Device related thrombus after left atrial appendage closure: State of the art.

Atrial fibrillation (AF), the most common arrhythmia, is a major cause of stroke and systemic embolism. Patients with AF are at higher risk of stroke with the left atrial appendage (LAA) being the most common site for thrombus formation. Although oral anticoagulation (OAC) remains the standard of care for stroke prevention in AF patients, there are still several limitations, including increased risk of bleeding and noncompliance. LAA closure (LAAC) has been found to be non-inferior to OAC in preventing all-cause strokes and systemic embolisms in randomized clinical trials, and is increasingly performed for stroke prevention in patients with nonvalvular AF (NVAF). However, device-related thrombus (DRT) after LAAC and a potentially increased risk of stroke related to DRT were observed in several registered studies, and attract wide concern. This review provides a comprehensive update on the incidence, mechanism, risk factors, prevention, diagnosis, and treatment of DRT after LAAC in patients with NVAF.

Combination of ablation and left atrial appendage closure as "One-stop" procedure in the treatment of atrial fibrillation: Current status and future perspective.

Atrial fibrillation (AF), the most common arrhythmia, is a major cause of stroke and systemic embolism. Left atrial appendage closure (LAAC) has been proved to be noninferior to traditional Vitamin K antagonists (VKAs) as well as novel oral anticoagulants (NOACs), which is becoming an important alternative to prevent stroke in non-valvular AF. Catheter-based AF ablation (CA) is recommended to be a standard of care in patients with AF refractory to drug therapy due to a better rhythm control and improvement of life quality than antiarrhythmic drugs. Theoretically, the one-stop combination with LAAC and CA tends to bring more benefits in patients with AF, as it not only relieves symptoms, but also reduces the risk of stroke significantly. However, several important questions still need to be considered in the combination procedure although quite a few attempts have already been made in clinical practice. This review provides a comprehensive update on the concept, technique, perioperative management, benefits and other critical issues of the "one-stop" procedure.

A Novel Nomogram Predicting Distant Metastasis in T1 and T2 Gallbladder Cancer: A SEER-based Study.

Background: Gallbladder cancer (GBC) is the most common malignancy of the biliary system. Early T stage GBC patients with distant metastasis are proven to have a worse prognosis. In this study, our aim was to construct and validate a novel nomogram for predicting distant metastasis in T1 and T2 GBC. Methods: Between 2004 and 2014, patients with T1 and T2 GBC were identified in the Surveillance, Epidemiology, and End Results (SEER) database. All of the eligible patients were randomly divided into training and validation cohorts. Univariate and multivariate analyses were used to assess significant predictive factors associated with distant metastasis. A nomogram was developed and validated by a calibration curve and receptor operating characteristic curve (ROC) analysis. Results: According to the inclusion and exclusion criteria, 3013 patients with historically confirmed AJCC stage T1 and T2 GBC were enrolled. Younger age, high pathological grade, nonadenocarcinoma, T1, N1 and larger tumor size correlated positively with the risk of distant metastasis. A novel nomogram was established to predict distant metastasis in early T stage GBC patients. Internal validation with a calibration plot in the training cohort showed that this nomogram was well calibrated. Through ROC curve analysis, the areas under the ROC curves in the training and validation cohorts were 0.723 and 0.679, respectively. Conclusions: Although some limitations exist in this predictive model, the nomogram revealed the relationship between the clinicopathological characteristics of T1 and T2 GBC patients and the risk of distant metastasis. The novel nomogram will assist in patient counseling and guide treatment decision making for T1 and T2 GBC patients.

Atorvastatin ameliorates LPS-induced inflammatory response by autophagy via AKT/mTOR signaling pathway.

