Alzheimer's disease(AD)has attracted widespread attention due to its extremely complex pathogenic mechanisms,multiple pathogenic factors,and its heavy burden on patients and the society.In recent years,several studies have revealed various pathogenic mechanisms of AD,and the AD treatments based on these mechanisms become research hotspot in nanomedicine.Nanomaterials with unique physi-cochemical properties show great potential in AD treatment.Nanomaterials possess good biocompatibility.Moreover,they can regulate and release therapeutic drugs continuously and steadily to ensure the ideal concentrations of drugs reach in the target site.Meanwhile,they can bind with the therapeutic targets precisely to treat AD.Therefore,the development of novel nanodrugs has become an important research area in AD treatment.This article reviews the main pathological features and pathogenic mechanisms of AD,including β-amyloid plaque aggregation,Tau protein hyperphosphorylation,oxidative stress,and neuroinflammation.Additionally,this review mainly discusses the therapeutic strategies of nanomaterials in clearing pathological proteins(such as β-amyloid and Tau proteins),inhibiting oxidative stress,and alleviating neuroinflammation.Finally,this review prospects the risks and challenges faced on current AD treatment strategies by nanomaterials,such as low drug delivery efficiency to the brain and potential side effects after treatment.We also provide suggestions for the future directions in this research field.This review aims to promote the clinical translation of nanomaterials in AD treatment by discussing the research status of this field.

Alzheimer's disease(AD)has attracted widespread attention due to its extremely complex pathogenic mechanisms,multiple pathogenic factors,and its heavy burden on patients and the society.In recent years,several studies have revealed various pathogenic mechanisms of AD,and the AD treatments based on these mechanisms become research hotspot in nanomedicine.Nanomaterials with unique physi-cochemical properties show great potential in AD treatment.Nanomaterials possess good biocompatibility.Moreover,they can regulate and release therapeutic drugs continuously and steadily to ensure the ideal concentrations of drugs reach in the target site.Meanwhile,they can bind with the therapeutic targets precisely to treat AD.Therefore,the development of novel nanodrugs has become an important research area in AD treatment.This article reviews the main pathological features and pathogenic mechanisms of AD,including β-amyloid plaque aggregation,Tau protein hyperphosphorylation,oxidative stress,and neuroinflammation.Additionally,this review mainly discusses the therapeutic strategies of nanomaterials in clearing pathological proteins(such as β-amyloid and Tau proteins),inhibiting oxidative stress,and alleviating neuroinflammation.Finally,this review prospects the risks and challenges faced on current AD treatment strategies by nanomaterials,such as low drug delivery efficiency to the brain and potential side effects after treatment.We also provide suggestions for the future directions in this research field.This review aims to promote the clinical translation of nanomaterials in AD treatment by discussing the research status of this field.

In this study, Illumina sequencing platform was applied in sequencing rat pancreas, counting expression of target points, analyzing expression differences among blank group, model group and Huangqi Liuyi decoction group and exploring the therapeutic effect and mechanism of Huangqi Liuyi decoction on type 2 diabetes mellitus. According to the result, 24.25% of these genes belonged to the unknown functional class, which was the largest classification unit according to the classification analysis of genes by eggNOG. The rest were classified as energy conversion, amino acid transport and metabolism, nucleotide transport and metabolism, carbohydrate transport and metabolism, coenzyme transport and metabolism, and lipid transport and metabolism, etc.Huangqi Liuyi decoction may play a therapeutic role in the treatment of type 2 diabetes mellitus through four metabolic pathways, namely environmental information processing, cellular process, organismal system and human diseases according to KEGG enrichment analysis. This study shows that, Huangqi Liuyi decoction can significantly improve the fasting blood glucose and glycosylated hemoglobin in type 2 diabetic rats.

Animals ; Cellular Reprogramming ; Dentate Gyrus ; cytology ; Fibroblasts ; cytology ; Mice ; Neural Stem Cells ; cytology ; transplantation ; Swine

OBJECTIVETo determine the effect of berberine (Ber) on norepinephrine (NE)-induced apoptosis in neonatal rat cardiomyocytes.

