Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the degeneration of upper and lower motor neurons selectively. Although the motor system lesion is the most predominant clinical manifestation of ALS, with the progression of the understanding of the pathogenesis and clinical detection of the disease, more and more patients are found to have extra-motor features of ALS, such as somatosensory involvement, etc. The research results demonstrated that ALS might be a kind of disorder combined with sensory disturbance according to the electrophysiology, neuropathology, neuroimaging, animal model simulation, genetic evidence, and other methods detected. We, herein, review the prevalence and detection methods especially the aspect of genetic associations implicated in the sensory nerve disturbance of ALS.

BACKGROUND: The event of paroxysmal deplorizing shift (PDS) is the cellular hallmark of brain neurons of epileptiform activities. Its development used to be considered to be related to abnormal synaptic interactions. Recertly, the intrinsic nature of PDS has received more attention.OBJECTIVE: To observe the characteristics of epileptiform activities of rat hippocampal CA1 pyramidal neurons induced by low-dosage veratridine and investigate its possible ion mechanism.DESIGN: An exploratory and observational trial.SETTING: Institute of Neuroscience, Fourth Military Medical University of Chinese PLA.MATERIALS: This study was conducted at the Institute of Neuroscience,Fourth Military Medical University of Chinese PLA, from October 2002 to October 2004. Forty healthy SD rats of 14 days old were selected. Drugs were provided from Tianjin Drug Company and Sigma Company.METHODS: Rats were anesthetized by intraperitoneal injection, and their brain was removed and cut into slices. Epileptiform activities were induced by 0.5 μ mol/L veratridine. Then 80 nmol/L tetrodotoxin was added into the perfused solution on 6 cerebral slices, and 5 μmol/L phenytoin was used on another 5 cerebral slices. The electrophysiological characteristics of the cells under the effect of different kinds of drugs were observed.MAIN OUTCOME MEASURE: Discharge pattern of cells and tetrodotoxin-sensitive sodium currents under voltage-clamp configuration through Ⅰ-Ⅴ reaction.RESULTS: After perfusion of 0.5 μmol/L veratridine, the rat pyramidal neurons in CA1 area displayed relatively fixed-mode of runs of PDS bursting,followed by the hyperpolarization of cell membrane. Such epileptiform activities were blocked either by 80 nmol/L tetrodotoxin or 5 μnol/L phenytoin. The tetrodotoxin-sensitive sodium currents in epileptic neurons and normal controls under voltage-clamp configuration on holding potential of -55 rmV, -60 rmV, -65 mV. This shows that persistent sodium currents could be improved by low-dosage veratridine in a voltage-dependent manner.CONCLUSION: Low-dosage veratridine may induce runs of PDS like epileptiform activities on rat CA1 pyramidal neurons. Such changes can be blocked by low-dosage tetrodotoxin or phenytoin. Its ion mechanism may be related to persistent sodium currents.

Objective To prepare and characterize docetaxel incorporated phosphatidylcholine -sodium desoxycholate mixed micelles (DOX EPC/SDC MMs).Methods Docetaxel mixed micelles (DOX MMs) were prepared using the co-precipitation method .An optimized formulation was obtained by single factor method , which was used to study the effect of several factors on water solubility of DOX in MMs, including EPC/total(EPC+SDC)concentration, total(EPC+SDC) concentration, the pH and ionic strength of the hydrated solution .Then, the obtained DOX MMs were characterized by investigating particle size distribution and morphology , and by conducting dilute experiments to examin micelle stability . Results The EPC/total ( EPC+SDC) concentration ratio was 0.4.The total supplementary material concentration was 2.5%.Pure water was used to disperse the film .The drug loaded MMs had an average size of 18.56 nm and average zeta potential of -24.3 mV.A roundlike shape was observed under a transmission electron microscope ( TEM).Conclusion DOX EPC/SDC MMs, prepared by a simple and convenient method , can enhance water solubility , is physically compatible with injection solutions and is expected to become a new drug delivery system .

