinc alone treated. Lung carcinogenesis was induced by a single intra-peritoneal (IP) injection of BP (100 mg/kg body weight). Zinc was supplemented to mice at dose levels of 227 mg/kg body weight in drinking water. All the treatments were continued for 20 weeks. RESULTS: The BP caused a significant rise in the expression of p53. On the other hand, protein expressions of acetylated (lys382)-p53 were significantly decreased, following BP treatment. Also, a significant decrease was observed in the enzyme activities of caspase 3 and caspase 9. Moreover, BP treatment brought about a significant increase in the activity of COX-2. Supplementation of zinc to BP treated mice stimulated acetylation of p53 as observed by an increase in the protein expression of acetylated (lys382)-p53. Also, the enzyme activities of caspase 3 and caspase 9 showed a significant elevation upon zinc supplementation. On the other hand, the zinc supplementation brought about moderation in the expression of enzymatic activity of COX-2 which was restored within the normal limits. Further, BP treatment recorded increased 3H-thymidine uptake as well as enhanced 14C-glucose uptake and its turnover which were reduced significantly following simultaneous treatment with zinc. CONCLUSIONS: The treatment with zinc has the potential to modulate p53 acetylation to stimulate apoptosis against experimentally induced lung carcinogenesis.

Anti-reflux anastomosis following esophagectomy for adenocarcinoma of the esophagogastric junction: impact of duodenogastroesophageal reflux and expression of cyclooxygenase-2 in the remnant esophagus.

OBJECTIVE: Reflux is the principal complication for patients after esophagectomy with gastric reconstruction. The aim of this study was to investigate the effect of the modified Nissen fundoplication after resection of adenocarcinoma from the esophagogastric junction (AEG) on controlling the reflux and the role of duodenogastroesophageal reflux (DGER) and cyclooxygenase-2 (COX-2) expression level in the remnant esophagus. PATIENTS AND METHODS: Sixty patients with AEG were randomly divided into two groups: (i) the conventional anastomosis group and (ii) the anti-reflux anastomosis group. Fifty esophagectomized patients were invited to participate in postoperative follow-up after 6 to 12 months. Among those we had 29 cases in the conventional anastomosis group and 21 in the anti-reflux anastomosis group. We used endoscopy, simultaneous 24 hours esophageal pH and bilirubin monitoring in this study. The COX-2 expression level in the remnant esophagus was detected using real-time PCR. RESULTS: The reflux esophagitis prevalence in anti-reflux anastomosis group was comparable to that in the conventional group (p = 0.154). DeMeester score and fraction time of bilirubin abs >0.14 decreased more intensely in the anti-reflux anastomosis group (p < 0.05). The COX-2 expression level in of anti-reflux anastomosis group was evidently lower than that in the conventional anastomosis group (p = 0.022) while it was meaningfully higher compared to the normal control group (p = 0.046). COX-2 up-regulation as well as high prevalence of esophagitis were observed in simultaneous acid reflux and DGER (p < 0.05). CONCLUSIONS: Although modified fundoplication following resection of AEG did not achieve an optimal effect on controlling reflux, it was very effective in decreasing the reflux. COX-2 expression monitoring can be considered as a possible new way to evaluate the impact of anti-reflux surgery. DGER occurring in acidic environment could develop severe reflux esophagitis and up-regulate the COX-2 expression.

GLI2 induces genomic instability in human keratinocytes by inhibiting apoptosis.

