Memory dysfunction in type 2 diabetes mellitus correlates with reduced hippocampal CA1 and subiculum volumes / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Little attention has been paid to the role of subcortical deep gray matter (SDGM) structures in type 2 diabetes mellitus (T2DM)-induced cognitive impairment, especially hippocampal subfields. Our aims were to assess the in vivo volumes of SDGM structures and hippocampal subfields using magnetic resonance imaging (MRI) and to test their associations with cognitive performance in T2DM.</p><p><b>METHODS</b>A total of 80 T2DM patients and 80 neurologically unimpaired healthy controls matched by age, sex and education level was enrolled in this study. We assessed the volumes of the SDGM structures and seven hippocampal subfields on MRI using a novel technique that enabled automated volumetry. We used Mini-Mental State Examination and Montreal Cognitive Assessment (MoCA) scores as measures of cognitive performance. The association of glycosylated hemoglobin (HbA1c) with SDGM structures and neuropsychological tests and correlations between hippocampal subfields and neuropsychological tests were assessed by partial correlation analysis in T2DM.</p><p><b>RESULTS</b>Bilaterally, the hippocampal volumes were smaller in T2DM patients, mainly in the CA1 and subiculum subfields. Partial correlation analysis showed that the MoCA scores, particularly those regarding delayed memory, were significantly positively correlated with reduced hippocampal CA1 and subiculum volumes in T2DM patients. Additionally, higher HbA1c levels were significantly associated with poor memory performance and hippocampal atrophy among T2DM patients.</p><p><b>CONCLUSIONS</b>These data indicate that the hippocampus might be the main affected region among the SDGM structures in T2DM. These structural changes in the hippocampal CA1 and subiculum areas might be at the core of underlying neurobiological mechanisms of hippocampal dysfunction, suggesting that degeneration in these regions could be responsible for memory impairments in T2DM patients.</p>

Amplitude of low-frequency oscillations in Parkinson's disease: a 2-year longitudinal resting-state functional magnetic resonance imaging study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Neuroimaging studies have found that functional changes exist in patients with Parkinson's disease (PD). However, the majority of functional magnetic resonance imaging (fMRI) studies in patients with PD are task-related and cross-sectional. This study investigated the functional changes observed in patients with PD, at both baseline and after 2 years, using resting-state fMRI. It further investigated the relationship between whole-brain spontaneous neural activity of patients with PD and their clinical characteristics.</p><p><b>METHODS</b>Seventeen patients with PD underwent an MRI procedure at both baseline and after 2 years using resting-state fMRI that was derived from the same 3T MRI. In addition, 20 age- and sex-matched, healthy controls were examined using resting-state fMRI. The fractional amplitude of low-frequency fluctuation (fALFF) approach was used to analyze the fMRI data. Nonlinear registration was used to model within-subject changes over the scanning interval, as well as changes between the patients with PD and the healthy controls. A correlative analysis between the fALFF values and clinical characteristics was performed in the regions showing fALFF differences.</p><p><b>RESULTS</b>Compared to the control subjects, the patients with PD showed increased fALFF values in the left inferior temporal gyrus, right inferior parietal lobule (IPL) and right middle frontal gyrus. Compared to the baseline in the 2 years follow-up, the patients with PD presented with increased fALFF values in the right middle temporal gyrus and right middle occipital gyrus while also having decreased fALFF values in the right cerebellum, right thalamus, right striatum, left superior parietal lobule, left IPL, left precentral gyrus, and left postcentral gyrus (P < 0.01, after correction with AlphaSim). In addition, the fALFF values in the right cerebellum were positively correlated with the Unified PD Rating Scale (UPDRS) motor scores (r = 0.51, P < 0.05, uncorrected) and the change in the UPDRS motor score (r = 0.61, P < 0.05, uncorrected).</p><p><b>CONCLUSIONS</b>The baseline and longitudinal changes of the fALFF values in our study suggest that dysfunction in the brain may affect the regions related to cortico-striato-pallido-thalamic loops and cerebello-thalamo-cortical loops as the disease progresses and that alterations to the spontaneous neural activity of the cerebellum may also play an important role in the disease's progression in patients with PD.</p>

An uncontrolled open-label, multicenter study to monitor the antiviral activity and safety of inhaled zanamivir (as Rotadisk via Diskhaler device) among Chinese adolescents and adults with influenza-like illness / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It is the first multicenter clinical study in China to investigate zanamivir use among Chinese adolescents and adults with influenza-like illness (ILI) since 2009, when inhaled zanamivir (RELENZA(®)) was marketed in China.</p><p><b>METHODS</b>An uncontrolled open-label, multicentre study to evaluate the antiviral activity, and safety of inhaled zanamivir (as Rotadisk via Diskhaler device); 10 mg administered twice daily for 5 days in subjects ≥ 12 years old with ILI. Patients were enrolled within 48 hours of onset and followed for eight days. Patients were defined as being influenza-positive if the real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) test had positive results.</p><p><b>RESULTS</b>A total of 400 patients ≥ 12 years old were screened from 11 centers in seven provinces from March 2010 to January 2011. Three hundred and ninety-two patients who took at least one dose of zanamivir were entered into the safety analysis. The mean age was 33.8 years and 50% were male. Cardiovascular diseases and diabetes were the most common comorbidities. All the reported adverse events, such as rash, nasal ache, muscle ache, nausea, diarrhea, headache, occurred in less than 1% of subjects. Mild sinus bradycadia or arrhythmia occurred in four subjects (1%). Most of the adverse events were mild and did not require any change of treatment. No severe adverse events (SAE) or fatal cases were reported. Bronchospasm was found in a 38 years old woman whose symptoms disappeared after stopping zanamivir and without additional treatment. All the 61 influenza virus isolates (43 before enrollment, 18 during treatment) proved to be sensitive to zanamivir.</p><p><b>CONCLUSIONS</b>Zanamivir is well tolerated by Chinese adolescents and adults with ILIs. There is no evidence for the emergence of drug-resistant isolates during treatment with zanamivir.</p>

