Diabetic mellitus (DM) is a common degenerative chronic metabolic disease often accompanied by severe cardiovascular complications (DCCs) as major causes of death in diabetic patients with diabetic cardiomyopathy (DCM) as the most common DCC. The metabolic disturbance in DCM generates the conditions/substrates and inducers/triggers and activates the signaling molecules and death executioners leading to cardiomyocyte death which accelerates the development of DCM and the degeneration of DCM to heart failure. Various forms of programmed active cell death including apoptosis, pyroptosis, autophagic cell death, autosis, necroptosis, ferroptosis and entosis have been identified and characterized in many types of cardiac disease. Evidence has also been obtained for the presence of multiple forms of cell death in DCM. Most importantly, published animal experiments have demonstrated that suppression of cardiomyocyte death of any forms yields tremendous protective effects on DCM. Herein, we provide the most updated data on the subject of cell death in DCM, critical analysis of published results focusing on the pathophysiological roles of cell death, and pertinent perspectives of future studies.

OBJECTIVE：To p rovide reference for improving the level of technological innovation and promoting the high-quality development of pharmaceutical industry in Fujian province. METHODS ：A total of 452 people were interviewed by relevant departments of pharmaceutical industry ，industry associations ，pharmaceutical enterprises and some consumers in Fujian province. After sorting out the interview data ，based on the theory of causal loop diagram and problem basic model methods ，the key variables and problem basic models affecting the technological innovation system of pharmaceutical industry in Fujian province were investigated . The leverage solutions and suggestions were put forward. RESULTS & CONCLUSIONS：The scientific and technological innovation environment ，managers’innovative ideas ，scientific and technological innovation motivation ，enterprise profits，product’s market competitiveness ，social organizations of pharmaceutical industry ，and industrialization of scientific and technological innovation achievements in the technological innovation system of pharmaceutical industry in Fujian province were closely related to the technological improvement of pharmaceutical industry in Fujian province. There were basic modes of “the rich getting richer ”for the technological innovation system of pharmaceutical industry in Fujian province ，i.e. the investment of external resources on scientific and technological innovation of pharmaceutical enterprises was mostly concentrated in the pharmaceutical enterprises above designated size. At the same time ，due to the lack of industry-research-university interaction and the unsmooth achievement transformation channel ，some small and medium-sized pharmaceutical enterprises with the potential of scientific and technological innovation or with traditional advantages may form the problem basic model “to attend to trifles and neglect the essentials”. It is suggested that the subjects related to pharmaceutical industry should give full play to the role of various scientific and technological platforms ，strengthen the attention and support to innovative small and medium-sized pharmaceutical enterprises ， create and optimize the financial service environment for scientific and technological innovation of pharmaceutical enterprises ，and support pharmaceutical enterprises with innovation power and potential to carry out technological innovation projects.

Cell division cycle associated 8 (CDCA8) is involved in the accurate regulation of cell division cycle. The expression change of CDCA8 can affect the progression of many kinds of tumors as well as the prognosis of patients. In recent years, studies have suggested that CDCA8 may play an important role in maintaining the stemness of cancer stem cells. Exploring the mechanism of CDCA8 affecting tumor is of great significance for the diagnosis and treatment of tumors.

Objective:To compare the tropism of different adeno-associated virus (AAV) serotypes in retinal cells.Methods:The plasmids pFastBacDual-inCap and pFastBacDual-ITR-CMV-EGFP were constructed for AAV packaging with the baculovirus expression system.Recombinant adeno-associated virus type 2(rAAV2), 6, 8 and 9 serotypes were packaged, and the infectivity of rAAV was evaluated by infecting HEK293T cells at multiplicity of infection(MOI)2000.Twenty-five C57BL/6 mice were divided into five groups, with five mice per group.In the three experimental groups, both eyes of each mouse were injected 1 μl rAAV intravitreally, and 1 μl phosphate buffered saline (PBS) for the eyes of the control group.Two weeks after injection, the retinal tissues were collected for preparing flat mounts and cryosections.Enhanced green fluorescent protein (EGFP) gene expression was observed via fluorescence microscopy and laser scanning confocal microscopy.The study protocol was approved by the Ethics Committee of Suzhou Institute of Biomedical Engineering and Technology.Results:The infection efficiency of the recombinant virus to HEK293T cells was rAAV2>rAAV6>rAAV8>rAAV9, and the transduction efficiency was 39.5%, 18.4%, 8.7% and 4.6%, respectively.In mouse retinal transduction, rAAV2 and rAAV6 were highly expressed in the ganglion cells, and rAAV8 and rAAV9 were highly expressed in the retinal pigment epithelium (RPE) and photoreceptor cells.rAAV2-mediated EGFP expression in retinas was stable within three months after injection.Conclusions:Different rAAV serotypes have varying tropism and transduction efficiencies in retinal cells through intravitreal injection, rAAV2 has a high transduction efficiency and it can be stably expressed in retinas within three months after injection.