Abnormal Sonic Hedgehog signalling leads to increased transcriptional activation of its downstream effector, glioma 2 (GLI2), which is implicated in the pathogenesis of a variety of human cancers. However, the mechanisms underlying the tumorigenic role of GLI2 remain elusive. We demonstrate that overexpression of GLI2-ß isoform, which lacks the N-terminal repressor domain (GLI2ΔN) in human keratinocytes is sufficient to induce numerical and structural chromosomal aberrations, including tetraploidy/aneuploidy and chromosomal translocations. This is coupled with suppression of cell cycle regulators p21(WAF1/CIP1) and 14-3-3σ, and strong induction of anti-apoptotic signalling, resulting in a reduction in the ability to eliminate genomically abnormal cells. Overexpression of GLI2ΔN also rendered human keratinocytes resistant to UVB-mediated apoptosis, whereas inhibition of B-cell lymphoma 2 (BCL-2) restored endogenous (genomic instability (GIN)) and exogenous (UVB) DNA damage-induced apoptosis. Thus, we propose that ectopic expression of GLI2 profoundly affects the genomic integrity of human epithelial cells and contributes to the survival of progenies with genomic alterations by deregulating cell cycle proteins and disabling the apoptotic mechanisms responsible for their elimination. This study reveals a novel role for GLI2 in promoting GIN, a hallmark of human tumors, and identifies potential mechanisms that may provide new opportunities for the design of novel forms of cancer therapeutic strategies.

Association between DNA methylation of HSPB1 and death in low Gleason score prostate cancer.

BACKGROUND: Heat shock protein 27 (Hsp-27) encoded by gene HSPB1 is a critical regulator of the behavioral phenotype of human prostate cancer (PCa) cells, enhanced expression being associated with highly aggressive disease and poor clinical outcome. In contrast, the protein is not expressed in PCas of low malignant potential. To gain insight into the mechanism regulating its expression, we tested the hypothesis that differential methylation of CpG islands within HSPB1 controls transcription and subsequent translation of the gene. METHODS: We studied prostate epithelial cell lines and tissue biopsies, including 59 BPH and 415 PCas, of which 367 were a cohort of men with up to 20 years of follow-up. Methylation across the gene (DNA methylation (DNAme)) was assayed by pyrosequencing. Hsp-27 expression was assessed by western blot and immunohistochemistry. RESULTS: In cancer tissues, methylation increased in a 3' direction (P < 0.0001) whereas in benign hyperplasia methylation was constantly below 5%, a cutoff giving a specificity of 100% and sensitivity of 50%. Although methylation of the promoter region was significantly discriminating between benign and malignant prostatic epithelia, it compared poorly with methylation of the first intron. The prognostic value of HSPB1 DNAme was confirmed by both univariate (hazard ratio 1.77 per 50% increment, P = 0.02) and multivariate models. Interaction between HSPB1 methylation and Gleason score revealed high DNAme to be a reliable prognostic marker of poor outcome in men with low Gleason score (P = 0.014). CONCLUSIONS: Our data indicate CpG methylation of the first HSPB1 intron to be an important biomarker that identifies aggressive PCas otherwise regarded as low risk by current clinical criteria but that, biologically, require immediate active management.

Imaging characteristics of primary spinal primitive neuroectodermal tumors. A report of five cases and literature review.

Primary spinal primitive neuroectodermal tumors (PNETs) are rare and classified into peripheral and central types because the treatment strategy and outcome are different. This study describes five cases of primary spinal peripheral type PNETs. Magnetic resonance imaging showed large extradural masses in the cervical and thoracic spine with bony invasion and paraspinal extension in four cases and a transdural mass in the sacral spinal canal in one case. We also briefly summarize the imaging characteristics of 36 peripheral type and six central type primary spinal PNETs in the literature.

Alleviating psychological distress of suicide survivors: evaluation of a volunteer care programme.

The crisis level in the worldwide suicide rate has revealed a severe suicide problem in Taiwan that is now well above the world average of 16 per 100,000 individuals. Many countries have relied on suicide care volunteers training programmes to conduct suicide prevention programmes. However, there is a dearth of research evaluating the effect of volunteers on psychological distress and the impact of volunteer experience level. An evaluation of the impact of experienced and novice volunteers in alleviating psychological distress of suicide survivors was conducted. A supervised programme trained 15 volunteers at Years 1 and 2. Year 1 volunteers completed 400 h of service with continuing education. Programme evaluation occurred after Year 2 volunteers had completed training. Eighty-two suicide survivors were recruited. With 60 suicide survivors completing 3 month of volunteer care, a significant group difference with time interaction in suicide survivors who exhibited moderate to severe distress between the veteran care and novice care groups was found. Compared with novice volunteers, veteran volunteers with at least 1 year of experience are more effective with suicide survivors reporting higher psychological distress.

