Objective To investigate alterations of blood perfusion in subcortical regions in patients with Parkinson′s disease (PD) by three dimentional arterial spin labeling (ASL) magnetic resonance imaging (MRI). Methods Thirty patients with PD and 40 control subjects were recruited from the inpatient and outpatient of the Department of Neurology of Northern Jiangsu People′s Hospital during October 2014 to October 2016, and routine brain MRI and 3D pseudo?continuous pulse ASL were performed on all the subjects. The cerebral blood flow (CBF) maps derived from 3D ASL were coregistered to the Montreal Neurological Institute brain space. The stereo?templates of bilateral caudate nucleus, putamen nucleus, globus pallidum and thalamus from Anatomical Automatic Labeling were used as region of interest (ROI) to exstract absolute CBF values in these subcortical regions, respectively. The CBF ratio (rCBF) values represented by individual whole brain CBF divided by each of the regional CBF were also calculated in consideration of the difference between individual whole brain CBF. The CBF and rCBF values were compared respectively between groups by one?way analysis of variance. Results The subcortical CBF values (ml·100 g-1·min-1) for each ROI in PD (caudate nucleus (left: 35.32±6.47, right: 36.17±7.07), globus pallidum (left: 40.42 ± 5.83, right: 40.18 ± 5.70), putamen nucleus (left: 41.97 ± 6.12, right: 42.91 ± 6.43) and thalamus (left: 46.58 ± 7.71, right: 49.11 ± 7.10)) were significantly lower than that in the control group (caudate nucleus (left: 41.38±7.05,right: 41.63±6.85), globus pallidum (left: 45.65±8.35,right: 45.53±8.94), putamen nucleus (left: 48.49±8.78, right: 48.99±8.88) and thalamus (left: 54.32±11.94,right: 56.21±11.98), F=13.58, 10.56, 12.11, 10.06, 8.59, 8.23, 9.57, 8.30, P=0.000, 0.002, 0.005, 0.005, 0.001, 0.002, 0.003, 0.005, respectively ). The whole brain mean CBF values of each subject were also extracted and compared bewteen groups, and mean CBF values (ml·100 g-1·min-1) in PD patients (42.14±9.61) decreased significantly than those in the control group (51.59±9.67, F=16.42, P<0.01), and there was a 18.31% decrement in whole brain mean CBF in the patient group. However, rCBF values for almost all subcortical ROIs of the patients significantly increased when compared with the control group. Conclusions The decreased absolute cerebral blood perfusion involved not only subcortical regions, but also the whole brain level in the course of PD. The CBF metabolism in patients with PD may have been redistributed, with relative hyperperfusion in the subcortical brain regions contrast to the whole brain perfusion level of patients themselves.

The E3 ligase HERC4 is overexpressed in human breast cancer and its expression levels correlated with the prognosis of breast cancer patients. However, the roles of HERC4 in mammary tumorigenesis remain unclear. Here we demonstrate that the knockdown of HERC4 in human breast cancer cells dramatically suppressed their proliferation, survival, migration, and tumor growth in vivo, while the overexpression of HERC4 promoted their aggressive tumorigenic activities. HERC4 is a new E3 ligase for the tumor suppressor LATS1 and destabilizes LATS1 by promoting the ubiquitination of LATS1. miRNA-136-5p and miRNA-1285-5p, expression of which is decreased in human breast cancers and is inversely correlated with the prognosis of breast cancer patients, are directly involved in suppressing the expression of HERC4. In summary, we discover a miRNA-HERC4-LATS1 pathway that plays important roles in the pathogenesis of breast cancer and represents new therapeutic targets for human breast cancer.

Objective To analyze the genetic characteristics of VP1-VP4 genes carried by cox-sackievirus A6 (CVA6) strains isolated from severe cases of hand, foot, and mouth disease (HFMD) in Shenzhen during 2012 to 2015. -ethods The VP1-VP4 genes of CVA6 strains isolated from severe HFMD cases in Shenzhen during 2012 to 2015 were amplified and sequenced. Phylogenetic analysis was performed to analyze the VP1-VP4 genes of CVA6 isolates and sequences downloaded from GenBank by using DNASTAR6. 0 and MEGA6. 02 software packages. Results Four cases of severe HFMD were caused by CVA6 in Shenzhen during 2012 to 2015. All of the patients had the symptom of fever, skin rash and aseptic encephalitis. The CVA6 strain causing severe HFMD in 2013 shared 98. 8％-98. 9％ homology in nucleotide sequences and 99. 3％-99. 8％ in amino acid sequences with the strains isolated in 2012. Two amino acid mutations were found in the CVA6 strain isolated in 2013, which were G73E in VP2 region and S13G in VP1 region. However, the CVA6 strain isolated in 2015 only shared 95. 0％ homology in nucleotide sequences and 99. 3％ homology in amino acid sequences with the strain isolated in 2013. Six amino acid mutations were identified including E73G in VP2 region and T5A, S27N, A30V, N137S and V242I in VP1 region. The phylogenetic analysis revealed that the four CVA6 strains belong to D3 sub-genotype. The CVA6 strains causing severe cases in 2012 had the nearest genetic relationship with the strain isolated in Changsha in 2012 (KJ156349). The CVA6 strain isolated in Shenzhen in 2013 had the nearest genetic relationship with the strain isolated in Shanghai in 2013 (KJ612513). The Shenzhen CVA6 isolate in 2015 showed high similarity to Weifang CVA6 isolate in 2014 (KX752785). Conclusions All CVA6 strains causing severe HFMD ca-ses in Shenzhen during 2012 to 2015 belongs to D3 sub-genotype. Mutations of S27N and A30V in the VP1 region of the CVA6 isolate in 2015 are located in the B cell epitopes. In addition, the VP1-V242I mutation in the CVA6 strain isolated in 2015 is located in the binding site of PSGL-1 receptor. These mutations may affect the binding of CVA6 strains to the cellular receptors and their infectivity to people.