METHODSThe cultured neonatal rat cardiomyocytes were treated with NE in the presence or absence of Ber. The activity of lactate dehydrogenase (LDH) in the culture medium was examined, and apoptosis of cardiomyocytes was assessed by Hoechst 33258, isothiocyanate (FITC)-conjugated annexin-V, and propidine iodide (PI) staining. In addition, the activities of caspases-2 and-3 were measured by a fluorescent assay kit. The level of secreted tumor necrosis factor α (TNF-α) and production of intracellular reactive oxygen species (ROS) were also determined.

RESULTSNE at a concentration of 50 μ mol/L induced an obvious increase in the activity of LDH in the culture medium (P<0.05), which was inhibited by coincubation with 0.5, 1.0, or 2.0 μ mol/L Ber (P<0.05). Ber also significantly attenuated NE-induced apoptosis in a dose-dependent manner (P<0.01). Moreover, Ber at a dose of 2 μ mol/L markedly decreased the ROS and TNF-α productions (P <0.05) and inhibited the activation of caspases-2 and -3 in cardiomyocytes exposed to NE (P<0.05)h.

CONCLUSIONThe present study suggested that Ber could reduce NE-induced apoptosis in neonatal rat cardiomyocytes through inhibiting the ROS-TNF-α-caspase signaling pathway.

Animals ; Animals, Newborn ; Annexin A5 ; metabolism ; Apoptosis ; drug effects ; Berberine ; pharmacology ; Caspase 2 ; metabolism ; Caspase 3 ; metabolism ; Caspases ; metabolism ; Cell Nucleus ; drug effects ; metabolism ; Cell Shape ; drug effects ; DNA ; metabolism ; Enzyme Activation ; drug effects ; Flow Cytometry ; Fluorescein-5-isothiocyanate ; metabolism ; Immunohistochemistry ; L-Lactate Dehydrogenase ; metabolism ; Myocytes, Cardiac ; drug effects ; enzymology ; pathology ; Norepinephrine ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism ; Signal Transduction ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo explore the clinical effects of diaplastic external fixator on the treatment of unstable fractures of distal radius.

METHODSA clinical data of 60 patients with unstable fractures of distal radius admitted to Wangjing Hospital from August 2005 to September 2009 were retrospectively analyzed with the paired design. According to the paired design, 60 patients were equally divided into two groups (internal fixation group and external fixation group), which were respectively treated with open reduction and steel plate internal fixation (internal fixation group) or closed reduction and external fixation (external fixation group), including 8 males and 52 females, with an average age of 60.27 years ranging from 34 to 85 years. Left side was in 33 cases and right side was in 27 cases. All fractures were closed and caused by hand supporting when falling down. According to AO classification, type A3 was in 22 cases, type B2 was in 4 cases, type B3 was in 2 cases, type C1 was in 20 cases, type C2 was in 8 cases, type C3 was in 4 cases. Palmar flexion, dorsiflexion, radial deviation, ulnar deviation, pronation, supination, grip strength, radial angle, radial length, volar tilt were observed before and after operation.

RESULTSAll the patients were followed up from 12 to 18 months with an average of 15.4 months. The radial length was (4.85 +/- 2.75) mm,volar tilt (14.66 +/- 10.77) degrees, radial angle (7.90 +/- 4.70) degrees in the external fixation group,while those were (4.29 +/- 1.53) mm, (14.39 +/- 5.01) degrees, (6.19 +/- 3.15) degrees in the internal fixation group, but with no statistical significance (P>0.05). Function comparison of internal and external fixation group, P-value of every function is more than 0.05 or equal to 0.05, with no statistical significance except for supination and radial deviation. The functions of wrist joints were evaluated according to Batra scoring system at 1 year after operation. The average radiological scores of external fixation group was 86.27,in which 15 cases were excellent, 11 good, 1 fair,3 poor,while the average functional scores was 94.93, and all the cases were excellent. The average radiological scores of internal fixation group was 91.27, 16 cases were excellent, 12 good, 2 fair, while the average functional scores was 94.23, in which all the cases were excellent.

