Vessel wall magnetic resonance imaging in patients with ischemic stroke / 国际脑血管病杂志

Ischemic stroke is a multifactorial disease, and accurate identification of the etiology is an important link in developing treatment strategies and evaluating outcomes. Vessel wall magnetic resonance imaging has significant advantages in identifying the characteristics of vessel wall lesions, and may provide information for exploring the pathogenesis, follow-up monitoring, and outcome judgment of ischemic stroke.

Liuwei Dihuangwan Regulate Brain Microvessels in SAMP8 Mice Through RAGE/LRP1 Receptors / 中国实验方剂学杂志

ObjectiveTo investigate the protective effect of Liuwei Dihuangwan on neurovascular injury in SAMP8 mice. MethodThe Alzheimer's disease （AD） model with insufficiency of kidney essence was induced in 75 SAMP8 mice aging 6 months. The model mice were divided into model group， positive control group （donepezil hydrochloride， 0.747 mg·kg-1·d-1）， and high-， medium-， and low-dose Liuwei Dihuangwan groups （2.700， 1.350， 0.675 g·kg-1·d-1）， with 15 mice in each group. Fifteen SAMR1 mice were assigned to a normal control group. All mice were administered continuously for 2 months. The spatial memory of mice was tested by the Morris water maze. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in the hippocampus and cortex of brain tissues. The immunohistochemical method （IHC） was used to detect the deposition of amyloid β-protein （Aβ） and the expression of von Willebrand factor （vWF） and CD34 in the hippocampus and cortex of brain tissues. Electron microscopy was used to observe the ultrastructural changes in cerebral microvessels. Western blot was used to detect the protein expression levels of the receptor of advanced glycation endproduct （RAGE）， low-density lipoprotein receptor-related protein 1 （LRP1）， vascular endothelial growth factor A （VEGF-A）， and P-selection in the hippocampus and cortex of brain tissues. ResultCompared with the normal control group， the model group showed prolonged escape latency and swimming distance （P<0.01）， increased number of glial cells， decreased number of nerve cells， blurred tight junctions or enlarged gap of the brain microvascular endothelial cells， severely injured membrane structure， swollen mitochondria of endothelial cells， ruptured membrane， massive dissolution in cristae， increased protein expression of Aβ and vWF in the hippocampus and cortex （P<0.01）， reduced protein expression of CD34 （P<0.05）， elevated protein expression of RAGE and P-selection in the cortex （P<0.01）， and decreased protein expression level of LRP1 and VEGF-A （P<0.01）. Compared with the model group， the Liuwei Dihuangwan groups showed shortened escape latency and swimming distance （P<0.05）， reduced number of glial cells in the cortex and hippocampus， increased number of microvessels in the cortex， clear double-layer membrane structure in tight junctions between the microvascular endothelial cells， increased number of mitochondria with intact membrane and recovered mitochondrial cristae， decreased protein expression of Aβ， vWF， RAGE， and P-selection in the hippocampus and cortex （P<0.05）， and increased protein expression of CD34， LRP1， and VEGF-A （P<0.05）. ConclusionLiuwei Dihuangwan can regulate Aβ metabolism through the RAGE/LRP1 receptor system and promote cerebral microvascular angiogenesis by inhibiting vWF expression and increasing VEGF-A and CD34， thereby improving cerebral microvascular injury in SAMP8 mice.

