Altered static and dynamic functional network connectivity in individuals with subthreshold depression: a large-scale resting-state fMRI study.

Dynamic functional network connectivity (dFNC) is an expansion of static FNC (sFNC) that reflects connectivity variations among brain networks. This study aimed to investigate changes in sFNC and dFNC strength and temporal properties in individuals with subthreshold depression (StD). Forty-two individuals with subthreshold depression and 38 healthy controls (HCs) were included in this study. Group independent component analysis (GICA) was used to determine target resting-state networks, namely, executive control network (ECN), default mode network (DMN), sensorimotor network (SMN) and dorsal attentional network (DAN). Sliding window and k-means clustering analyses were used to identify dFNC patterns and temporal properties in each subject. We compared sFNC and dFNC differences between the StD and HCs groups. Relationships between changes in FNC strength, temporal properties, and neurophysiological score were evaluated by Spearman's correlation analysis. The sFNC analysis revealed decreased FNC strength in StD individuals, including the DMN-CEN, DMN-SMN, SMN-CEN, and SMN-DAN. In the dFNC analysis, 4 reoccurring FNC patterns were identified. Compared to HCs, individuals with StD had increased mean dwell time and fraction time in a weakly connected state (state 4), which is associated with self-focused thinking status. In addition, the StD group demonstrated decreased dFNC strength between the DMN-DAN in state 2. sFNC strength (DMN-ECN) and temporal properties were correlated with HAMD-17 score in StD individuals (all p < 0.01). Our study provides new evidence on aberrant time-varying brain activity and large-scale network interaction disruptions in StD individuals, which may provide novel insight to better understand the underlying neuropathological mechanisms.

Prenatal nicotinic exposure suppresses fetal adrenal steroidogenesis via steroidogenic factor 1 (SF-1) deacetylation.

This study aimed to investigate the suppressive effect of nicotine on fetal adrenal steroidogenesis and to explore the potential role of epigenetic modification of steroidogenic factor-1 (SF-1) transcriptional activity in this process. Nicotine was intragastrically administered to pregnant rats and NCI-H295A cells were treated with nicotine or trichostatin A (TSA). The pathomorphology of fetal adrenals, steroid hormone levels, the expression of SF-1 and its target genes, and histone deacetylase (HDAC) mRNA were analyzed. Histone modification and DNA methylation of the SF-1 promoter region were assessed using chromatin immunoprecipitation (ChIP) and bisulfite sequencing PCR. The interaction between SF1 and its target genes was observed. Prenatal nicotinic exposure decreased fetal body weight, increased the IUGR rate and caused detrimental changes in fetal adrenal. In addition, the levels of corticosterone, the expression of SF-1 and its target genes were decreased while HDAC2 expression was enhanced. Nicotine treatment decreased histone H3K9 and H3K14 acetylation levels while there was no effect on the methylation frequency on the SF-1 promoter region. Furthermore, in nicotine-treated NCI-H295A cells, lower levels of steroidogenic synthesis, lower expression of SF-1 and its target genes were observed while the expression of HDACs was enhanced. The interaction between SF1 and StAR decreased with nicotine treatment. Nicotine treatment decreased histone H3K9 and H3K14 acetylation levels, and addition of TSA reversed the inhibition of nicotine-mediated SF-1 and its partial target genes. Thus, nicotine-mediated reduction of SF-1 expression resulted in an inhibitory effect on the expression of its target genes and steroid production via histone deacetylation.

[Application of factor analysis to evaluate deformation behaviors of frequently-used tablet excipients].

The present work is to investigate the correlation between physical properties and deformation behaviors of tablet excipients, and rank them according to their plastic performances during compaction. The excipients selected were compacted using Korsch XP1 after measuring their physical properties where the compression parameters for evaluating deformation behaviors were Heckle equation, compression work and elastic stretch in die. The correlations between compaction descriptors and physical parameters were analyzed by canonical correlation analysis, and factor analysis was simultaneously employed to synthetically assess deformation behaviors for all our samples. The canonical variables show that true density (Pa) correlated negatively with plastic coefficient (PL) and positively with yield pressure (YP); compression degree (Cp) correlated negatively with fast elastic stretch (FES) as well as YP and positively with PL. When factor scores were used in combination with original data, the plasticity of our samples was sorted and ranked as high (-0.56 < F' < 0.21), intermediate (-0.16 < F' < 0.36), or low (0.38 < F' < 0.84), which are in accord with plasticity rankings previously reported in literature. This study indicates factor analysis can be an approach to evaluate deformation behaviors of pharmaceutical powders.

