Objective To synthesize aristolochic acid Ⅰ(AAⅠ)-DNA adduct in vitro and to develop a method for the characterization of the adduct. Methods Aristolochic acid (AA) was incubated with 2′-Deoxyadenosine 5′-monophosphate in vitro using either enzymatic activation (by xanthine oxidase) or chemical activation (by zinc) to synthesize AAⅠ-DNA adduct. The AAⅠ-DNA adduct was characterized by the liquid chromatography electrospray ionization/tandem mass spectrometry (LC-ESI-MS/MS). Results AAⅠ-DNA adduct was prepared by two activation methods. Full scan spectra were obtained in the negative ion mode and the quasi-molecular ion peak was m/z 621. Analysis by electrospray ionization/tandem mass spectrometry (ESI-MS/MS) provided useful structural information about AAⅠ-DNA adduct. Conclusion AAⅠ can bind covalently to the exocyclic amino group of purine nucleotides to form AAⅠ-DNA adduct. LC/MS/MS is a practical tool to detect AAⅠ-DNA adduct.

Objective To evaluate the effect of curcumin on spinal inflammatory factor in rats with diabetic neuropathy. Methods Diabetic neuropathy was induced by intraperitoneal injection with 1% STZ (60 mg/kg) in sprague-dawley rats. These diabetic rats were randomly allocated to diabetic group (D group, n=10) and curcumin group ( C group , n = 10 ) . Another 10 age-matched normal rats served as controlled group ( N group , n = 10 ) . 28 days after STZ injection, the rats in C group received daily intragastric administration of curcumin (200 mg/kg) whereas those in D group received the same volume of normal saline for 2 weeks. Caudal vein blood glucose levels at T1( before STZ injection)and at T2-T8(2、7、14、21、28、35、42 days after STZ injection)from all rats were detected. Responses to the mechanical stimulus were measured with von Frey filament, and paw withdraw threshold (PWT) was recorded at T1 and at T3 to T8. At T8,the rats were killed and lumbar segments of spinal cord were removed to detect TNF-αand IL-6 content. Results Compared to N group, rats in both C and D group showed hyperglycemia at T2 to T8 (P<0.05) and lower PWT at T4~ 8 (P < 0.01). Compared to D group, C group showed higher PWT at T7,8(P<0.05). Both D and C group showed higher levels of blood sugar at T2 ~ 8 than that at T1 (P < 0.05). C group showed higher PWT at T7,8 than that at T6(P<0.05). Compared to N group,spinal TNF-αand IL-6 content increased in both D and C groups (P<0.05). Compared to D group, C group had reduction of TNF-αand IL-6 concentration (P < 0.05). Conclusion Curcumin can attenuate diabetic neuropathic pain on rats probably by reducing inflammatory factor in spinal cord.

Objective To investigate the recent effect and safety of magnetic resonance guided focused ultrasound (MRgFUS) for treating uterine fibroids with a Meta analysis. Methods Such databases as Cochrane Library,PubMed,EMbase, CBM,CNKI,CQVIP and Wanfang were searched from their establishment. After thestudy selected, assessment and data extraction conducted by two reviewers independently, Meta-analysis were performed by using the Comprehensive Meta-analysis V2 software. The volume of non-perfusion ratio (NPVR), fibroid shrinkage, clinical symptom severity (SSS score) and adverse reactions were analyzed.Results Nighteen retrieved articles were included, with a total of 1 549 patients. The results of Meta-analysis showed that:(1)nonperfused volume ratio (NPVR),Mean=57.1%(95%CI 45.0% —69.2%).(2)Percentage of FBs shrinkage:mean=31.4% (95% CI 29.2% —33.6%).(3)Symptom severity score (SSS):baseline mean=51.00(95%CI 41.61—60.40),3 months mean=32.50 (95%CI 25.90—39.10),6 months mean=28.62(95%CI(23.57—33.66),12 months mean=24.46(95%CI 15.44—33.49), the average of the severity score of the patient symptoms had a tendency to reduce.(4)The degree of adverse reactions were mild and could relieve itself, there was fewer serious adverse reactions. Conclusions The current evidence indicates that MRgFUS in treatment of uterine fibroidsis reliable and safe. MRgFUS can significantly reduce the volume and the symptom severity score ofthe patients.

