Mechanism of Cervi Cornu Pantotrichum in Treatment of Osteoarthritis Based on Network Pharmacology / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Cervi Cornu Pantotrichumin in the treatment of osteoarthritis by network pharmacology. MethodThe active ingredients and the corresponding targets of Cervi Cornu Pantotrichumin were screened out by a Bioinformatics Analysis Tool of Molecular mechANism of Traditional Chinese Medicine （BATMAN-TCM）. The targets related to osteoarthritis were obtained through GeneCards and Online Mendelian Inheritance in Man （OMIM）. The targets corresponding to the active ingredients and those related to osteoarthritis were intersected to reveal the common targets， and STRING was adopted to build a protein-protein interaction （PPI） network. DAVID was used for gene ontology （GO） annotation and Kyoto encyclopedia of genes and genomes （KEGG） pathway enrichment on the anti-osteoarthritis targets of Cervi Cornu Pantotrichumin， and R x64 3.6.3 was employed to produce the advanced bubble charts of GO terms and KEGG pathways. Cytoscape 3.7.2 was used to establish the “Chinese medicinal herb-active ingredient-target-signaling pathway” network. In vitro experiments were performed to detect the viability of RAW 264.7 cells exposed to oxidative stress and the tumor necrosis factor （TNF）-α level in RAW 264.7 cells with inflammation under the treatment by Cervi Cornu Pantotrichumin. ResultA total of 20 active ingredients of Cervi Cornu Pantotrichum were obtained， of which ceramide， 6'-O-β-D-glucosylgentiopicroside， cerebroside， oleuropein， sphingomyelin， and cholesterol ferulate did not meet the screening conditions. Therefore， a total of 14 active ingredients were finally screened out， and 303 and 3 093 targets of active ingredients and osteoarthritis were respectively obtained. The two target sets were taken to intersect， which revealed 92 common targets. GO annotation and KEGG pathway enrichment showed that the targets were mainly involved in redox process， positive regulation of RNA polymerase Ⅱ promoter transcription， inflammatory response， protein synthesis， osteoclast differentiation， TNF signaling pathway， signaling pathways in cancer， mammalian target of rapamycin （mTOR） signaling pathway， mitogen-activated protein kinase （MAPK） signaling pathway， and cyclic adenosine monophosphate （cAMP） signaling pathway. The results of in vitro experiments showed that a certain concentration of protein in Cervi Cornu Pantotrichum significantly increased the viability of RAW 264.7 cells exposed to H2O2-induced oxidative damage （P<0.05， P<0.01） and reduced the level of TNF-α in the RAW 264.7 cells experiencing lipopolysaccharide （LPS）-induced inflammation （P<0.05）. ConclusionBased on the network pharmacology method， the mechanism of the multi-component， multi-target and multi-pathway treatment of OA by antler antler was explained， and the anti-inflammatory and antioxidant activities of antler antler were confirmed， which provided theoretical guidance and scientific basis for further research on the treatment of OA by antler antler.

Effect of Bushen Shugan Prescription on Oxidative Stress and TGF-β1/Smad Signaling Pathway in Hippocampus of Senile Depressed Mice / 中国实验方剂学杂志

