Objective: To study the role of inducible nitric oxide synthase (iNOS) in activated macrophages and nitric oxide (NO) in the defence against tumors. Methods: Macrophages were obtained by alveolar lavages of mice and activated through incubation with recombinant murine INF? in vitro. P815 cells were added to the culture. Culture supernates were collected to measure the activity of iNOS and NO. Tumoricidal activity of macrophages was determined in presence and absence of the specific inhibitor of NO synthase: L NMMA. Results: NO production and activity of iNOS induced by activated macrophages were positively related with concentration of INF? in macrophage P815 coculture. The addition of L NMMA to the culture suppressed NO production, the inhibitory rate of activated macrophages against P815 cells was reduced distinctly ( P

OBJECTIVE:To observe clinical efficacy and safety of edaravone combined with butyl phthalide in the treatment of acute ischemic stroke (AIS). METHODS:258 AIS patients were randomly divided into observation group and control group, with 129 cases in each group. Both groups were given routine treatment as antiplatelet,improving microcirculation,controlling blood pressure,lowering blood glucose,regulating blood lipid,keeping plaque stable,nourishing brain cells. Control group was additionally given Butyl phthalide capsules orally,200 mg,tid. Observation group was additionally given Edaravone injection 30 mg added into Sodium chloride injection 100 ml,ivgtt,bid,on the basis of control group. Both groups continuously received 14 days of treatment. The serum inflammatory factor,miR-222 and neurologic impairment score of 2 groups were observed before treatment,7,14 d after treatment. Clinical efficacies and the occurrence of ADR were compared between 2 groups. RESULTS:There was no statistical significance in the serum inflammatory factor,miR-222 and neurologic impairment score between 2 groups before treatment(P>0.05). The serum inflammatory factor and neurologic impairment score of 2 groups were decreased significant-ly 7,14 d after treatment,while serum levels of miR-222 were increased significantly;the observation group was significantly bet-ter than the control group,with statistical significance(P<0.05). Total effective rate of observation group was 92.2%,which was significantly higher than that of control group (69.8%),with statistical significance (P<0.05). No obvious ADR was found in 2 groups. CONCLUSIONS:Edaravone combined with butyl phthalide is effective in the treatment of AIS,and can significantly de-crease serum inflammatory factor level,promote the expression of miR-222 and improve neurologic function with good safety.

BACKGROUND: The frequency of body ailments combined with depression is relatively higher, and hence post stoke depression(PSD) has gained more and more concentration.OBJECTIVE: To investigate the morbidity, related factors and pathophysiological mechanism of PSD.DESIGN: Case analysis and observation study.SETTING: Department of eurology in a hospital of a university; Third department of internal medicine in a hospital of Chinese People' s Armed Police Force; Department of neurology in a province hospital.PARTICIPANTS: This study was carried out at the Neurological Department of First Clinical Hospital Affiliated to Harbin Medical University and the General Hospital of Armed Police Army in Heilongjiang Province from January 2001 to May 2004. A cohort of 312 stroke patients was followed up in this study.METHODS: All 312 patients scored for Hamilton rating scale for depression (HAMD) and European stroke scale(ESS) within 48 hours of hospitalization. Meanwhile their clinical presentations and social-psychological factors were also collected.MAIN OUTCOME MEASURES: The stroke morbidity in patients with different sex, age, personality, educational degree, as well as stroke type, lesion location and extent of neurological functional deficit.RESULTS: The morbidity of PSD was 40. 1%, predominated by mild and medium stroke; amongst which PSD was found more frequent in women than men( P ＜ 0.01), as well as in elders than youngers( P ＜ 0.01); Patients who has diffidence personality are liable to suffer from PSD; and it was found more common in patients with over middle school education than those received only elementary school education ( P ＜ 0.01 ); depression was more frequent in left-sided stroke than right-sided stroke( P ＜ 0.01 ), especially in frontal lobal stroke; PSD was found negatively correlated with the scores for ESS(r= -0.846, P ＜0.05).CONCLUSION: As the result of the interaction of multiple factors, the development of PSD is found accorded with biology-psychology-society mode.

Malignant middle cerebral artery infarction (mMCAI) is a critically ill neurological disease, which often leads to the rapid deterioration of neurological function, resulting in consciousness disturbance and even death. Therefore, early identification and judgment of mMCAI to determine the need for lateral craniectomy decompression is essential to improve the survival rate of patients. With the development of neuroimaging technology, some CT and MRI parameters have been able to predict mMCAI. This article reviews the predictive value of CT and MR related parameters to mMCAI.

