Trichostatin C attenuates TNFα-induced inflammation in endothelial cells by up-regulating Krüppel-like factor 2 / 药学学报

Krüppel-like transcription factor 2 (KLF2) plays a key regulatory role in endothelial inflammation, thrombosis, angiogenesis and macrophage inflammation and polarization, and up-regulation of KLF2 expression has the potential to prevent and treatment atherosclerosis. In this study, trichostatin C (TSC) was obtained from the secondary metabolites of rice fermentation of Streptomyces sp. CPCC 203909 as a KLF2 up-regulator by using a high throughput screening model based on a KLF2 promoter luciferase reporter assay. TSC significantly inhibited the adhesion of tumor necrosis factor-α (TNFα) induced monocytes (THP-1) to human umbilical vein endothelial cells (HUVECs). Western blot results showed that TSC decreased TNFα induced the protein expression increase of vascular cell adhesion molecule-1 (VCAM-1), and thereby inhibited endothelial inflammation. The results of histone deacetylase (HDAC) overexpression and molecular docking experiments showed that TSC upregulated the expression of KLF2 by inhibiting subtypes of HDAC 4/5/7. In conclusion, this study suggests that TSC up-regulates the expression of KLF2 through inhibiting HDAC 4/5/7 and thus inhibits TNFα induced endothelial inflammation, and it has the potential to prevent and treat atherosclerosis.

Rutaecarpine exerted anti-osteroporosis / 药学学报

Osteoprotegerin (OPG), secreted by osteoblasts, is a marker of bone turnover. OPG can inhibit osteoclastic differentiation by binding receptor activator of nuclear factor-κB ligand (RANKL). In this study, we found that rutaecarpine (RUT) had the up-regulating OPG activity, and it could significantly increase OPG protein levels in both mouse embryonic osteogenic precursor MC3T3-E1 and human osteosarcoma U-2OS cells. Osteoblastogenic differentiation calcified nodules staining results showed that RUT significantly promoted the osteogenic differentiation of MC3T3-E1 cells. Osteoclastic differentiation tartrate resistant acid phosphatase (TRAP) staining results showed that RUT obviously inhibited the osteoclast differentiation of mouse macrophages RAW264.7 induced by RANKL. In vivo studies showed that low-dose RUT group (5 mg·kg-1·day-1) and high-dose RUT group (45 mg·kg-1·day-1) treatments for 3 months significantly increased bone density in ovariectomized (OVX) rats; calcein double labeling experiment and toluidine blue staining results indicated that low-dose RUT group promoted bone formation and decreased bone loss in vivo; immunohistochemistry results showed that low-dose RUT group increased the expression of OPG in rat femur. All animal procedures were performed in accordance with the regulations of the Institutional Animal Care and Use Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences. In summary, this study demonstrated that RUT could up-regulate OPG expression and had promoting osteoblastic differentiation and inhibiting osteoclastic differentiation effects in vitro and in vivo.

Selection and evaluation of laparoscopic digestive tract reconstruction after gastrectomy for early gastric cancer / 中国实用外科杂志

In recent years, with the development of laparoscopic technology and the improvement of surgeons' skill, laparoscopic radical gastrectomy for early gastric cancer has been widely achieved in large centers worldwide. But digestive reconstruction under laparoscopy is still the most important for totally laparoscopic surgery. At present, the oncological safety of totally laparoscopic gastrectomy for early gastric cancer has been preliminarily confirmed. Digestive tract reconstruction after totally laparoscopic distal gastrectomy includes Billroth-Ⅰanastomosis, Billroth-Ⅱ anastomosis and Roux-en-Y anastomosis; after proximal gastrectomy, it includes traditional esophagogastric anastomosis and evolutionary anti-reflux surgery;for total gastrectomy, itincludes esophageal jejunal anastomosis by using circular stapler and linear stapler. These reconstruction methods have their own characteristics, and no consensus has been reached at present. However, in clinical practice, it is necessary to focus on the patient, adjust measures to local conditions, and select the appropriate digestive tract reconstruction method on the premise of ensuring the radical cure of tumors.