[Characterization of flowability of pharmaceutical powders based on multivariate analysis method].

The main methods of characterizing the flowability of pharmaceutical powders include repose angle method, HR method, Carr's index method, Jenike flow function method, fractal dimension method, and mass flow rate method, etc. Regarding powders with different flowabilities as the research subject, comprehensive features of pharmaceutical materials were investigated and characterized. The multivariate analysis method was employed to evaluate and analyze flowability values of the tested pharmaceutical materials. Comparing with the method of the mass flow rate, it was feasible to use multivariate analysis method to evaluate the flowability of powders. Simultaneously, the flowability of pharmaceutical materials could be ranked and definitely quantified, and critical values be determined according to the actual production, which has promoted the previous methods dependent only on the single parameter, i.e. repose angle and compression degree methods. A relatively objective standard method of evaluating flowability of powders is formed.

[The increase of micronuclei frequencies of peripheral blood lymphocyte in plywood workers exposed accumulatively to formaldehyde].

OBJECTIVE: To investigate the effects of occupational exposure to formaldehyde on the micronuclei frequencies in peripheral blood lymphocytes of workers. METHODS: Two hundred thirty six plywood workers were divided into 3 exposure groups (low, middle and high) according to internal exposure biomarker (formaldehyde human serum albumin conjugate, FA-HSA), which was detected by ELISA. The concentrations of formaldehyde (FA) in air of two workshops were measure using the high performance liquid chromatography. Cytokinesis-block micronucleus (CBMN) test was used to detect the micronuclei frequencies of peripheral blood lymphocyte in 236 workers. RESULTS: The average concentrations of FA in the low and high exposure workshops were 0.58 +/- 0.20 and 1.48 +/- 0.61 mg/m3, respectively, there was significant difference (P < 0.01). The average concentrations of serum FA-HAS of workers in two workshops were 69.22 +/- 15.37 and 136.29 +/- 89.49 pg/ml, respectively, there was significant difference (P < 0.01). The results of CBMN test showed that the micronucleus frequencies in low, middle and high exposure groups were 1.94 +/- 1.72, 2.10 +/- 1.92 and 2.10 +/- 1.70 per thousand, respectively, there were no significant differences between groups. However, the micronucleus frequencies in accumulative low, middle and high exposure groups were 1.36 +/- 1.36, 2.31 +/- 1.81 and 2.49 +/- 1.92 per thousand, respectively, there were significant differences between different accumulative exposure groups (P < 0.01). The results of correlation analysis indicated that there was a positive correlation between accumulative exposure levels and micronucleus frequencies (r(s) = 0.321, P < 0.01). The accumulative exposure doses may be a risk factor for high micronucleus frequencies in workers exposed to FA (P(trend) = 0.002). CONCLUSION: FA-HSA levels can serve as an internal exposure biomarker for assessing the exposure level of workers exposed to FA. Accumulative formaldehyde exposure resulted in an increase of micronuclei frequencies of peripheral blood lymphocyte in plywood workers.

[Using the stable HSPA1A promoter-driven luciferase reporter HepG2 cells to assess the overall toxicity of coke oven emissions].

