ABSTRACT:The aim of the present study was to investigate the inhibitory effects of TLR7 on Mycobacterium tuberculosis . TLR7 on infected RAW264 .7 cells was activated by chemical synthesis of TLR7 activation motif ssRNA .Activated RAW264 .7 cells were inoculated with Mycobacterium tuberculosis ,quantitative PCR method was applied to detect the phagocytosis rate of cell to bacteria at different time after infection .Cytokine production was measured by ELISA from cell supernatant .Cells were cultured on Roche medium and counted after sterile cracked with TritonX‐100 and diluted with PBS .Scanning electronic micro‐scope ( SEM ) was applied to detect the morphological changes of cells treated with TLR7 activation motif ssRNA .The highest phagocytosis rate of bacteria of RAW264 .7 cells was at 3 hours post infection (P>0 .05) .Compared with that of the control group ,treatment after 36 hours intracellular bacterial quantity in ssRNA treated group was lower (P<0 .05) ,levels of IL‐12 (P<0 .05) and IL‐4 (P<0 .05) were increased .For treatment after 48 hours ,level of IL‐4 (P<0 .05) was decreased ,and TNF‐α (P<0 .05) was increased .For treatment after 3 hours ,cell morphology of the ssRNA group was obviously better than the control group and appeared lots of phagosomes .Results suggested that TLR7 could enhance macrophages in killing Myco‐bacterium tuberculosis by forming phagosomes and regulating cytokines production ,and TLR7 activation motif ssRNA could be used in the treatment of tuberculosis .

AIM: To study the bioequivalence of domestic and imported Metoprolol Tartrate Tablets in Chinese healthy volunteers.METHODS: According to the rule published by SFDA,the serum concentration of 20 selected volunteers among 18 to 40 years old was determined by HPLC-fluorescence detection after giving domestic and imported Metoprolol Tartrate Tablets 0.1g,and the pharmacokinetic parameters were calculated by DAS software.RESULTS: The method of HPLC-fluorescence detection to study the pharmakokinetics of Metoprolol Tartrate was sensitive,reliable,accurate and reasonable.The main pharmakokinetics parameters of domestic and imported Metoprolol Tartrate Tablets were T_(max):(1.11)?(0.36 h) and(1.39)?(0.65 h) respectively;C_(max):(269.20)?(87.15)(?g?L~(-1)) and(262.03)?(75.52)(?g?L~(-1)) respectively;AUC_(0-12h):(1088.91)?(510.52)(?g?L~(-1)?h) and(1098.29)?5(55.14)(?g?L~(-1)?h) respectively.The relative bioavailability of domestic Metoprolol Tartrate Tablets was(100.09)%.CONCLUSION: The domestic and imported Metoprolol Tartrate Tablets was bioequivalents.

Chemical constituents of ethyl acetate extract of Illicium burmanicum were isolated and purified by various chromatographic methods,including Silica gel, Sephadex LH-20, C18 reverse-phased silica gel, Preparative TLC and Preparative HPLC. Their structures were identified by spectral analysis including NMR and MS data. Fourteen compounds were separated from I. burmanicum and their structures were identified as 7S,8R-erythro-4,7,9,9'-tetrahydroxy-3,3'-dimethoxy-8-O-4'-neolignan (1), 7R,8R-threo-4,7, 9,9'-tetrahydroxy-3,3 '-dimethoxy-8-O-4'-neolignan(2) ,polystachyol(3), (-) -massoniresinol(4), angustanoic acid F (5), trans-sobrerol(6), (3S,6R) -6,7-dihydroxy-6,7-dihydrolinalool (7), (3S, 6S) -6,7-dihydroxy-6,7-dihydrolinalool (8), 2,6-dimethoxy-4-allyl-phenol (9), 3,5-dihydroxy4-hydroxy benzaldehyde (10), 3-hydroxy4-methoxybenzaldehyde (11), methyl vanillate (12), shikimic acid ethylester (13) and beta-sitosrerol (14). Except compound 14, the rest thirteen compounds were separated from this plant for the first time.
Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Illicium ; chemistry ; Molecular Structure ; Spectrometry, Mass, Electrospray Ionization