Fundamental principles for planning, design and construction of clinical laboratory / 医疗卫生装备

Objective To discuss the fundamental principles and methods for planning,design and construction of the clinical laboratory.Methods The principles for planning,designing and constructing the clinical laboratory were summarized,and the key points for planning and designing,the considerations and etc were discussed.Results The principles took considerations on the characteristics of the clinical laboratory,practicability and feasibility,and contributed to establishing the clinical laboratory with advantages in bio-safety,internal partition and optimized clinical laboratory examination.Conclusion The principles can facilitate the building,reconstruction,rebuilding and expansion for other laboratories and standardize the planning,design and construction of the clinical laboratory.

Fundamental principles for planning, design and construction of clinical laboratory / 医疗卫生装备

Objective To discuss the fundamental principles and methods for planning,design and construction of the clinical laboratory.Methods The principles for planning,designing and constructing the clinical laboratory were summarized,and the key points for planning and designing,the considerations and etc were discussed.Results The principles took considerations on the characteristics of the clinical laboratory,practicability and feasibility,and contributed to establishing the clinical laboratory with advantages in bio-safety,internal partition and optimized clinical laboratory examination.Conclusion The principles can facilitate the building,reconstruction,rebuilding and expansion for other laboratories and standardize the planning,design and construction of the clinical laboratory.

Impacts on carotid arterial vessel and blood flow in treatment of carotid atherosclerosis with acupuncture and moxibustion / 中国针灸

<p><b>OBJECTIVE</b>To assess the impacts of acupuncture and moxibustion on carotid arterial vascular structure and blood flow parameters for the patients with carotid arteriosclerosis.</p><p><b>METHODS</b>Sixty-eight cases were randomized into an acupuncture-moxibustion group (35 cases) and a medication group (33 cases). In the acupuncture-moxibustion group, Renying (ST 9), Neiguan (PC 6), Zusanli (ST 36), etc. were selected, moxibustion was applied at Zusanli (ST 36). In the medication group, Enteric-coated aspirin was taken orally. The high-frequency ultrasonography was applied to detect common carotid artery (CCA), intima-media thickness (IMT), peak systolic velocity (PSV), end diastolic velocity (EDV), pulsatility index (PI) and resistance index (RI) before and after treatment for the comparative analysis.</p><p><b>RESULTS</b>After treatment, in comparison between acupuncture-moxibustion group and medication group, CCA got bigger [(8.16 +/- 0.80) mm vs (7.69 +/- 0.61) mm, P < 0.01], IMT became thinner [(1.05 +/- 0.09) mm vs (1.10 +/- 0.09) mm, P < 0.05], PSV and EDV were accelerated (all P < 0.01), and PI and RI were down-regulated (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>Acupuncture and moxibustion provides a good efficacy on the improvement in carotid arteriosclerosis and blood flow in carotid artery, which contributes to the alleviation of ischemic cerebrovascular diseases and prevention from the occurrence and development of them.</p>

Neuroprotective effect of ceftriaxone on focal cerebral ischemia in rats and its mechanism / 中华神经医学杂志

Objective To explore the neuroprotective effect of ceftriaxone on cerebral ischemia injury in rats with focal cerebral ischemia and its possible mechanism. Methods Focal cerebral ischemic models were established in Wistar rats and randomly divided into ischemic group (performed middle cerebral artery occlusion [MCAO]), ceftriaxone (CTX) therapy group (given CTX at a dosage of 200 mg/kg 90 min after MCAO) and control group (given physiological saline only). Twenty-four and 48 h, and 7 d after MCAO, neurological behaviors and cerebral edema level were evaluated in these 3 groups;glutamate transporter function in the cortex and hippocampus of rats was compared between each 2 groups. Results With time extended, neurological behaviors scores were obviously elevated in every group;and cerebral edema became worse at 24 and 48 h and decreased 7 d after MCAO. As compared with that in the ischemic group, glutamate transporter function, level of edema and neurological behaviors scores in cortex and hippocampus of rats in the CTX therapy group were statistically increased at different ischemic time points (P<0.05). Conclusion Ceftriaxone has a neuroprotective effect against focal cerebral ischemia in rats, which may relate to increased glutamate transporter function and reduced glutamate neurotoxicity.

