OBJECTIVE: To explore the feasibility of preparing gastric floating formulations by fused de-position modeling (FDM) 3D printing technology, to evaluate the in vitro properties of the prepared FDM 3D printed gastric floating formulations, and to compare the influence of different external shapes of the formulation with their in vitro properties. METHODS: Verapamil hydrochloride and polyvinyl alcohol (PVA) were used as the model drug and the excipient, respectively. The capsule-shaped and hemisphere-shaped gastric floating formulations were then prepared by FDM 3D printing. The infill percentages were 15%, the layer heights were 0.2 mm, and the roof or floor thicknesses were 0.8 mm for both the 3D printed formulations, while the number of shells was 3 and 4 for capsule-shaped and hemisphere-shaped formulation, respectively. Scanning electron microscopy (SEM) was used to observe the morpho-logy of the surface and cross section of the formulations. Gravimetric method was adopted to measure the weights of the formulations. Texture analyzer was employed to evaluate the hardness of the formulations. High performance liquid chromatography method was used to determine the drug contents of the formulations. The in vitro floating and drug release behavior of the formulations were also characterized. RESULTS: SEM showed that the appearance of the FDM 3D printed gastric floating formulations were both intact and free from defects with the filling structure which was consistent with the design. The weight variations of the two formulations were relatively low, indicating a high reproducibility of the 3D printing fabrication. Above 800.0 N of hardness was obtained in two mutually perpendicular directions for the two formulations. The drug contents of the two formulations approached to 100%, showing no drug loss during the 3D printing process. The two formulations floated in vitro without any lag time, and the in vitro floating time of the capsule-shaped and hemisphere-shaped formulation were (3.97±0.41) h and (4.48±0.21) h, respectively. The in vitro release of the two formulations was significantly slower than that of the commercially available immediate-release tablets. CONCLUSION The capsule-shaped and hemisphere-shaped verapamil hydrochloride gastric floating formulations were prepared by FDM 3D printing technology successfully. Only the floating time was found to be influenced by the external shape of the 3D printed formulations in this study.
Drug Liberation ; Excipients ; Printing, Three-Dimensional ; Reproducibility of Results ; Tablets

Aim To observe the protective effect of ginsenoside Re pretreatment on rats with isoproterenol-induced acute myocardial ischemia via JAK 2/STAT3 signaling pathway .Methods SD rat model with acute myocardial ischemia was established using isoprotere-nol.Seventy-five rats were randomly divided into five groups: control group, model group , puerarin group (PUE), high dose group (Re-H, 20 mg· kg -1) and Re low-dose group ( Re-L, 10 mg kg -1 ) .The blood flow on the heart surface of rats in each group was ob-served by moor laser blood flow imaging system .The levels of CK , LDH, SOD, MDA and GSH in myocar-dium were measured by ELISA .The expressions of Bax and Bcl-2 proteins were detected by immunohistochem-istry.The expressions of JAK , p-JAK, STAT3 and p-STAT3 proteins were detected by Western blot .Re-sults Compared with the control group , the mean blood flow on the heart surface of rats in the model group significantly decreased , the levels of CK , LDH and MDA in the myocardium increased , the levels of GSH and SOD decreased , the ratio of Bcl-2/Bax de-creased ( P <0.05 ) , and the expression of JAK 2/STAT3 pathway related proteins was enhanced ( P <0.05 ) . The mean blood flow on the heart surface markedly increased , the levels of CK , LDH and MDA decreased , the level of GSH-Px increased , the ratio of Bcl-2/Bax increased, and the expression of JAK2/STAT3 pathway proteins evidently increased in the Re-H group compared with those of the model group ( P<0.05 ) .Conclusion Ginsenoside Re pretreatment has a good protective effect on the myocardium in rats with acute myocardial ischemia , which may be related to the activation of JAK2/STAT3 signaling pathway .

Objective To access the effects of different doses of recombinant fusion protein of human tumor necrosis factor receptor mutant and Fc fragment [rhTNFR(m):Fc] after a single subcutaneous injection on the plasma concentration of tumor necrosis factor-α (TNF-or) in Chinese healthy volunteers.Methods A total of 56 healthy Chinese volunteers were randomly divided into 6 groups to receive a single injection of 10,20,35,65,75 mg of rhTNFR(m):Fc.The plasma concentrations of TNF-α and total TNF-α were determined at 1 h pre-dose and at 4,48,96,168,216,264,312,384,480 h post-dose.Results After administration of rhTNFR(m):Fc at 0-264 h,the plasma concentrations of free TNF-α and total TNF-α increased significantly in the each group.At 264-480 h post-dose,the concentration of them began to decrease,and at 480 h the concentration of free TNF-α almostly decreased to normal levels.In the dose range of 10-75 mg,the exposure of free TNF-α and total TNF-α (Cmax) had no significant correlation with the dose of rhTNFR (m):Fc.Conclusion After giving the single dose of rhTNFR (m):Fc,there was an increase of free and total TNF-α plasma concentration in Chinese healthy volunteers.As a result,the plasma concentration of free and total TNF-α may not be a suitable pharmacodynamic evaluation index.