Macrophages play crucial roles in immune response and atherosclerosis-related cardiovascular disease. Recent evidence of macrophage autophagy has demonstrated a novel pathway through which contributes to vascular inflammation. The aim of this study was to elucidate the role of autophagy in the inhibition of inflammatory response in macrophages by atorvastatin. We found that atorvastatin promoted autophagy flow determined by up-regulating the expression of autophagy-related protein microtubule-associated protein light chain (LC3B), inducing the formation of autophagosomes and down-regulating the expression of SQSTM1/P62, which is consumed during autophagy. Atorvastatin also inhibited the expression of inflammatory factors IL-1ß and TNFα induced by LPS in RAW264.7 cells. Furthermore, pretreatment with an autophagy inhibitor 3MA or LY294002 attenuated the suppressive effect of atorvastatin on LPS-induced IL-1ß and TNFα expression. Additionally, knockdown autophagy-related gene 5(Atg5) with a special siRNA also prevented the role of atorvastatin in decreasing IL-1ß and TNFα release induced by LPS. Finally, we detected that AKT/mTOR/P70S6K signaling pathway was involved in atorvastatin-induced autophagy in macrophages. These data suggest that atorvastatin attenuates LPS-induced inflammatory factors secretion, at least in part, through enhancing autophagy by AKT/mTOR signaling pathway. Our findings provide a novel evidence that statins exert anti-inflammatory effect in atherosclerosis by autophagy activation.

Cannabinoid-2 receptor activation protects against infarct and ischemia-reperfusion heart injury.

Endocannabinoid system is reported to be activated during myocardial ischemia-reperfusion (IR) injury and protects against heart injury. We, therefore, observed changes in endocannabinoids levels during acute myocardial infarction (AMI) and myocardial IR injury and evaluated the role of cannabinoid-2 (CB2) receptor in infarct and IR heart injury. In contrast to 16 control patients with normal coronary artery angiogram, the endocannabinoid 2-arachidonoylglycerol level in the infarct-side coronary artery of 23 AMI patients increased significantly, with increased reactive oxygen species and tumor necrosis factor-α levels in both infarct-side coronary artery and radial artery. Then, 35 C57BL/6J mice were made into SHAM, AMI, or IR models. AMI and IR groups were treated with CB2-selective agonist HU308 ((+)-(1aH,3H,5aH)-4-[2,6-dimethoxy-4-(1,1-dimethylheptyl)phenyl]-6,6-dimethylbicyclo[3.1.1]hept-2-ene-2-carbinol), with or without CB2-selective antagonist AM630 [6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl)methanone through intraperitoneal injection. Compared with the SHAM, expressions of cannabinoid CB1/CB2 receptor proteins in AMI/IR animals were upregulated; production of 2-arachidonoylglycerol and anandamide and release of reactive oxygen species and tumor necrosis factor-α also increased. HU308 significantly decreased the infarct size and the levels of reactive oxygen species and tumor necrosis factor-α in AMI/IR animals. However, these effects were blocked by AM630. In conclusion, the endocannabinoid system was activated during AMI and IR, and CB2 receptor activation produces a protective role, thus offering a novel pharmaceutical target for treating these diseases.

Pharmacoinvasive therapy for ST elevation myocardial infarction in China: a pilot study.

Most patients with acute ST-elevation myocardial infarction (STEMI) cannot receive timely primary percutaneous coronary intervention (PCI) because of lack of facilities or delays in patient transfer or catheterization team mobilization. In these patients, early routine post-thrombolysis PCI might be a reasonable, useful strategy. This study investigated feasibility and safety of early PCI after successful half-dose alteplase reperfusion in a Chinese population. Patients with STEMI received half-dose alteplase if expected time delay to PCI was ≥90 min. Patients who reached clinical criteria of successful thrombolysis reperfusion were recommended to undergo diagnostic angiography within 3-24 h after thrombolysis. Patients with residual stenosis ≥70% in the infarct-related artery underwent PCI, regardless of flow or patency status. Epicardial arterial flow was assessed using thrombolysis in myocardial infarction (TIMI) flow grade and TIMI frame count (CTFC). Myocardial perfusion was assessed using myocardial blush grade (MBG) and TIMI myocardial perfusion frame count (TMPFC). Forty-nine patients were enrolled and underwent diagnostic angiography 3-11.3 h (median 6.5 h) after thrombolysis. Forty-six patients underwent PCI. No procedure-related complications occurred, except two patients who had no reflow after PCI. Twenty-two (47.8%) patients had TIMI grade 3 flow before PCI and 33 (71.7%) after PCI. CTFC was significantly improved after PCI (48.5 ± 32.1 vs. 37.9 ± 25.6, P = 0.01). MBG and TMPFC exhibited a similar improving trend after PCI, and the best myocardial perfusion tended to be achieved 3-12 h after lysis. During the 30-day follow-up, there were two deaths. The composite end point of death, cardiogenic shock, heart failure, reinfarction, and recurrent ischemia occurred in four patients. TIMI minor bleeding occurred in four patients. No TIMI major bleeding and stroke occurred. Early routine PCI after half-dose alteplase thrombolysis in Chinese population appears feasible. A larger clinical trial should be designed to further elucidate its efficacy and safety. Early PCI after thrombolysis in STEMI: The EARLY-PCI pilot feasibility study, ChiCTR-TNC-11001363.