Effect of 15-hydroxyeicosatetraenoic acid on calcium ion concentration of cerebral arterial smooth muscle cells in rats / 中华神经医学杂志

Objective To observe the effect of 15-hydroxyeicosatetraenoic acid (15-HETE) on the intracellular calcium ion ([Ca2+]i) concentration of cerebral arterial smooth muscle and discuss the source of ([Ca2+]i) mobilization induced by 15-HETE to reveal the mechanism underlying the vasoconstriction aroused by 15-HETE. Methods First, papain and collagenase were employed to isolate the cerebral artery smooth muscle cells (SMCs) from the rats. The cells were separated into experimental group (treated with 15-HETE) and control group. Confocal laser scanning microscope was used to investigate the ([Ca2+]i) signaling in cultured SMCs. Then, Ca2+ channel blockers and Ca2+ store depletion agent were added to identify the source of Ca2+ transients in SMCs of the 2 groups. Finally, internal carotid artery (ICA) rings were used to observe the effect of non-Ca2+ solution on 15-HETE-induced ICA vasoconstriction on both groups. Results Compared with the control group, 15-HETE treatment group enjoyed a significantly increased level of ([Ca2+]i) in cultured SMCs (P＜0.05). After the addition of Ca2+channel blockers (nifedipine, lanthanum ion) and calcium-free solution, 15-HETE treatment group still enjoyed a significantly increased level of ([Ca2+]i) in cultured SMCs as compared with the control group (P＜0.05), while after the addition of Ca2+ store depletion agent (caffeine), no obvious difference was noted between the 2 groups (P＞0.05). Non-Ca2+ solution had no effect on 15-HETE induced vasoconstriction.Conclusion 15-HETE may activate Ca2+ releasing from intracellular stores to rise. ([Ca2+]i) level in SMCs, which subsequently induce the constriction of cerebral arterial smooth muscle.

The mechanisms of brain ischemic insult and potential protective interventions / 神经科学通报·英文版

The mechanisms of brain ischemic insult include glutamate excitoxicity, calcium toxicity, free radicals, nitric oxide, inflammatory reactions, as well as dysfunctions of endoplasmic reticulum and mitochondrion. These injury cascades are interconnected in complex ways, thus it is hard to compare their pathogenic importances in ischemia models. And the research in cellular and molecular pathways has spurred the studies in potential neuroprotections mainly in pharmacological fields, such as anti-excitotoxic treatment, calcium-channel antagonism, approaches for inhibition of oxidation, inflammation and apoptosis, etc. Besides, other protective interventions including thrombolysis, arteriogenesis, regeneration therapy, and ischemia preconditioning or postconditioning, are also under investigations. Despite the present difficulties, we are quite optimistic towards future clinical applications of neuroprotective agents, by optimizing experimental approaches and clinical trials.

beta-Secretase inhibitor increases amyloid-beta precursor protein level in rat brain cortical primary neurons induced by okadaic acid / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Senile plaques and neurofibrillary tangles (NFTs) represent two of the major histopathological hallmarks of Alzheimer's disease (AD). The plaques are primarily composed of aggregated amyloid beta (Abeta) peptides. The processing of amyloid-beta precursor protein (AbetaPP) in okadaic acid (OA)-induced tau phosphorylation primary neurons was studied.</p><p><b>METHODS</b>Primary cultures of rat brain cortical neurons were treated with OA and beta-secretase inhibitor. Neurons' viability was measured. AbetaPP processing was examined by immunocytochemistry and Western blotting with specific antibodies against the AbetaPP-N-terminus (NT) and AbetaPP-C-terminus (CT).</p><p><b>RESULTS</b>Ten nmol/L OA had a time-dependent suppression effect on primary neurons' viability. The suppression effect was alleviated markedly by pretreatment with beta-secretase inhibitor. After OA treatment, both AbetaPP and beta-C-terminal fragment (betaCTF) were significantly increased in neurons. AbetaPP level was increased further in neurons pretreated with beta-secretase inhibitor.</p><p><b>CONCLUSIONS</b>In OA-induced tau phosphorylation cell model, inhibition of beta-secretase may protect neurons from death induced by OA. Because of increased accumulation of AbetaPP in neurons after OA treatment, more AbetaPP turns to be cleaved by beta-secretase, producing neurotoxic betaCTF. As apotential effective therapeutic target, beta-secretase is worth investigating further.</p>