CONCLUSIONCompared with the open reduction and steel plate fixation, the unstable fractures of distal radius treating by diaplastic external fixator can be achieved a similar result, with no statistical significance.

Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; External Fixators ; Female ; Fracture Fixation, Internal ; methods ; Humans ; Male ; Middle Aged ; Radius Fractures ; surgery ; Retrospective Studies

Objective To observe the impact of various application time of aspirin and clopidogrel on the circadian rhythm changes of platetet aggregation in patients with acute coronary syndrome.Methods Patients with acute coronary syndrome were divided into day-time (8:00) and night-time (20:00)medication group (n = 15 each).After plasma concentration reached steady state,platelet aggregation was assessed at 5 time points within 24 hours with a mobile four-channel whole blood impedance aggregometer.The plateht aggregation was induced by ADP and arachidonic acid.Thereafter,the two groups were exchanged and platelet aggregation was assessed in the same way post plasma steady state.Results Arachidonic acid-induced platelet aggregation was the highest at 10:00 Am[(7.96±3.64) ohm]and the lowest at 0:00[(6.12±3.29)ohm,P＞0.05]in day-time group.Platelet aggregation was the highest at 20:00[(9.40±5.39)ohm]and the lowest at 10:00[(5.46±3.93)ohm],P ＜0.05).ADP- induced platelet aggregation was the highest at 10:00 and the lowest at 16:00 in day-time group (P＞0.05) and was the highest at 20:00 and the lowest at 10:00 in night-time group(P ＞0.05).Platelet aggregation induced by two inducers was significantly higher at 10:00 in day-time group compared to values in night-time group(all P＜0.05).Conclusion Taking aspirin and clopidogrel at 20:00 was superior to taking the same medications at 8:00 for inhibiting peak platelet aggregation in the morning.

OBJECTIVEThe staging and treatment of bronchioloalveolar carcinoma (BAC) with pulmonary metastasis are still controversial. This study aimed at evaluating the current staging of BAC with ipsilateral intrapulmonary metastatic nodules and the therapeutic effectiveness of surgical resection.

METHODSThe clinicopathological data of 729 completely and surgically resected patients with non-small cell lung cancer (NSCLC) from December 1999 to December 2006 were retrospectively reviewed. Prognostic factors affecting the overall survival were analyzed by the Kaplan-Meier method and compared by the log rank test.

RESULTSAmong 67 NSCLC patients with ipsilateral intrapulmonary metastatic nodules, 54 had multiple nodules in the lobe with primary lesion (T4, PM1) and 13 had additional nodules in the other ipsilateral lobes (M1, PM2). This series consisted of 40 males and 27 females, with a median age of 60.0 years. Of those, 28 had the lesions containing pure or some bronchioloalveolar carcinoma component, while the other 39 had a NSCLC lesions containing non-bronchioloalveolar carcinoma components. The median overall survival time of this series was 24.0 months. Prognostic study demonstrated that bronchioloalveolar carcinoma histology and mediastinal lymph node metastasis had significant adverse impact on the overall survival. The median survival time of the patients with bronchioloalveolar carcinoma was 58.0 months versus 27.0 months in patients with other subtypes of NSCLC (P < 0.01). The median survival times were 39.0 months for the patients with N0 or N1 versus 14.0 months for patients with N2, with a significant difference between the two groups (P < 0.01). There was no significant difference in the survival time between the patients with PM1 (36 months) and those with PM2 (24 months) (P > 0.05).

CONCLUSIONSurgical resection is effective for NSCLC patients with ipsilateral intra-pulmonary metastasis, especially for those with bronchioloalveolar carcinoma components. Our results suggest that the current TNM classification system may be inappropriate for the NSCLC patients with ipsilateral intrapulmonary metastatic nodules, and may need a modification.