Objective:To observe the changes in oxidative stress and transforming growth factor-<italic>β</italic>₁ （TGF-<italic>β</italic>₁）/Smad signaling pathway in hippocampal tissue of senile depressed mice after chronic unpredictable mild stress and to explore the possible anti-depression mechanism of Bushen Shugan prescription. Method:Ninety five-month-old mice were randomly divided into six groups， namely the normal group， senile depression model group， high-， medium-， and low-dose Bushen Shugan prescription groups， and fluoxetine group， with 15 in each group. Mice in all groups， except for the normal group， were exposed to chronic unpredictable mild stress （CUMS） for inducing the senile depression. Since the first day of modeling， the mice in the high-， medium- and low-dose Bushen Shugan prescription groups were gavaged with 19.5， 9.75， 4.87 g·kg^-1 Bushen Shugan prescription， the ones in the fluoxetine group with 0.033 g·kg^-1fluoxetine， and those in the normal and senile depression model groups with an equal volume of normal saline for 21 successive days. The behavioral responses of mice in each group were evaluated in the open field test （OFT）， and the hippocampal tissues of mice were collected for testing the relevant indexes. The superoxide dismutase （SOD） content was determined by WST-1 method， malondialdehyde （MDA） content by TBA method， glutathione （GSH） content by micro enzyme-linked immunosorbent assay （ELISA）， and mRNA expression of TGF-<italic>β</italic>₁， Smad2， Smad3， and Smad7 by Real-time polymerase chain reaction （Real-time PCR）. Result:Compared with the normal group， the senile depression model group exhibited significantly lowered horizontal and vertical scores in OFT， decreased SOD and GSH contents in hippocampal tissues， elevated MDA （<italic>P</italic><0.05）， up-regulated TGF-<italic>β</italic>₁， Smad2， and Smad3 mRNA expression， and down-regulated Smad7 （<italic>P</italic><0.05）. Compared with the senile depression model group， Bushen Shugan prescription at the high， medium， and low doses and fluoxetine all increased SOD and GSH contents in mouse hippocampal tissues， decreased the MDA content （<italic>P</italic><0.05）， down-regulated the mRNA expression of TGF-<italic>β</italic>₁， Smad2， and Smad3 in hippocampal tissues， and up-regulated the Smad7 mRNA expression （<italic>P</italic><0.05）. The comparison with the high-dose Bushen Shugan prescription group showed that the SOD and GSH contents in hippocampal tissues of mice in the medium- and low-dose Bushen Shugan prescription groups declined significantly， while the MDA contents rose significantly （<italic>P</italic><0.05）. Besides， the mRNA expression levels of TGF-<italic>β</italic>₁， Smad2 and Smad3 in the hippocampal tissues of mice in the medium- and low-dose Bushen Shugan prescription groups were significantly up-regulated， and those of Smad7 were significantly down-regulated （<italic>P</italic><0.05）. Conclusion:Bushen Shugan prescription alleviates the depression symptoms in aged SAPM8 mice possibly by regulating the hippocampal oxidative stress and TGF-<italic>β</italic>₁/Smad signaling pathway.

Dynamic three-dimensional blood vessel modeling for analyzing 4 dimensional phase contrast MRI of Stanford B type aortic dissection / 第二军医大学学报

Objective: To apply dynamic three-dimensional blood vessel modeling for analyzing the blood flow parameters obtained by 4 dimensional phase contrast MRI (4D PC-MRI) of Stanford B type aortċc dissection, so as to demonstrate the blood flow characteristics of both healthy controls and patients with Stanford B type aortic dissection. Methods: Dynamic 3D models of blood vessel were captured from 3D PC-MRI with temporal resolution. A reference vascular cross-sectional plane was defined, and the displacement contour information at the same plane was all used to determine the pulsatility of the target vascular cross-sectional planes at multiple time points. The pulsatility parameters of target vascular cross-sectional planes were obtained by temporal tracking. The hemodynamic differences between healthy adults (n=19) and patients (n=8) with Stanford B type aortic dissection were analyzed by comparing 4D PC-MRI data of the two groups. Results: Qualitative blood flow visualization showed laminar flow in the aorta of healthy volunteers, without turbulences or vortex formation, with slight helical flow pattern found in the ascending aorta; there were little changes in the wall shear stress in the entire thoracic aorta. The blood flow in the false lumen was multidirectional and complex, with a high incidence of reverse flow, and the true lumens were dominated by aortic flow direction. The peak velocity of blood flow arrived earlier in the false lumen, not in the true lumen. The stroke volume was greater in the true lumen (media [M]54.3 mL, interquartile range [IQR] 43. 2-64. 8 mL) compared with the false one (M 31.6 mL, IQR 19. 8-47. 6 mL, P < 0.01). The majority of the flow in the true lumen was forward flow (M 91. 4%,IQR 90. 0%-94.2%), whereas the false lumen had a high proportion of backward flow (M 40.3%, IQR 23. 2% 53.3%). The average velocity of blood flow in the false lumen (M 7.1 cm/s, IQR 4. 9-9. 8 cm/s) was lower than that in the true lumen (M 18.0 cm/s, IQR 13.9-20. 6 cm/s, P<0.01). The maximum velocity occurred earlier in the false lumen during the cardiac cycle 166.0 ms after the R-wave (IQR 132. 8-210. 0 ms) compared with that in the true lumen (M 215. 0 ms, IQR 196.3-249.0 ms,P<0. 01). Helical flow mainly occurred at early-systole stage, at 158 ms (IQR 145-249 ms) after the R-wave, and lasted for 310 ms (IQR 217-537 ms), with the maximum rotation being 820° per cardiac cycle. Conclusion: Dynamic 3D modeling method can effectively analyze the flow parameters obtained from 4D PC-MRI and can provide qualitative blood flow information. Flow direction, time to peak velocity, and development and changes of helical flow may be involved in the pathology of aortic dissection.