Effect of β-secretase inhibitor on amyloid protein precursor metabolism in okadaic acid-induced PC12 cells / 中华神经医学杂志

Objective To observe the effect of β-secretase inhibitor on amyloid protein precursor (APP) metabolism in okadaic acid (OA)-induced PC12 cells. Methods PC12 cells were pretreated with β-secretase inhibitor followed 30 min later by treatment with 10 nmol/L OA for 4, 8, 16, 24 or 48 h to induce tau phosphorylation. The viability of the PC12 cells was measured by MTT assay, and APP metabolism in the cells was examined by immunocytochemistry and Western blotting with specific antibodies against the APP-N-terminus (NT) and APP-C-terminus (CT). Results OA at the concentration of 10 nmol/L time-dependently inhibited PC12 cell viability, and this effect was obviously attenuated by pretreatment of the cells with β-secretase inhibitor. After OA treatment, both APP and β-C-terminal fragment (βCTF) were significantly increased in PC12 cells, and pretreatment with β-secretase inhibitor further increased the intracellular APP level and reduced the level of βCTF. Conclusion OA treatment causes a shift in APP metabolism to the β-secretase pathway that produces neurotoxic βCTF in PC12 cells. Inhibition of β-secretase may alleviate OA-induced cytotoxicity by decreasing the level of βCTF, but the application of β-secretase inhibitor may further increase APP level in the cells.

Morphological study of growth of immature deflected skull / 中华神经医学杂志

Obiective To study the morphological changes of immature defected skull in later growth. Methods Twenty 2-month small-tail Han sheep (female/male ratio 1:1) were randomly divided into operation group(n=10)and control group(n=10).In the former,the parietal skull of 4 cm in diameter was removed in each sheep so as to observe the growth condition of defected bone.In the latter,the sheep were kept in the same envimnmem as the operation group,but without any operation.Results In the operation group, 2 sheep died from complications and trauma, 2 suffered from cerebral atrophy right under defected area,accompanied with psychiatric symptom,and 1 developed everted growth on the margin of bone window;in the others,the margin of bone window appeared afferent growth,which made the defected area smaller, but the new bone was thin and weak relatively. The rest indexes were not different between the 2 groups. Conclusions Skull defect won't lead to skull development malfomlation, and it can be repaired to some extent by bone growth, but the growth can not close completely the defect and make it strong enough for protecting the brain tissue.

Polymorphisms of neural nicotinic cholinergic receptor alpha 4 gene of Chinese / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To screen for polymorphisms in alpha 4 subunit (principal subunit of nAChR) gene (CHRNA4).</p><p><b>METHODS</b>DNA was extracted from leukocytes of all subjects including 100 healthy senior people and 100 patients with Parkinson's disease (PD). The exons and adjacent intron regions of CHRNA4 were amplified with PCR. SNPs were screened by denatured high performance liquid chromatography (DHPLC) techniques and restriction fragment length polymorphisms. Potential mutations were confirmed by sequencing.</p><p><b>RESULTS</b>Total 10 polymorphisms were detected and identified in coding and adjacent intron regions of nAChR alpha 4 gene, that are 420C/T (0.873/0.127), 870C/T (0.828/0.172), 1440A/C (0.858/0.142), 1860C/T (0.738/0.262), 1890C/T (0.605/0.395), intron 5 +14T/C (0.553/0.447), intron 2 +22G/A (0.873/0.127), intron 3 +182 Del22bp (0.813/0.187), 1758C/T and 1809C/T (reference for coding sequence is GenBank SNPs 000744), of which the last three are novel mutations. PD patients appeared higher frequency of deletion in intron 3+182(0.235) than normal controls (0.140)(P=0.015).</p><p><b>CONCLUSION</b>nAChR alpha 4 gene is polymorphic. PD patients take higher frequency of intron3+182 Del 22 bp.</p>

