Case report form (CRF) is a key document for data collection in clinical trials. A well-designed CRF is required for database construction, data accuracy, data query/cleaning, CRF completion and statistical analysis. A well-defined process or SOP should be in place for CRF design. Data collection should fully meet the demand of study protocol. The layout of CRF should be clear with well-structured fields and standard coding for fields.
Clinical Trials as Topic ; standards ; Data Collection ; standards ; Documentation ; standards ; Research Design ; standards

OBJECTIVE: To develop an easy to scale-up preparation process for exenatide-loaded long-acting microspheres, and develop a method that can be used to rapidly evaluate the in vitro release properties of the microspheres. METHODS: The primary emulsion could be made by high shear emulsification process combined with high pressure homogenization method, then exenatide-loaded microspheres were prepared by a modified coacervation method. In the coacervation step, static mixer was used for mixing the primary emulsion and the coacervation reagent. RESULTS: High pressure homogenization could reduce the size of the primary emulsion to about 200 nm. The encapsulation efficiency of microspheres was greater than 96.8%, and the amount of burst release in 1 h was less than 0.5%. When the scale of microspheres preparation was magnified by five times, the characteristics of the obtained microspheres was the same as the small scale batch. The in vitro release curves showed that the continued release time lasted for nearly 4 weeks after the 17 d lag phase. The drug release rate at 45℃ was as high as 2.5 times of that at 37℃, with same release curves. CONCLUSION: The established preparation process of exenatide-loaded long-acting microspheres, which uses static mixer for mixing the primary emulsion and coacervation reagent, is easy for scaling-up and industrialization. Accelerated test at 45℃ can be used to rapidly evaluate the in vitro release profile of the microspheres.

OBJECTIVE: To prepare freeze-dried alprostadil lipid microspheres and investigate their stability and pharmacokinetic characteristics. METHODS: The alprostadil lipid microspheres were prepared by two-step emulsifying method and then freeze-dried. The physicochemical properties were characterized.The stability in vitro and pharmacokinetics in Beagle dogs were also studied. RESULTS: The freeze-dried alprostadil lipid microspheres presented a good appearance and the rehydrated time was short. The size after reconstruction was (164.1±3.9) nm, the encapsulation efficiency was (92.5±3.3)% and the content of PGA1 was (1.38±0.21)%. It showed good stability after storing for 6 months as indicated by the size and contents of alprostadil and PGA1. After intravenous injection in Beagle dogs, the half time and peak time were (7.5±3.7) and (7.6±2.9) min respectively, and the peak plasma concentration of PGE1 was (105±40.4) ng·L-1, which was similar to the reference formulation. CONCLUSION: The freeze-dried alprostadil lipid microspheres can significantly improve the stability of alprostadil lipid microspheres with good pharmacokinetic characteristics, which indicates a promising prospect in clinic use.

AIM: To investigate the role of nitric oxide synthase (NOS), soluble guanylyl cyclase (sGC) and protein kinase C (PKC) signaling in tumor necrosis factor-? (TNF-?)-induced cardioprotection against hypoxia/reoxygenation (H/R) injury. METHODS: Neonatal rat ventricular myocytes were pretreated with TNF-? or sodium nitroprusside (SNP) or L-arginine (L-Arg), respectively, for 12 h and then subjected to continuous hypoxia for 12 h, followed by reoxygenation for 6 h. The manganese superoxide dismutase (Mn-SOD) activity of the cells was measured after H/R. Myocyte injury was determined by the release of lactic dehydrogenase (LDH). RESULTS: TNF-? (10~5 (U/L)) significantly increased the Mn-SOD activity and decreased release of LDH from ventricular myocytes. The cardioprotection against H/R injury was induced by the pretreatment with SNP (5 ?mol/L) or L-Arg (5 mmol/L), which was blocked by ODQ (10 ?mol/L), the specific sGC inhibitor, and Chel (5 ?mol/L), the specific PKC inhibitor. Pretreatment with L-NAME (100 ?mol/L), ODQ, Chel, antoxidant 2-MPG (400 ?mol/L) or tyrosine kinase inhibitor genistein (50 ?mol/L) attenuated the increased Mn-SOD activity and reduced LDH level induced by TNF-?. CONCLUSION: The results suggest that NO may play a role in TNF-?-induced cardioprotection, which is mediated by sGC and PKC. [

The aim of this research is to refine the protocol of purification of SA and identify the character of SA. By utilizing the cold-denaturing method, most of other kinds of protein were screened out and SA was purified from the fermentation broth of L-183 by using the refined affinity chromatography method. The rate of recollection was checked to be 75%～85%. By identification, it is indicated that the molecular weight of self-made SA was 74.5kD, the biotin-combining number 3.2, the activity 11.2u/mg, the pI around 7.4. So, the essential characters of SA are same as described by documents.

OBJECTIVETo evaluate the efficacy and safety of Yigan Fupi Decoction (YFD) in the treatment of irritable bowel syndrome with diarrhea (IBS-D) patients.

METHODSA randomized controlled clinical trail was carried out in patients with IBS-D. All patients were randomly assigned to the treatment group (58 cases, treated with YFD) and the control group (58 cases, treated with Pinaverium Bromide Tablet). The treatment course was 4 weeks for all patients. The total effective rate, the stool property and state, the quality of life (QOL), and TCM syndrome efficacy were assessed by IBS bowel symptom severity scale (IBS-BSS), IBS defecation state questionnaire (IBS-DSQ), IBS quality of life questionnaire (IBS-QOL), and traditional Chinese medicine pattern curative effect scoring system (TCM-PES) before and after treatment.