OBJECTIVE: Using the stable HSPA1A (HSP70-1) promoter-driven luciferase reporter HepG2 cells (HepG2/HSPA1A cells) to assess the overall toxicity of coke oven emissions. METHODS: The stable HepG2/HSPA1A cells were treated with different concentrations of coke oven emissions (COEs) collected from the top, side, and bottom of a coke oven battery for 24 h. After the treatments, luciferase activity, cell viability, malondialdehyde (MDA) concentration, Olive tail moment, and micronuclei frequency were determined, respectively. RESULTS: The bottom COEs induced significant increases (P < 0.01) in relative luciferase activity up to 1.4 times the control level at 0.15 µg/L. The low dose of side COEs (0.02 µg/L) led to a significant increase (P < 0.01) in relative luciferase activity that progressively increased to 2.1 times the control level at 65.4 µg/L. The top COEs produced a strong dose-dependent induction of relative luciferase activity up to over 5 times the control level at the highest concentration tested (202 µg/L). In HepG2/HSPA1A cells treated with the bottom COEs, relative luciferase activity was positively correlated with MDA concentration (r = 0.404, P < 0.05). For the three COEs samples, positive correlations were observed between relative luciferase activity and Olive tail moment and micronuclei frequency. CONCLUSION: The relative luciferase activity in HepG2/HSPA1A cells can sensitively reflect the overall toxicity of COEs. The stable HepG2/HSPA1A cells can be used for rapid screening of the overall toxicity of complex air pollutants in the workplace.

[Characteristics of particulate matter pollution in coke oven plant].

OBJECTIVE: To explore the characteristics of particulate matter pollution in coke oven plant, so as to provide scientific data for establishing occupational exposure limits for coke oven emissions. METHODS: Concentrations of CO, SO2, BSM, BTEX (concentrations of benzene, toluene and xylene were determined in this study), PM10, PM2.5, 16 selected PAHs in PM10 and PM2.5 were determined in the work environment of a coke oven plant in Wuhan. The work environment was divided into the adjunct area, the bottom of, the side of and the top of coke oven. RESULTS: The concentrations of CO, SO2, BSM, BETX, PM10, PM2.5, PAHs in PM10 and PM2.5 were significantly related to working environmental categories, respectively, and were increasing as the adjunct area < bottom < side < top (P (trend) < 0.05). PM10 was statistically significantly correlated with CO, SO2, benzene, BTEX and BSM (0.705, 0.823, 0.664, 0.624 and 0.734, respectively). PM2.5 was statistically significantly correlated with CO, SO2, benzene, BTEX and BSM (0.635, 0.916, 0. 680, 0.553 and 0.726, respectively). BSM was statistically significantly correlated with benzene (0.689). The ratios of PM2.5 to PM10 between different work environments were not significantly different in one-way ANOVA (P > 0.05). The distribution of aromatic rings and the concentrations of total benzo[a] pyrene equivalents in PM10 and PM2.5 were not statistically different between work environments. CONCLUSION: The concentrations of particulate matter was related with other contents of coke oven emissions in coke work environment, and the contents and types of PAHs in PM10 and PM2.5 were similar.

[Effects of smoking on the concentrations of urinary 10 metabolites of polycyclic aromatic hydrocarbons in coke oven workers].

OBJECTIVE: To explore the effects of smoking on urinary 10 metabolites of polycyclic aromatic hydrocarbons (PAHs) in the coke oven workers. METHODS: Occupational health examination was performed on 1401 coke oven workers in one coking plant, their urine were collected respectively. The concentrations of the ten monohydroxy polycyclic aromatic hydrocarbons in urine were detected by gas chromatography/mass spectrometry. The 1401 workers were divided into four groups, namely control, adjunct workplaces, bottom and side, top group according to their workplaces and the different concentrations of PAHs in the environment. The concentrations of the ten monohydroxy polycyclic aromatic hydrocarbons between smokers and nonsmokers in each workplace group were compared using analysis of covariance, respectively. RESULTS: The levels of concentrations of the sixteen polycyclic aromatic hydrocarbons we detected at control were significantly higher than those at other areas (P < 0.05). Comparing the ten monohydroxy polycyclic aromatic hydrocarbons levels between smokers and nonsmokers, the levels of 1-hydroxynaphthalene and 2-hydroxynaphthalene among smokers were higher than nonsmokers with statistically significance in control, adjunct workplaces, bottom and side and top groups (P < 0.05). However, the levels of 1-hydroxypyrene had no statistically significant differences between the four areas. CONCLUSION: Urinary 1-hydroxynaphthalene and 2-hydroxynaphthalene may be used as biomarkers for the impact of smoking on monohydroxy polycyclic aromatic hydrocarbons in the coke oven workers.

