This study investigated a nano drug delivery system built by one sort of modified trimethyl chitosan (TMC). The TMC was modified by cRGDyk, ligand of integrin receptor avβ3. Single factor screening was used to optimize the prescription in which the particle sizes of TMC nanoparticle (TMC NPs) and cRGDyk modified TMC nanoparticle (C-TMC NPs) were (240.3 ± 4.2) nm and (259.5 ± 3.3) nm. Electric potential of those two nanoparticles were (33.5 ± 0.8) mV and (25.7 ± 1.6) mV. Encapsulation efficiencies were (76.0 ± 2.2) % and (74.4 ± 2.0) %. Drug loading efficacies were (50.1 ± 2.1) % and (26.1 ± 1.0) %. Then the cellular uptake, uptake mechanism and transport efficacy of TMC NPs and C-TMC NPs were investigated using Caco-2 cell line. The uptake rate and accumulating drug transit dose of C-TMC NPs were 1.98 and 2.84 times higher than TMC NPs, separately. Mechanism investigations revealed that caveolae-mediated endocytosis, clathrin-mediated endocytosis and macropinocytosis were involved in the intercellular uptake of both TMC NPs and C-TMC NPs. What is more, free cRGDyk could remarkably inhibit the uptake of C-TMC NPs.
Biological Transport ; Caco-2 Cells ; Caveolae ; Chitosan ; chemistry ; Clathrin ; Endocytosis ; Humans ; Integrin alphaVbeta3 ; chemistry ; Nanoparticles ; Particle Size ; Pinocytosis

This study investigated a nano drug delivery system built by one sort of modified trimethyl chitosan (TMC). The TMC was modified by cRGDyk, ligand of integrin receptor avβ3. Single factor screening was used to optimize the prescription in which the particle sizes of TMC nanoparticle (TMC NPs) and cRGDyk modified TMC nanoparticle (C-TMC NPs) were (240.3 ± 4.2) nm and (259.5 ± 3.3) nm. Electric potential of those two nanoparticles were (33.5 ± 0.8) mV and (25.7 ± 1.6) mV. Encapsulation efficiencies were (76.0 ± 2.2) % and (74.4 ± 2.0) %. Drug loading efficacies were (50.1 ± 2.1) % and (26.1 ± 1.0) %. Then the cellular uptake, uptake mechanism and transport efficacy of TMC NPs and C-TMC NPs were investigated using Caco-2 cell line. The uptake rate and accumulating drug transit dose of C-TMC NPs were 1.98 and 2.84 times higher than TMC NPs, separately. Mechanism investigations revealed that caveolae-mediated endocytosis, clathrin-mediated endocytosis and macropinocytosis were involved in the intercellular uptake of both TMC NPs and C-TMC NPs. What is more, free cRGDyk could remarkably inhibit the uptake of C-TMC NPs.

OBJECTIVESpinal muscular atrophy (SMA) is a common autosomal recessive disorder and represents one of the most common genetic causes of death in childhood. The last 10 years have seen major advances in the field of SMA, but no curative treatment is available so far. This study aimed to analyze the clinical characteristics of SMA, improve the clinical diagnosis of SMA, and explore the importance of gene diagnosis and prenatal diagnosis of SMA by gene deletion analysis.

METHODSTotally 83 cases with SMA including 55 males and 28 females were enrolled in this study. The age was between 1 day and 14 years (average 23.7 months). The clinical characteristics and changes of electromyography were assessed in all cases. The muscular biopsy was performed in 2 of 83 cases. The deletion of survival of motor neuron gene (SMN) was detected by PCR and restriction endonuclease spectrum analysis in 13 of 83 cases.

RESULTSThe 83 cases were subdivided into three clinical groups based on age of onset of symptom, age at death and achievement of certain motor milestone, 60 cases with type I, 19 cases with type II and 4 cases with type III. They were all characterized by symmetric muscle weakness (more proximal than distal) associated with atrophy, absence or marked decrease of deep tendon reflexes. Electromyographic studies showed a pattern of denervation with neither sensory involvement nor marked decrease of motor nerve conduction velocities in all cases. Muscle biopsy provided evidence of skeletal muscle denervation with groups of atrophy in 2 cases. The SMN detection revealed deletion of exon 7 and exon 8 in 11 of 13 cases, only lacking exon 7 in 1 of 13 cases and lacking exon 8 in 1 of 13 cases.

