Mesoscale visualization of three-dimensional microvascular architecture and immunocyte distribution in intact mouse liver lobes.

Rational: The complex vascular architecture and diverse immune cells of the liver are critical for maintaining liver homeostasis. However, quantification of the network of liver vasculature and immunocytes at different scales from a single hepatic lobule to an intact liver lobe remains challenging. Methods: Here, we developed a fast and fluorescence-preserving transparency method, denoted liver-CUBIC, for systematic and integrated analysis of the microcirculation and the three-dimensional distribution of dendritic cells (DCs)/macrophages in intact liver lobes. Results: Whole-mount imaging at mesoscale revealed that the hepatic classical lobule preferred the oblate ellipsoid morphology in the mouse liver and exhibited hepatic sinusoids with heterogeneous arrangement and intricate loop structure. Liver fibrosis not only induces sinusoidal density increase but also promotes sinusoidal arrangement with increased sinusoidal branch and loop structure. Meanwhile, we found that CD11c+ DCs followed a lognormal distribution in the hepatic lobules, skewing toward lobular boundary in steady state. CCl4-induced chronic liver injury promoted CD11c+ DC rearrangement at the lobular border before the formation of liver fibrosis. Furthermore, through whole-mount imaging of tumor-immune cell-vascular crosstalk in intact lobes based on liver-CUBIC, we characterized an accumulation of CX3CR1+CCR2+F4/80+ macrophages at metastatic foci in early colorectal liver metastases. Importantly, colorectal cells secrete CCL2 to mobilize CX3CR1+CCR2+F4/80+ macrophages to accumulate at liver micrometastases, and the interruption of CCL2-induced macrophage accumulation inhibits early colonization of metastasis in the liver. Conclusions: Our investigation of the sinusoidal network and DC/macrophage arrangements through the liver-CUBIC approach and whole-mount imaging provide a powerful platform for understanding hepatic circulatory properties and immune surveillance in the liver.

Diagnostic value of autofluorescence laryngoscope in early laryngeal carcinoma and precancerous lesions: A systematic review and meta-analysis.

OBJECTIVE: We aim to evaluate the diagnostic value of autofluorescence laryngoscope (AFL) in early laryngeal carcinoma and precancerous lesions. aWe also assess the value of AFL in diagnosis of early laryngeal carcinoma and precancerous lesions in comparison with that of white light laryngoscope (WL). METHODS: The databases consisting of PubMed, Cochrane Library, Web of science and CNKI were systematically searched to find pertinent literatures of AFL in diagnosing early laryngeal carcinoma and precancerous lesions. We made a quality evaluation of every study we included using the modified Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). The pooled sensitivities, specificities were calculated using Meta-Disc 1.4. And we estimated the summary receiver operating characteristic curves (SROC) and area under the curves (AUC). RESULTS: We finally included 23 studies. The results of AFL in diagnosing early laryngeal carcinoma and precancerous lesions showed higher sensitivity of 0.91 (95%CI: 0.89-0.93; χ²=43.78, p = 0.0025) and specificity of 0.80 (95%CI: 0.77-0.82; χ²=130.64, p = 0.000), and the weighted AUC of AFL was 0.948 ± 0.013 (95%CI: 0.921-0.974) and the diagnostic accuracy (Q*) was 0.887 ± 0.018. The sensitivity and specificity of WL were 0.74 (95%CI: 0.70-0.77; χ²=52.40, p = 0.000) and 0.89 (95%CI: 0.87-0.90; χ²=299.22, p = 0.000), and the weighted AUC of WL was 0.835 ± 0.029 (95%CI: 0.777-0.892) and the diagnostic accuracy (Q*) was 0.767 ± 0.027. CONCLUSION: The meta-analysis and systematic review suggested that AFL had high diagnostic value in early laryngeal carcinoma and precancerous lesions, and its diagnostic value was higher than that of WL. These results indicated that AFL can provide good guidance for the early detection of laryngeal carcinoma and precancerous lesions.

Simple transabdominal minimally invasive direct coronary artery bypass surgery with right gastroepiploic artery.

