Current status of basic and clinical research on metformin in endometrial cancer / 国际肿瘤学杂志

Endometrial cancer is one of the most common gynecological malignancies, which is closely related to metabolic syndrome such as diabetes mellitus. In recent years, epidemiological studies have found that metformin has a positive effect on the prevention and treatment of endometrial cancer, and a large number of basic and clinical studies have supported this theory, indicating that metformin may become the new treatment for patients with endometrial cancer, especially with advanced and recurrent endometrial cancer, and endometrial dysplasia.

miR-34a Inhibitor May Effectively Protect against Sevoflurane-Induced Hippocampal Apoptosis through the Wnt/β-Catenin Pathway by Targeting Wnt1

PURPOSE: Research has shown that sevoflurane-induced toxicity causes neurodegeneration in the developing brain. miR-34a has been found to negatively regulate ketamine-induced hippocampal apoptosis and memory impairment. However, the role of miR-34a in sevoflurane-induced hippocampal neurodegeneration remains largely unclear. MATERIALS AND METHODS: C57/BL6 mice (7-day-old) inhaled 2.3% sevoflurane for 2 h/day over 3 consecutive days. miR-34a expression was reduced through intracerebroventricular injection with miR-34a interference lentivirus vector (LV-anti-miR-34a) into mouse hippocampus after anesthesia on the first day of exposure. Hippocampal apoptosis was detected by TUNEL assay and flow cytometry analysis. Spatial memory ability was evaluated by the Morris water maze test. The interaction between miR-34a and Wnt1 was confirmed by luciferase reporter assay, RNA immunoprecipitation, Western blot, and immunofluorescence staining. The effects of miR-34a on protein levels of B-cell lymphoma 2 (Bcl-2), bcl-2-like protein 4 (Bax), and Wnt/β-catenin pathway-related proteins were evaluated using Western blot analysis. RESULTS: Sevoflurane upregulated hippocampal miR-34a, and miR-34a inhibitor attenuated sevoflurane-induced hippocampal apoptosis and memory impairment. miR-34a negatively regulated Wnt1 expression by targeting miR-34a in hippocampal neurons. Moreover, forced expression of Wnt1 markedly undermined miR-34a-mediated enhancement of sevoflurane-induced apoptosis of hippocampal neurons, while Wnt1 silencing greatly restored anti-miR-34a-mediated repression of sevoflurane-induced apoptosis of hippocampal neurons. Increased expression of miR-34a inhibited the Wnt/β-catenin pathway in hippocampal neurons exposed to sevoflurane, while anti-miR-34a exerted the opposite effects. CONCLUSION: miR-34a inhibitor may effectively protect against sevoflurane-induced hippocampal apoptosis via activation of the Wnt/β-catenin pathway by targeting Wnt1.

Two-year postoperative use of zoledronic acid prevents secondary fractures following percutaneous kyphoplasty / 中国组织工程研究

BACKGROUND:Percutaneous kyphoplasty is the main treatment for senile osteoporotic thoracolumbar fractures, but increasing number of patients who have not been treated with anti-osteoporosis therapy after operation develop secondary fractures due to decreased bone mineral density and changes of stress. OBJECTIVE:To investigate the feasibility of consecutive 2-year zoledronic acid treatment following percutaneous kyphoplasty for preventing secondary vertebral fracture. METHODS: 186 elderly patients with thoracolumbar compressive fractures were divided into experimental (n=84) and control (n=102) groups based on their willingness to receive zoledronic acid treatment or not after percutaneous kyphoplasty. The experimental group was treated with calcium and alfacalcidol fololwed by 2 years of zoledronic acid treatment, while only calcium and alfacalcidol treatment was done in the control group. The bone mineral density, pain and function were respectively assessed by dual energy X-ray absorptiometry, visual analogue scale and Oswestry disability index, and the number of refractures was calculated at baseline and at the 2nd year after the second injection of zoledronic acid. RESULTS AND CONCLUSION:The bone mineral density, visual analogue scale and Oswestry disability index scores at 2 years after treatment in both two groups were significantly superior to those at baseline (P < 0.05). The number of refractures in the experimental group (n=1) was significantly less than that in the control group (n=9) (P < 0.05). These results suggest that zoledronic acid can prevent secondary fractures after percutaneous kyphoplasty in the elderly with osteoporotic thoracolumbar fractures, improve long-term function and clinical effectiveness.