[Collation between Za Liao of Qian Jin Yi Fang and Xin Xiu Ben Cao].

To analyze specific content of Za Liao of Qian Jin Yi Fang, this essay compares its content with related content of Xin Xiu Ben Cao, finding that Za Liao of Qian Jin Yi Fang is derived from the part of Jin An of Xin Xiu Ben Cao, which complements with herbal chapters from volume II to IV of Qian Jin Yi Fang. The texts in Za Liao can verify and collate part of Jin An, and thereby showing important literature value and great help for further studies on traditional Chinese medicines of Tang dynasty.

Risk of device-related thrombosis following short-term oral anticoagulation with low-dose dabigatran versus warfarin after Watchman left atrial appendage occlusion.

BACKGROUND: Percutaneous left atrial appendage occlusion (LAAO) provides an alternative for poor candidates for long-term oral anticoagulation (OAC). To prevent device-related thrombosis (DRT), OAC should be continued for the first 45 days to allow complete endothelialization post-LAAO implantation. Whereas, evidence is limited on the feasibility and safety of direct oral anticoagulants (DOACs) used after LAAO. METHODS: This was a retrospective observational single-center study of AF patients undergoing LAAO with a Watchman device and receiving either low-dose dabigatran (110mg twice daily) or warfarin in the peri- and post-procedural period for 45 days. Transesophageal echocardiography was scheduled to perform at 6 weeks, 6 months, and 12 months after the procedure to assess the stability of the device and to detect DRT. Incidence of thromboembolic and bleeding events were also evaluated during the follow-up period. RESULTS: There were a total of 84 patients who successfully underwent Watchman implantation, with 38 patients (45.2%) receiving low-dose dabigatran and 46 patients (54.8%) using warfarin post-LAAO. Peri-procedural complications occurred in 10 patients, with 3 patients in the dabigatran group and 7 patients in the warfarin group (7.9% vs. 15.2%, p = 0.30). During the 12-month follow-up, 1 patient experienced major bleeding and 16 patients suffered minor bleeding in the warfarin group, while 5 patients treated with dabigatran had minor bleeding (34.8% vs. 13.2%, p = 0.02). Besides, 6 DRT (15.8%) were detected in dabigatran groups, and the incidence was higher than in the warfarin group (15.8% vs. 2.2%, p = 0.03). No DRT-related ischemic events were found. CONCLUSIONS: This study suggested that short-term low-dose dabigatran (110 mg twice daily) could significantly decrease the risk of bleeding compared with warfarin at the expense of increased risk of DRT post-LAAO. Therefore, low-dose dabigatran should be used with caution for post-implant anticoagulation of LAAO. Further studies are urgently needed on the feasibility and safety of DOACs post-LAAO.

The cannabinoid WIN55,212-2 protects against oxidized LDL-induced inflammatory response in murine macrophages.

The endocannabinoid system has recently been attracted interest for its anti-inflammatory and anti-oxidative properties. In this study, we investigated the role of the endocannabinoid system in regulating the oxidized low-density lipoprotein (oxLDL)-induced inflammatory response in macrophages. RAW264.7 mouse macrophages and peritoneal macrophages isolated from Sprague-Dawley (SD) rats were exposed to oxLDL with or without the synthetic cannabinoid WIN55,212-2. To assess the inflammatory response, reactive oxygen species (ROS) and tumor necrosis factor alpha (TNF- alpha) levels were determined, and activation of the mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-kappa B signaling pathways were assessed. We observed that: i) oxLDL strongly induced ROS generation and TNF- alpha secretion in murine macrophages; ii) oxLDL-induced TNF- alpha and ROS levels could be lowered considerably by WIN55,212-2 via inhibition of MAPK (ERK1/2) signaling and NF-kappa B activity; and iii) the effects of WIN55212-2 were attenuated by the selective CB2 receptor antagonist AM630. These results demonstrate the involvement of the endocannabinoid system in regulating the oxLDL-induced inflammatory response in macrophages, and indicate that the CB2 receptor may offer a novel pharmaceutical target for treating atherosclerosis.