Indole-3-carbinol enhances the resolution of rat liver fibrosis and stimulates hepatic stellate cell apoptosis by blocking the inhibitor of κB kinase α/inhibitor of κB-α/nuclear factor-κB pathway.

Hepatic stellate cells (HSC) play a pivotal role in liver fibrosis, and the clearance of activated HSC by apoptosis is associated with the resolution of liver fibrosis. The development of strategies that promote this process in a selective way is therefore important. We evaluated the effects of indole-3-carbinol (I3C), a nutritional component derived from vegetables from the Brassica family, on liver fibrosis and HSC apoptosis. The in vivo therapeutic effects of I3C were monitored in three rat models of liver fibrosis induced by porcine serum, bile duct ligation, or multiple hepatotoxic factors, and its proapoptotic effect and molecular mechanism were studied in vitro in HSC-T6, a rat HSC line. The results showed that I3C treatment significantly reduced the number of activated HSC in the livers of rats with liver fibrosis. In histopathology, I3C reduced hepatocyte degeneration and necrosis, accelerated collagen degradation, and promoted the reversal of liver fibrosis. I3C prescribed to HSC-T6 resulted in morphologic alterations typical of apoptosis and DNA cleavage to a nucleosomal ladder. Moreover, I3C significantly increased the HSC-T6 apoptosis rate and the expression ratio of Bax to Bcl-2. High-throughput protein array analysis indicated that the tumor necrosis factor-α/nuclear factor-κB (NF-κB) signal pathway participated in I3C-induced HSC-T6 apoptosis. Western blot and electrophoretic mobility-shift assay confirmed that I3C inhibited the phosphorylation of inhibitor of κB kinase α and inhibitor of κB-α and NF-κB DNA binding activity. In conclusion, I3C could promote the reverse process of liver fibrosis in vivo and induce apoptosis of activated HSC in vitro, which indicates the use of I3C as a potential therapeutic agent in liver fibrosis treatment.

Protective effects of panax notoginseng saponin on dextran sulfate sodium-induced colitis in rats through phosphoinositide-3-kinase protein kinase B signaling pathway inhibition.

BACKGROUND: Intestinal inflammation is a common digestive tract disease, which is usually treated with hormone medicines. Hormone medicines are effective to some extent, but long-term use of them may bring about many complications. AIM: To explore the protective effects of panax notoginseng saponin (PNS) against dextran sulfate sodium (DSS)-induced intestinal inflammatory injury through phosphoinositide-3-kinase protein kinase B (PI3K/AKT) signaling pathway inhibition in rats. METHODS: Colitis rat models were generated via DSS induction, and rats were divided into control (no modeling), DSS, DSS + PNS 50 mg/k, and DSS + PNS 100 mg/kg groups. Then, the intestinal injury, oxidative stress parameters, inflammatory indices, tight junction proteins, apoptosis, macrophage polarization, and TLR4/AKT signaling pathway in colon tissues from rats in each of the groups were detected. The PI3K/AKT signaling pathway in the colon tissue of rats was blocked using the PI3K/AKT signaling pathway inhibitor, LY294002. RESULTS: Compared with rats in the control group, rats in the DSS group showed significantly shortened colon lengths, and significantly increased disease activity indices, oxidative stress reactions and inflammatory indices, as well as significantly decreased expression of tight junction-associated proteins. In addition, the DSS group showed significantly increased apoptotic cell numbers, and showed significantly increased M1 macrophages in spleen and colon tissues. They also showed significantly decreased M2 macrophages in colon tissues, as well as activation of the PI3K/AKT signaling pathway (all P < 0.05). Compared with rats in the DSS group, rats in the DSS + PNS group showed significantly lengthened colon lengths, decreased disease activity indices, and significantly alleviated oxidative stress reactions and inflammatory responses. In addition, this group showed significantly increased expression of tight junction-associated proteins, significantly decreased apoptotic cell numbers, and significantly decreased M1 macrophages in spleen and colon tissues. This group further showed significantly increased M2 macrophages in colon tissues, and significantly suppressed activation of the PI3K/AKT signaling pathway, as well as a dose dependency (all P < 0.05). When the PI3K/AKT signaling pathway was inhibited, the apoptosis rate of colon tissue cells in the DSS + LY294002 group was significantly lower than that of the DSS group (P < 0.05). CONCLUSION: PNS can protect rats against DSS-induced intestinal inflammatory injury by inhibiting the PI3K/AKT signaling pathway, and therefore may be potentially used in the future as a drug for colitis.

