Using chemoproteomic techniques, we first identified EIF2AK2, eEF1A1, PRDX3 and VPS4B as direct targets of berberine (BBR) for its synergistically anti-inflammatory effects. Of them, BBR has the strongest affinity with EIF2AK2 via two ionic bonds, and regulates several key inflammatory pathways through EIF2AK2, indicating the dominant role of EIF2AK2. Also, BBR could subtly inhibit the dimerization of EIF2AK2, rather than its enzyme activity, to selectively modulate its downstream pathways including JNK, NF-κB, AKT and NLRP3, with an advantage of good safety profile. In EIF2AK2 gene knockdown mice, the inhibitory IL-1β, IL-6, IL-18 and TNF-α secretion of BBR was obviously attenuated, confirming an EIF2AK2-dependent anti-inflammatory efficacy. The results highlight the BBR's network mechanism on anti-inflammatory effects in which EIF2AK2 is a key target, and inhibition of EIF2AK2 dimerization has a potential to be a therapeutic strategy against inflammation-related disorders.

Hepatocellular carcinoma (HCC) is a highly prevalent tumor in China. It has an insidious onset, rapid progression, early recurrence and poor prognosis. Most patients are already in the middle and late stages when they are diagnosed and lose the best time for surgery. Therefore, early diagnosis and treatment of HCC is crucial for patients. In recent years, contrast-enhanced ultrasound (CEUS) technology has been widely used in the diagnosis of liver diseases, especially in the diagnosis and treatment of HCC, which has an irreplaceable role. Meanwhile, the image fusion technology developed on the basis of CEUS can highlight the value of CEUS in the diagnosis and treatment of HCC.

Twenty-six novel tricyclic sophoridinic and matrinic derivatives containing a common chlorinated benzene fragment were designed, synthesized and evaluated for their anti-ebolavirus (EBOV) activities. Structure-activity relationship analysis indicated: (i) 12-dichlorobenzyl motif was beneficial for the activity; (ii) the chiral configuration at C5 atom might not affect the activity much. Among the target compounds, compound exhibited the most potent potency against EBOV with an IC value of 5.29 μmol/L and an SI value of over 37.8. Further anti-EBOV assay of identified its high effectiveness, and anti-MARV assay of suggested its inspiring broad-spectrum anti-filovirus activity. The results provided powerful information on further strategic optimization and development of this kind of compounds against filoviruses.

ABSTRACT:Objective To establish a rapid molecular method for the detection of aldehyde dehydrogenase-2 (ALDH2)and investigate the gene polymorphisms of ALDH2?2 and determine whether the polymorphic ALDH2 gene is associated with drinking behavior in a Chinese population.Methods The gene polymorphisms of ALDH2?2 were detected using pyrosequencing,TaqMan Real-time PCR and GeneChip microarray technologies;genotyping of 302 volunteers was performed to assess their genetic associations with alcohol use behavior.Results We developed pyrosequencing,TaqMan Real-time PCR and GeneChip microarray methods to identify ALDH2? 2 polymorphisms.The allele frequency of ALDH2?2 was 20.36% in the Chinese population:16.33% in the alcoholic group and 27.83% in non-drinkers (P=0.001).In contrast,the genotype frequency of heterozygous ALDH2?1/?2 plus homozygous ALDH2?2/?2 was 45.28% in non-drinkers and 32.65% in the alcoholics group (P=0.030). Allele frequency of ALDH2 genotypes differed significantly between our Chinese sample and other ethnic groups in Asia,and it was significantly higher than that in European and American countries.Conclusion The developed pyrosequencing,TaqMan Real-time PCR and GeneChip microarray methods are rapid,accurate,high-throughput, convenient,and reliable for detecting ALDH2 polymorphisms.ALDH2?2 gene can protect against the development of alcoholism.The allele frequency of ALDH2 in this Chinese population differs from that in other ethnic groups.

Objective: To explore the relationship between serum level of high-sensitivity cardiac troponin T (hs-cTnT) and atrial ifbrillation (AF) occurrence in patients with stable coronary artery disease (CAD).
Methods: A total of 1011 patients with stable CAD treated in our hospital from 2013-01 to 2015-09 were retrospectively studied. According to quartiles of hs-cTnT, the patients were divided into 4 groups: Group① the patients with hs-cTnT≤7ng/L, n=283, Group② hs-cTnT 7-10ng/L,n=238, Group③ hs-cTnT 10-15ng/L,n=272 and Group④ hs-cTnT>15ng/L,n=218. The relationship between hs-cTnT level and AF occurrence rate was studied; the risk factors for AF occurrence were explored by multi stepwise Logistic regression analysis.
Results: There were 127/1011 (12.6%) patients combining AF and 884 (87.4%) with simple type stable CAD. AF patients had the higher serum level of hs-cTnT than non-AF patients 17.0 (12.0, 25.0) ng/L vs 10.0 (7.0, 13.0) ng/L,P<0.01. With baseline hs-cTnT level increasing, AF occurrence rates were elevated from group① to Group④ as 4.6% (13/283), 4.6% (11/238), 11.0% (30/272) and 33.5% (73/218), Ptrend<0.05. Multi stepwise Logistic regression analysis revealed that with adjusted common risk factors of age and gender, the risk for stable CAD patients suffering from AF in Group④ was 5.324 times higher than group① (95% CI 2.285-12.405,P<0.01).
Conclusion: Increased serum level of hs-cTnT was closely related to AF occurrence in patients with stable CAD.