Objective:To explore the expression of indoleamine 2, 3-dioxygenase 1(IDO-1), lymphocyte-activation gene 3 (LAG-3) and T cell immunoglobulin domain and mucin domain-containing molecule 3 (TIM-3) in differentiated thyroid cancer (DTC), and the value of them on prognosis.Methods:From May 2014 to November 2015, 119 DTC patients (33 males, 86 females, media age: 42 years) who underwent surgical treatment in Shanghai Sixth People′s Hospital were retrospectively analyzed. The expressions of IDO-1, LAG-3 and TIM-3 in the specimens were analyzed by immunohistochemistry and the expression differences between cancer tissues and normal tissues were analyzed by χ2 test. The correlation of IDO-1, LAG-3 and TIM-3 with clinical characteristics were analyzed using logistic regression analysis. The patients were followed up for 5 years, and the relationships of the progression-free survival (PFS) rate with the expressions of the three immune checkpoints were analyzed by Kaplan-Meier method, log-rank test and Cox proportional hazard models. Results:The overall 5-year PFS rate for 119 DTC patients (median follow-up time: 55(2-66) months) was 76.47%(91/119). The positive expression rates of LAG-3 and TIM-3 in cancer tissues were 21.85%(26/119) and 78.15%(93/119) respectively, which were significantly higher than those in normal thyroid tissues (7.34%(8/109) and 62.39%(68/109); χ2 values: 9.43, 6.81, both P<0.05). While the positive expression rate of IDO-1 was 70.59%(84/119) in cancer tissues, which did not show a significant difference from that in normal thyroid tissues (64.22%(70/109); χ2=1.05, P>0.05). Factors associated with the positive expression of LAG-3 included tumors with a single lesion (odds ratio ( OR)=0.248, 95% CI: 0.086-0.716, P=0.010). Log-rank test ( χ2=4.96, P=0.026) and multivariate Cox regression analysis (hazard ratio ( HR)=2.239, 95% CI: 1.013-4.592, P=0.046) suggested that LAG-3 positive expression was an independent risk factor of PFS. The same analysis of TIM-3 found no clinicopathological factors related to TIM-3 positive expression ( OR: 0.309-3.084, all P>0.05) and no association between TIM-3 positive expression and PFS ( χ2=0.008, P=0.929). Conclusion:The expressions of LAG-3 and TIM-3 are significantly increased in DTC tissues, and the higher expression of LAG-3 is associated with the worse prognosis, suggesting that LAG-3 may be a potential target for immunotherapy in DTC patients.

The damage of nervous system caused by fluorosis has been paid more and more attention. Fluorosis can lead to memory loss, mental retardation and cognitive deficits in children. Advance in the understanding of the mechanism of fluorosis induced nervous system damage will be summarized here from several aspects, including oxidative stress, signal transduction and neurotransmitters and receptors. Oxidative stress is the central link in the mechanism of fluorotoxic nerve damage. Studies have suggested that in addition to some antioxidant drugs and preparations, black garlic, which is a food, has many biological effects such as antioxidants. It suggested that black garlic may have protective effects on fluorosis nerve injury through analyzing the antioxidant property and neuroprotective effects of black garlic, further studies are needed to address the effect and the underlying mechanism of black garlic.

OBJECTIVETo study the toxic effect of toremifene (TOR) and its synergistic effect with cisplatin (DDP) on human lung adenocarcinoma cell line A549.

METHODSThe cytotoxic effects of these agents on human lung cancer cell line A549 were monitored by a tetrazolium-based colorimetric assay (MTT assay). The cell cycle and DNA content were detected by flow cytometer technic. p21 expression level was monitored by Western blot.

RESULTSToremifene inhibited the growth of A549 cell, with > or = 5 micromol/L significantly enhancing the chemosensitivity of cisplatin. TOR enhanced the antitumor activity of DDP at S, G(2) and M phases of cells. And p21 expression was increased after TOR and DDP had been given.

CONCLUSIONToremifene (> or = 5 micromol/L) combined with cisplatin shows significant synergistic anti-tumor effect on A549 cells.

Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; Cell Division ; drug effects ; Cisplatin ; pharmacology ; Drug Resistance, Neoplasm ; Drug Screening Assays, Antitumor ; Drug Synergism ; Humans ; Lung Neoplasms ; pathology ; Toremifene ; pharmacology ; Tumor Cells, Cultured

A large number of studies have confirmed that endothelial dysfunction is one of the important pathogenesis of cerebral small vessel disease (CSVD). Endothelial dysfunction interacts with blood-brain barrier dysfunction, chronic cerebral hypoperfusion, oxidative stress, inflammation and other mechanisms to jointly promote the occurrence and development of CSVD. This article reviews the role of endothelial dysfunction in the pathogenesis of CSVD and its intervention strategies.

Pericytes are located between capillary endothelial cells, astrocytes and neurons. They have many functions such as maintaining the integrity of blood-brain barrier and regulating cerebral blood flow. Loss of pericytes can lead to pathological processes such as brain microcirculation dysfunction and blood-brain barrier destruction, and is associated with a variety of diseases, but there are few studies on the correlation between them and cerebral small vessel disease. This article mainly reviews the role of pericytes in the pathogenesis of cerebral small vessel disease.

As an important imaging marker of cerebral small vessel disease, white matter hyperintensity is closely associated with the clinical manifestations such as cognitive impairment, gait abnormalities, and urinary incontinence. Current studies have shown that the destruction of blood-brain barrier and inflammation response are the important pathophysiological mechanisms of white matter hyperintensity. As the most common immune cell in the inflammatory response of the central nervous system, microglia activation is the key to the occurrence and development of white matter hyperintensity. This article reviews the pathophysiological mechanisms of microglia involved in brain white matter hyperintensity.