Clinical study on acupuncture and moxibustion for treatment of plaque of carotid atherosclerosis / 中国针灸

<p><b>OBJECTIVE</b>To observe effect of acupuncture and moxibustion on carotid plaque in the patient of carotid atherosclerosis due to ischemic cerebrovascular disease.</p><p><b>METHODS</b>Sixty cases were randomly divided into an acup-mox group and a drug group, 30 cases in each group. Plaque of carotid atherosclerosis and quality of the plaque were investigated by color B-ultrasonography and the thickness and area of the plaque were calculated.</p><p><b>RESULTS</b>The resolution rate of the plaque was 53.9% in the acup-mox group and 10.0% in the drug group with a significant difference between the two groups (P < 0.01), and with better effects on flat plaque and soft plaque. And the thickness and area of the plaque of corotid atherosclerosis were significantly reduced.</p><p><b>CONCLUSION</b>Acupuncture and moxibustion can improve the plaque of corotid atherosclerosis, so as to alleviate and prevent from occurrence and development of ischemic cerebrovascular diseases.</p>

Roles of Th_1/Th_2 type cytokines in experimental autoimmune neuritis / 中华神经科杂志

Objective To establish the model of P2 peptide-induced experimental autoimmune neuritis(EAN)in rats and explore the roles of Th_1/Th_2 type eytokines in EAN.Methods Lewis rats were grouped into EAN rats and control rats.The EAN rats were immunized by injection into both hind footpads of inoculums containing 100 ?g or 200 ?g of P2_(57-81)peptide and FCA while the control rats were immunized with FCA only.Clinical scores were compared at the maximum of disease.Supernatant productions of IFN- ?, IL-4 and IL-10 secreted by lymphocytes and obtained on day 14 after the immunization were examined. Histopathological assessment of sciatic nerves was made.Results Peak clinical scores of P2_(57-81)200 ?g (3.6?0.3)group were significantly higher than P2_(57-81)100 ?g group(2.2?0.6,P

Mechanism of cellular immunity accommodation in prophylactic effects of nasal tolerance with dual analogue on experimental autoimmune myasthenia gravis in Lewis rats / 中华预防医学杂志

<p><b>OBJECTIVE</b>To study the mechanism of prophylactic effects of nasal tolerance with a dual analogue (Lys262-Ala207) on experimental autoimmune myasthenia gravis (EAMG).</p><p><b>METHODS</b>Clinical and immunological changes were observed in Lewis rats administered with dual analogue Lys262-Ala207 nasally, to compare the effects between the rats with predetermined dosage of Lys262-Ala207 and control peptides at two different time points, before the day (Group A or C) or on the day (Group B or D) of immunization with acetylcholine receptor (AChR) in complete Freud's adjuvant for 10 consecutive days. The clinical scores was evaluated for 50 days post immunization. Numbers of MNC expressing IFN-gamma, IL-4 or IL-10 and CD4+ and/or CD25+ from lymph nodes were enumerated by flow cytometry. Proliferative response, expressed as stimulation index (SI), was suppressed in response to antigen-specific stimulation in the rats receiving dual analogue, as compared with the rats receiving saline buffer only.</p><p><b>RESULTS</b>Group A and group B of Lewis rats developed EAMG with reduced severity, as compared to the control groups. Number of cells synthesizing IFN-gamma, IL-4 or IL-10 decreased, whereas numbers of CD4+CD25+ cells increased in group A and B than those in the control groups. Proliferative response was suppressed in response to antigen-specific stimulations in the rats receiving dual analogue Lys262-Ala207.</p><p><b>CONCLUSIONS</b>Nasal administration with a dual analogue Lys262-Ala207 at two different time points, before the day and on the day of immunization, could delay symptoms of muscular weakness in EAMG rats, which was associated with suppression of immune function in AChR antigen-specific T cells and lay a scientific foundation for treatment of human MG with nasal dual analogue.</p>