OBJECTIVE: To explore the efficacy of individualized subcutaneous immunotherapy (SCIT) in allergic rhinitis(AR) maintain phase. METHOD: Compare nasal symptom scores (VAS) and special disease scale--nasal conjunctivitis quality of life questionnaire(RQLQ) score after 3 years treatment to evaluate the therapeutic effect of each group and the level of improving patients quality of life. Take patients' blood to detect the serum level of IL-10 by enzyme linked immunosorbent test (enzyme linked immunosorbent assay). RESULT: After 3 years treatment, there was no difference of VAS between the conventional SCIT group and the individualized SCIT group. ELISA results showed that the level of IL-10 was significantly higher in the drug symptomatic treatment group than that in the healthy group, the levels of IL-10 were significantly lower in the conventional SCIT group and the individualized SCIT group than that in the healthy group, but there was no difference between the conventional SCIT and the individualized SCIT group. CONCLUSION After 3 years treatment, there was no difference between conventional and individualized SCIT groups. But the efficacy of the conventional and individualized SCIT groups were significantly better than that in the drug symptomatic treatment group.
Desensitization, Immunologic ; Enzyme-Linked Immunosorbent Assay ; Humans ; Injections, Subcutaneous ; Interleukin-10 ; blood ; Precision Medicine ; Quality of Life ; Rhinitis, Allergic ; drug therapy ; Surveys and Questionnaires

Posterior circulation ischemia (PCI) is a common disease and frequent encountered disease in clinical practice. It refers to the transient ischemic attack and the cerebral infarction in vertebral-basilar artery system. Vertebral aretery atherosclerosis is one of the common causes of PCI. Imaging examinations for PCI include transcranial Doppler (TCD), digital subtraction angiography (DSA), computerized tomographic angiography (CTA), magnetic resonance angiography (MRA), color Doppler ultrasound (CDU) and so on. TCD can serve as initial screening tool in diagnosis of PCI. DSA is still thegold standardin diagnosis of vertebral-basilar abnormalities, although the operation injury and photography drugs poisonousness have not been resolved. CTA has almost the same defects as DSA, while MRA is noninvasive. Some researches have reposed that MRA can exaggerate the vertebral artery depression level. The inner diameter and hemodynamics of the vertebral artery can be accurately measured by CDU, and it can be seen as a noninvasive examination for PCI,which is direct, accurate, convenient and repeatable. It can provide positive evidence for diagnosis and treatment of PCI. This article reviews the progess of CDU in diagnosis of vertebral aretery atherosclerosis.

Objective To conduct comparative study of vertebral artery blood flow of arteriosclerosis patients and healthy people using color Doppler ultrasound (CDUS),and to discuss the effect of arteriosclerosis on vertebral arterial blood flow.Methods Two hundred and eighty-five cases of vertebral artery test were collected and divided in to normal group of one hundred and thirty-five cases and vertebral artery sclerosis group of one hundred and fifty cases according to the presence of vertebral artery sclerosis.Time averaged maximum velocity (TAMV) and vertebral artery diameter(D) of vertebral artery were measured using CDUS technique.Unilateral vertebral artery blood flow and total blood flow were calculated.Results The vertebral artery TAMV and total blood flow of arteriosclerosis group was both lower than that of normal group (P＜0.05).Left side vertebral artery diameters of the two groups were higher than that of the right side.Conclusions Arteriosclerosis can reduce vertebral artery TAMV and blood flow.The inner diameter of the left side vertebral artery dominates the artery blood flow.

Objective To conduct comparative study of healthy vertebral artery (VA) blood flow of subjects from plain and plateau region using color Doppler ultrasound (CDUS) measurement,and to investigate the influence of plateau on blood flow of VA.Methods One hundred and thirty-five subjects from plain region and eighty from high altitude region were recruited.Time averaged maximum velocity and inradium (D) of VA were measured with CDUS technology.Unilateral VA blood flow and total blood flow were calculated.Peripheral blood viscosity measurement was carried out by testing low cut,mid cut,high cut,plasma viscosity and red blood cell count (RBC),hemoglobin concentration (HGB),hematocrit (HCT).Results VA diameter,blood viscosity,RBC,HGB,and HCT of plateau group are all higher than that of the plain group (P＜0.05),while the total blood flow was lower than that of plain group and the value of male was higher than that of female (P＜0.05).The inradiums of right side VA were larger than that of the left side (P＜0.05) in plain group,while no difference was observed in plateau group (P＞0.05).Conclusions Long term (＞10 years) living in plateau hypoxia (altitude＞3 000 m) environment can reduce the average flow velocity and the blood flow of VA.

Objective To investigate the correlation of ankle-brachial index( ABI)., color doppler ultrasound spectrum and toe-brachial index (TBI) of lower extremity artery in diabetic patients. Methods ABI, TBI and color doppler ultrasound spectrum measurement were carried out on 109 lower extremity artery of 55 diabetic patients. Croups were assigned according to ABI and TBI values and the correlation of ABI and color doppler ultrasound spectrum as well as ABI and TBI. Results The changes of ABI and of color doppler ultrasound spectrum in Group A1(0.9