Objective To evaluate the effect of intrathecal rapamycin on diabetic neuropathic pain in rats.Methods Thirty adult male Sprague-Dawley rats,weighing 180-220 g,in which IT catheters were successfully implanted,were randomly divided into 5 groups (n =6 each) using a random number table:control group (group C),diabetic neuropathic pain group (group DN),rapamycin 1 μg group (group R1),rapamycin 3 μg group (group R3) and rapamycin 10 μg (group R10).Diabetes mellitus was induced by intraperitoneal streptozotocin (STZ) 60 mg/kg on 5 days after IT catheters were implanted in DN,R1,R3 and R10 groups.Citric acid-sodium citrate buffer 6 ml/kg was injected intraperitoneally in group C.In R1,R3 and R10 groups,rapamycin (dissolved in 10 μl 4％ dimethyl sulfoxide) 1,3 and 10 μg were intrathecally injected,respectively,once a day for 7 consecutive days starting from day 21 after STZ injection,while the equal volume of 4％ dimethyl sulfoxide was given instead in C and DN groups.Paw withdrawal threshold (PWT) to yon Frey filament stimulation was measured before IT catheters were implanted,before STZ injection,on 7,14 and 21 days after STZ injection,and on 1,3,5 and 7 days after rapamycin administration.After measurement of PWT,the rats were sacrificed and L2-5 segments of the spinal cord were removed for determination of the expression of mTOR and phosphorylated mTOR (p-mTOR),S6K and phosphorylated S6K (p-S6K) (by Western blot) and expression of mTOR mRNA and S6K mRNA (by RT-PCR).Results Compared with group C,MWT was significantly decreased at 14 and 21 days after STZ injection in DN,R1,R3 and R10 groups,and the expression of mTOR,p-mTOR,S6K,p-S6K,mTOR mRNA and S6K mRNA was up-regulated in group DN (P ＜ 0.01).Compared with group DN,MWT was significantly increased at 5 and 7 days after rapamycin administration in group R1,at 3,5 and 7 days after rapamycin administration in group R3,and at 1,3,5 and 7 days after rapamycin administration in group R10,and the expression of mTOR,p-mTOR,S6K,p-S6K,mTOR mRNA and S6K mRNA was down-regulated in R1,R3 and R10 groups (P ＜ 0.01).Conclusion Intrathecal rapamycin can alleviate diabetic neuropathic pain in rats.

Objective To investigate the effects of Plasmodium vivax merozoite surface protein 1(PvMSP1)on differentia-tion,maturation and function of dendritic cells(DC)and the mechanisms of PvMSP1 on the activation of DC via toll like receptors (TLR). Methods DCs were incubated with different doses of PvMSP1(1.0,10.0,100.0μg/ml)in vitro. The changes of CD83, CD86,and HLA-DR on DC were detected by flow cytometry(FCM);the expressions of cytokine IL-10 and IL-12 of DC were mea-sured by ELISA;the expressions of TLR4 and TLR9 mRNA of DC were measured by RT-PCR;the proliferation induction to autol-ogous lymphocytes of DC was measured by MTT. Meanwhile,the untreated DC and LPS inducing DC were as the negative control and positive control,respectively. All the data were analyzed statistically. Results Compared with the untreated DC,the propor-tions of CD83,CD86 and HLA-DR on DC induced by LPS and PvMSP1 increased significantly(all P<0.05);the expressions of IL-10 and IL-12 of DC induced by LPS increased significantly(P<0.01),and those induced by PvMSP1 also increased signifi-cantly(all P<0.05). In the LPS inducing group,the TLR4 mRNA production increased(P<0.05)and the TLR9 mRNA produc-tion had no significantly changes(P>0.05). In the PvMSP1-treated group,the DC TLR4 mRNA production increased(P<0.01) and the TLR9 mRNA production had no significantly changes(P>0.05);DC stimulated the proliferation of autologous lympho-cytes. Conclusion PvMSP1 enhances DC differentiation and maturation,and the mature DC induced by PvMSP1 has the ability of antigen presenting. The route for PvMSP1 inducing DC maturation might be TLR4 pathway rather than TLR9 pathway.