OBJECTIVE： To investigate the situation and problems of clinical microecological preparations in pediatrics department of China， and to provide reference for rational application of microecological preparations in children. METHODS： Outpatient/emergency prescriptions of microecological preparations during Jan.-Mar. 2019 were retrieved from information system of 5 “Third Grade Class A” children hospitals， and were investigated and analyzed in respects of the type of microecological agents， age distribution， clinical diagnosis， drug combination， off-label medication， etc. RESULTS： A total of 74 210 outpatient/emergency prescriptions were collected， involving 18 kinds of microecological preparations. Among them， Clostridium butyricum combined viable powder ranked first （31 146， accounting for 41.97％）， followed by Brucella yeast powder （14 289， accounting for 19.25％） and Compound Lactobacillus acidophilus tablets （10 281， 13.85％）. The age of children was less than 18 years old， and the proportion of children aged 1-＜3 years old was the highest （33 753， 45.48％）. The most common clinical diagnosis     was digestive tract diseases （54 009， 72.78％）， followed    by respiratory infectious diseases （11 744， 15.83％）. In combination with microecological agents， there were Chinese patent medicine for invigorating the spleen and stomach     （18 546， 24.99％）， antibacterial medicine （10 595， 14.28％） and oral rehydration salt Ⅲ （8 238， 11.10％）. Off-label drug use was found in 19 532 prescriptions （26.32％）， mainly manifesting as super-indications （15 590， 21.01％）， super-usage and dosage （8 098， 14.52％）， super crowd medication （48， 3.91％） was found in a few prescriptions. CONCLUSIONS： There is a high incidence of off-label use of microecological agents in children. Medical staff should standardize prescription behavior and promote rational use of drugs. At the same time， the improvement of the information of children’s medication in drug instructions to ensure the safety and effectiveness of children’s medication should be encouraged.

Objective To explore the clinical effectiveness of deferasirox, deferiprone and desferrioxamine in the treatment of iron overload in patients with thalassemia major.Methods Among the severe thalassemia patients with iron overload being diagnosis,treated and followed up in Guigang City People′s Hospital,fifty cases were tested by MRI T2 and were detected with cardiac and liver iron overload,the patients were selected and randomly divided into the deferoxamine treatment(DFO)group(18 case),deferiprone treatment(DFP)group(22 cases)and deferasirox treatment(DFX)group(10 case),The baseline data of the three groups were statistically analyzed.the serum ferritin(SF)value,the cardiac MRI T2 value and the liver MRI T2 value before and after treatment were measured.Results The patients completed the treatment,after 1 years of treatment,the serum SF value,cardiac and liver MRI T2 values of the patients were improved than those before the treatment(P<0.05); the differences in serum SF among the three groups were not statistically significant(F=3.089,P>0.05); the differences in liver MRI T2 value among the three groups were not statistically significant(F=0.131,P>0.05),There were significant differences in heart iron load MRI T2 values among the three groups((34.27 ± 6.30)ms vs.(23 ± 2.79)ms vs.(21.8 ± 2.20)ms,F=39.54,P<0.05) .Conclusion Deferoxamine,deferiprone and deferasirox can effectively alleviate the iron load in patients with thalassemia major.in terms of cardiac iron overload,the curative effects of deferiprone treatment in patients with thalassemia is superior than desferrioxamine and deferasirox treatment,it is worthy of clinical promotion.

Aim Paclitaxel(PTX)has shown an effect against human cancer. However, serious drawbacks hamper PTX clinical use.Overcoming paclitaxel limi-tations is one of the best approaches to enhance water solubility.Methods In this study,water-soluble pa-clitaxel prodrug was prepared,folic acid-polyethylene glycol-glutamic-paclitaxel (FA-PEG-Glu-PTX ) com-posed of folic acid (FA,target),amino acids (Glu, linker),and polyethylene glycol(PEG)in order to im-prove the solubilization and stability. The chemical structure and physicochemical property of prodrug were measured by LC-MS,solubility,drug release rate to e-valuate the antitumor activity and cytotoxicity of FA-PEG-Glu-PTX.MTT assays were conducted on MDA-MB-231,MCF-7,A549 and HELF cell lines.FA-PEG-Glu-PTX prodrugs were labeled with 5 amino flu-orescence visible fluorescent dye (5 AF ) for fluores-cence microscopy.Results The successful conjugation of FA-PEG-Glu-PTX was confirmed by LC-MS,and had better water solubility,release rate curve.In vitro studies indicated that foliate receptor(FR-α)mediated uptake of PTX-conjugated multi-small molecules carri-ers induced highly targeting ability,and antitumor ac-tivity,as well as reduced side toxicity effects of PTX. Conclusion FA-PEG-Glu-PTX has a good antitumor activity.