To construct a eukaryotic expression plasmid containing the luciferase reporter gene (Fluc) to quickly detect apoptosis. Four amino acids, Asp-Glu-Val-Asp (DEVD), the recognize motif of Caspase-3, were introduced into the middle of the Fluc-C and N fragment. Meanwhile, four amino acids, Asp-Glu-Val-Gly (DEVG), were selected as a negative control. Subsequently, the recombinant gene was cloned into the N and C terminal end of the split intein, and named as pFluc-DEVD and pFluc-DEVG. Then the plasmids were transfected into cells and renilla luciferase was co-transfected in each sample as an internal control for transfection efficiency. Then the apoptosis level was detected by the double luciferase reporter gene and the Western blotting analysis. The results showed that when apoptosis occurred, the content of firefly luciferase expressed in the pFluc-DEVD plasmid transfected group was about 3 times higher than pFluc-DEVG plasmid transfected group. Furthermore, Western blotting detection indicated that the Fluc level was significantly increased in pFluc-DEVD transfected group when pre-treated by apoptosis stimulants. The activation degree of Caspase-3 was closely related to the expression of Fluc, and had a significant statistical difference. These results confirmed that firefly luciferase protein expressed by pFluc-DEVD plasmid can be cleaved by the intracellular Caspase-3 enzyme, and this plasmid can accurately reflect the cell apoptosis level, which provides a useful method for quantitative detection of apoptosis.
Apoptosis ; Genes, Reporter ; Luciferases, Firefly ; Transfection

OBJECTIVE: To select the optimized treatment plan of acupuncture for lateral femoral cutaneous neuritis by using multiple indexes decision-making method based on the clinical evidence. METHODS: The randomized control trials (RCTs) regarding acupuncture for lateral femoral cutaneous neuritis in the CNKI database, CBM database, WANFANG database, VIP database, PubMed, Cochrane Library and Embase published before December 31, 2017 were comprehensively collected. The modified Jadad scale was used to evaluate the quality of the RCTs. Then the evaluation indexes were selected and the dimensions of evaluation indexes were standardized by using extreme difference transformation method. The weight of each index was determined by using relative comparison method and the standardized matrix was weighted. Thus, the ideal solution and the negative ideal solution were obtained, and the relatively degree of each treatment plan to the ideal solution was calculated to propose the optimized plan of acupuncture for lateral femoral cutaneous neuritis. RESULTS: A total of 18 RCTs were included, the optimized plan of acupuncture for lateral femoral cutaneous neuritis was using thin fire needle to rapidly prick the abnormal skin region with fast needle insertion-withdrawal technique; the fire needle was applied repeatedly; intensive pricking to form a treatment area; the treatment was given once every 5 days. CONCLUSION Based on the current clinical evidence, the optimized plan of acupuncture for lateral femoral cutaneous neuritis is using thin fire needle to prick the abnormal skin region; the multiple methods of plum-blossom needling met the characteristic of lateral femoral cutaneous neuritis and is suitable for clinical selection. The main acupoints are points in the abnormal skin area or the acupoints in the foot- meridian and foot- meridian, combined with lumbar Jiaji (EX-B2) points.
Acupuncture Therapy ; Humans ; Meridians ; Needles ; Neuritis ; therapy ; Randomized Controlled Trials as Topic

Afatinib ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoembryonic Antigen ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Gallbladder Neoplasms ; drug therapy ; pathology ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; Neoplasm Staging ; Tomography, X-Ray Computed