Synergistic protection of astragalus polysaccharides and matrine against ulcerative colitis and associated lung injury in rats.

BACKGROUND: Ulcerative colitis (UC) is a main form of inflammatory bowel disease. Due to complicated etiology and a high rate of recurrence, it is quite essential to elucidate the underlying mechanism of and search for effective therapeutic methods for UC. AIM: To investigate the effects of astragalus polysaccharides (APS) combined with matrine on UC and associated lung injury. METHODS: UC was induced in rats by colon mucosal tissue sensitization combined with trinitro-benzene-sulfonic acid-ethanol. Then, the effects of the treatments of salazopyrine, APS, matrine, and APS combined with matrine on histopathological changes of lung and colon tissues, disease activity index (DAI), colon mucosal damage index (CMDI), serum endotoxin (ET) level, serum diamine oxidase (DAO) activity, the contents of tumor necrosis factor-α and interleukin-1ß, and the activities of myeloperoxidase, superoxide dismutase, and malondialdehyde in lung tissues, as well as the protein expression of zonula occludens (ZO)-1, Occludin, and trefoil factor 3 (TFF3) were detected in UC rats. RESULTS: The treatments of salazopyrine, APS, matrine, and APS combined with matrine reduced DAI scores and improved histopathological changes of colon and lung tissues, as well as decreased CMDI scores, ET levels, and DAO activities in UC rats. Moreover, in lung tissues, inflammatory response and oxidative stress injury were relieved after the treatments of salazopyrine, APS, matrine, and APS combined with matrine in UC rats. Furthermore, the expression of ZO-1, Occludin, and TFF3 in lung and colon tissues was increased after different treatments in UC rats. Notably, APS combined with matrine exerted a better protective effect against UC and lung injury compared with other treatments. CONCLUSION: APS combined with matrine exert a synergistic protective effect against UC and lung injury, which might be associated with regulating TFF3 expression.

[Regional lymph nodes targetting with enrichment of polyphase liposome].

OBJECTIVE: To investigate the feasibility of regional lymph nodes targetting with enrichment of radioactive 99mTc-polyphase liposome of 5-fluorouracil (99mTc-FL, FL). METHODS: 18 rabbits were randomly divided into 3 groups, 6 rabbits per group. All rabbits were injected hypodermally with of 99mTc-FL in the right and left big toe webs, 18.5 MBq each side. The post-injection interval was 3 h in group 1, 6 h in group 2, and 8 h in group 3. The radioactivity was examined in the resected local lymph nodes, non-draining lymph nodes, liver, spleen, kidney, heart, lung, intestines, and in blood and urine. RESULTS: The radioactive isotope uptake percentage (%) was 2.32 +/- 0.75 in group 1, 5.37 +/- 1.73 in group 2, 8.61 +/- 1.89 in group 3. The radioactive isotope uptake percentage (%) per gram in local lymph nodes was significantly different between each two groups among the 3 groups (P < 0.05). The ratios of x of regional lymph nodes/non-draining lymph nodes, regional lymph nodes/blood, regional lymph nodes/urine, regional lymph nodes/liver, regional lymph nodes/spleen, regional lymph nodes/kidney, regional lymph nodes/heart, regional lymph nodes/lung, regional lymph nodes/intestine in group 1 were 232.00, 16.57, 23.20, 29.00, 19.33, 25.78, 46.40, 46.40 and 25.78, respectively. The ratios in group 2 were 89.50, 41.31, 18.52, 67.13, 41.31, 25.57, 134.25, 59.67 and 59.67, respectively. The ratios in group 3 were 86.10, 61.50, 16.56, 53.81, 57.40, 10.01, 107.63, 107.63 and 86.10, respectively. The differences of radioactive isotope uptake percentage were statistically significant (P < 0.01) between regional lymph nodes and other organs, i. e. non-draining lymph nodes, blood, urine, liver, spleen, kidney, heart, lung and intestine per gram in each group. CONCLUSION: The radioactive 99mTc-FL may slowly flow into regional lymphatic chains rather than directly enter blood circulation. So 99mTc-FL can be highly accumulated in the local lymph nodes. This regional lymph nodes targetting with enrichment of radioactive 99mTc-FL evidently indicates the feasibility of regional lymph system chemotherapy for pulmonary malignancies.