Effect of atorvastatin on MMP-9 and TIMP-1 levels in bronchoalveolar lavage fluid and serum of rats with bleomycin-induced pulmonary fibrosis / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effects of atorvastatin on matrix metalloproteinase-9 (MMP-9) and the tissue inhibitor-1 of matrix metalloproteinase (TIMP-1) levels in bronchoalveolar lavage fluid (BALF) and serum of rats with experimental pulmonary fibrosis.</p><p><b>METHODS</b>Pulmonary fibrosis was induced by intratracheal administration of bleomycin in 30 female rats, which were further divided into two groups: Group M (without treatment) and Group A (treated with atorvastatin 10 mg/kg); control group (n = 5, Group C) was intratracheally administrated with same volume of saline. Five animals were sacrificed at 2 weeks (M2 and A2), 4 weeks (M4 and A4) and 6 weeks (M6 and A6) after model establishment, respectively. Lung tissue samples were harvested and prepared for HE and Masson's trichrome staining. Concentrations of MMP-9 and TIMP-1 in BALF and serum were measured by ELISA.</p><p><b>RESULT</b>The severity of inflammation and pulmonary fibrosis was significantly reduced in Group A than that in Group M, especially at week 6. No significant difference was noted in the serum concentrations of MMP-9 and TIMP-1 among the Group M, A and Group C. The BALF concentrations of MMP-9 in Group M2 and M6 were significantly higher than those in Group C (P < 0.01 and 0.05), whereas those in the atorvastatin groups (A2, A4 and A6) were lower than those in M2, M4 and M6. Although the MMP-9 was still higher in Groups A2 and A4 than in the Group C, there was no significant difference in MMP-9 between Group A6 and Group C. TIMP-1 levels in BALF were significantly higher in M4 and M6 than Group C (P < 0.01 and 0.05), there were no significant differences between Group M2 and Group C. The TIMP-1 levels in BALF of atorvastatin groups were significantly lower than those of model groups and control group (P < 0.01 and 0.05), which resulted in a significantly increased ratio of MMP-9 to TIMP-1 in the atorvastatin groups.</p><p><b>CONCLUSION</b>Atorvastatin inhibits the synthesis and release of MMP-9 and TIMP-1 in the lung tissue of rats with bleomycin-induced pulmonary fibrosis, and has no significant effect on circulating MMP-9 and TIMP-1, which may be associated with the attenuation of experimental pulmonary fibrosis in rats.</p>

The interventional effect of anti-basic fibroblast growth factor on the model of bleomycin-induced pulmonary fibrosis in rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To study the effect of anti-basic jibroblast grouth factor (bFGF) on bleomycin-induced pulmonary fibrosis in rats and its possible mechanism.</p><p><b>METHODS</b>Pulmonary fibrosis was induced in Wistar rats by intratracheal instillation of bleomycin (model group, group M). Then the rats received anti-bFGF on 1, 2, 3, 8, 12, 19, 25 days intracavitary injection (group K), normal saline(group C) orally. Normal controls received normal saline both intratracheally and orally. Five rats in each group were sacrificed on 1.4 week after intratracheal instillation. Histological changes of the lungs were evaluated by HE stain and Massons trichrome stain. Lung expression of bFGF proteins was assessed by immunohistochemistry and the level of bFGF protein in serum and BALF was further measured by ELISA.</p><p><b>RESULTS</b>Pulmonary fibrosis of group M was higher than that of group C. bFGF in group M was higher than that in group C in lung, serum and BALF on 1.4 week. Pulmonary fibrosis of group K was lower than that of group M. bFGF in group K was lower than that in group M in lung, serum and BALF on 1.4 week.</p><p><b>CONCLUSION</b>Anti-bFGF alleviates bleomycin-induced pulmonary fibrosis in rats. Inhibiting the expressions of bFGF in lung tissues may be one of the mechanisms.</p>

Inhalation of glucocorticosteroid in the rat model of bleomycin-induced pulmonary fibrosis and its impact on the expression of basic fibroblast growth factor / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To study the effect of inhalation of glucocorticoid on bleomycin-induced pulmonary fibrosis in rats and its possible mechanism.</p><p><b>METHODS</b>Pulmonary fibrosis was induced in Wistar rats by intratracheal instillation of bleomycin (group M, group B, group D). Group B inhaled glucocorticoid daily from the next day of received bleomycin. Group D intraperitoneal injection glucocorticoid daily from the next day of received bleomycin. Normal controls received normal saline both intratracheally. Five rats in each group were killed at 1, 4 week after intratracheal instillation. Histological changes of the lungs were evaluated by HE, Masson trichrome stain. Lung expression of bFGF proteins was assessed by immunohistochemistry and the level of bFGF protein in serum and BALF was further measured by ELISA.</p><p><b>RESULTS</b>Pulmonary fibrosis of group M was higher than that of group C, pulmonary fibrosis of group B, D was lower than that of group M at 1, 4 week. bFGF in group M was higher than that in group C, bFGF in group B, D was lower than that in group M in lung, serum and BALF on 1, 4 week.</p><p><b>CONCLUSION</b>Inhalation of glucocorticosteroid alleviates bleomycin-induced pulmonary fibrosis in rats. The mechanism may be related to the changes that bFGF is degrade or prevent it step up.</p>