Objective To explore the effects of acupuncture and individualized occupational therapy on the rehabilitation of patients with unilateral spatial neglect ( USN ) after stroke.Methods Stroke patients with hemiplegia were evaluated by neuropsychological tests,including line bisection,a cancellation test,clock drawing,and figure and shape copying.Sixty-nine right hemispheric stroke patients identified with USN were randomly assigned to 3 groups:20 patients as a control group received conventional rehabilitation therapy ; another 22 patients as an occupational group received type-specific individualized occupational therapy combined with conventional rehabilitation therapy; the remaining 23 patients as an acupuncture combined with occupational therapy group received acupuncture in addition to both conventional rehabilitation therapy and occupational therapy.These three groups were evaluated with neuropsychological tests and the modified Barthel index (MBI) before and after treatment.Results ①MBI scores in the occupational therapy group and the combined group were significantly higher after treatment,but no significant difference was observed in the control group.②The increased MBI scores in the combined and occupational groups were higher than those in the control group.At the same time the increase in MBI scores in the combined group was significantly greater than in the occupational therapy group.③The assessment results with both line bisection and cancellation tests in all three groups were significantly different after treatment.The line bisection results in the occupational therapy group and the combined group were significantly better than in the control group.The cancellation test results in the combined group were significantly better than in the control group.Conclusion These findings show that acupuncture combined with occupational therapy can have a positive effect on neglect recovery and greatly improve the daily life of USN patients.

BACKGROUNDThe role of epigenetics in gene expression regulation and development significantly enhances our understanding of carcinogenesis. All the tumor related genes may be the target of epigenetical or genetic regulation. We selected some epigenetically regulated genes for cDNA array analysis and observed variability in the expression of the DICER1 gene in distinct stages of gastric cancer. The aim of this study was to assess the correlation between the expression of DICER1, an epigenetically regulated gene, and gastric cancer.

METHODSTo detect the expression of 506 tumor-associated genes, including DICER1, in the matched cancerous mucosa, pre-malignant lesion (adjacent mucosa), non-cancerous gastric mucosa and distant lymphocyte metastatic lesion in 3 cases of gastric cancers using cDNA array. DICER1 mRNA expression and DICER1 protein expression were further analyzed by Real-time PCR and Western blot in 32 cases of progressive gastric cancer. DICER1 protein expression was also detected in 33 early and 30 progressive gastric cancers by the immunohistochemistry (IHC) method.

RESULTSIn 3 cases of gastric cancer cDNA array showed dramatically decreased expression of DICER1 in pre-malignant lesion, cancerous mucosa and distant lymphocyte metastatic lesions compared with matched noncancerous gastric mucosa, pre-malignant lesion and cancerous mucosa. Real-time PCR results showed that the expression level of DICER1 mRNA in gastric cancer was significantly down-regulated compared to normal gastric tissue (P < 0.05). The IHC assay also showed that the expression of DICER1 was significantly decreased in progressive gastric cancer. Among the 63 cases of gastric cancers, 13/33 early (39.4%) and 19/30 (63.3%) progressive cancers showed negative expression of DICER1 (50.8%). The difference in expression of DICER1 between early and progressive gastric cancers was significant (P < 0.01). The result of Western blotting showed that DICER1 protein was down-regulated significantly in advanced gastric cancer (P < 0.05).

CONCLUSIONSDICER1 expression is decreased during the progression of gastric cancer, especially in progressive gastric cancers, which indicating DICER1 may play an important role in the development of cancer and the epigenetical regulation involved.

Blotting, Western ; DEAD-box RNA Helicases ; analysis ; genetics ; physiology ; Endoribonucleases ; analysis ; genetics ; physiology ; Epigenesis, Genetic ; Humans ; Immunohistochemistry ; Oligonucleotide Array Sequence Analysis ; Polymerase Chain Reaction ; Ribonuclease III ; Stomach Neoplasms ; chemistry ; etiology ; genetics