Involvement of p21 (waf1) in merlin deficient sporadic vestibular schwannomas.

Previous studies have demonstrated that merlin acts as a tumor suppressor by blocking Ras-mediated signaling. However, the mechanism by which merlin controls cell proliferation has remained obscure. Here we show that merlin deficient tumors exhibited loss of p21, concomitant with elevated CDKs/cyclin D1 levels in sporadic vestibular schwannomas (VS) from clinic patients. Likewise, silencing of merlin gene expression in the cell lines resulted in down-regulation of p21. Furthermore, we find that merlin-enhanced p21 protein stability, rather than increased RNA accumulation, was responsible for the elevated p21 levels. Interestingly, p21 was required to maintain merlin levels and the inhibitory effect of merlin on Ras signaling was partially overridden by knockdown of p21. Consistent with the observation that over-expression of merlin arrested cell growth at G1-phase, the current study indicates that merlin exerts its antiproliferative effect, at least in part, by maintaining p21 expression, and loss of p21 is a prominent feature of merlin deficient schwannomas.

The identification of chromosomal translocation, t(4;6)(q22;q15), in prostate cancer.

Our previous work identified a chromosomal translocation t(4;6) in prostate cancer cell lines and primary tumors. Using probes located on 4q22 and 6q15, the breakpoints identified in LNCaP cells, we performed fluorescence in situ hybridization analysis to detect this translocation in a large series of clinical localized prostate cancer samples treated conservatively. We found that t(4;6)(q22;q15) occurred in 78 of 667 cases (11.7%). The t(4;6)(q22;q15) was not independently associated with patient outcome. However, it occurs more frequently in high clinical T stage, high tumor volume specimens and in those with high baseline PSA (P=0.001, 0.001 and 0.01, respectively). The t(4;6)(q22;q15) occurred more frequently in samples with two or more TMPRSS2:ERG fusion genes caused by internal deletion than in samples without these genomic alterations, but this correlation is not statistically significant (P=0.0628). The potential role of this translocation in the development of human prostate cancer is discussed.

Resveratrol protects against arsenic trioxide-induced cardiotoxicity in vitro and in vivo.

BACKGROUND AND PURPOSE: The clinical use of arsenic trioxide (As(2)O(3)), a potent antineoplastic agent, is limited by its severe cardiotoxic effects. QT interval prolongation and apoptosis have been implicated in the cardiotoxicity of As(2)O(3). The present study was designed to evaluate the effects of resveratrol on As(2)O(3)-induced apoptosis and cardiac injury. EXPERIMENTAL APPROACH: In a mouse model of As(2)O(3)-induced cardiomyopathy in vivo, QT intervals and plasma enzyme activities were measured; cardiac tissues were examined histologically and apoptosis assessed. In H9c2 cardiomyocyte cells, viability, apoptosis, generation of reactive oxygen species (ROS) and cellular calcium levels were measured. KEY RESULTS: In the mouse model, resveratrol reduced As(2)O(3)-induced QT interval prolongation and cardiomyocyte injury (apoptosis, myofibrillar loss and vacuolization). In addition, increased lactate dehydrogenase activity and decreased activities of glutathione peroxidase, catalase and superoxide dismutase were observed in the plasma of As(2)O(3)-treated mice; these changes were prevented by pretreatment with resveratrol. In As(2)O(3)-treated H9c2 cardiomyocytes, resveratrol significantly increased cardiomyocyte viability and attenuated cell apoptosis as measured by acridine orange/ethidium bromide staining, TdT-mediated dUTP nick end labelling assay and caspase-3 activity. As(2)O(3)-induced generation of ROS and intracellular calcium mobilization in H9c2 cells was also suppressed by pretreatment with resveratrol. CONCLUSIONS AND IMPLICATIONS: Our results showed that resveratrol significantly attenuated As(2)O(3)-induced QT prolongation, structural abnormalities and oxidative damage in the heart. In H9c2 cardiomyocytes, resveratrol also decreased apoptosis, production of ROS and intracellular calcium mobilization induced by treatment with As(2)O(3). These observations suggested that resveratrol has the potential to protect against cardiotoxicity in As(2)O(3)-exposed patients.