Objective To compare the curative effect of Epalrestat and mecobalamine .Methods Epalrestat to treat 48 pa-tionts in DPN and mecobalamine to treat 42,measuring blood sugar ,blood pressure, blood fat and body mass index (BMI) prior and post treatment ,and measuring the MCV and SCV of nervus medianus ,nervus peronaeus connunis and nervus tibialis with EMG .Re-sults The symptom of the two sets have all been improved after the treatment ,and the effective power of Epalrestat and mecobalamine is 92.7% and 80.5% respectively.mean while there is improvement in MCV and SCV of nervus medianus ,nervus peronaeus connunis and nervus tibialis,and is more obvious in the set of Epalrestat ( P <0.01).In the whole process of the treat of the two sets ,no one appear to have adverse reactions .Conclusions Epalrestat has significant curative effect with less adverse reactions , and deserves to be spreaded in clinic.

OBJECTIVETo investigate whether the antioxidation and the regulation on the Extracellular Regulated Protein Kinases (ERK) signaling pathway are involved in the protective effects of blueberry on central nervous system.

METHODS30 Senescence-accelerated mice prone 8 (SAMP8) mice were divided into three groups and treated with normal diet, blueberry extracts (200 mg/kg•bw/day) and cyaniding-3-O-galactoside (Cy-3-GAL) (50 mg/kg•bw/day) from blueberry for 8 weeks. 10 SAMR1 mice were set as control group. The capacity of spatial memory was assessed by Passive avoidance task and Morris water maze. Histological analyses on hippocampus were completed. Malondialdehyde (MDA) levels, Superoxide Dismutase (SOD) activity and the expression of ERK were detected.

RESULTSBoth Cy-3-GAL and blueberry extracts were shown effective functions to relieve cellular injury, improve hippocampal neurons survival and inhibit the pyramidal cell layer damage. Cy-3-GAL and blueberry extracts also increased SOD activity and reduced MDA content in brain tissues and plasma, and increased hippocampal phosphorylated ERK (p-ERK) expression in SAMP8 mice. Further more, the passive avoidance task test showed that both the latency time and the number of errors were improved by Cy-3-GAL treatment, and the Morris Water Maze test showed significant decreases of latency were detected by Cy-3-GAL and blueberry extracts treatment on day 4.

CONCLUSIONBlueberry extracts may reverse the declines of cognitive and behavioral function in the ageing process through several pathways, including enhancing the capacity of antioxidation, altering stress signaling. Cy-3-GAL may be an important active ingredient for these biological effects.

Aging ; drug effects ; Animals ; Anthocyanins ; pharmacology ; Avoidance Learning ; Blueberry Plants ; chemistry ; Dietary Supplements ; Galactosides ; pharmacology ; Hippocampus ; drug effects ; metabolism ; Malondialdehyde ; metabolism ; Maze Learning ; Memory ; drug effects ; Mice ; Mitogen-Activated Protein Kinase 3 ; metabolism ; Phosphorylation ; Plant Extracts ; pharmacology ; Superoxide Dismutase ; metabolism

One hundred and sixty non-diabetic patients with cerebral ischemia of primary onset were enrolled in the study. The patients were divided into impaired glucose tolerance (IGT) group and normal glucose tolerance (NGT) group according to the oral glucose tolerance test (OGTT). Carotid atherosclerosis and carotid artery stenosis were examined with vascular Doppler ultrasonic detection. The incidence rates of carotid atherosclerosis in IGT group and NGT group were 87. 5% (70/80)and 63.8% (51/80)respectively (χ2= 12.240,P <0.001);the incidence rates of carotid stenosis in IGT group and NGT group were 63.8% (51/80) and 47. 5 % (38/80), respectively(χ2 =4. 279, P =0. 039);the degree of carotid artery stenosis in IGT group was higher than that in NGT group(χ2= 21.95, P < 0. 01). The results indicate that IGT may be related to atherosclerosis and stenosis of carotid artery in cerebral ischemic patients.