For three patients with isolated right coronary artery disease who had drug resistance and were intolerant to interventional therapy, simple transabdominal small incision bypass grafting of the right gastroepiploic artery and the posterior descending branch of the right coronary artery was conducted without cardiopulmonary. All three patients were discharged smoothly without complications, and were followed up for three months, during which time the myocardial bridges were unobstructed and the cardiac functions were good. The surgery needs no thoracotomy and the injury is small, and avoids influences of sternum and pericardium adhesion on other cardiac surgery in the future. The risk of median sternotomy can be avoided for patients undergoing reoperation for coronary artery bypass surgery.

Design, Synthesis and Molecular Docking Analysis of Flavonoid Derivatives as Potential Telomerase Inhibitors.

Based on the structural scaffolds of natural products, two series of flavonoid derivatives, for a total of twelve compounds, were designed and synthesized as potential human telomerase inhibitors. Using a modified TRAP-PCR assay, compound 5c exhibited the most potent inhibitory activity against human telomerase with an IC50 value of less than 50 µM. In vitro, the results demonstrated that compound 5c had potent anticancer activity against five classes of tumor cell lines. The molecular docking and molecular dynamics analyses binding to the human telomerase holoenzyme were performed to elucidate the binding mode of active compound 5c. This finding helps the rational design of more potent telomerase inhibitors based on the structural scaffolds of natural products.

Synthesis, biological evaluation and structure-activity relationship studies of hederacolchiside E and its derivatives as potential anti-Alzheimer agents.

Inspired by the previously reported neuroprotective activity of hederacolchiside E (1), we synthesized hederacolchiside E for the first time along with eleven of its derivatives. The neuroprotective effects of these compounds were further evaluated against H2O2- and Aß1-42-induced injury using cell-based assays. The derivatives showed obvious differences in activity due to structural variations, and two of them exhibited better neuroprotective effects than 1 in the Aß1-42-induced injury model. Compound 7 was the most active derivative and had a relatively simple chemical structure. Moreover, 1 and 7 can significantly reduce the release of lactate dehydrogenase (LDH), level of intracellular reactive oxygen species (ROS) and extent of malondialdehyde (MDA) increase resulting from Aß1-42 treatment, which demonstrated that these kinds of compounds show neuroprotective effects in Alzheimer's disease (AD) models via modulating oxidative stress. Compound 7 could be used as promising lead for the development of a new type of neuroprotective agent against AD.

In vivo imaging the motility of monocyte/macrophage during inflammation in diabetic mice.

Diabetes, as a chronic metabolic disease, can impair the immune function of monocytes/macrophages (MMs). However, it is unclear how MM immune response to inflammation with the development of diabetes, and whether immune response around the inflammatory foci depends on the depth in tissue. Footpad provides a classical physiological site for monitoring cellular behavior during inflammation, but limited to the superficial dermis due to the strong scattering of footpad. Herein, we used confocal microscopy to monitor the motility of MMs in deeper tissue around inflammatory foci with the development of type 1 diabetic (T1D) mice through a switchable footpad skin optical clearing window. Delayed-type hypersensitivity (DTH) model was elicited on the footpad of T1D. Results demonstrated that progressive T1D led to the gradually potentiated MM recruitment and increased expression of monocyte chemoattractant protein-1 during DTH, but MM migration displacement, motion velocity and motility coefficient were significantly attenuated. Besides, MMs from the deeper dermis had a much larger migration displacement than those from superficial dermis at early stages of DTH but an opposite tendency at late stages for non-T1D, while progressive T1D obscured this difference gradually. This study will be helpful for investigating the influences of progressive metabolic diseases on immune response. MM motion trajectory at depth of superficial dermis and the deeper dermis at AOVA (heat-aggregated ovalbumin)-4 hours and AOVA-72 hours on non-T1D (A) and T1D-4 weeks (B). Mean motility coefficient (C) at the 2 depths. Data were pooled from 6 mice per group. *P < .05 and **P < .01 compared among different T1D disease durations. #P < .05 compared between different depths.

Design, Synthesis, Molecular Docking Analysis, and Carbonic Anhydrase IX Inhibitory Evaluations of Novel N-Substituted-ß-d-Glucosamine Derivatives that Incorporate Benzenesulfonamides.