Effect of Liuwei Dihuangwan on Cognitive Ability of SAMP8 Mice by Regulating Autophagy Through PI3K/Akt/FoxO3a Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Liuwei Dihuangwan on memory function of senescence-accelerated mouse prone 8 （SAMP8） mice by regulating autophagy through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/forkhead box O3a （FoxO3a） pathway. MethodSix male senescence-accelerated mouse resistant 1 （SAMR1） mice of SPF grade aging 6 months were assigned to a normal group， and 24 male SAMP8 mice of SPF grade aging 6 months were randomly divided into a model group， a donepezil group （0.747 mg·kg-1）， and high- and low-dose Liuwei Dihuangwan groups （2.700 and 1.350 g·kg-1）， with 6 mice in each group. The mice were treated with drugs by gavage for 2 months. Morris water maze was used to detect the learning and memory abilities of mice in each group. Nissl staining was used to observe the neurons in the cortex and hippocampus. The positive expression of microtubule-associated protein 1 light chain 3B （LC3B） in the cortex and hippocampus was detected by immunohistochemistry （IHC）. Western blot was used to detect the protein expression of the mammalian ortholog of yeast ATG6 （Beclin-1）， B cell lymphoma-2 （Bcl-2）， autophagy-related gene 5 （ATG5）， cysteinyl aspartate-specific protease 3 （Caspase-3）， Caspase-9， Akt， p-Akt， FoxO3a， and p-FoxO3a. ResultCompared with the normal group， the model group showed prolonged escape latency （P<0.05，P<0.01）， reduced number of platform crossings and the residence time in the target quadrant （P<0.01）， decreased neurons with reduced volume and dispersed distribution in the cortex and hippocampus， increased positive expression of LC3B （P<0.01）， elevated expression of Beclin-1 and ATG5 in the cortex （P<0.01）， declined Bcl-2 expression （P<0.01）， up-regulated Caspase-3 and Caspase-9 expression （P<0.01）， and decreased expression levels of p-Akt/Akt and p-FoxO3a/FoxO3a （P<0.01）. Compared with the model group， the donepezil group and the Liuwei Dihuangwan groups showed shortened 3 d escape latency （P<0.05，P<0.01）， increased number of platform crossings （P<0.01）， and prolonged residence time in the target quadrant （P<0.01）. In the donepezil group， the number of neurons in the cortex and hippocampus was increased. In the Liuwei Dihuangwan groups， the number of neurons and Nissl bodies increased with denser distribution and lower degree of cell damage. The positive expression of LC3B in the cortex and hippocampus was decreased in the donepezil group and Liuwei Dihuangwan groups （P<0.01）. The expression of Beclin-1 was decreased in the Liuwei Dihuangwan groups （P<0.01）. The expression of ATG5 was decreased in the donepezil group and the low-dose Liuwei Dihuangwan group （P<0.01）. The donepezil group and the Liuwei Dihuangwan groups showed the increased expression level of Bcl-2 in the cortex （P<0.01）， decreased expression level of Caspase-3 （P<0.01）， reduced expression level of Caspase-9 （P<0.05，P<0.01）， and elevated expression levels of p-Akt/Akt and p-FoxO3a/FoxO3a （P<0.01）. ConclusionLiuwei Dihuangwan can effectively improve the learning and memory abilities of the SAMP8 mice and protect neurons. Its mechanism may be related to the regulation of the PI3K/Akt/FoxO3a signaling pathway， down-regulation of the expression of ATG5， Beclin-1， and LC3B， and the inhibition of apoptosis.

Stimuli-responsive nano vehicle enhances cancer immunotherapy by coordinating mitochondria-targeted immunogenic cell death and PD-L1 blockade

Induction of immunogenic cell death promotes antitumor immunity against cancer. However, majority of clinically-approved drugs are unable to elicit sufficient ICD. Here, our study revealed that mitochondria-targeted delivery of doxorubicin (DOX) massively amplified ICD via substantial generation of reactive oxygen species (ROS) after mitochondrial damage. The underlying mechanism behind increased ICD was further demonstrated to be ascribed to two pathways: (1) ROS elevated endoplasmic reticulum (ER) stress, leading to surface exposure of calreticulin; (2) ROS promoted release of various mitochondria-associated damage molecules including mitochondrial transcription factor A. Nevertheless, adaptive upregulation of PD-L1 was found after such ICD-inducing treatment. To overcome such immunosuppressive feedback, we developed a tumor stimuli-responsive nano vehicle to simultaneously exert mitochondrial targeted ICD induction and PD-L1 blockade. The nano vehicle was self-assembled from ICD-inducing copolymer and PD-L1 blocking copolymer, and possessed long-circulating property which contributed to better tumor accumulation and mitochondrial targeting. As a result, the nano vehicle remarkably activated antitumor immune responses and exhibited robust antitumor efficacy in both immunogenic and non-immunogenic tumor mouse models.

Surgical treatment of Crohn disease / 中华普通外科杂志

Objective To investigate the surgical indication and surgical procedures for Crohn disease.Methods Clinical data of 47 cases with Crohn disease were retrospectively analyzed.Results The main clinical manifestations were abdominal pain (35 cases),diarrhea (16 cases),emaciation and fatigue(12 cases),abdominal mass (9 cases),intestinal obstruction (31 cases),intestinal adhesion (18 cases),intestinal perforation(8 cases),intestinal bleeding (1 1 cases),internal fistula (4 cases),abdominal abscess (4 cases).Preoperative enteroscopy was performed in 23 cases,and 7 cases were diagnosed as Crohn's disease.Operative procedures included colectomy in 15 cases,small bowel resection and intestinal adhesion lysis in 29 cases,ileostomy in 3 cases.Postoperative complications occurred in 13 cases,including incision dehiscence in 2 cases,intestinal fistula in 5 cases,there were 2 cases of stress ulcer,pulmonary infection in 1 case and short bowel syndrome in 1 case,early postoperative inflammatory bowel obstruction in 2 cases and death in 1 case.44 patients were followed-up,for an average of 6.8 years.Recurrence of Crohn's disease was found in 11 cases and canceration in 3 cases.Conclusions Surgery is still the mainstay for Crohn's disease,and close follow-up is important for disease recurrence and canceration.