CONCLUSIONSMA is characterized by degeneration of lower motor neuron associated with muscle paralysis and atrophy. The definite diagnosis of SMA will rely on the typical clinical characteristics, changes of electromyogram and muscle biopsy and gene deletion analysis. Gene diagnosis of SMA can provide a basis for prenatal diagnosis which is of great importance in preventing SMA.

Adolescent ; Biopsy ; Child ; Child, Preschool ; Electromyography ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Muscle, Skeletal ; pathology ; Prenatal Diagnosis ; Spinal Muscular Atrophies of Childhood ; diagnosis ; genetics

Objective To investigate the effects of standardized tertiary rehabilitation (STR) on limb motor function (LMF) after stroke.Methods Eighty-two patients were divided into a primary cerebral infarction group (PCI group) and a primary cerebral hemorrhage group (PCH group),and then randomly further divided into experi- mental and control sub-groups.All patients received routine internal medicine treatment,supplemented with stand- ardized tertiary" rehabilitation in the experimental groups.All patients were assessed with the simplified Fugl-Meyer motor function assessment (S-FMMFA) at enrollment,and 1,3 and 6 months after their stroke.Results The scores of the experimental groups were higher than those of the controls.The experimental groups scores were 26.10% of normal at the time of the enrollment,and improved to 42.52%,65.62% and 83.71% by the end of the 1st,3rd and 6th month,respectively.The control groups started at 18.51%,and progressed to 24.85% ,37.24% and 45.84% over the same interval.Conclusion STR was associated with improved LMF scores of stroke pa- tients.

The arm span is the sum of the length of the arm and the width of the chest.It is highly correlated with height and can be used as an accurate and reliable alternative measure to estimate height.The arm span/height ratio reflects the relationship between long bones and the trunk and can be used to evaluate the body proportion.A correct understanding of the development patterns and characteristics of arm span can help pediatricians to find the deviation of body proportion in time, which is of great significance to the etiological analysis of short stature.

OBJECTIVETo observe the effect of repeated esophageal acid infusion on specific airway resistance (sRaw) and airway reactivity in the guinea pigs and explore the mechanism.

METHODSsRaw and airway reactivity were measured by double-chamber plethysmography in normal control group (group N), saline control group (group NS), and repeated acid irrigation group (group H). The initial measurement was used as the baseline sRaw and airway reactivity (1d1), and 2 h after the initial measurement, sRaw and airway reactivity were measured again (1d2). Similarly, such measurements were repeated on the 15th day for all the guinea pigs (15d1, 15d2) with a 2-h interval. The content of Substance P (SP) and vasoactive intestinal peptide (VIP) in lung tissue, trachea, BALF and ganglion were detected by ELISA.

RESULTSThe percent change of sRaw, (15d2-1d1)/1d1 in group H was significantly higher than that in group N. The differences in the airway reactivity of the group N, group NS, and group H were not statistically significant. The SP content in the lung, trachea, ganglion and bronchoalveolar lavage fluid (BALF) in group H was significantly higher than those in group N. The SP content in ganglion showed a significant positive correlation to that in the trachea. No significant differences were found in the VIP content in the lung, trachea, ganglion or BALF between the groups.

CONCLUSIONRepeated esophageal acid infusion increases the airway resistance, but not the airway reactivity in normal guinea pigs. SP may be involved in development of high sRaw through the esophageal-tracheobronchial reflex.

Airway Resistance ; Animals ; Bronchoalveolar Lavage Fluid ; chemistry ; Esophagus ; Gastroesophageal Reflux ; metabolism ; physiopathology ; Guinea Pigs ; Lung ; metabolism ; Male ; Respiratory System ; Substance P ; metabolism ; Trachea ; metabolism ; Vasoactive Intestinal Peptide ; metabolism

OBJECTIVETo establish a method for measurement of airway resistance (sRaw) and reactivity in guinea pigs.

METHODSMethacholine spray at gradient concentrations was given to guinea pigs. PC100 was defined as the concentration of methacholine when the sRaw doubled in the guinea pigs using a double-chamber plethysmograph. The time for the recovery of PC100 resistance to baseline levels was measured. The sRaw and PC100 were measured twice on days 1 and 15 (4 time points) in the guinea pigs before and after OVA challenge.