The application of lentil lectin-reactive alpha-fetoprotein ratio in the differential diagnosis of primary liver cancer / 国际检验医学杂志

Objective To explore the application of lentil lectin‐reactive alpha‐fetoprotein ratio (AFP‐L3% ) applied in the dif‐ferential diagnosis between hepatitis B infection of primary liver cancer and benign liver disease .Methods We included 108 cases of chronic HBV infection ,including 50 cases of primary liver cancer ,42 cases of cirrhosis ,16 cases of chronic hepatitis .Chemilumines‐cence detection was used to detect alpha‐fetoprotein (AFP) and AFP‐L3 content ,AFP‐L3 and the ratio of AFP (AFP‐L3% ) was calculated .Results AFP≥400 ng/mL as primary liver cancer diagnostic threshold ,the sensitivity and specificity were 36% ,84% , when used AFP‐L3% ≥ 10% as primary liver cancer diagnostic threshold ,the sensitivity and specificity were 62% ,83% . Conclusion AFP‐L3% is a better clinical indicator to distinguish between primary liver cancer and benign liver disease .AFP‐L3%can be used as a clinical indicator to differential diagnosis between HBV infection of primary liver cancer and benign liver disease .

The effects of DO2-directed hemodynamic management on oxygen metabolism and postoperative prognosis of orthotopic liver transplantation patients / 临床麻醉学杂志

Objective To investigate the effects of different DO2-directed hemodynamic man-agement on postoperative prognosis of orthotopic liver transplantation (OLT)patients with different degrees of liver function insufficiency.Methods Seventy patients (male 48 cases,female 22 cases, aged 37-66 years,ASA grade Ⅲ or Ⅳ)scheduled non veno-venous bypass OLT were divided into two groups (n = 35 each ).The oxygen delivery (DO2 )maintained respectively between 350 ml·min-1 ·m-2 and 500 ml·min-1 ·m-2 (group control)and more than 500 ml·min-1 ·m-2 (group study).After induction of anesthesia,the left radial artery was cannulated,allowing continu-ous blood pressure monitoring as well as serial blood sampling,then the Swan-Ganz catheter was in-serted via the right internal jugular vein to continuously monitor CI and S-vO2 .After anesthesia induc-tion and before operation (T1 ),10 min before anhepatic phase (T2 ),30 min after onset of anhepatic phase (T3 ),30 min after neohepatic phase (T4 )and the end of surgical procedure (T5 ),the SaO2 , PaO2 ,Hb,CI and S-vO2 were recorded to calculate the DO2 ,VO2 and ERO2 .Postoperatively,ICU and hospital length of stay,quality of life (QOL)and 1-5 year survival rate were recorded.Results In the two groups,CI,DO2 and VO2 declined at T3 to a statistically significant degree in comparison with T1 (P <0.05).CI,DO2 and VO2 in group study significantly higher than those of group control (P <0.05).ERO2 in group study was lower than that of group control significantly (P <0.05).ICU and hospital length of stay were significantly shorten in group study in comparison with group control (P <0.05).Survival rate and QOL in group study tended to be slightly higher than those of group control until the end of study period,but there was no significant difference.Conclusion The DO2-directed hemodynamic management can improve prognosis with enhanced DO2 in OLT patients with different degrees of hepatic insufficiency.It has a positive impact on their outcome of shortening ICU stay and the hospitalization days.

A clinical analysis of onset of high-risk demyelinating events in patients with neuromyelitis optica / 中华内科杂志

Objective To explore the clinical characteristics of the lesions of spinal cord and optic nerve as the onset of neuromyelitis optica (NMO).Methods A total of fifty-one patients with myelitis or optic neuritis (ON) as the onset of NMO who hospitalized in our Neurology Department during October 2010 to October 2012 were enrolled in the study.Clinical presentations and MRI findings of the spinal cord and brain were studied.Results (1) A total of 26 cases (51.0％) presented with myelitis as the index event,in which 30.8％ (8/26) were the longitudinally extensive transverse myelitis (LETM) and 69.2％ (18/ 26) were non-LETM (short segmental myelitis or non-transverse myelitis).Patients with non-LETM as the onset were found to have better prognosis than those with LETM (full recovery ratio was 13/18 vs 2/8,P ＜ 0.05),while shorter recurrence interval of myelitis and higher recurrence frequency of events were shown in patients with non-LETM (11.1 vs 18.6 months,3 times per year vs once per year,with all P ＜ 0.05).(2) A total of 25 cases (49.0％) presented with ON as the index event with 24.0％ (6/25) of unilateral ON and 76.0％ (19/25) of bilateral ON.Patients with bilateral ON had more severe visual impairment and shorter first remission period than those with unilateral ON (P ＜ 0.05).Conclusion Non-LETM and bilateral ON are the most common index demyelinating events in NMO cases.