Carboxymethylated chitosan protects Schwann cells against hydrogen peroxide-induced apoptosis by inhibiting oxidative stress and mitochondria dependent pathway.

Carboxymethylated chitosan (CMCS) has many beneficial effects, including anti-oxidant and anti-apoptotic actions. However, the mechanisms by which CMCS protect against oxidative stress induced damage to Schwann cells (SCs) remains unclear. The present study aimed to investigate the mechanism by which CMCS protects SCs against hydrogen peroxide (H2O2) induced damage. H2O2 was used to establish a model of oxidative stress injury in SCs to mimic the development of nerve injury in vitro. Different concentrations (50, 100 and 200 µg/ml) of CMCS were added to test whether CMCS was capable of protecting SCs from H2O2 induced damage. MTT, LDH release and Annexin V/FITC assays were then performed. Levels of reactive oxygen species were detected using a reactive oxygen species assay kit, the mitochondrial membrane potential (ΔΨm) of SCs was analyzed by rhodamine123 fluorescence staining, the synthesis of Bcl-2, Bax, cytochrome c and caspase-3 were analyzed by real-time PCR and Western blot analysis. The results showed that CMCS protected SCs from apoptosis, decreased LDH release and enhanced cell viability, also decreased reactive oxygen species levels and increased ΔΨm. Additional experiments demonstrated that CMCS could decrease protein expression of Bax, cytochrome c and caspase-3, while promote Bcl-2 protein expression induced by H2O2. Taken together, the finding of this study indicated that CMCS prevented H2O2-induced damage to SCs through the mitochondrial dependent pathway.

[The metabolic transformation of (-)-securinine].

AIM: To study the in vitro and in vivo metabolism of (-)-securinine. METHODS: The metabolic transformation of (-)-securinine was studied by using phenobarbital-induced rat liver microsomal incubate containing the NADPH-generating system in vitro and the constitution of the system was optimized. A reversed phase HPLC method was established to analyze the parent drug and its metabolites. The major metabolites were isolated and purified by liquid-liquid extraction, preparative TLC and HPLC, and their structures were elucidated as 6-hydroxyl securinine, 6-carbonyl securinine, 5 beta-hydroxyl securinine and 5 alpha-hydroxyl securinine by 1HNMR, 13CNMR and MS spectral analysis. An HPLC method was developed to analyze securinine and its metabolites in biofluids (bile, urine) of rat. The bile, urine and their enzymatic hydrolyzed samples of the rat i.p. administrated with (-)-securinine were determined by using this method. RESULTS: Four main metabolites of (-)-securinine in rat hepatic microsome incubation were obtained and their structures were elucidated. Metabolites from in vitro study were confirmed in biofluids (bile, urine) which were collected from rats given securinine i.p. It was suggested that 6-hydroxyl securinine was excreted in conjugated form as well by analyzing enzymatic hydrolyzed bile. CONCLUSION: The main metabolic pathway of (-)-securinine in vitro and in vivo is basically elucidated.

[Study on the chiral separation of securinine by high-performance capillary electrophoresis and its stereoselective metabolism in rat].