Objective To evaluate the efficacy and safety of CT-guided 125I radioactive seed implantation combined with gemcitabine and Gio (gemcitabine and S-1, GS scheme) chemotherapy in treating advanced pancreatic carcinoma. Methods Sixty-eight patients with inoperable advanced pancreatic carcinoma were randomly divided into two groups. Patients in group A(n=38) were treated with CT-guided 125I radioactive seed implantation combined with GS chemotherapy scheme, while patients in group B (n=30) received GS chemotherapy scheme only. The short-term effect, the median progression-free survival time, the median survival time and adverse reactions of the two groups were determined , and the results were compared between the two groups. Results The objective response rate (ORR), disease control rate (DCR) and clinical benefit rate (CBR) of the group A were 57.9%, 73.7%and 84.2%respectively, while those of group B were 26.7%, 46.7% and 60.0% respectively. The differences between the two groups were statistically significant (P<0.05). In group A the median progression-free survival time and the median survival time were 8.00 months and 11.84 months respectively, which were strikingly higher than those in group B (5.63 months and 10.40 months respectively), the differences between the two groups were statistically significantly (P<0.05). No significant differences in gastrointestinal reactions, blood toxicity, liver toxicity and other adverse reactions existed between the two groups (P>0.05). Conclusion For advanced pancreatic carcinoma, CT-guided 125I radioactive seed implantation combined with GS program is a safe and effective treatment.

[ ABSTRACT] AIM:To observe the effect of ursodeoxycholic acid ( UDCA) on the treatment of infantile hepatitis syndrome ( HIS) and to investigate its mechanism.METHODS:The children with infantile hepatitis syndrome were divid-ed into conventional treatment group and the UDCA treatment group.Twenty healthy children were selected as normal con-trol.The children in conventional therapy group were given antiviral and hepatoprotective treatments.The children in UD-CA treatment group were given ursodeoxycholic acid (10 mg? kg-1? d-1 ) in addition to the conventional treatment group for 2 to 3 weeks.The levels of total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), glu-tamyltransferase ( GGT) , total bile acids ( TBA) and TNF-α, IL-6 were detected before admission and 2 weeks later.RE-SULTS:The levels of TNF-αand IL-6 were significantly higher in the children with IHS than those in the normal control (P<0.01).The levels of TBIL, DBIL, ALT, GGT, TBA, TNF-αand IL-6 in conventional treatment group were reduced after therapy (P<0.01).All the above index in UDCA treatment group were decreased compared with conventional treat-ment group (P<0.01).CONCLUSION:On the basis of conventional therapy, ursodeoxycholic acid effectively alleviates the systemic inflammatory response in the children with IHS, reduces the liver damages.

Objective To investigate the value of CT-guided 125I particles implantation combined with gemcitabine plus S-1 (GS) regimen in the treatment of locally advanced pancreatic cancer.Methods 42 patients with unresectable local advanced pancreatic cancer were given with CT-guided 125I seed implantation.3-4 cycles of GS regimen was given based on the tolerance of patient s body within 3-7 d after implantation of particles.Review of blood,CA199,chest X-ray,CT scan + enhanced or MRI were performed at 2nd,4th,6th,12th month after surgery.Results 2nd,4th,6th month after surgery,tumor lesions were significantly reduced,ORRs were 59.5 ％ (25/42),66.7 ％ (28/42) and 73.8 ％ (31/42),respectively,DCRs were 83.3 ％ (35/42),78.6 ％ (33/42) and 76.2 ％ (32/42),respectively.No serious adverse reactions were observed,patient could tolerate these reactions.The 6th,12th,24th month survival rates were 100 ％ (42/42),47.6 ％ (20/42) and 11.9 ％ (5/42),respectively,mPFS was 8.27 months and mOS was 12.00 months.Conclusion CT-guided 125I particles implantation combined with GS regimen is convenient,safe,high efficacy in the treatment of locally advanced pancreatic cancer.

Pharmacology , pharmacokinetics , clinical study and safety of enzalutamide in the treatment of castration-resistant pros-tate cancer (CRPC) were reviewed in the paper.Enzalutamide, a pure second-generation androgen receptor antagonist , can inhibit multiple points in the androgen receptor signaling pathway , including the inhibition of androgen binding to the androgens receptor , nu-clear translocation of the androgens receptor complex and binding of the androgens receptor complex to deoxyribonucleix acid ( DNA) . The phase 3 clinical trials have revealed that enzalutamide is effective to delay the progression of metastatic CRPC , reduce the prostate-specific antigen (PSA) levels, decrease the progression time of PSA and prolong the overall survival time and the time of first skeletal -related events .Enzalutamide has become a novel treatment option for CRPC patients .Enzalutamide is well tolerated with low incidence of side effects .