Polysaccharide from traditional Chinese herb, Saposhnikovia divaricata (Turcz.) Schischk. (SD) was extracted, fractionated and characterized in this work. Four fractions were prepared. Their molecular weight, monosaccharide compositions, linkage modes and structural properties were characterized with SEC-MALS-RI, HPAEC-PAD, GC-MS and NMR. SDP1 was assigned as a 1, 4-α-glucan with small amount of O-6 linked branches. SDP2 contained a big amount of the 1, 4-α-glucan and a small amount of arabinogalactan, while SDP3 possessed relatively lower amount of the 1, 4-α-glucan and a big amount of the arabinogalactan. SDP4 was defined as a pectic arabinogalactan. Four fractions showed antioxidant activities in both molecular and cellular levels and their activity was ranked as SDP4 ≈ SDP3>SDP2>SDP1. The 1, 4-α-glucan in SDP1 had the weakest, while SDP3 and SDP4 showed similar and the highest antioxidant activity. The arabinogalactan was the major component of both SDP3 and SDP4, which significantly contributed to the antioxidant activity of SDP.

The blood brain barrier can selectively block the uptake of xenobiotics from peripheral blood into the brain. Although this is important for maintaining the stability of the brain environment and normal function of the central nervous system, it presents a challenge for delivery of therapeutic drugs to the brain. Passive brain-targeting drug carrier is able to increase the drug concentration in the brain by enhancing the affinity to blood-brain barrier and/or inhibiting the efflux absorbed drug via P-glycoprotein. The active brain-targeting drug carrier can be obtained by linking specific ligands or antibodies onto passive target carriers to achieve precise delivery of drugs to the brain. Dual targeting drug carriers obtained by combining tumor cell targeting with brain targeting have shown their advantages for treatment of brain tumors. The targeted drug delivery to brain will provide a unique manner for the treatment of brain diseases such as Alzheimer's, Parkinson's, brain tumors, and stroke. Among the drug delivery systems of passive brain-targeting, active brain-targeting and dual brain-targeting, we evaluated the strategies to improve brain drug delivery efficiency, such as by reducing carrier size, opening tight junctions between cells at the blood-brain barrier, incorporating hydrophilic groups on the surface of the carrier, and alternative intranasal drug administration.

Objective: To synthesize and analyze ¹⁸F-prostate specific membrane antigen (PSMA)-1007, followed by its imaging in prostate cancer. Methods: Based on one-step method, ¹⁸F-PSMA-1007 was produced by the CFN-MPS-200 automatic synthesis module and its quality analysis was conducted. ¹⁸F-PSMA-1007 PET/CT imaging was performed in a prostate cancer patient (66 years old). Results: The synthesis time of ¹⁸F-PSMA-1007 was about 50 min, and the radiochemical yield was (25.0±5.0) % (attenuation correction, n=3). The radiochemical purity was above 99.0% and was above 98.0% after 6 h. The product was colorless transparent solution with pH value of 7.0-7.5, and the specific activity was (410.0±11.0) MBq/ml and the radioactive nuclear purity was above 99.0%. PET/CT imaging in the patient showed that ¹⁸F-PSMA-1007 was highly concentrated in prostate cancer with maximum standardized uptake value (SUV_max) of 40.9. Conclusion Based on CFN-MPS-200 multifunction synthesis module, ¹⁸F-PSMA-1007 can be stably synthesized with high radiochemical yield and can be concentrated in prostate cancer.

Objective: To investigate the gut microbiota diversity between the elderly supported by institution-based care and home-based care. Methods: Fresh stool samples were collected from 18 aged persons supported by institution-based care (G1 group), 20 aged persons with home-based care (G2 group) and 20 middle-aged and young adults (G3 group). The V3-V4 hypervariable region of 16S rDNA was amplified and sequenced by next generation sequencing technology. Operational taxonomic units (OTUs) were analyzed by QIIME analysis platform for species annotation, diversity analysis, and inter-group difference analysis. Statistical analysis was performed using RStudio software. Results: The top 6 microbiological taxa in the three groups were Firmicute, Bacteroidetes, Proteobacteria, Actinobacteria, Fusobacteria and Verrucomicrobia. The abundance of the Firmicute in the G1 and G2 groups showed significant differences [(61.47±5.58)% vs (76.55±3.64)%, P<0.05]. The G1 and G3 groups had a statistically significant difference in the abundance of the Proteobacteria [(9.59±12.68)% vs (2.15±2.47)%, P<0.05]. The abundance of both Bacteroidetes and Proteobacteria was higher in the G1 group than in the G2 group without significant difference between the two groups. No significant differences in diversity indices (Shannon, Simpson and Chao1) were found between G1 and G2 groups (P>0.05). Results of the NMDS analysis showed that the intra-group differences were greater than inter-group differences in G1 and G2 groups. Conclusions No significant difference in the diversity of gut microbiota was detected between the elderly supported by institution-based care and home-based care, but there were differences in the composition of the predominant gut microbiota.