The characteristics of clinical manifestations, brain MRI and cerebrospinal fluid findings in patients with anti-N-methyl-D-aspartate receptor encephalitis / 中华神经科杂志

Objective To analyze the clinical manifestations and the features of brain MRI and cerebrospinal fluid (CSF) findings in adult Chinese patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis.Methods We reviewed the clinical manifestations,brain MRI and CSF examinations of 29 patients who were diagnosed as anti-NMDAR encephalitis.Results The major clinical features of anti-NMDAR encephalitis patients included psychiatric symptoms (86％,25/29),seizures (83％,24/29),decreased consciousness (55％,16/29),involuntary movements (55％,16/29),central hypoventilation (34％,10/29),and hypersalivation (17％,5/29).Some patients also experienced autonomic instability,hemiplegia and aphasia.Underlying ovarian teratoma was identified in 14％ of affected patients(4/29).Brain MRI was found abnormal in up to 62％ patients (18/29),located in the temporal lobes,hippocampus,thalamus,brain stem,cingulate gyrus,frontal and parietal cortex,corpus callosum,internal capsule,basal ganglia and periventricular area.CSF findings were abnormal in 83％ of patients with anti-NMDAR encephalitis.Oligoclonal banding in CSF was positive in 95％ patients (19/20).The recurrence rate during 3 years was 31％ (9/29).Conclusions Anti-NMDAR encephalitis is a treatable disease,yet with high recurrence rate.Its predominant clinical features are psychiatric symptoms and seizures,while involuntary movements,central hypoventilation and hypersalivation are its characteristic manifestations.Lesions in MRI are widespread,not only restricted to limbic lobe.

Meta analysis of euthyrox on the blood lipid of patients with hypothyroidism / 中国生化药物杂志

Objective To study the effect of euthyrox on blood lipids in patients with hypothyroidism throngh the meta analysis.Methods Patients with clinical hypothyroidism theated by euthyrox on blood lipid effect of randomized controlled trials were retried by Pubmed(2000/2014-07),EMbase (2000/2014-07),the Cochrane library(2014,7),the Chinese biomedical literature database(2000/2014-07),retrieved the time limit from January 2000 to July 2014.The paper were objective evaluated of the quality,Meta analysis with Rev Man 5.3 software system applicated by Cochrane collaboration.Results Euthyrox could significantly reduce cholesterol levels of hypothyroidism patients ,it was statistically significant difference(OR=0.63,95%CI:0.71 ~0.55,P<0.001);Euthyrox could significantly reduce triglyceride levels of hypothyroidism patients,difference was statistically significant(OR =0.29,95%CI:0.34 ~0.25,P <0.001 );Euthyrox could significantly reduce low-density lipoprotein cholesterol levels of hypothyroidism patients,it was statistically significant difference(OR=0.22,95%CI:0.30 ~0.14,P<0.001);euthyrox could obviously increase high-density lipoprotein cholesterol levels, it was statistically significant difference (OR =0.21, 95% CI:0.17 ~0.26, P <0.001 ). Conclusion Euthyrox could significantly reduce total cholesterol,triglyceride,low-density lipoprotein cholesterol(hdl-c)of hypothyroidism patients,and promote the synthesis of high-density lipoprotein cholesterol(hdl-c),could effectively promote the lipid metabolism,reduce blood fat level,prevent the happening of the disease of heart head blood-vessel hypothyroidism patients,have the guide meaning to clinical treatment.

Basic characteristics and functional outcomes of 3123 consecutive patients in Chengdu stroke registry / 中华神经科杂志