OBJECTIVE: To study the compatibility stability of aztreonam after mixing with fructose injection, calorose injection and xylital injection. METHODS: The content of solution, quantity of particles, pH value and physical changes were observed after aztreonam mixing with 3 kinds of injections for 6 hours at room temperature. RESULTS: The content of solution, quantity of particles, pH value and physical changes were up to the standard. CONCLUSION: Aztreonam mixed with fructose injection, calorose injection or xylital injection is keeping stable.

Objective To explore the effect of platelet-rich plasma (PRP) on flap graft survival.Methods Two random skin flaps were elevated on the back of the rabbits with spinal symmetry in fifteen healthy rabbits.We selected randomly one side as PRP side,another side as blank control side.And then the autologous PRP was daubed to the basement of the skin flap in PRP side,while the blank control side was treated with normal saline of the same volume.At 3 d,7 d,and 14 d after the surgical operation,the immunohistochemistry was conducted to detect the microvessel density by CD34,and the the flap graft survival rate was tested and the histological changes of the flaps were observed by HE staining.Results The survival rates of skin flap graft were that the PRP side in 3 d (74.4±4.7) ％,while the control side (65.8+6.8)％;the PRP side in 7 d (72.4±7.5)％,while the control side (58.5+7.0)％；the PRP side in 14 d (74.5±5.0)％,while the control side (65.0±5.4) ％.The inflammatory reaction became declining with the extension of time,while density of blood vessels was increasing.In 14 d inflammatory reaction was the lowest and blood vessels' density was the largest.In all the control sides inflammatory response was obvious than that of the PRP side.CD34 positive count in 3 d PRP side microvascular density (MD) was (13.9±2.0)/HP,controlled side (11.1±1.3)/HP;in 7 d PRP MD was (15.7±1.5)/HP,controlled side (12.1±1.2)/HP;in 14 d PRP MD was (19.6±1.2)/HP,controlled side (12.7±0.8)/HP.There were significant differences in the MD at 3 d,7 d,and 14 d (P＜0.05) between PRP side and control side.Conclusions Platelet-rich plasma is able to promote the survival of random rabbit flap.

ObjeclJve To definine the corresponding value to glycated albumin(GA)for a specific target of HbAlc,and to elvaluate the relationship between GA and HbA1c.Methods From Oct.2006 TO Apr.2009, 2 532 subjects were enrolled who accepted oral glucose tolerance test(OGtt)in out-patient department,including 898 with normal glucose regulation,695 with impaired glucose regulation,and 939 with newly-diagnosed diabetes.GA was measured with liquid enzymatic method.HbA1c was measured with high performance liquid chromatography method.The plasma glucose was measured at fasting,0.5 h,1 h,2 h,and 3h after glucose load.The correlation among GA,HbA1c and the other parameters monitored was analyzed.Results (1)The levels of HbA1c and GA in 2 532 subjects were(6.3±1.1)% and(17.9±4.5)%.The ratio of GA/HbA1c was 2.85±0.51.(2)HbAlc and GA were positively correlated with fasting,0.5 h,1 h,2 h and 3 h plasma glucose(r was in 0.567-0.776,atl P<0.01).(3)GA was significantly correlated with HbA1c(r=0.701,P<0.01).Linear regression analysis,using GA and HbA1c summarized by patient(n=2 532),produced a relationship of GA=2.871×HbA1c-0.112.The change in GA per increase of 1% HbA1c was 2.87%.When HbA1c level was 6.5%,the expected value of GA was 18.5%.The sensitivity,specificity,positive predictive value,negative predictive value,and accuracy with GA≤18.5% to predict HbA1c≤6.5% were 82.32%,72.49%,86.48%.65.73%,and 79.19%,respectively.When HbA1c level was 7.0%,the expected value of GA was 20.O%.When HbA1c level was 7.5%.the expected value of GA was 21.4%.Conclusions We initially establish the corresponding value to GA for a specific target of HbA1c and provide the basis for clinical application.