RESULTSThere was no statistical difference in the total effective rate between the two groups (82.76% vs. 77.59%, P > 0.05). The treatment group was superior in the total IBS-BSS integral to the control group (P < 0.05). The total effective rate of improving the stool property was better in the treatment group than in the control group (81.03% vs. 72.41%, P < 0.05). Besides, the number of days for emergent defecation among 10 days was less in the treatment group than in the control group (P < 0.05). The improvement of the total IBS-QOL integral and the total integral of TCM syndrome were better in the treatment group than in the control group (P < 0.01). The total effective rate of TCM-PES was better in the treatment group than in the control group (84.48% vs. 70.69%, P < 0.05).

CONCLUSIONYFD was effective in the treatment of IBS-D patients of Gan-qi invading Pi syndrome, and could effectively relieve bowel symptoms, improve the stool property and the defecation frequency, elevate their QOL, and attenuate Gan-qi invading Pi syndrome with favorable safety and compliance.

Adult ; Diarrhea ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Irritable Bowel Syndrome ; drug therapy ; Male ; Middle Aged ; Morpholines ; therapeutic use ; Quality of Life ; Treatment Outcome

[ ABSTRACT] AIM: To observe the effect of circadian rhythms on wound healing of mouse corneal epithelium. METHODS:The C57BL/6 male mice were used in the study.A part of corneal epithelium (2 mm in diameter) was struck off by a golf-like knife to form a round wound area.The dynamics of epithelial healing in the wound area were ob-served under microscope with fluorescein staining.In addition, with related antibodies and DAPI, the dynamic changes of the neutrophils, platelets and dividing cells were also investigated.RESULTS:The healing rates in LL group (12 h light/12 h light) and DD group (12 h dark/12 h dark) were obviously slower than that in LD group (12 h light/12 h dark), mainly showing delayed re-epithelialization, decreased epithelial cells, increased diameter of blood vessel, and delayed re-cruitment of neutrophils and platelets, but more cell number.CONCLUSION:Disruption of circadian rhythms significant-ly inhibits the wound healing of corneal epithelium, mainly through delaying the inflammation and re-epithelialization, but aggravating the inflammatory responses.

Objective To assess the rotational set-up errors in patients with thoracic neoplasms. Methods 224 kilovohage cone-beam computed tomography (KVCBCT) scans from 20 thoracic tumor pa-tients were evaluated retrospectively. All these patients were involved in the research of " Evaluation of the residual set-up error for online kilovohage cone-beam CT guided thoracic tumor radiation". Rotational set-up errors, including pitch, roll and yaw, were calculated by 'aligning the KVCBCT with the planning CT, using the semi-automatic alignment method. Results The average rotational set-up errors were -0.28°±1.52°, 0.21°± 0.91° and 0.27°± 0. 78° in the left-fight, superior-inferior and anterior-posterior axis, respective-ly. The maximal rotational errors of pitch, roll and yaw were 3.5°, 2.7° and 2.2°, respectively. After cor-rection for translational set-up errors, no statistically significant changes in rotational error were observed. Conclusions The rotational set-up errors in patients with thoracic neoplasms were all small in magnitude. Rotational errors may not change after the correction for translational set-up errors alone, which should be e-valuated in a larger sample future.

Objective To investigate the changes of CD4~+ T cell subset in the role of immuno-pathogenesis of type 1 diabetes mellitus(T1DM). Methods Real-time PCR was used to evaluate the ex-pression levels of transcriptional factors (T-bet, GATA-3, Foxp3, ROR-γt), cytokines (IFN-γ, IL-4, IL-10, IL-17A) and negative regulatory factors (CTLA-4, GITR) mRNA from CD4~+ T cells. The proportions of Th1, Th2, Tr and Th17 cells in peripheral blood were detected by flow cytometric analysis. Plasma cyto-kine (IFN-γ, IL-4, TGF-β and IL-6) concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Results (1) The proportions of Th1 cells in peripheral blood from children with T1DM were siguificanfly increased than that of healthy controls, and proportions of Th2 were decreased (P < 0.01). There were no significant differences between diabetic patients and healthy controls regarding the proportions of Tr cells and Th17 cells(P >0.05). (2) Transcription levels of T-bet and IFN-γ mRNA were significantly up-regulated, while GATA3 and IL-4 were significantly down-regulated in children with T1DM. The mRNA expression levels of Tr negativity regulatory factors such as IL-10, CTLA-4 and GITR were lower in CD4~+ T cells from children with TIDM compared with the controls(P <0.01). There were no statistically differences to be observed in mRNA expression levels of ROR-γt and IL-17A genes between two groups(P > 0.05).(3) In comparison with controls, serum concentrations of IFN-γ or IL-4 were remarkable increased or de-creased respectively (P < 0. 01), while TGF-β and IL-6 did not change in children with T1DM (P > 0.05). Conclusion The Th1/Th2 imbalance might be play an important role in immunopathogenesis of T1DM. Functional deficiency of Tr cell might further exacerbate Th1/Th2 imbalance and lead to disturbance of cellu-lar immune response.