Chemotaxis is the response ability of motile cells to chemicals gradients in environment and the migration toward higher concentration of chemoattractant or lower concentration of repellent. This mechanism is a basic nature of microorganisms to adapt to the environmental changes. The research of microbial chemotaxis is of great significance in utilizing bacteria to solve environment problems, control the pathogen infection, and develop microbial industrial projects. Microfluidic devices can realize qualitatively and quantitatively detect of bacterial chemotaxis. In comparison with traditional detect methods, microfluidic assay has an accurate control over bacterial microenvironment, with a higher sensitivity. In the past few years, bacterial chemotaxis study based on microfluidic assay was developed rapidly. In this paper, the microfluidic chemotaxis detectors that appeared in recent years were introduced from the aspect of chip structure, working principle and their applications. Finally, we provided insights into the challenges of bacterial chemotaxis and provided future perspectives.

BACKGROUND/AIMS: A large number of studies have shown that function constipation (FC) has an extremely high incidence of mental and psychological disorders. Cranial electrotherapy stimulation (CES) was applied to the treatment of psychological disorders such as anxiety and depression. We explored the effects of CES combined with biofeedback therapy (BFT) on the psychological state, clinical symptoms, and anorectal function in patients with FC. METHODS: A total of 74 patients with FC were randomly divided into 2 groups. The control group received BFT. CES combined with BFT was carried out in the experiment group. All patients were assessed using the self-rating anxiety scale (SAS), self-rating depression scale (SDS), and Wexner constipation score at baseline and the end of each course. Anorectal manometry and balloon expulsion tests were performed before and after treatment. RESULTS: After treatment, the participants in the experiment group had significantly lower score SAS, SDS, and Wexner constipation scores than the control group (all P < 0.05). The number of successful expulsion in the experiment group was larger than the control group (P = 0.016). CONCLUSIONS: CES combined with BFT was effective in improving the psychological status of anxiety, depression, and bowel symptoms in patients with FC.
Anxiety ; Biofeedback, Psychology* ; Constipation* ; Depression ; Electric Stimulation Therapy* ; Humans ; Incidence ; Manometry ; Treatment Outcome

OBJECTIVETo determine the regulatory role and mechanism of nitric oxide (NO) in the development and hatching of mouse blastocysts.

METHODSThe Kunming female mice were superovulated and then mated with mature male mice. On the day 2.5 of their pregnancy, morulae were flushed from their uterine horns with culture media. Morulae were cultured in different concentrations of N-nitro-L arginine methyl ester (L-NAME), sodium nitroprusside (SNP), or the combination of L-NAME and SNP in culture media for 48 hours. The development and hatching of blastocysts were examined on day 4 and day 5 and the total numbers of blastocyst cells and cysteinyl aspartate specific proteinase 3 (caspase 3) were observed under confocal laser scanning microscope.

RESULTSWith the increase of the concentration of L-NAME or SNP, the hatching rate of blastocysts and the total number of blastocyst cells were significantly reduced. The addition of 10 nmol/L SNP in culture media with 5 mmol/L L-NAME significantly increased the development of blastocysts and promoted hatching of blastocysts. However, with increase of SNP concentration in culture media with 5 mmol/L L-NAME, the development and hatching rates of blastocysts were significantly decreased. L-NAME had no obvious effect on the expression of active caspase 3 in blastocyst cells. However,when being above 500 nmol/L,SNP significantly increased the expression of caspase 3 in blastocyst cells.

CONCLUSIONSNO plays an important role in development and hatching of mouse blastocysts. Excessively high or low NO can damage the division of blastomeres, resulting in the failure of the blastocyst development and hatching. Also, excessively high NO can lead to the apoptosis of the blastocyst cells.