Adenocarcinoma, Bronchiolo-Alveolar ; pathology ; surgery ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung ; pathology ; surgery ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; pathology ; secondary ; surgery ; Lymph Node Excision ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Male ; Mediastinum ; Middle Aged ; Neoplasm Staging ; Pneumonectomy ; methods ; Retrospective Studies ; Survival Rate

OBJECTIVETo explore the apoptosis resistance induced by Leptin and its mechanism in breast cancer cells in vitro.

METHODSThe leptin-mediated reduction of docetaxel-induced apoptosis in human breast cancer T47D cells was evaluated by TransAM ELISA, MTT and caspase-9 assay. The leptin-promoted survivin expression was analyzed by Western-blot and RT-PCR. The reversing effect of STAT3 knockdown on leptin-induced survivin upregulation was measured by Western-blot and RT-PCR.

RESULTSLeptin promoted T47D cells proliferation and the inhibitory rate was -63.6%. It reduced docetaxel-induced apoptosis in T47D cells by 31.9%. Leptin at different concentrations promoted survivin protein and mRNA expression in T47D cells. The expression of survivin mRNA was 4.6 fold compared with the T47D cells not treated with leptin(10 nmol/L). The expression of survivin mRNA in T47D cells was 0.55 +/- 0.15 fold after transfected with small interfering RNA (siRNA) of STAT3. The expression of survivin mRNA in STAT3 siRNA group and mock transfected group were 0.56 +/- 0.18 fold and 1.61 +/- 0.22 fold after treated by leptin, respectively. The survivin protein level of T47D mock transfected cells was increased after treated by leptin, but the protein level of T47D transfected with STAT3 siRNA cells were not changed significantly.

CONCLUSIONLeptin/STAT3 signaling is a novel pathway for up-regulation of survivin expression in breast cancer cells.

Apoptosis ; drug effects ; Breast Neoplasms ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Female ; Humans ; Inhibitor of Apoptosis Proteins ; Leptin ; pharmacology ; Microtubule-Associated Proteins ; genetics ; metabolism ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; STAT3 Transcription Factor ; genetics ; metabolism ; Signal Transduction ; Transfection ; Up-Regulation

OBJECTIVESThe staging and treatment of multi-focal non-small cell lung cancer (NSCLC) are controversial. This study evaluated the effectiveness of surgical treatment for the ipsilateral multi-focal NSCLC.

METHODSSixty-eight patients with multi-focal NSCLC underwent complete resection from December 1999 to December 2006. This series included 44 males and 24 females, with a mean age of 60.3 years old (range from 33 to 81 years old). Fifty-four patients had multiple nodules in primary lobe (T4) and 13 patients had additional nodules in non-primary lobe (M1), and a patient was proved to have synchronous primary NSCLC lesions. Surgical treatments included lobectomy in 53 cases, bilobectomy in 4 cases, pneumonectomy in 2 cases, and lobectomy combined with wedge resection in 9 cases.

RESULTSThe median overall survival time of this series was 30 months. Prognostic study demonstrated that mediastinal lymph node metastasis and bronchioloalveolar carcinoma histology had significant impact on overall survival. The median survival times were 39 months for patients with N0 and N1, and 14 months for patients with N2, respectively, and there was significant difference between the groups (P < 0.01). The difference in survival was significant between patients with bronchioloalveolar carcinoma components and other NSCLC histologic types (P < 0.01), and the median survival times were 46 months and 20 months, respectively.

CONCLUSIONSurgery could provide choice for multi-focal NSCLC patients (T4 and M1), especially for patients with bronchioloalveolar carcinoma components and without mediastinal lymph node metastasis.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung ; surgery ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; surgery ; Lymph Node Excision ; Male ; Mediastinum ; Middle Aged ; Pneumonectomy ; Survival Analysis ; Treatment Outcome