Vesicle glutamate transporter (VGLUT) specifically transfers glutamate into synaptic vesicle, determines the amount of glutamate released into the synaptic cleft, then regulates the efficiency of glutamatergic synaptic transmission. VGLUT plays an important role in the pathogenesis of Alzheimer's diseases (AD). VGLUT is significantly decreased in the brain of AD patients and closely correlated with cognitive dysfunction, beta- amyloid aggregation, tau protein phosphorylation and glutamate excitoxicity. VGLUT, the possible specific biomarker of glutamatergic neuron, has been considered a potential drug target in the treatment of AD and biomarkers in the early diagnosis of AD. There are some advances on chemicals targeting on VGLUT.

The external treatmen of traditional Chinese medicine, the enema and the acupuncture is the current methods of external treatment of traditional Chinese medicine treatment for cirrhosis ascites. In the field of external application and enema, most literature reported specific herbal formular for specific disease, while little literature reported combination of oral administration of herb and external application, or external application based on TCM pattern differentiation, or external application on the acupoints. Acupuncture can reduce drug use and avoid their damage on the liver. This paper summarized the current researches of Chinese medicine external treatment, and points out the direction of the research on the external treatment of traditional Chinese medicine.

AIM: To study the effect l-menthol pretreated nasal cavity on insulin pharmacological bioavailability(PBA). METHODS: To set up diabetic rats model, nasal cavities were pretreated with l-menthol for two hours, insulin was dripped, blood glucose concentrations of different time were determined, and the area over the curve (AOC) and pharmacological bioavailability (PBA) were calculated. RESULTS: After rats nasal cavity was pretreated with different concentrations l-menthol, nasal cavity absorption of insulin markedly increased between 2 h and 3 h, and PBA of insulin nasal cavity absorption increased respectively 5.77, 7.00 and 3.12 times than control group. CONCLUSION: l-Menthol promotes the nasal cavity absorption of insulin.

OBJECTIVE: To observe the impact of catgut embedding on histopathological changes and expression of phosphorylated-Janus kinase-2 (p-JAK 2), phosphorylated-signal transducer and activator of transcription 3 (p-STAT 3), Cyclin D 1, Bcl-2, and suppressor of cytokine signaling (SOCS) of the gastric mucosa in chronic atrophic gastritis (CAG) rats, so as to explore its mechanisms underlying improving CAG. METHODS: Forty-one SD rats were randomly divided into normal (n＝12), model (n＝9), natural recovery (n＝10) and catgut embedding (n＝10) groups. The CAG model was established by free drinking of N-methyl-N'-nitro-N-nitroso-guanidine (MNNG) solution (100µg/mL) and irregular diet for 24 weeks. Catgut embedding was applied at bilateral "Zusanli" (ST 36), "Pishu" (BL 20) and "Zhongwan" (CV 12), once every 10 days, 6 times altogether. The histopathological changes of the gastric mucosa were observed by naked eye and light microscope after H．E. staining. Wes-tern blot was used to detect the expression of p-JAK 2, p-STAT 3, CyclinD 1, Bcl-2 and SOCS 3 proteins in the gastric antrum tissue. RESULTS: After modeling, the regional gastric tissue showed pale thinner gastric wall, and poorer elasticity with fewer plica, congestion of blood vessels, reduction of regional glands with necrosis and disordered arrangement as well as evident hyperplasia of the connective tissue, which was evidently milder in the catgut embedding group. Compared with the normal group, the expression levels of p-JAK 2, p-STAT 3, CyclinD 1, Bcl-2, SOCS 3 proteins were significantly up-regulated in both model group and natural recovery group (P<0.01), without significant differences between the latter two groups (P>0.05). After catgut embedding intervention, the expression levels of p-JAK 2, p-STAT 3, Cyclin D 1, Bcl-2 proteins were considerably down-regulated (P<0.01), and that of SOCS 3 protein was notably further increased relevant to the natural recovery group (P<0.01)．. CONCLUSION: Catgut embedding may improve pathological changes of gastric mucosa in CAG rats, which possibly associated with its effects in up-regulating gastric SOCS 3 protein expression and in inhibiting the activation of JAK 2-STAT 3 signaling pathway to reduce the expression of CyclinD 1 and Bcl-2 proteins.