Animals ; Arginine ; analogs & derivatives ; Blastocyst ; Culture Media ; Female ; Humans ; Male ; Mice ; Nitric Oxide ; Nitroprusside ; Pregnancy ; Uterus

Incretin is a hormone released from the L -cells in the gut wall under the stimulation of food and can promote the insulin secretion.The related agents used in the clinic mainly include two types , the gluca-gon-like peptide-1 ( GLP-1 ) receptor agonists and dipeptidyl pepti-dase -4 ( DPP -4 ) inhibitors.Pharmacokinetic/pharmacodynamic ( PK/PD) models of incretin related agents can be useful tools in optimal drug therapy in patients and support the design of future clinical trials.Meanwhile , a mechanism-based model can be more powerful at predic-ting physiological characteritics and the probability of successful outcome of anti -diabetic treatment for different dosage regimens of the drugs , which will be beneficial for new drugs development and dosage regimens regulation.The present review is focused on the mechanism -based PK/PD models of representative drugs which belong to GLP -1 receptor agonists and DPP-4 inhibitors.

ATP-binding cassette ( ABC ) transporters at blood-brain barrier, such as, P-glycoprotein ( P -gp ) , multidrug -resistance -associated protein ( Mrp ) , and breast cancer related protein ( Bcrp ) , can limit central nervous system ( CNS ) uptake of foreign chemicals, drugs and toxicant.ABC transporters are neuroprotective, but they also distinguish poorly between neurotoxicants and therapeutic drugs.So they are major obstacles to CNS pharmacotherapy.Clarifying the mechanisms of these transporters can provide new targets for drugs to get through the blood-brain barrier, which helps to reduce the occurrence of drug re-sistance and improve the effect of treatment.The present review is fo-cused on new findings about ABC transporters and three main signal path-ways, whose are TNF-α/PKCβ/S1PR1 signaling, vascular endothelial growth factor signaling and estrogen signaling.

OBJECTIVETo study the changes of lower esophageal sphincter (LES) high-pressure zone, and to determine the accurate length of myotomy on the esophageal and gastric sides.

METHODSThere were 15 patients undergoing the Heller's cardia-myotomies and Toupet fundoplications from May 2006 to December 2007. Among them, 9 patients were female and 6 was male. The age ranged from 28 to 61 years old, and the disease duration ranged from 6 months to 9 years. The intraoperative oesophageal manometry underwent in the surgical procedures to investigate the changes of the lower esophageal sphincter pressure and the length of myotomy.

RESULTSThere was no postoperative death. After (5.3 +/- 1.5) cm of esophageal side myotomy and (0.8 +/- 0.4) cm of gastric side myotomy, the mean LES pressure decreased from (33.6 +/- 13.3) mm Hg (1 mm Hg = 0.133 kPa) to (9.7 +/- 4.6) mm Hg and (4.8 +/- 3.1) mm Hg respectively (P < 0.05). The lower esophageal sphincter length ranged from 5 to 8 cm.

CONCLUSIONIntraoperative esophageal manometry helps determine the accurate myotomy length of myotomy on the esophageal and gastric sides of the gastroesophageal junction and provides valuable information for the Heller's myotomy.

Adult ; Esophageal Achalasia ; surgery ; Esophagus ; physiopathology ; surgery ; Female ; Humans ; Intraoperative Care ; Male ; Manometry ; Middle Aged ; Monitoring, Intraoperative

OBJECTIVETo explore novel pathogenic mutation in the mitochondrial DNA gene in diabetic pedigree.

METHODSTwenty-eight suspected mitochondrial DNA diabetic families were recruited. The gene fragment was produced by PCR, and mutation was detected by direct sequencing.

RESULTSIn one pedigree, the proband and her mother were found carrying the most common nt3243 A --> G mutation and another 16S rRNA 3205C --> T mutation. But only 3205C --> T was found in her affected brother. All the two patients were deaf and developed diabetes in early age, characterized by impaired beta cell function and low body mass index (BMI). The proband had relatively higher lactic acid concentration than normal individuals. A novel ND1 gene 3434 A --> G(TAT --> TGT) mutation was explored in another proband with deafness and her affected family members.

CONCLUSION16SrRNA 3205C --> T mutation was found in a mitochondrial diabetes mellitus pedigree, implying its potential pathogenic role in diabetes. Another novel ND1 3434 A --> G mutation was found in another diabetic pedigree. Because this mutation causes amino acid change (Tyr --> Cys) and is co-segregated with diabetes, it may be diabetogenic.

Adult ; Asian Continental Ancestry Group ; genetics ; DNA Mutational Analysis ; DNA, Mitochondrial ; genetics ; Diabetes Mellitus ; genetics ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Pedigree ; RNA, Ribosomal, 16S ; analysis ; genetics