High-resolution MRI of cranial nerves in posterior fossa at 3.0 T

OBJECTIVE@#To evaluate the influence of high-resolution imaging obtainable with the higher field strength of 3.0 T on the visualization of the brain nerves in the posterior fossa.@*METHODS@#In total, 20 nerves were investigated on MRI of 12 volunteers each and selected for comparison, respectively, with the FSE sequences with 5 mm and 2 mm section thicknesses and gradient recalled echo (GRE) sequences acquired with a 3.0-T scanner. The MR images were evaluated by three independent readers who rated image quality according to depiction of anatomic detail and contrast with use of a rating scale.@*RESULTS@#In general, decrease of the slice thickness showed a significant increase in the detection of nerves as well as in the image quality characteristics. Comparing FSE and GRE imaging, the course of brain nerves and brainstem vessels was visualized best with use of the three-dimensional (3D) pulse sequence.@*CONCLUSIONS@#The comparison revealed the clear advantage of a thin section. The increased resolution enabled immediate identification of all brainstem nerves. GRE sequence most distinctly and confidently depicted pertinent structures and enables 3D reconstruction to illustrate complex relations of the brainstem.

Longitudinal follow-up of patients with mild traumatic brain injury by magnetic resonance spectroscopic technique

OBJECTIVE@#To explore the changes in the concentrations of neural markers immediately or several months after mild traumatic brain injury (mTBI).@*METHODS@#The metabolic markers of neurons in white matter tissues above the lateral ventricle were semi-quantitatively determined by employing 1H magnetic resonance spectroscopic technique (1-H-MRS) in 30 clinically diagnosed cases of mTBI. At the same time, the neurological functions of the subjects, including ability to pay attention, memory, working memory and operational capacity etc were also assessed.@*RESULTS@#The patients were followed up for, on average, 13 days after mTBI and the results showed that Cre, PCre and Glx in the white matter tissues were significantly elevated in mTBI patients. 17 patients (57%) recovered from the injury during the follow-up (median was defined as the 40th post-trauma day). Comparison in terms of intelligence among groups revealed that the levels of neural markers of intelligence development was positively related with intelligence scores).@*CONCLUSIONS@#Change in Glx concentrations is most sensitive during trauma or in ensuing repairing processes, and might be different from normal status in the following months and Glx level tends to be accompanied with change in Cre, another energy-related marker.

Comparison between magnitude reconstruction and phase-sensitive mR imaging in the detection of myocardial infarction

OBJECTIVE@#To determine the deference between phase sensitive magnetic resonance (MR) imaging and magnitude reconstruction to detect infracted myocardium.@*METHODS@#Twenty patients (16 men; 4 women; mean age, 56 years). experienced Q-wave myocardial infarction 2 weeks earlier were examined with a 3.0-T MR system 10 minutes after administration of 0.1 mmol/kg body weight gadobenate dimeglumine. To determine the optimal TI, a TI scout sequence was used. A segmented 2D IR true fast imaging with steady-state precession (trueFISP) sequence that produces both phase-sensitive and magnitude-reconstructed images were used at TI values of 200-600 msec (TI values were varied in 100-msec steps) and at optimal TI (mean value, 330 msec). Contrast-noise ratios (CNRs) of normal and infarcted myocardium and the area of infarcted myocardium were determined. Two-tailed unpaired sample Student t test was used to compare CNRs, and area of infarction.@*RESULTS@#MMean CNR phase-sensitive and magnitude-reconstructed images at optimal TI (mean value, 330 msec) were 6.2, and 6.1, respectively. For a TI of 200 msec, CNR values were 5.5, and 4.2, respectively; for TI of 600 msec, CNR values were 5.8 and 4.3, respectively. Area of infarcted myocardium was underestimated on magnitude-reconstruction images (P = 0.002-0.03) for short TI values (ie., 200 msec) but not on phase sensitive reconstructed when compared with IR tureFISP images obtained at optimal TI.@*CONCLUSIONS@#LPhase-sensitive image reconstruction results in reduced need for precise choice of TI and more consistent image quality.