OBJECTIVE: To investigate the inhibitory effects of novel phosphodiesterase 4 inhibitor ZL-n-91 to the proliferation of leukemia cells L1210 and K562. METHODS: CCK-8 method was used to detect the effect of ZL-n-91 to the proliferation of L1210 and K562 cells, and the proliferation rate, IC RESULTS: ZL-n-91 showed a significant inhibitory effect to the proliferation of leukemia cells L1210 and K562 in a dose-dependent manner (P<0.001). After treated by ZL-n-91, the leukemia cells L1210 and K562 in the S-phase in cell cycle decreased significantly compared with those in control group (P<0.01). The apoptosis of leukemia cells L1210 and K562 could be induced by ZL-n-91 (P<0.001), and the expression level of apoptosis related protein BAX significantly increased. In the animal experiment, the result showed that ZL-n-91 could significantly inhibit the growth of subcutaneously transplantation tumor (P<0.05). CONCLUSION The novel phosphodiesterase 4 inhibitor ZL-n-91 can effectively inhibit the proliferation of leukemia cells L1210 and K562, which has the potential of anti-leukemia drug development.
Animals ; Cell Proliferation ; Humans ; K562 Cells ; Leukemia ; Mice ; Mice, Nude ; Phosphodiesterase 4 Inhibitors/pharmacology*

BACKGROUNDPercutaneous balloon pulmonary valvuloplasty (PBPV) is the preferred therapy for pulmonary valve stenosis (PVS). This study retrospectively reviewed recent PBPV outcomes in infants with PVS. The aim of this study was to evaluate factors associated with immediate therapeutic outcomes and restenosis during medium-term follow-up.

METHODSThe study included 158 infants with PVS who underwent PBPV from January 2009 to July 2015. Demographic characteristics and patient records were reviewed, including detailed hospitalization parameters, hemodynamic data before and immediately after balloon dilation, cineangiograms, and echocardiograms before PBPV and at each follow-up. All procedures were performed by more than two experienced operators.

RESULTSImmediately after balloon dilation, the pressure gradient across the pulmonary valve decreased from 73.09 ± 21.89 mmHg (range: 43-151 mmHg) to 24.49 ± 17.00 mmHg (range: 3-92 mmHg; P < 0.001) and the right ventricular systolic pressure decreased from 95.34 ± 23.44 mmHg (range: 60-174 mmHg) to 52.07 ± 18.89 mmHg (range: 22-134 mmHg; P < 0.001). Residual transvalvular pressure gradients of 67.31 ± 15.19 mmHg (range: 50-92 mmHg) were found in 8.2% of patients, indicating poor therapeutic effects; 6.4% of patients had variable-staged restenosis at follow-up and 3.8% underwent reintervention by balloon dilation or surgical repairs. Further analysis demonstrated that the balloon/annulus ratio showed statistically significant differences (P < 0.05) among groups with different therapeutic effects and between the restenosis and no-stenosis groups. Binary logistic regression analysis further revealed that higher balloon/annulus ratio (odds ratio: 0.005, 95% confidence interval: 0-0.39) was an independent protective factor for restenosis. The rate of severe complications was 1.9%.

CONCLUSIONSPBPV is a definitive therapy for infants with PVS based on its effectiveness, feasibility, and safety. Restenosis upon medium-term follow-up is relatively rare.

Objective: To detect the CHRNA7 gene mutation and polymorphism in Southern Han Chinese patients with nocturnal frontal lobe epilepsy (NFLE). Methods: Blood samples were collected from 215 Southern Han Chinese patients with NFLE and 200 healthy Southern Han Chinese control subjects. Genomic DNA was extracted, and CHRNA7 whole genome exons were amplified by the polymerase chain reaction and subjected to Sanger sequencing. Results: No CHRNA7 gene mutation was detected in all of the NFLE patients. However, five single nucleotide polymorphisms (SNPs) in sporadic cases were found, located in exons 5, 6, and 7 of the CHRNA7 gene. Among them, c.690G>A and c.698A>G are known SNPs, while c.370G>A, c.654C>T, and c.497-498delTG were newly discovered SNPs. These SNPs were also found in some of the healthy controls. Conclusions: No CHRNA7 gene mutation was identified in Southern Han Chinese patients with NFLE. The CHRNA7 gene is probably not responsible for NFLE in this population.

OBJECTIVETo compare the clinical efficacy of trapezoid pad coordinate with small splint fixation treatment with plaster slab fixation treatment for comminuted Colles fracture.

