This study was to evaluate the risk factors of nocturnal hypoglycemia in elderly patients with type 2 diabetes by continuous glucose monitoring system. Fifty-one type 2 diabetic patients aged 60 or above were enrolled and the episodes of nocturnal hypoglycemia were documented. The risk factors of nocturnal hypoglycemia were analyzed by logistic regression and the cut-off of glucose levels at bedtime for nocturnal hypoglycemia was evaluated. There were twenty-two patients with total 681 nocturnal hypoglycemic episodes. Logistic regression analysis showed that the lowest glucose level at bedtime was the risk factor of nocturnal hypoglycemia (OR=0.36, 95% CI:0.13-1.00, P<0.05), while the gender, age, diabetes duration, therapy regimen, the highest and average glucose levels at bedtime were not associated to nocturnal hypoglycemia. Receiver operating characteristic curve (ROC) showed that the bedtime glucose at≤6.2 mmol/L was the best cut-off point for predicting nocturnal hypoglycemia.

Objective:To study the change of regulatory T cells in PBMC and the effects of CpG ODN in patients with lung cancer.Methods: Lymphocytes isolated from blood of 30 patients with lung canaer and 30 healthy volunteers were analyzed for the proportion of CD4 ~+CD25~+ T cells by flow cytometry.The mRNA expression of Foxp3 was detected by real-time PCR and the levels of TGF-β and IFN-γ were tested by ELLSA.The PBMC of 30 patients with lung cancer were randomly divided into treated group(CpG ODN 2006)and placebo group(CpG ODN 1612).The proportion of CD4 ~+ CD25~+ T cells,the mRNA expression of Foxp3 and the levels of TGF-β and IFN-γ were compared before and after treatment.Results:Tbe proportion of CD4~+ CD25~+ T cells,the mRNA expression of Foxp3 and the levels of TGF-β in patients with lung cancer were higher than those in healthy volunteers,but there was no significant difference in such parameters among subgroups of pathologic classification and clinical stage patients.The proportion of CD4 ~+ CD25~+ T cells, the mRNA expression of Foxp3 and the levels of TGF-β were dropped in CpG ODN 2006 group after treatment.There was no significant difference in these parameters before and after treatment in CpG ODN 1612 group.Conclusion: The proportion of CD4~+ CD25 ~+ T cells, the mRNA expression of Foxp3 and the levels of TGF-β of PBMC in lung cancer patients are higher than those in healthy volunteers.Treating by CpG ODN 2006 could down-regulate the proportion of CD4~+ CD25~+ Foxp3~+ regulatory T cells and the levels of TGF-β of PBMC from the patients with lung cancer.

Objective To study the effect of calorie restriction at early age of rats on their islet β cell mass in adulthood.Methods Sixteen 8-week-old male SD rats were randomized to control group (n=7) and calorie restricted group (n =9).The rats in control group took food freely,while the ones in calorie restricted group were given 70％ calorie of the control group.After 24 week calorie restriction,cholesterol (TC),triglyceride (TG),high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C) were tested.The β cell mass was measured by immunohistochefistry and the activity of superoxide dismutase (SOD) as well as the level of malondialdehyde (MDA) in pancreas homogenate were determined by ELISA.Results The increase of the body weights(45 g vs.184 g)and the level of TG [(0.61±0.15)mmol/L vs.(0.78±0.14)mmol/ L]of the rats in the calorie restricted group were lower than those of the control group (P＜0.05),while the β cell mass [(43.6±9.8)mg vs.(31.9± 11.6)mg],β cell mass of every milligram pancreas tissue[(89.7 ± 7.4) μg/mg vs.(44.8g ± 14.1) μg/mg] and β cell mass per body weight[(11.5±2.5) × 10-5 vs.(6.3 ±2.3) × 10-5]of the rats in the calorie restricted group were higher than those of the control group (P＜0.05).There were no differences in the SOD activity [(0.91±0.30)nmol/ mg protein vs.(0.68±0.14)nmol/ mg protein]and MDA level [4.97± 0.65)U /mg protein vs.(6.05 ±2.14)U/mg protein] in pancreas homogenate between the two groups (P＞0.05).Conclusions Calorie restriction at early age of rats may increase the islet β cell mass in their adulthood.

ABSTRACT:Objective To investigate the effects of phenytoin (PHT)on the secretion of vascular endothelial growth factor (VEGF)and stem cell factor (SCF)based on the establishment of indirect co-culture system of rat bone marrow mesenchymal stem cells (BMSCs)and vascular endothelial cells (VECs).Methods Indirect co-culture model of rat BMSCs and VECs was established.Experimental groups:indirect co-culture groups (PHT concentrations were 0,20 and 40 μg/mL);the control group:BMSCs culture group and VECs culture group (PHT concentrations were 0,20 and 40μg/mL).The contents of VEGF and SCF in the culture supernatant were measured using double antibody sandwich ABC-ELISA method on cultivation days 2,4,6.Results ELISA assay of the rBMSCs and rVECs in indirect co-culture supernatants,collected on culture days 2,4 and 6 showed that:① VEGF:On culture day 2,VEGF level in the co-culture groups was significantly higher than those in BMSCs group (P <0.05)and rVECs group (P <0.001).As culture time prolonged and PHT concentration increased to 20 μg/mL and 40 μg/mL,VEGF level increased too (P <0.001,P <0.05 ).② SCF testing results showed that the secretion of SCF in co-culture groups was higher than that in the control groups.When PHT was 20 μg/mL,the secretion of
SCF increased as the incubation time increased;but as the incubation time increased, PHT concentration of 40 μg/mL made SCF content decrease.Each group did not significantly differ (P > 0.05 ).Conclusion PHT promotes the secretion of VEGF and may reduce the secretion of SCF.