Effects of epidermal growth factor receptor inhibitor genistein on proliferative cholangitis in rats.

BACKGROUND: Many strategies for treating hepatolithiasis neglect the therapy for associated proliferative cholangitis (PC), which is the root cause of residual and recurrent stones and biliary strictures, resulting in an unsatisfactory therapeutic outcome. Epidermal growth factor receptor (EGFR) expression is a dominant component in cell proliferation. The aim of this study was to investigate the effect of EGFR inhibitor genistein on PC in rats. METHODS: The rat PC model was established by introducing a nylon thread into the bile duct. Different doses of genistein were administered directly into the bile duct. The effectiveness of genistein on PC was assessed by histology, immunohistochemistry for EGFR, and RT-PCR for EGFR mRNA. RESULTS: The proliferation of biliary epithelium, and fibrous tissue, and the hyperplasia of peribiliary gland in PC were indeed suppressed by genistein, and this antiproliferative effect presented a significant dose-response relationship. The structure of biliary tissue in the high-dose group (genistein 6.0mg/kg) had approached that of the normal bile duct. Compared with the PC model, the levels of expression of EGFR mRNA and protein in the genistein-treated groups were reduced gradually with the increase of genistein dosage, and the level of expression of EGFR mRNA and protein in the high-dose group had neared that of the normal bile duct. CONCLUSIONS: Direct administration of genistein into the bile duct suppressed PC in a rat model, and may provide a novel strategy towards improving the prognosis of patients with hepatolithiasis.

Initial anticoagulation experience with standard-dose rivaroxaban after Watchman left atrial appendage occlusion.

BACKGROUND: Warfarin is now recommended as the standard anti-thrombotic regimen to allow complete endothelialization over the Watchman device post percutaneous left atrial appendage occlusion (LAAO). However, the need for frequent monitoring, narrow therapeutic range, dietary restrictions and multiple drug interactions associated with warfarin have contributed to increasing uptake of non-vitamin K oral anticoagulants (NOACs) worldwide. At present, the feasibility and safety of NOACs instead of warfarin post-LAAO is lacking. METHODS: Patients who underwent successful Watchman device implantation between October 1, 2016 and September 30, 2017 were enrolled in a retrospective database. And only patients who received rivaroxaban in the periprocedural period were included in this study. Transesophageal echocardiography (TEE) follow-up was scheduled at 6 weeks, at 6 months, and at 12 months post-implantation to detect device-related thrombosis (DRT) or peri-device leak. Meanwhile, thromboembolic and bleeding events were also evaluated at the time of follow-up. RESULTS: Totally, 57 Watchman devices were successfully implanted and 10 patients who were allocated to rivaroxaban at the dosage of 20 mg once daily were included. During the follow-up, none of the patients using rivaroxaban experienced DRT, peri-device leak, thromboembolic complications and major bleeding events, except for 2 patients who suffered minor bleeding during the 6 weeks follow-up. CONCLUSIONS: This study suggests that a short course of standard-dose rivaroxaban following Watchman LAAO is associated with low incidence of thrombotic complications and bleeding events, and might be a feasible alternative regimen in Chinese. Further randomized trials and large sample of real-world studies are needed to validate our finding.

Proliferating cell nuclear antigen shRNA treatment attenuates chronic proliferative cholangitis in rats.