Objective To analyze basic data and outcomes in Chengdu Stroke Registry.Methods The stroke patients consecutively admitted to Department of Neurology,West China Hospital,Sichuan University since March 1,2002 were prospectively registered.The baseline demographic,risk factors,treatment,and outcome data was recorded with standardized stroke register form by trained specialists.The patients were followed up at seven days,one,three,six months and one year after onset of the stroke for death and disability.Results A total of 3123 consecutive patients were registered between March 1,2002 and August 31,2006,of which 65.5％ came from urban areas and 34.5％ from rural areas.The age was (63.05 ± 17.98) years old and male accounted for 60.3％.Ninety-seven percent (3028/3123) of patients completed CT or MRI scanning during hospitalization.A total of 1804 patients were included between March 2002 and September 2004,of which ischemic stroke accounted for 62.1％ (1120/1804),intracranial hemorrhage 28.4％ (513/1804),subarachnoid hemorrhage 4.0％ (72/1804) and TIA 5.5％ (99/1804).The median NIHSS score on admission was 8(3-15) points in patients with cerebral hemorrhage,and 5(2-10) points in patients with ischemic stroke.Compared with the patients with intracranial hemorrhage,patients with ischemic stroke more frequently had a history of diabetes (OR =2.427,95％ CI 1.811- 3.253,P=0.000),atrial fibrillation (OR=6.121,95％ CI3.535-10.60,P=0.000),coronary heart disease (OR=4.144,95％ CI 2.944-5.832,P =0.000) and TIA (OR=4.342,95％ CI 1.726-10.92,P =0.001 ),and less alcohol consumption ( OR =0.740,95％ CI 0.611-0.896,P =0.002 ).The proportion of in-hospital treatments were thrombolysis 0.9％,anti-platelet therapy 83.0％,mannitol 23.5％,neuroprotective agents (citicoline) 68.1％,and Chinese herbal medicine 89.7％.Case fatality rate was 10.7％ and 13.9％ respectively at 7 days and one month for patients with intracranial hemorrhage,3.0％ and 5.2％ respectively for ischemic stroke.Death or disability was 40.4％,40.3％ and 38.9％ in patients with intracranial hemorrhage and 37.1％,35.0％ and 33.4％ for ischemic stroke at the end of 3,6,12 months respectively.Conclusions Our stroke registry is featured with the largest sample,and the longest period of consecutively registration.It provides an important platform for clinical investigation of stroke.Our study suggested case fatality and disability is lower in this group than in other ethics.Above features should be considered in design of future clinical trials in China.

Comparative Proteomics Analysis of Hippocampal Proteins From Chronic Stressed Rats / 生物化学与生物物理进展

Chronic stress can induce hippocampus injury such as neuron loss, dendrite atrophy, but its mechanism and molecular basis remain unclear up to now. To understand the molecular mechanism on protein level and find the crucial proteins which correlated with chronic stress-induced injury, two-dimensional electrophoresis was applied to separate the hippocampal total proteins of control group and restraint stressed rats, then the differential expressed proteins were detected by image analysis and identified by matrix assisted laser desorption /ionization time of flight mass spectrometry (MALDI-TOF-MS) as well as database searching. Moreover, the 2-DE results were verified on the mRNA level by semi-quantitative RT-PCR. The hippocampal 2-DE map with high resolution and good reproducibility of control and stress group rats were obtained. Fourteen differentially expressed protein spots were detected and eleven proteins were successfully identified, most of these proteins were involved in the process of energy metabolism and signal transduction. These results provide a clue for elucidating the mechanism of chronic stress-induced hippocampal injury and are useful for elevating the adaptability to stress.

Study of gait footprint parameters of children and its value in diagnosis and treatment of cerebral palsy / 中华物理医学与康复杂志

Objective To study the gait footprint parameters of the normal children and the cerebral palsy (CP) children, and to explore its clinical value. Methods A total of 2 800 normal children aged 3 to 10 years and 139 spastic CP children aged 3 to 5 years were recruited in this study. The normal children were divided into seven groups with one year interval, and were measured with regard to the length of foot and step, step width and foot angle of footprint of every age group with self made oil printed carpet. The footprint of the CP children were measured and compared with that of the normal children at the same age. Results It was revealed that there was significant difference between the normal and the CP children ( P

Construction and expression of human disulfide-stabilized Fv fragment gene to Rabies Virus / 解放军医学杂志

Objective To realize the construction and expression of human dsFv genes to rabies virus. Methods The genes of dsFv VH and VL were amplified by PCR-based point mutagenesis strategy. Then the genes were cloned into plasmid pET-22b (+). E. coli BL21(DE3) was transformed with the recombinant expression plasmid and the protein was induced in Luris-Bertani medium by addition of IPTG. The inclusion body proteins of VH and VL were denaturalized by GuHCl, and then re-naturalized in refolding solution to form dsFv fragments. Afterwards, we evaluated the antigen-binding activity of the dsFv and its stability as compared with its originative scFv. Results The fragment genes of dsFv to rabies virus were constructed successfully by PCR-based point mutagenesis strategy. Sequence analysis proved that cysteines were introduced into the position 44 aa of VH and position 100 aa of VL. The dsFv VH and VL genes were expressed in PET22b(+)/BL21(DE3). The VH and VL protein folded into the active dsFv antibody fragments which showed specific binding capability to rabies virus. Conclusion We succeeded in achieving the stabilization of the human scFv to rabies virus and obtaining the active human dsFv antibody fragments. This established a solid basis for further study of the biological activaty and clinical application of dsFv to rabies virus.