RESULTSPC100 in a normal guinea pig airway was shown to recover the baseline level within 1 h. Double-chamber plethysmographical measurement of the sRaw and PC100 in normal guinea pigs did not show significant differences between the time points [sRaw: 3.25-/+0.67, 3.33-/+0.58, 3.30-/+0.56, and 3.32-/+0.75 cm H2O.s; log2PC100: 8.48-/+0.94, 8.64-/+1.04, 8.56-/+0.67, and 8.64-/+0.60, respectively, P>0.05]. The sRaw and airway reactivity were significantly increased in guinea pigs challenged with OVA [sRaw: 7.08-/+1.82 vs 2.87-/+0.53 cmH2O.s, P<0.01; log2PC100: 6.64-/+1.26 vs 8.48-/+1.17, P<0.01].

CONCLUSIONA double-chamber plethysmography for measurement of sRaw and airway reactivity in guinea pig is established successfully.

Airway Resistance ; Animals ; Asthma ; chemically induced ; physiopathology ; Bronchial Hyperreactivity ; etiology ; physiopathology ; Guinea Pigs ; Male ; Methacholine Chloride ; Plethysmography ; instrumentation ; methods ; Random Allocation

Aged ; Aged, 80 and over ; Carcinoma, Hepatocellular ; diagnosis ; pathology ; surgery ; Humans ; Keratin-18 ; analysis ; Keratin-19 ; analysis ; Male ; Pancreatic Neoplasms ; diagnosis ; pathology ; surgery ; alpha-Fetoproteins ; analysis

OBJECTIVETo evaluate the correlation between the efficacy of interferon-alpha-2a and the kinetics of viral load in serum.

METHODSThe authors conducted a trial including 58 patients with chronic hepatitis B. Patients were treated with interferon-alpha-2a three times a week for 6 months. Viral kinetics were assessed by serial quantitive measurements of HBV-DNA.

RESULTSA significant decline of serum HBV-DNA was seen after interferon-alpha-2a administration for 1 month, the decreases were (2.50 +/- 0.44) log10, (1.62 +/- 1.12) log10 and (1.05 +/- 1.35) log10 for complete responders, partial responders and no-responders, respectively. After 1 month of treatment, HBV-DNA level was (3.99 +/- 0.91) log10 for complete responders versus (5.63 +/- 1.31) log10 for partial responders, and (6.69 +/- 1.42) log10 for no-responders (P < 0.05). Multivariate analysis suggested that undetectable serum HBV-DNA after 1 month of interferon-alpha-2a treatment was associated with better efficacy; higher baseline ALT or/and no family history were also correlated with better treatment outcomes.

CONCLUSIONKinetics of HBV-DNA level under interferon-alpha-2a treatment are highly predictive of therapeutic response.

Antiviral Agents ; therapeutic use ; CD13 Antigens ; blood ; China ; DNA, Viral ; blood ; genetics ; Hepatitis B virus ; drug effects ; genetics ; Hepatitis B, Chronic ; blood ; drug therapy ; virology ; Humans ; Interferon-alpha ; therapeutic use ; Multivariate Analysis ; Polymerase Chain Reaction ; Treatment Outcome

Background and Objective: As an index of inflammation,neutrophil-to-lymphocyte ratio(NLR)is regarded as one of prognostic factors of hepatocellular carcinoma (HCC). This study was to evaluate the correlation of preoperative NLR to the prognosis of young HCC patients after radical resection. Methods: Clinical data of 91 HCC patients with age of younger than 35 years who underwent radical resection from 2000 to 2005 were analyzed. According to preoperative NLR, the patients were divided into the low NLR group (NLR≤2) and the high NLR group (NLR＞2). The overall and disease-free survival rates of the two groups were compared.Results. The 1-and 3-year overall survival rates were 92.9% and 85.6% in the low NLR group,89.8% and 57.1% in the high NLR group;the 1-and 3-year disease-free survival rates were 85.3% and 80.0% in the low NLR group,69.1% and 43.5% in the high NLR group. The difference between the two groups was significant (P＜0.05). Cox multivariate analysis showed that preoperative NLR and tumor size were independent prognostic factors of disease-free survival and overall survival for young HCC patients after radical resection. Conclusion: Preoperative NLR＞2 was a negative prognostic factor of disease-free and overall survival for young HCC patients after radical resection.