BACKGROUND AND AIM: Chronic proliferative cholangitis (CPC) is currently considered as a pathological basis and major cause for the high recurrence rate of intrahepatic stones. Since CPC is a form of chronic proliferative disease, this study was designed to preliminarily investigate the inhibitory effect of proliferating cell nuclear antigen (PCNA) shRNA on the hyperplastic behavior and lithogenic potentiality of CPC. METHODS: The rat model of CPC was given an intralumenal administration of 0.5 mL PCNA shRNA through a 20-gauge venous retained needle. PCNA shRNA-mediated effects on CPC-associated hyperplastic behavior and lithogenic potential were assessed by investigating histological changes, immunohistochemistry for Ki-67, biochemistry for beta-glucuronidase, real-time polymerase chain reaction, and western blot analysis of PCNA, procollagen I, and mucin-3. RESULTS: PCNA shRNA treatment could efficiently inhibit the mRNA and protein expressions of the proliferation-related gene, PCNA, and Ki-67, which efficiently inhibited the hyperplastic behavior of the biliary epithelium, submucosal gland, and collagen fibers in the diseased bile duct wall. This novel treatment could efficiently inhibit the formation of acidic mucus glands, the expression of mucin-3 mRNA, and the secretion of endogenous beta-glucuronidase, thus effectively inhibiting the lithogenic potentiality of CPC. A further analysis revealed that PCNA shRNA-1 might display a more robust inhibitory effect on CPC-associated hyperplastic behavior and lithogenic potential than other gene sequences targeted in this study. CONCLUSIONS: PCNA shRNA-1 treatment could effectively inhibit the hyperplastic behavior and lithogenic potentiality of CPC, which might facilitate the prevention of stone recurrence and biliary restenosis.

Significance of controlling chronic proliferative cholangitis in the treatment of hepatolithiasis.

BACKGROUND: Recently, high stone recurrence and biliary restenosis rates in hepatolithiasis patients have been confirmed to be closely related to chronic proliferative cholangitis (CPC). However, the effective management of CPC has not yet been established. METHODS AND RESULTS: A vicious cycle exists between the presence of intrahepatic calculi and CPC: both the stone itself and secondary biliary infection can stimulate persistent hyperplasia in the biliary duct wall, leading to the occurrence of CPC and biliary stricture. The recurrent attacks of CPC will, in turn, facilitate new stone formation via mucoglycoprotein production, or induced biliary stricture and cholestasis. Thus, even when the stone is completely removed and the biliary tract stenosis is corrected, residual CPC will persist and progress, with an underlying risk for postoperative stone recurrence and biliary tract restenosis. Therefore, the perfect hepatolithiasis treatment would target stone removal and correction of the biliary tract stricture, as well as control of postoperative residual CPC. In fact, CPC, the management of which has been traditionally ignored, is the key to breaking this vicious cycle. CONCLUSIONS: Overall, the subsequent treatment of residual CPC after operation or choledochoscopic lithotomy would be helpful to decrease postoperative stone recurrence and the rate of biliary restenosis. Adding such treatment would reduce the incidence of surgical reintervention and choledochoscopic lithotomy, and it would also improve the postoperative hepatolithiasis outlook.

Practical value of applying cdc2 kinase shRNA to chronic proliferative cholangitis in treatment of hepatolithiasis.

BACKGROUND/AIMS: High stone recurrence and biliary restenosis rates in hepatolithiasis patients have been confirmed to be closely related to postoperatively-remnant chronic proliferative cholangitis (CPC), but effective management strategies have not yet been developed. Since CPC is a type of hyperplastic disease, this study was designed to investigate inhibitory effectiveness of cdc2 k ShRNA on hyperplastic behavior and lithogenic potentiality of CPC. METHODOLOGY: 0.5 ml of P-cdc2 shRNA was injected transpapillarily into the bile duct lumen in a rat model of cholangitis. Then, the effects of cdc2 k ShRNA on CPC were evaluated by histology, immunohistochemistry, RT-PCR, Western blot, biochemistry and enzymatic histochemistry for cdc2 k, PCNA, Ki-67, Procollagen III, Mucin 5AC, beta-glucuronidase and hydroxyproline. RESULTS: cdc2 k shRNA-3 treatment could efficiently inhibit hyperplasia of biliary epithelium, submucosal gland, and collagen fiber by inhibiting mRNA and protein expressions of the proliferation-related gene, cdc2 k, PCNA and Ki-67, thus holding the promise to control or reverse CPC and its secondary biliary stricture. Also of note, this novel treatment may decrease the lithogenic potential of CPC via inhibition of endogenous beta-glucuronidase and Mucin 5AC expression, hereby facilitating the prevention of stone recurrence. CONCLUSION: cdc2 k shRNA-3 treatment could effectively inhibit the hyperplastic behavior and lithogenic potentiality of CPC, which might help to prevent the biliary restenosis and stone recurrence.