Nasopharyngeal carcinoma (NPC) is among the most common malignancies in southern China. Deletion of genomic DNA, which occurs during the complex pathogenesis process for NPC, represents a pivotal mechanism in the inactivation of tumor suppressor genes (TSGs). In many circumstances, loss of TSGs can be detected as diagnostic and prognostic markers in cancer. The short arm of chromosome 3 (3p) is a frequently deleted chromosomal region in NPC, with 3p21.1-21.2 and 3p25.2-26.1 being the most frequently deleted minimal regions. In recent years, our research group and others have focused on the identification and characterization of novel target TSGs at 3p, such as RASSF1A, BLU, RBMS3, and CHL1, in the development and progression of NPC. In this review, we summarize recent findings of TSGs at 3p and discuss some of these genes in detail. A better understanding of TSGs at 3p will significantly improve our understanding of NPC pathogenesis, diagnosis, and treatment.
Cell Adhesion Molecules ; genetics ; Chromosome Deletion ; Chromosomes, Human, Pair 3 ; genetics ; Epigenesis, Genetic ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Heterotrimeric GTP-Binding Proteins ; genetics ; Humans ; Nasopharyngeal Neoplasms ; genetics ; RNA-Binding Proteins ; genetics ; Trans-Activators ; genetics ; Tumor Suppressor Proteins ; genetics

OBJECTIVETo explore the clinical characteristics,diagnosis and treatment of abdominal cocoon.

METHODSClinical data of 203 cases with abdominal cocoon including 7 cases in our hospital and 196 cases reported in Chinese literature from January 1995 to June 2005 were analyzed retrospectively.

RESULTSThe male to female ratio was approximately 1.2:1. The mean age at diagnosis was 33 years. The main clinical manifestations included recurrent acute or chronic intestinal obstruction in 147 cases (72.4%), abdominal mass in 53 cases (26.1%). Of the 203 cases, abdominal plain X-ray were performed in 163, B-ultrasound in 85, CT in 68 and barium meal in 32 cases, however, only 6 cases (3.0%) were diagnosed as abdominal cocoon preoperatively. All the cases received operations included partial or total excision of the membrane and enterolysis in 172 cases (84.7%), together with bowel resection in 34 cases (16.7%) and appendectomy in 51 cases (25.1%). Postoperative complications included recurrent obstruction in 55, and death in 11 cases (5.4%).

CONCLUSIONSThe preoperative diagnosis of abdominal cocoon is difficult. Operations should be performed on the cases with intestine obstruction. Recurrent adhesive intestinal obstruction is the main postoperative complication.

Abdominal Cavity ; pathology ; Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Female ; Humans ; Intestinal Obstruction ; diagnosis ; pathology ; surgery ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

AIM:To investigate the changes of choroidal thickness in patients with severe non-proliferative diabetic retinopathy (NPDR) after vitreous injection of ranibizumab,and to analyze the relationship between the thickness of choroid and the visual acuity of the patients.METHODS:Eighty patients with severe non-proliferative diabetic retinopathy were selected from January 1,2014 to January 1,2017.All patients were divided into observation group and control group according to the random number table,40 cases in each group.The control group was treated in a conventional manner,and the observation group was injected with ranibizumab in the vitreous.The thickness of the choroid in the macular area and the thickness of the retinal neuroepithelium in the macular area were compared between the two groups before and after treatment.The changes of the corrected visual acuity were analyzed at 1mo before and after treatment.The relationship between the thickness of the choroid and the thickness of the retinal neuroepithelium and the best corrected visual acuity were compared.The complications and adverse events were compared between the two groups after 6wk of treatment.RESULTS:The thickness of the choroid and the retinal neuroepithelium in the macular area before were 219.57± 51.24μm and 474.76 ± 95.56μm,respectively,in the observation group and the control group,217.56± 50.36μm and 473.27 ± 96.48μm,respectively.The thickness of the choroid and the thickness of the retinal neuroepithelium in the macular area after treatment were 180.15±42.06μm and 382.18±84.26,202.48±48.28μm and 407.88± 44.25μm,respectively.The difference between the two groups was statistically significant (P＜0.05).The best corrected visual acuity in the observation group and the control group were 0.47±0.19 and 0.53±0.25 respectively (P＜0.05).There was a positive correlation between the choroidal thickness and the best corrected visual acuity in the macular fovea (regression coefficient=1.12,S=0.48,OR=1.376,P＜ 0.05).There was a positive correlation between retinal neuroepithelial thickness and best corrected visual acuity in the macular area (regression coefficient =0.95,S=0.27,OR=1.020,P＜ 0.05).There were 2 eyes (5％) with subconjunctival hemorrhage,1 eyes (2.5％) of glaucoma,1 eyes (2.5％) of vitreous hemorrhage,0 of choroidal detachment,retinal detachment in 0 in observation group at 6wk after treatment.There were 4 eyes (10％) with subconjunctival hemorrhage,2 eyes (5％) of glaucoma,2 eyes of vitreous hemorrhage (5％),2 eyes of choroidal detachment (5％),retinal detachment in 2 eyes (5％) in the control group,and the difference between the two groups on the complications and adverse reactions was statistically significant (P＜0.05).CONCLUSION:The choroidal thickness of patients with macular edema in severe non-proliferative diabetic retinopathy is correlated with the best corrected visual acuity.Intravitreal injection of ranibizumab can effectively reduce the macular fovea choroidal thickness,reduce macular edema and improve vision,and less complications.