A series of novel N-substituted-ß-d-glucosamine derivatives that incorporate benzenesulfonamides were designed using a fragment-based drug design strategy. Each derivative was synthesized and evaluated in vitro for its inhibitory activity against human carbonic anhydrase (hCA) IX; several derivatives displayed desirable potency profiles against this enzyme. The molecular docking studies provided the design rationale and predicted potential binding modes for carbonic anhydrase (CA) IX and three target compounds, including the most potent inhibitor, compound 7f (IC50 = 10.01 nM). Moreover, the calculated Log P (cLog P) values showed that all the compounds tended to be hydrophilic. In addition, topological polar surface area (TPSA) value-based predictions highlighted the selectivity of these carbohydrate-based inhibitors for membrane-associated CA IX.

Stented elephant trunk procedure with left subclavian artery transposition for acute type B dissection with distal arch involvement.

OBJECTIVE: Complete or partial supra-aortic debranching, after thoracic endovascular aortic repair, is appealing treatment for complicated acute type B dissection (ABAD) with aortic arch involvement (AAI) because of reduced surgical trauma. However, unsatisfactory outcomes have been reported. We retrospectively reviewed our experience of left subclavian artery (LSCA) transposition with stented elephant trunk (SET) implantation for complicated ABAD with distal AAI. METHODS: From April 2011 to December 2014, 19 patients (all men; mean age: 44 years) who had complicated ABAD and distal AAI underwent LSCA transposition with SET implantation via a median sternotomy under hypothermic cardiopulmonary bypass with selective cerebral perfusion. Preoperative renal dysfunction was observed in 3 patients, visceral ischemia in 2 patients, and lower-limb ischemia in 1 patient. RESULTS: No in-hospital deaths occurred. Seventeen patients required mechanical ventilation for <24 hours, and 2 cases for <48 hours. The mean time of mechanical ventilation and duration of stay in the intensive care unit was 18 ± 6 hours and 44 ± 16 hours, respectively. Ischemia of the viscera and lower limbs after surgery was ameliorated. Continuous renal replacement therapy was not required in 3 patients who had preoperative renal dysfunction. Complete thrombosis of the false lumen at the distal end of the SET was observed in 17 of 18 (94.4%) patients during follow-up. CONCLUSIONS: This method preserves autologous brachiocephalic vessels, excludes the false lumen, promotes thrombosis and remodeling of the distal aorta, and repairs proximal aortic lesions simultaneously. Satisfactory surgical outcomes and follow-up results were achieved using LSCA transposition with SET implantation.

Surgery for acute type A dissection using total arch replacement combined with stented elephant trunk implantation: Preservation of autologous brachiocephalic vessels.

OBJECTIVE: Various techniques have been introduced to treat acute type A dissection during aortic arch reconstruction. We retrospectively reviewed our experience of total arch replacement, with implantation of a stented elephant trunk, using preservation of autologous brachiocephalic vessels in patients with acute type A dissection. METHODS: Between August 2011 and April 2013, 20 patients (16 men, 4 women; mean age, 45 ± 10 years, range, 24-62 years) with acute type A dissection underwent total arch replacement combined with stented elephant trunk implantation, using preservation of autologous brachiocephalic vessels under hypothermic cardiopulmonary bypass with selective antegrade cerebral perfusion. RESULTS: No in-hospital deaths occurred. A transient neurologic deficit occurred in 1 patient, who ultimately required tracheotomy. Reoperation was indicated in 1 patient for bleeding. All patients survived and were discharged. During the mean follow-up period of 26 ± 7 months, 1 patient underwent thoracoabdominal aortic replacement, and 1 patient was lost to follow up. The patency of the anastomotic site between the left subclavian artery and the left common carotid artery was confirmed on computed tomography scanning. CONCLUSIONS: This technique simplified hemostasis and anastomosis, reduced the size of the residual aortic wall, and preserved the autologous brachiocephalic vessels, yielding satisfactory surgical results. This technique is an alternative approach for suitable patients with acute type A dissection. However, outcomes are preliminary, and long-term follow up is required.