Objective:To analysis the construction of the world's top PhaseⅠclinical trial registration agencies, compare their size, composition, operation and funding, to provide further reference for the construction of clinical trial agency in China.Methods:Search for PhaseⅠclinical trial research agencies by region on clinicaltrials.gov. Collecting information about the agency’s management, staffing, implementation in Asia, America and Europe. Descriptive analysis was carried out to explore the type, proportion and operation among different regions, the organizational structure, operational management and effectiveness of each agency from different regions were compared.Results:The United States, Europe and East Asia are dense areas of PhaseⅠclinical research around the world. The types of agencies in the United States, Britain, France, Germany, South Korea, Japan, and Israel are mainly enterprises. Among other types of agencies, the organizational models are diversified. The agencies have different spatial distances from medical institutions, but possess relatively consistent scale and institutional operation. All the agencies have a stable source of funding.Conclusions:In order to strengthen the construction of clinical trial agencies in China, we should speed up the establishment of a close connection mechanism to promote deep cooperation in clinical trials. Control the construction scale and maintain stable input of the agency. Meanwhile, establish and strengthen international exchanges and cooperation.

Objective To investigate the osteogenic properties of a methacrylated gelatin(GelMA)/bone marrow mesenchymal stem cells(BMSCs)composite hydrogel applied to the skull defect area of rats and to provide an experi-mental basis for the development of bone regeneration biomaterials.Methods This study was approved by the Animal Ethics Committee of Nanjing University.A novel photocurable composite biohydrogel was developed by constructing photoinitiators[lthium phenyl(2,4,6-trimethylbenzoyl)phosphinate,LAP],GelMA,and BMSCs.The surface morphology and elemental composition of the gel were examined using scanning electron microscopy(SEM)and energy-dispersive X-ray spectroscopy(EDX).The compressive strength of the gel was evaluated using an electronic universal testing ma-chine.After in vitro culture for 1,2,and 5 days,the proliferation of the BMSCs in the hydrogels was assessed using a CCK-8 assay,and their survival and morphology were examined through confocal microscopy.A 5 mm critical bone de-ficiency model was generated in a rat skull.The group receiving composite hydrogel treatment was referred to as the Gel-MA/BMSCs group,whereas the untreated group served as the control group.At the 4th and 8th weeks,micro-CT scans were taken to measure the bone defect area and new bone index,while at the 8th week,skull samples from the defect ar-ea were subjected to H&E staining,van Gieson staining,and Goldner staining to evaluate the quality of bone regenera-tion and new bone formation.Results SEM observed that the solidified GelMA showed a 3D spongy gel network with uniform morphology,the porosity of GelMA was 73.41％and the pore size of GelMA was(28.75±7.13)μm.EDX results showed that C and O were evenly distributed in the network macroporous structure of hydrogel.The hydrogel compres-sion strength was 152 kPa.On the 5th day of GelMA/BMSCs culture,the cellular morphology transitioned from oval to spindle shaped under microscopic observation,accompanied by a significant increase in cell proliferation(159.4％,as determined by the CCK-8 assay).At 4 weeks after surgery,a 3D reconstructed micro-CT image revealed a minimal re-duction in bone defect size within the control group and abundant new bone formation in the GelMA/BMSCs group.At 8 weeks after surgery,no significant changes were observed in the control group's bone defect area,with only limited evi-dence of new bone growth;however,substantial healing of skull defects was evident in the GelMA/BMSCs group.Quan-titative analysis at both the 4-and 8-week examinations indicated significant improvements in the new bone volume(BV),new bone volume/total bone volume(BV/TV),bone surface(BS),and bone surface/total bone volume(BS/TV)in the GelMA/BMSCs group compared to those in the control group(P＜0.05).Histological staining showed continuous and dense formation of bone tissue within the defects in the GelMA/BMSCs group and only sporadic formation of new bone,primarily consisting of fibrous connective tissue,at the defect edge in the control group.Conclusion Photocur-ing hydrogel-based stem cell therapy exhibits favorable biosafety profiles and has potential for clinical application by inducing new bone formation and promoting maturation within rat skull defects.

Objective To investigate the dosimetric differences between volumetric modulated arc therapy (VMAT) with a flattening filter (FF) and flattening filter-free (FFF) VMAT in fractionated stereotactic radiotherapy for brain metastases. Methods Seventeen patients with brain metastases were divided into FF-VMAT group (VMAT plans with the FF mode) and FFF-VMAT group (VMAT plans with the FFF mode). The two groups were compared in terms of target volume dose parameters (D_98%, D_2% and D_mean), the conformal index (CI), the gradient index (GI), the gradient, normal brain tissue dose parameters (V_5Gy, V_10Gy, V_12Gy and D_mean), monitor units, and beam-on time. Results Compared with the FF-VMAT group, the FFF-VMAT group had significantly lower GI (3.33 ± 0.37 vs 3.27 ± 0.35, P = 0.001), a significantly lower gradient [(0.85 ± 0.20) cm vs (0.84 ± 0.19) cm, P = 0.002], a significantly shorter beam-on time [(177.05 ± 62.68) s vs (142.71 ± 34.59) s, P = 0.001], and significantly higher D_2% [(65.69 ± 2.15) Gy vs (66.99 ± 2.03) Gy, P = 0.001] and D_mean [(58.77 ± 1.60) Gy vs (59.95 ± 1.43) Gy, P <0.001]. There were no significant differences in the CI, the D_98% of the target volume, the V_5Gy, V_10Gy, V_12Gy and D_mean of the normal brain tissue, and monitor units between FFF-VMAT and FF-VMAT. Conclusion FFF-VMAT can better protect the normal tissue around the target volume, reduce the beam-on time, and improve treatment efficiency.