Characteristics of neurovascular compression in facial neuralgia patients by 3D high-resolution MRI and fusion technology

OBJECTIVE@#To evaluate the anatomical characteristics and patterns of neurovascular compression in patients suffering trigeminal neuralgia, using 3D high-resolution magnetic resonance imaging methods and fusion technologies.@*METHODS@#The analysis of the anatomy of the facial nerve, brain stem and the vascular structures related to this nerve was made in 100 consecutive patients for TN. 3D high resolution MRI studies (3D SPGR, T1 enhanced 3D MP-RAGE and T2/T1 3D FIESTA) simultaneous visualization were used to assessed using the software 3D DOCTOR.@*RESULTS@#In 93 patients (93%), there were one or several locals of neurovascular compression (NVC). The superior cerebellar artery was involved in 71 cases (76%), the other vessels including the antero-inferior cerebellar artery, the basilar artery, the vertebral artery, and some venous structures. The mean distance between NVC and nerve origin site in the brainstem was (3.76 ± 2.90) mm). In 39 patients (42%), the vascular compression was located proximally and in 42 (45%) the compression was located distally. Nerve dislocation or distortion by the vessel was observed in 30 cases (32%).@*CONCLUSIONS@#This 3D high resolution MRI and image fusion technology could be useful for diagnostic and therapeutic decisions in TN.

Characterization of neurovascular compression in facial neuralgia patients by 3D high-resolution MRI and image fusion technique

OBJECTIVE@#To describe the anatomical characteristics and patterns of neurovascular compression (NVC) in patients suffering trigeminal neuralgia (TN) by 3D high-resolution magnetic resonance imaging (MRI) method and image fusion technique.@*METHODS@#The anatomic structure of trigeminal nerve, brain stem and blood vessel was observed in 100 consecutive TN patients by 3D high resolution MRI (3D SPGR, contrast-enhanced T1 3D MP-RAGE and T2/T1 3D FIESTA). The 3D image sources were fused and visualized using 3D DOCTOR software.@*RESULTS@#One or several NVC sites, which usually appeared 0-9.8 mm away from brain stem, were found on the symptomatic side in 93% of the TN cases. Superior cerebellar artery was involved in 76% (71/93) of these cases. The other vessels including antero-inferior cerebellar artery, vertebral artery, basilar artery and veins also contributed to the occurrence of NVC. The NVC sites were found to be located in the proximal segment in 42% of these cases (39/93) and in the distal segment in 45% (42/93). Nerve dislocation or distortion was observed in 32% (30/93).@*CONCLUSIONS@#Various 3D high resolution MRI methods combined with the image fusion technique could provide pathologic anatomic information for the diagnosis and treatment of TN.

Structural abnormalities of trigeminal root with neurovascular compression revealed by high resolution diffusion tensor imaging

OBJECTIVE@#To detect neurovascular compression-induced structural abnormalities of trigeminal nerves (TGN) by diffusion tensor imaging (DTI).@*METHODS@#The affected ipsilateral TGN (iTGN) and unaffected contralateral TGN (cTGN) of 20 trifacial neuralgia (TN) patients as well as the bilateral TGN of 10 normal controls (nTGN) were examined by DTI and 3D high resolution MRI using a 3.0 T MRI scanner. The fractional anisotropy and apparent diffusion coefficient (ADC) were determined.@*RESULTS@#Compared with the cTGN and nTGN, the iTGN had significantly lower fraction of anisotropy (FA), significantly higher ADC, and significantly smaller volume and cross-sectional area (P<0.05).@*CONCLUSIONS@#The increase in ADC and decrease in FA has a close relationship with morphological changes of TGN, and the DTI could provide valuable diagnostic information on TGN structure for TN patients.

Delay enhancement patterns in apical hypertrophic cardiomyopathy by phase-sensitive inversion recovery sequence

OBJECTIVE@#Late gadolinium enhancement (LGE) patterns of cardiovascular magnetic resonance (CMR) relying on PSIR (phase-sensitive inversion recovery sequence) techniques had been used to determine the characteristics of LGE in apical hypertrophic cardiomyopathy (ApHCM).@*METHODS@#Forty patients pure ApHCM [age, (60.2±10.4) years, 31 men] were enrolled. LGE images were acquired using PSIR, and analyzed using a 17-segment model. Summing the LGE areas in all short axis slices yielded the total volume of late enhancement, which was subsequently presented as a proportion of total LV myocardium (% LGE).@*RESULTS@#Mean maximal apical wall thickness was (17.9±2.3) mm, and mean left ventricular (LV) ejection fraction was (67.7±8.0)%. LGE was detected in 130 segments of 30 patients (75.0%), occupying (4.9±5.5)% of LV myocardium. LGE was mainly detected at the junction between left and right ventricles in 12 (30%) and at the apex in 28 (70%), although LGE-positive areas were widely distributed, and not limited to the apex. Focal LGE at the non-hypertrophic LV segments was found in some ApHCM patients, even without LGE of hypertrophied apical segments.@*CONCLUSIONS@#LGE was frequently observed not only in the thickened apex of the heart but also in other LV segments, irrespective of the presence or absence of hypertrophy. The simple presence of LGE on CMR was not representative of adverse prognosis in this population.