METHODSFrom October 2010 to March 2012,80 outpatients with comminuted Colles fracture were divided into two groups. There were 40 patients in trapezoid pad splint fixation treatment group and 40 patients in pipe type plaster control group. There were 13 males and 27 females in trapezoid pad splint fixation treatment group,with an average age of (62.1 +/- 19.2) years old. And there were 15 males and 25 females in pipe type plaster control group,with an average age of (60.2 +/- 19.5) years old. After treated with manipulative reduction,the fractures were fixed with pipe plaster in the control group, and were fixed with trapezoid pad joint by small splint in the treatment group. The patients in both groups were regularly taken X-ray recheck and changed dressings to obtain the clinical healing. Patients were guided to do functional exercise after splints were taken off. The therapeutic effects were evaluated according to Gartland-Werlley wrist score when splints taken off and after 2 months.

RESULTSAccording to wrist score, the average scores in the treatment group were (8.1 +/- 2.8) when splints taken off and (5.3 +/- 4.5) after 2 months. And the average scores in the control group were (10.3 +/- 2.6) when splints taken off and (8.4 +/- 5.8) after 2 months. The score in the treatment group was higher than that of control group. The average shortened lengths of radius were (4.8 + 1.7) mm in the treatment group and (8.2 +/- 2.1) mm in the control group. The shortened length of control group was larger than that of treatment group.

CONCLUSIONTrapezoid pad coordinated with small splint fixation is better than traditional pipe type plaster for treating comminuted Colles fracture.

Adult ; Aged ; Case-Control Studies ; Casts, Surgical ; Colles' Fracture ; surgery ; Female ; Fractures, Comminuted ; surgery ; Humans ; Male ; Middle Aged ; Splints

BACKGROUNDDrug resistance to targeted therapies occurs in lung cancer, and resistance mechanisms related to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are continuously being discovered. We aimed to establish a novel method for highly parallel multiplexed detection of genetic mutations related to EGFR TKI-resistant lung cancer using Agena iPLEX chemistry and matrix-assisted laser desorption ionization time-of-flight analysis on the MassARRAY mass spectrometry platform.

METHODSA review of the literature revealed 60 mutation hotspots in seven target genes (EGFR, KRAS, PIK3CA, BRAF, ERBB2, NRAS, and BIM) that are closely related to EGFR TKI resistance to lung cancer. A total of 183 primers comprised 61 paired forward and reverse amplification primers, and 61 matched extension primers were designed using Assay Design Software. The detection method was established by analyzing nine cell lines, and by comparison with LungCarta™ kit in ten lung cancer specimens. EGFR, KRAS, and BIM genes in all cell lines and clinical samples were subjected to Sanger sequencing for confirming reproducibility.

RESULTSOur data showed that designed panel was a high-throughput and robust tool, allowing genotyping for sixty hotspots in the same run. Moreover, it made efficient use of patient diagnostic samples for a more accurate EGFR TKIs resistance analysis. The proposed method could accurately detect mutations in lung cancer cell lines and clinical specimens, consistent with those obtained by the LungCarta™ kit and Sanger sequencing. We also established a method for detection of large-fragment deletions based on single-base extension technology of MassARRAY platform.

CONCLUSIONSWe established an effective method for high-throughput detection of genetic mutations related to EGFR TKI resistance based on the MassARRAY platform, which could provide more accurate information for overcoming cancers with de novo or acquired resistance to EGFR-targeted therapies.

Objective: To study the chemical structure and activity of secondary metabolites of the endophytic fungus Bipolaris sorokiniana A606 isolated from Pogostemon cablin. Methods: The compounds were isolated and purified from the ethyle acetate extract of the fungal fermentation broth by silica gel, reverse phase silica gel, Sephadex-LH20, HPLC, and so on. Their structures were identified by extensive spectroscopic analysis. The compounds were evaluated for their cytotoxic activities against human tumor cell lines by the SRB assay and their antibacterial activities against bacteria were evaluated by the filter paper method. Results: Two compounds were isolated from the fermentation broth extract of the strain A606 and identified as (3S*,4aS*,6aS*,12bS*)-3-(2-hydroxypropan-2-yl)-6a,12b-dimethyl-9-[(2R*,4R*)-4-methyl-3-oxohexan-2-yl]-1,2,3,4a,5,6-hexahydropyrano [3,2-a]xanthene-8,11-dione (1) and precochlioquinol D (2). Conclusion: Compound 1 is a new compound, named 11-hydroxy-12,13-dehydrocochlioquinone B. Compound 2 is isolated from the species of genus Bipolaris for the first time. Compound 1 shows the cytotoxic and antibacterial activities.