AIM: To establish a high-performance capillary electrophoresis (HPCE) chiral separation method for d-securinine and l-securinine, and use this method to investigate the stereoselective metabolism process of d- and l-securinine in Wistar rats. METHODS: The electrophoretic condition and parameters were investigated and the optimized conditions were as following: the electrophoretic medium was 40 mmol.L-1 Tris-H3PO4 buffer (pH adjusted to 6.0 with H3PO4) containing 32 mmol.L-1 HP-beta-CD as chiral selector. Determination was carried out with a UV detector at 254 nm. The separations were performed at 16 degrees C with a positive voltage of 15 kV. Samples were injected into the capillary by pressure for 6 s. The biological samples (urine, bile, plasma and feces) of rats were alkalized and extracted with ethyl acetate. RESULTS: The experimental results showed that the concentration of HP-beta-CD, the concentration of the running buffer and the pH value of the buffer were the main important factors which effected the resolution. d-Securinine and l-securinine were separated at baseline level under the determination conditions. The determination was not interfered by endogenous components and metabolites. After i.p. administration, the rats excreted more d-securinine than l-securinine through bile, urine and feces. The metabolism process in rats was stereoselective. CONCLUSION: This method is simple, reliable and suitable for studying the stereoselective metabolism of securinine in rats.

Extraesophageal saline enhances endoscopic ultrasonography to differentiate esophagus and adjacent organs.

AIM: To distinguish between the esophagus and adjacent organs using extraesophageal saline injection (ESI) in a canine model. METHODS: ESI was performed through the esophagus under the guidance of linear-array endoscopic ultrasonography (EUS). Approximately 15 mL of methylene blue saline (0.5%) was then injected through each of the extraesophageal puncture points using a 22 G needle. Radial EUS examinations were conducted before and after ESI. EUS images of the trachea, tracheal bifurcation, arcus aortae and thoracic aorta were recorded. Vital signs were monitored during the ESI procedure and EUS examination. The dogs were then sacrificed for exploratory thoracotomy. RESULTS: No obvious fluctuation in vital signs or serious adverse events occurred during the ESI procedure. On EUS imaging, an apparent hypoechoic area outside the esophagus, which separated the esophagus and adjacent organs, was visualized. The adventitious of the esophagus and adjacent organs were easily distinguished. The findings of subsequent exploratory thoracotomy confirmed the EUS findings: obvious accumulation of a blue liquid in the extraesophageal tissues, as well as in the esophageal-thoracic aorta space, esophageal-arcus aortae space and esophageal-tracheal space. CONCLUSION: The esophagus and adjacent organs were successfully separated by ESI, and extraesophageal saline acted as an effective ultrasonic contrast agent.

Medical thoracoscopy and gastroscopy for the treatment of intrathoracic anastomotic leakage following esophagectomy.

Intrathoracic anastomotic leakage following esophagectomy is extremely difficult to manage appropriately. The outcomes of conservative management strategies are often disappointing, particularly in patients who develop adhesions of the pleural cavity and multiloculated empyema. This study describes a novel approach using combined thoracoscopy and gastroscopy in two cases. Thoracoscopy under local anesthesia was used to dissect the septations within the multiloculated empyema and remove the infected focus by direct visualization, and gastroscopy was subsequently performed to place a nasogastric or sump tube around the leak. The outcomes of both procedures were satisfactory: the empyemas almost completely resolved, the anastomotic leak closed quickly and there was adequate lung re-expansion. Accordingly, the combination of thoracoscopy and gastroscopy for the treatment of intrathoracic anastomotic leak post-esophagectomy may be an effective, safe, minimally-invasive, simple and inexpensive procedure.

Superficial esophageal lesions detected by endoscopic ultrasound enhanced with submucosal edema.

AIM: To determine if there is consistency between endoscopic ultrasound (EUS) findings and pathological results for detecting lesions of different depth in the esophageal mucosa. METHODS: A canine (Beagle) model was established in which lesions of different depths were created in the esophageal mucosa by thermal burning. Seventy-two hours later, these lesions and adjacent tissue in the esophagus were examined by EUS. EUS findings including infiltrating depth, strength of echogenicity and homogeneity were recorded. Dogs were sacrificed and tissue specimens were obtained. We then compared the EUS findings with the pathology reports. RESULTS: Thermal burns created at different power settings caused lesions of different depth in the esophageal mucosa. When the echo strength was shifted from high, medium, to low echogenicity, an increase in the infiltrating depth of the lesion was noted, which coincided with results of the pathology examination. Obvious submucosal edema visualized by EUS was also detected by pathology. Furthermore, because of the enhancement caused by the submucosal edema, the lesions invading into the submucosa were easily visualized by EUS. CONCLUSION: There is consistency between EUS findings and pathological results of esophageal lesions with different depths. Submucosal edema can serve as an ultrasonic contrast agent.