Objective To explore the diagnosis and treatment of adrenocorticotropin-independent macronodular adrenal hyperplasia (AIMAH). Methods The clinical symptoms, endocrinological and radiological characteristics, treatment modalities, and postoperative clinical course of 12 AIMAH patients were retrospectively reviewed. There were 5 men and 7 women with an average age of 48 years old. Results All cases had some clinical features and biochemical evidence of Cushing's syndrome. The circadian rhythm of serum cortisol was abnormal. Low- and high-dose dexamethasone suppression tests failed to suppress cortisol secretion. CT or MRI scan showed bilateral enlargement of the adrenal glands with multiple macronodules. Bilateral adrenalectomy was performed in three patients and unilateral adrenalectomy combined with contralateral subtotal adrenalectomy was performed in one patient. Seven patients underwent unilateral adrenalectomy of the larger gland. The removed adrenal glands weighted within 8-96 g range and pathologic diagnoses were nodular or adenomatoid hyperplasia of adrenal cortex. The duration of postoperative follow-up was 14 to 124 months. Clinical symptoms of Cushing's syndrome disappeared after surgery in all cases and there was no Nelson's syndrome after bilateral adrenalectomy. Urinary free cortisol and serum cortisol were within normal ranges. No further enlargement of the contralateral gland has been noticed in patients who received unilateral adrenalectomy during the follow-up.Conclusions AIMAH had unique endocrinological and pathological features. Unilateral adrenalectomy appears to be an effective and safe alternative treatment for AIMAH. Bilateral adrenalectomy or unilateral adrenalectomy combined with contralateral subtotal adrenalectomy may be performed if the symptoms had not been improved or recurred after unilateral adrenalectomy.

Objective To evaluate left ventricular function in the way of intracavitary vortex by vector flow mapping(VFM),and to demonstrate the formation and variation of the vortex. Methods Twenty-six patients with dilated cardiomyopathy(DCM) and 44 healthy controls were involved. The velocity distribution imagings on the section plane of the flow in the left ventricle were obtained by VFM, the location of the vortex and its variation in every phase of cardiac cycle were focused,and series parameters were measured,such as the diameter of the vortex (transverse diameter, vertical diameter), number of the vertex. Results relaxation(e) period. Vortices were observed mostly during diastolic period, nearby the anterior leaflet of mitral valve,middle upper 1/3 of left ventricle,and their shapes changed 2 - 3 times. The diameters of the vortex (transverse diameter,vertical diameter) , number of the vertices in one cardiac cycle during 7 phases mostly nearby the cardiac apex, middle lower 2/3 of left ventricle, and their shapes changed 4 - 5 times.Compared with control group,the diameters of the vortex (transverse diameter, vertical diameter) during 7 phases in DCM group were bigger,and number of the vertices were more ( P ＜0.01 ). The diameters of the vortex (transverse diameter, vertical diameter), number of the vertices within DCM group in one cardiac cycle during 7 phases were significantly different ( P ＜ 0.01 ). Conclusions VFM can demonstrate the variation of intracavitary vortex. Vortex in DCM group were significantly bigger than those of control group.

Drug-induced liver injury (DILI) is a major reason for the recall of marketed drugs and the failure of clinical trials. Detection of potential liver injury remains a challenge for clinical management and preclinical drug safety studies. Currently, serum levels of alanine aminotransferase and aspartate aminotransferase are the gold standards for evaluating liver injury. However, these biomarkers are nonspecific and insensitive, and often result in false-positive results. Therefore, researchers have never stopped searching for the biomarkers of DILI with high sensitivity and specificity. This review summarizes recent research progress in the biomarkers of DILI to better predict and diagnose DILI.

Hepatitis B virus-associated glomerulonephritis (HBV-GN) is the most common extrahepatic injury induced by chronic hepatitis B virus (HBV) infection, which has been taken seriously by scholars in recent years. This article summarizes the research advances in related risk factors for HBV-GN, pathogenesis, and treatment. Since the diagnostic rate of HBV-GN is low and the sample size is small at present, there is still much space for research in this field. More clinical trials with good quality are needed in the future to investigate the therapeutic regimens for this disease.

Hepatic encephalopathy (HE) is a serious neuropsychological complication in advanced liver disease, and is a major cause of death in patients with liver disease. The paper briefly introduces the advances in application of HE grading, examination methods, and electroencephalography (EEG) in the diagnosis of HE, and points out that EEG has been developed greatly in the field of HE, with huge potentials for the diagnosis, evaluation, prognosis, and guidance for treatment of HE. However, the clinical value of EEG monitoring in HE has not been widely acknowledged in the medical world, and further investigation is still needed in the future.