[Influence of electroacupuncture of "Daling"(PC 7) on heart rate, duration of arrhythmia and plasma vasoactive intestinal peptide contents in ventricular tachycardia rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on heart rate (HR), arrhythmia duration, and plasma vasoactive intestinal peptide (VIP) level in ventricular tachycardia (VT) rats so as to study its underlying adjustment mechanism. METHODS: A total of 70 SD rats were randomly divided into normal control, model (VT), "Daling" (PC 7, EA-PC 7) and "Taiyuan" (LU 9, EA-LU 9) groups. VT model was duplicated by injection of CsCI (2 mol/L, 1.6 mmoL/kg, femoral vein). EA (2 Hz/15 Hz, 1 mA) was applied to "Daling" (PC 7) and "Taiyuan" (LU 9) for 5 min after inserting acupuncture needles. BL-410 Biofunctional System was used to record the ECG of the standard limb lead II, and plasma VIP content assayed by using radioimmunoassay. RESULTS: Following intravenous injection of CsCI, HR increased significantly in model, EA-PC 7 and EA-LU 9 groups (P < 0.05). Compared to model group, HR at 5 min, 10 min and 15 min after administration of CsCI and the duration of arrhythmia in EA-PC 7 group decreased considerably (P < 0.01). No significant differences were found between EA-LU 9 and model groups in HR and the duration of arrhythmia (P > 0.05). Compared with normal group, the content of plasma VIP in model group decreased apparently (P < 0.05), while in comparison with model group, plasma VIP level in EA-PC 7 group increased considerably (P < 0.01). CONCLUSION: Electroacupuncture of "Daling" (PC7) can effectively suppress CsCI-induced tachycardia which may be closely associated with its effect in reducing plasma VIP level.

Complications of open stent-graft in treatment of aortic dissection.

Open stent-graft has been used in the treatment of aortic dissection in recent years. Two device related complications happened in two patients. One was stenosis of the true lumen in the descending aorta caused by infolding of the distal end of the stent-graft immediately after its deployment. The other one was a new intima tear at the distal end of the stent-graft caused by full expansion of the stent-graft two years after stent-graft implantation. With the refinement of the device and enrichment of surgeons' experience, such complications could be avoided in the future.

Endovascular repair after stent elephant trunk procedure for extensive thoracic aortic aneurysm.

Hybrid surgical-endovascular procedure was conducted in a 46-year-old male with extensive thoracic aortic aneurysm. Ascending aorta and arch replacement combined with stent elephant trunk implantation was performed first. An open stent-graft was implanted into the descending aorta. One month later, endovascular repair was conducted. Postoperative CTA showed total coverage of the descending aorta by stent-grafts and the descending aortic aneurysm was totally thrombo-excluded. Stent elephant trunk may be a better alternative to conventional elephant trunk in hybrid surgical-endovascular approaches in treatment of extensive thoracic aortic aneurysm.

A study of aortic dimension in type B aortic dissection.

Difference between arch diameter and true lumen diameter in the descending aorta was studied in patients with type B aortic dissection. The diameters of the aortic arch (Proximal ) and mid-descending aorta (Distal ) were measured on computer tomography angiography (CTA) in 20 healthy adults. Forty-two patients with type B aortic dissection who underwent endovascular repair were divided into two groups: an acute group (23 patients) and a chronic group (19 patients). The diameters of the arch (Proximal ) and the true lumen of the mid-descending aorta (Distal ) were measured on digital subtraction angiography (DSA) and CTA. The taper ratio was defined as (Proximal -Distal )/(Proximal )x100%. In the control group, the taper ratio was 13.0+/-4.7% on CTA. In the acute patients group, the taper ratio was 23.6+/-11.3% on DSA and 21.9+/-12.1% on CTA. In the chronic patients group, the taper ratio was 31.5+/-13.6% on DSA and 30.1+/-11.4% on CTA. In both acute and chronic type B aortic dissection, the aorta tapers significantly from arch to true lumen in the descending aorta. Stent-graft with tapered design may be a viable treatment option for endovascular repair of type B aortic dissection.