[Analysis of learning process of video-assisted minimally invasive esophagectomy for thoracic esophageal carcinoma].

OBJECTIVE: To evaluate the learning process of video-assisted minimally invasive esophagectomy (MIE). METHODS: One hundred consecutive patients with thoracic esophageal carcinoma were treated by a same team of surgeons, and were divided into 3 groups in chronological order. The former two groups both consisted of 25 patients with thoracoscopy plus laparotomy. The remaining 50 patients were enrolled in the third group with thoracoscopy plus laparoscopy. Clinicopathological data including operative time, blood loss, protection of normal structures, complications, length of ICU stay, postoperative stay, and lymph nodes harvest, were collected and compared between groups. RESULTS: Procedures were accomplished successfully in 96 patients. Only 4 cases were converted to open thoracotomy and none to laparotomy. The median operative time was 310 min and blood loss was 200 ml. The median number of lymph node harvest was 22. The overall complication rate was 50%. Comparison of first two groups revealed that significant differences existed in the preservation rate of arch of azygos vein (P=0.010), bronchial vessels (P=0.038), and exposure rate of thoracic part of left recurrent laryngeal nerve( P=0.048). Comparison of the former and latter 50 patients revealed that significant differences existed in thoracic operative time (P<0.001), blood loss (P=0.025), preservation rate of arch of azygos vein (P=0.001) and bronchial vessels (P<0.001), the number of lymph node harvest in thoracoscopy (P=0.022) and in left recurrent laryngeal nerve chain (P<0.001), and exposure rate of initiate part of left recurrent laryngeal nerve (P=0.002). CONCLUSION: The learning curve of MIE is long and beginners should proceed step by step.

[A new retrievable nitinol alloy stents for treatment of refractory benign esophageal strictures].

OBJECTIVE: To explore long-term effect of the treatment of refractory benign esophageal strictures with a novel retrievable fully covered stent made of nitinol alloy. METHODS: From November 2009 to May 2011, the stents were placed in 8 patients with refractory benign esophageal strictures in the Department of Thoracic Surgery at the Cancer Center of Sun Yat-sen University. Esophago-gastro-duodenoscopy and barium swallow examinations were performed respectively on the 1st, 7th, 30th, 60th day after implantations of the stents and 1,2,3,6 months or even longer after removal of the stents in order to assess the long-term effect on the improvement of dysphagia and the development of complications. RESULTS: The stents were successful deployed in all the patients. The dysphagia scores were improved instantly and significantly as compared to the preoperative scores(P<0.05). Seven patients had long-term improvement of dysphagia. The dwelling time of all the stents ranged from 4 to 60 weeks, with a median of 16.8 weeks. Six patients had their stent removed after a dwelling time of 4 to 18 weeks(median 9.7 weeks). The follow-up period was 1.5-9 months (median 6.1 months). The improvement of dysphagia was also significant during follow-up after removal of the stents(P<0.05). At the most recent follow up, two patients still had the stent in place. The first one has already been followed up for 15 months and was still on regular diet. The other one experienced improvement of dysphagia score up to two months after placement, but downgraded to 3 by the third month. Relapse of stenosis occurred in 1 patient, migration in 2 patients, and tissue hyperplasia in 3 patients, of whom 2 developed inward growth of granulation tissue due to the rupture of the covering membrane. CONCLUSIONS: The new retrievable fully covered stent made of nitinol alloy significantly improves the swallowing function of patients with intractable benign esophageal strictures after implantation and after removal of the stents, with low incidence of long-term restenosis. However, the high rate of migrations and the poor quality of the covering membrane further implies that the design of the new stent still needs to be improved.