Synthesis of new 4-anilinoquinazoline analogues and evaluation of their EGFR inhibitor activity / 药学学报

Thirteen of 4-anilinoquinazoline derivatives with imine groups at position 6 of quinazoline ring were synthesized and their antitumor activities were evaluated by MTT assay and Western blotting analysis. Among these compounds, 13a-131 were reported first time. The MTT assay was carried out on three human cancer cell lines (A549, HepG2 and SMMC7721) with EGFR highly expressed. Among the tested compounds, 13i and 13j exhibited notable inhibition potency and their IC50 values on three cell lines were equivalent to or less than those of gefitinib. Compound 14, without imine group substituted, displayed excellent inhibitor potency only on A549 cell line. Compounds 14 and 13j were chosen to perform Western blotting analysis on A549. The results showed that both of the compounds could inhibit the expression level of phosphorylated EGFR remarkably. It was concluded that the inhibitor potency of compound 14 was almost equivalent to that of gefitinib and the inhibitor potency of 13j was better than that of gefitinib.

The effects of evodiamine on autophagy in human colon adenocarcinoma Lovo cells / 中华普通外科杂志

Objective To investigate the effects of evodiamine on autophagy of human colon a cleno carcinoma lovo cells, and to explore the role and mechanism of autophagy which was induced by evodiamine (EVO). Methods MTT assay combined with the morphologic changes were used to observe the cell viability. Monodansylcadaverine was used to detect autophagy by fluorospectrophotometer and the confocal laser fluorescence microscopy respectively. Immunoblotting assay was used to observe the microtubule-associated protein 1 light chain 3. Finally, evodiamine combined with 3-methyladenine to detect the cell viability with MTT assay and the apoptosis with the flow cytometry, respectively.Results Evodiamine inhibited the viability of Lovo cells in dose-dependent manner ( P ＜ 0. 05 ), especially in 60 μmol/L that was obviously(60% ). Further more, the cell lysis and cell gap widened was observed by the light microscope. Evo triggered the autophagy, and after inhibition the autophagy by 3-MA, the killing capacities of the Evo was enhanced ( P ＜ 0. 01 ). However, autophagy prohibited the apoptosis pathways.Conclusions Evodiamine can trigger the autophagy, which might play a self-defense role in evodiamineinduced cell death. The cytototoxicity of evodiamine can be augmented by the autophagy inhibitors. The joint application of autophagy regulators with the chemotherapeutic agents might enhance the cell killing effects of chemotherapeutic drugs and show a potent role in cancer drug resistance.

Clinical significance of miR-143 and miR-145 expression in gastric gastrointestinal stromal tumor / 中华普通外科杂志

Objective To evaluate the role of miR-143, miR-145 in the development of gastric gastrointestinal stromal tumor. Methods The expression levels of miR-143 and miR-145 in 21 cases of gastric gastrointestinal stromal tumor and the matched non-tumor adjacent tissue specimens were examined by stem-loop real-time RT-PCR, and its correlation with clinicopathologic features of gastric gastrointestinal stromal tumor were analyzed. Results Expression level of miR-145 were significantly higher in tumor than adjacent normal tissues (P＜0.01 ) and that with mitotic count ≥ 5/50HPF cases was significantly lower than that with mitotic count ＜5/50HPF cases (P=0.02). miR-145 expression in huge tumor (＞10 cm)was significantly lower than that in the large tumor (5～10 cm) and small tumor (2～5 cm) (P=0.048).By Fletcher risk stratification system, miR-145 expression in high-risk cases was significantly lower than that in the intermediate-risk and low-risk cases (P=0.048). While the expression of miR-145 in low-risk group was significantly different compared to that in intermediate-risk group and high-risk group (P=0.01).There was no difference between the expressions of miR-143 in tumor and that in normal tissue(P=0.06).Conclusion In gastric gastrointestinal stromal tumor, MiR-145 expression is significantly higher in tumor than adjacent normal tissues. miR-145 is closely associated with tumor size. mitotic counts and Fletcher risk stratification system.

Chemical constituents of Rheum emodi / 中草药

Objective To isolate and determine the structures of chemical constituents from the roots and rootstalks of Rheum emodi.Methods The chemical constituents were isolated and purified by silica gel and polyamide column chromatography.Chemical methods and spectroscopic methods,such as 1H-NMR,13C-NMR,and MS spectra were used for the structure identification.Results Eighteen compounds were obtained.Sixteen of them were identified as:chrysophanol(1),physcion(2),?-sitosterol(3),emodin(4),aloe-emodin(5),rheumin(6),daucosterol(7),d-catechin(8),piceatannol(9),piceatannol-4'-O-?-D-glucopyranoside(10),piceatannol-4'-O-?-D-(6″-O-p-coumaroyl)-glucopyranoside(11),chrysophanol-8-O-?-D-glucopyranoside(12),physcion-1 and 8-O-?-D-glucopyranoside(13a and 13b),emodin-8-O-?-D-glucopyranoside(14),and sucrose(15).Meanwhile,one compound structure simi-lar to rhein was detected.Conclusion Compound 11 is a new compound named rheoside,compounds 13a and 13b are obtained from R.emodi for the first time.