Fatigue is a common complication of type 2 diabetes mellitus (T2DM). We examined the relationship between T2DM fatigue and the skeletal muscle 5-hydroxytryptamine (5-HT) system. In animal experiments, a T2DM model was established in mice by feeding a high-fat diet with intraperitoneal injection of streptozotocin. The mice were treated with the 5-HT_2A receptor antagonist sarpogrelate hydrochloride (SH) and the 5-HT synthesis inhibitor carbidopa (CDP) (separately and in combination). In cell culture experiments, C2C12 cells were stimulated with D-glucose, palmitic acid or 5-HT. 5-HT_2AR, 5-HT synthesis and 5-HT degradation were inhibited by SH, CDP, or monoamine oxidase A (MAO-A) inhibitor. The animal experiments were in accordance with the regulations of the Animal Ethics Committee of China Pharmaceutical University. The results showed that 5-HT_2AR, 5-HT synthase and MAO-A were expressed in mouse skeletal muscle and C2C12 cells. The expression of these proteins was significantly up-regulated in T2DM mice or when C2C12 cells were exposed to palmitic acid and D-glucose; palmitic acid was a stronger stimulant of their expression than D-glucose. Rotating rod experiments and biochemical index tests have shown that T2DM fatigue is associated with an increase in skeletal muscle 5-HT_2AR, 5-HT synthesis and 5-HT degradation. 5-HT_2AR mediates the expression of MAO-A and the synthesis of 5-HT, which indirectly regulates the degradation of 5-HT. MAO-A regulates cell inflammation, mitochondrial ROS production and membrane potential depolarization by mediating 5-HT degradation. MAO-A also inhibits the expression of peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1), carnitine palmitoyltransferase-1 (CPT1) and ATP synthase-6 (ATP6), thus inhibiting mitochondrial functions such as fatty acid β oxidation and ATP synthesis. SH and CDP can effectively treat T2DM fatigue, and can also reduce blood glucose and blood lipid, and the combination of SH and CDP has a clear synergistic effect.

Isopentenyl diphosphate isomerase (IDI) is a key enzyme in the regulation of triterpenes biosynthesis and plays an important role in ginsenoside biosynthesis. In this study, two IDI genes, PvfIDI1 (GenBank No. MZ736417) and PvfIDI2 (GenBank No. MZ736418) were cloned from Panax vietnamensis var. fuscidiscus. The open reading frame of both PvfIDI1 and PvfIDI2 was 924 bp encoding 307 amino acids. The molecular weights of PvfIDI1 and PvfIDI2 were 34.84 kDa and 34.66 kDa, respectively, with theoretical pIs of 6.01 and 5.66. Bioinformatic analysis indicated that PvfIDI1 and PvfIDI2 contained two conserved sequences: TNTCCSHPL and WGEHELDY. Phylogenetic analysis showed that PvfIDI1 and PvfIDI2 were closely related to Panax notoginseng IDI. Expression analysis showed that both PvfIDI1 and PvfIDI2 genes are expressed in root, rhizome, stem and leaf of P. vietnamensis var. fuscidiscus. However, PvfIDI1 is highly expressed in the rhizome and PvfIDI2 is highly expressed in the stem. PvfIDI1 and PvfIDI2 recombinant proteins were expressed in E. coli; a functional coloration experiment showed that PvfIDI1 and PvfIDI2 could promote the accumulation of lycopene, indicating that both PvfIDI1 and PvfIDI2 encode functional IDI enzymes. The cloning and functional studies on PvfIDI1 and PvfIDI2 provide a foundation for the further study of IDI and the regulation of ginsenoside biosynthesis in P. vietnamensis var. fuscidiscus.