Treatment of hepatolithiasis by chemical bile duct embolization: report on 2 cases.

The high recurrence of hepatolithiasis has not been settled effectively until now, which lead us to present a new therapy of the chemical bile duct embolization to resolve it. In our selected 2 patients, multiple biliary calculi, complicated by biliary stricture, were found in the inferior branch of left lateral bile duct via preoperative cholangiography. After the choledochoscopic cholelithotomy, the combination of absolute ethanol and N-butyl-cyanoacrylate were injected into the diseased biliary duct lumen. Two months later, their T-tube cholangiography demonstrated that the targeted biliary ducts were completely embolized, thus effectively preventing the calculous recurrence. Twelve and 15 months later, their computed tomography scan showed that the inferior segments of left lateral lobes were almost completely atrophied and disappeared, thus successfully achieving the chemical "resection" of the diseased hepatic lobe. Chemical bile duct embolization may be a feasible and safe technique to prevent the calculous recurrence and concurrently achieve the effect of chemical hepatectomy for highly selected hepatolithiasis cases.

[Nuclear receptor Nur77 inhibits oxidized low density lipoprotein induced lipid loading in macrophages].

OBJECTIVE: To observe the effect of Nur77 on lipid loading in macrophages exposed to 40 microg/ml oxidized low density lipoprotein (ox-LDL). METHODS: Stable RAW264.7 strain expressing green fluorescent protein (GFP) or GFP-Nur77 was established by G418 screening after transfection with corresponding plasmids and identified by Western blot. After 24 h stimulation with ox-LDL, intracellular lipid loading of each strain was observed by Oil Red O dyeing, and the intracellular cholesterol level was measured by liquid chromatographic-mass spectrometry (LC-MS). The transcriptional changes of CD36 and ABCA1 were monitored by Real Time Quantitative-PCR, while the expressions of these two proteins were assayed by flow cytometry and Western blot, respectively. RESULTS: After 24 h stimulation with ox-LDL, intracellular total cholesterol and esterified cholesterol concentration in GFP-Nur77-RAW264.7 were significantly dropped by 26.15% and 30.93% respectively (P < 0.05 vs. GFP-RAW264.7). The transcription and expression of ABCA1 in GFP-Nur77-RAW264.7 were significantly increased while the transcription and expression of CD36 were significantly reduced (all P < 0.05 vs. GFP-RAW264.7). CONCLUSION: Orphan nuclear receptor Nur77 reduced ox-LDL induced intracellular lipid loading in macrophages by inhibiting lipid influx and enhancing lipid efflux.

Giant submucosal lipoma located in the descending colon: a case report and review of the literature.

Colonic lipoma is an uncommon tumor of the gastrointestinal tract. Most cases are asymptomatic, with a small tumor size, and do not need any special treatment. However, we encountered one patient with a giant submucosal lipoma, with a maximum diameter of 8.5 cm, which exhibited symptoms such as intermittent lower abdominal pain, changes in bowel habits with passage of fresh blood and mucus per rectum, abdominal distension, anorexia and weight loss. Unfortunately, the possibility of colonic malignancy could not be precluded and left hemicolectomy was planned. The exact diagnosis of this special case was accomplished by intraoperative pathology. In the end, local resection was performed instead of left hemicolectomy. To the best of our knowledge, colonic lipoma exceeding 8 cm in diameter has not been previously reported. We, therefore, present this case and discuss age and sex factors, clinical and histopathological findings, diagnostic methods and treatment by reviewing the available literature, to serve as a reminder that colonic lipoma can also exist in patients with significant symptoms. In addition, intraoperative pathology should be investigated in those doubtful cases, so as to guide the exact diagnosis and treatment plan.

The effect of bolus consistency on swallowing function measured by high-resolution manometry in healthy volunteers.

OBJECTIVES/HYPOTHESIS: This study evaluated the effects of three levels of bolus consistency (water, thick liquid, and paste) on the nature and duration of physiologic pressure while swallowing in healthy adults using high-resolution manometry (HRM). STUDY DESIGN: A case series of healthy adults. METHODS: Thirty-four healthy young adults (mean age: 24.29 years) were instructed to swallow 3 mL and 10 mL of water, thick liquid, and paste material, respectively, during which the upper esophageal sphincter (UES) and pharyngeal pressures were measured by HRM. Variables that included maximum pharyngeal pressure, duration of pharyngeal pressure, pharyngeal pressure rise rate, UES residual pressure, duration of UES relaxation, and maximum preopening as well as postclosure UES pressure were analyzed across the three bolus consistencies by one-way repeated measures analysis of variance. RESULTS: Maximum pharyngeal pressure, duration of pharyngeal pressure, duration of UES relaxation, maximum preopening UES pressure, and maximum postclosure UES pressure were significantly increased while swallowing water when compared with the thick liquid and paste materials. No significant differences were observed in UES residual pressure and pharyngeal pressure rise rate among the three different consistencies. CONCLUSION: Variations in bolus consistency appear to have a significant effect on physiologic pressure and duration in healthy adults while swallowing water when compared with thicker materials. Identification of the differences across various bolus consistencies could provide further insight into the pathophysiology of both normal and pathological swallowing. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:173-178, 2017.

Feasibility and effectiveness of chemical bile duct embolization for chemical hepatectomy: a preliminary study.

BACKGROUND: The high operative risk of hepatectomy for specially located intrahepatic stones is still a problem to be solved. This study was undertaken to investigate the feasibility and effectiveness of chemical bile duct embolization for chemical hepatectomy. METHODS: Oxybenzene or absolute ethanol plus N-butyl-cyanoacrylate was employed for embolization. The feasibility, effectiveness and mechanism of chemical hepatectomy were preliminarily analyzed histologically or by Fas, TIMP-1, TGF-beta(1), and collagen I. RESULTS: Oxybenzene plus cyanonacrylate can preferably destroy and embolize the intrahepatic biliary duct, leading to the disappearance of hepatocytes in the periphery of embolized lobe and the achievement of effective chemical hepatectomy. The expressions of Fas, TIMP-1 and TGF-beta(1) in oxybenzene embolism group (88.90 +/- 38.10, 619.43 +/- 183.42, 185.22 +/- 70.39) and ethanol embolism group (72.39 +/- 29.51, 407.55 +/- 134.74, 163.56 +/- 51.75) were higher than those of biliary duct-ligated group (26.31 +/- 12.07, 195.31 +/- 107.67, 74.84 +/- 40.73) (P<0.05). The collagen I-positive percentage in the oxybenzene embolism group was also greater than that of the ethanol embolism group (33.97 +/- 12.51% vs. 20.67 +/- 8.09%, P<0.05). CONCLUSION: The effect of chemical hepatectomy may be achieved by chemical bile duct embolization.

Neuroprotective Effect Is Driven Through the Upregulation of CB1 Receptor in Experimental Autoimmune Encephalomyelitis.

During immuno-mediated demyelinating lesions, endocannabinoid system participates in both inflammatory and neurodegenerative damage through several mechanisms that involve neuronal and immune cells. Here, we constructed lentiviral vector to upregulate CB1 receptor (CB1R) in the lumbar spinal cord 5-6 region and observe the effect of clinical score and possible mechanism on the occurrence and development of experimental autoimmune encephalomyelitis (EAE). The results show that overexpression of CB1R delayed the onset of clinical signs and ameliorated the severity of disease. Overexpression of CB1R significantly inhibited the expression of NF-kB/p65 and TLR-4 as well as levels of IL-1ß, IL-6, and TNF-α, followed by a decrease of IL-17 and an increase of IL-10 in the spinal cord of mice. The percentage of M1 marker CD11b(+)CD16/32(+) cells was decreased, while the percentage of M2 marker CD11b(+)CD206(+) and CD11b(+)IL-10(+) cells was elevated in splenic mononuclear cells (MNCs) of mice with overexpression of CB1R. Interestingly, overexpression of CB1R dramatically enhanced the expression of neurotrophic NT-3, BDNF, and GDNF in the spinal cord. These results indicate that local overexpression of CB1R in the spinal cord exhibited neuroprotective effects in EAE, mainly suppressing inflammatory microenvironment and elevating neurotrophic factors, slightly declining IL-1ß and IL-17 in the spleen, and increased IL-10 in the brain. Its complexity remains to be carefully considered and further studied in further investigation.