BACKGROUND:In view of the unavoidable problems of autogenous and al ogenous bone grafts, it is an urgent need to develop biodegradable bone substitute materials, among which is calcium phosphate material that has become a hot spot in the domestic and foreign research. OBJECTIVE:To develop a biodegradable calcium phosphate material for bone repair based on tetracalcium phosphate (TTCP). METHODS:The biodegradable calcium phosphate cement made from TTCP, dicalcium phosphate anhydrous and different constituents of curing liquids was prepared under room temperature (about 25 ℃). The effects of solid components, liquid components as well as calcinations and drying temperature on the physical and biological performances were detected through X-ray diffraction test, hardness test, decay in a simulated body fluid, hemolysis and cytotoxicity tests, respectively, to select the bone repair material with excel ent performances. RESULTS AND CONCLUSION:When the calcination temperature was lower than 1300 ℃, TTCP was rarely available;only close to 1400 ℃, the relatively pure TTCP was gained. A large number of pure TTCP were gained by rapid cooling because of avoidance of the moisture impact, but slow cooling made the main products to be hydroxyapatite, suggesting that rapid cooling is essential to obtain pure TTCP. With the increase of the proportion of citric acid solution in the liquid phase, the pH values and the hemolysis rate in the bone cement soak solution were increased gradually, illustrating that citric acid solution is easy to induce hemolysis. In vitro cel experiments showed that the hemolysis rate of bone cement with a solution of 2:1 NH4/Na ratio was the lowest, and the biocompatibility was the best, which was the most favorable to cel growth. Cements was made of calcined powders sieved at 1400 ℃ and showed the shortest initial setting time, least effect on pH values, lowest disintegration rate and hemolysis rate, and slightest inhibition effect on the cel proliferation, indicating that the bone cements made of sieved powder after 1400 ℃ calcination is more suitable for clinical application.

Local focal adhesion kinase (FAK) is a non-receptor intracellular tyrosine kinase that plays an important role in tumor initiation, development, metastasis and invasion, and is considered to be an important target for the development of antineoplastic drugs. It has both kinase-dependent and non-kinase-dependent scaffolding functions. However, traditional small molecular inhibitors can only inhibit its kinase-dependent activity, so it is difficult to target the kinase-independent scaffolding function. Therefore, there is an urgent need for novel strategies to enhance FAK targeting to lay the foundation for determining the druggability and discovery of FAK inhibitors. Proteolysis targeting chimera (PROTAC) is a new drug development strategy that can recruit E3 ligase to specifically ubiquitinylate target proteins for degradation through the proteasome system. The unique mechanism of action of the PROTAC system could be used to target and degrade the FAK protein, thus eliminating the scaffolding function of FAK. In this review, FAK protein, the signaling pathway, and small molecule inhibitors are briefly described, and the latest research progress in targeting the degradation of FAK using PROTAC technology is summarized.

Malignant tumors are major diseases that endanger human health. Due to their complex and variable microenvironment, most anti-tumor drugs cannot precisely reach the focal tissue and be released in a controlled manner. Intelligent responsive nano carriers have become a hot spot in the field of anti-tumor drug delivery systems. As an excellent nano material, mesoporous silica has the advantages of non-toxic, stable, adjustable pore volume and pore diameter, and easy functional modification on the surface. By virtue of its perceptive response to the tumor microenvironment or physiological changes, it can achieve the targeted drug release or controlled drug release of the drug delivery system in the tissue, making it an ideal carrier for intelligent response drug delivery system. In this paper, we review the design strategies and current research status of smart responsive anti-tumor drug delivery systems based on mesoporous silica, in order to provide a reference for the development of anti-tumor drug nanoformulations.

Vaccine is a principal and highly cost-effective medical method on controlling infectious diseases and improving population health.Various vaccines are badly needed in the low-income countries along the Belt and Road.With the good quality to reach WHO prequalification standard,and the abundant capacity to fulfill the demand from market aboard,upon the platform of China-proposed "the Belt and Road Initiative",the vaccines manufactured in China are exporting to counties worldwide.The independent innovative vaccines' R&D system,which fruited a series of innovative infectious diseases vaccines (EV71 vaccine,slPV,HEV,Ebola vaccine,etc.) to be launched in Chinese market,indicates that China has developed rapidly from "a great vaccine-production country" to "a powerful vaccine-innovation country".The implementation of National Innovation-driven Development Strategy would further push forward the development and internationalization process of Chinese innovative vaccines.Therefore,the China-invented vaccines will make an important role in the prevention and control of infectious disease in various countries and become one of the most powerful weapons in fighting the global epidemics event in the future.

Objective To explore the effects of forepaw sensorimotor deprivation in early life on hippocampus-dependent spatial reference learning and memory in rats. Methods Newborn SD rats were randomly assigned to experiment group (deprivation of forepaw sensorimotor function, n=53) and control group(n=55). Rats of postnatal day 13 (PN13) in experiment group were seleeted, and models of forepaw sensorimotor deprivation were established by microsurgical technique. Open field tests and Morris water maze tests were performed during the time periods of PN25(PN21-31), PN35 (PN31-39), PN45(PN41-50) and PN60(PN56-64) to evaluate the locomotor activity and spatial reference learning and memory, respectively. Results In open field tests, there was no significant difference in parameters of locomotor activity and exploratory behavior between the two groups (P>0.05). In Morris water maze tests, eontrol group performed significantly better than experiment group during training sessions and probe tests on PN25 and PN35 (P<0.05). While on PN45, although there was no significant difference between the two groups during training sessions, control group performed significantly better than experiment group during probe tests (P<0.05). Conclusion The deprivation of forepaw sensorimotor in early life has no signifieant effect on the locomotor activity and exploratory behavior of rats, but can impair the spatial reference learning and memory.

Objective To observe any effect of low-frequency transcranial magnetic stimulation (rTMS) on the sleep and mood of elderly insomniacs.Methods Thirty-four elderly insomniacs were divided randomly into an experiment group (n =18) and a control group (n =16).The experiment group received rTMS of the right dorsolateral prefrontal cortex,while the control group was given alternating magnetic field stimulation at the same site.Before and after 4 weeks of the treatments,all of the subjects were assessed using the Pittsburgh sleep quality index (PSQI),the Hamilton anxiety scale (HAMA) and the Hamilton depression scale (HAMD).They were also assessed with those instruments omitting the sleep items in order to reduce the possible impact of any sleep changes on the HAMA and HAMD scores.Results Before the treatment there were no significant differences in the groups' average PSQI,HAMA and HAMD scores.After 4 weeks all the measurements in both groups had decreased significantly,with the experimental group's averages significantly lower than those of the control group.Conclusions rTMS treatment is more effective than alternating magnetic field treatment for the elderly with insomnia,significantly improving their sleep and mood.

Low frequency sensorineural deafness is a common subtype of idiopathic sudden deafness. Certain patients suffered recurrent attacks without vertigo, much alike Meniere's disease. Few of them developed into definite Meniere's disease during long-term follow-up in many clinical studies. Although the pathophysiology of recurrent low frequency deafness is yet unknown, the desease is considered associated with early state of endolymphatic hydrops or migraine. Otologists shall be aware of its clinical course and careful explanation is necessary at time of initial informed consent.
Endolymphatic Hydrops ; complications ; Hearing Loss, Sensorineural ; complications ; diagnosis ; Hearing Loss, Sudden ; Humans ; Meniere Disease ; complications ; Vertigo

BACKGROUNDDiabetic macrovascular complications are important causes of cardiovascular and cerebrovascular diseases and also one of the major causes of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Phlorizin has been reported to be effective in reducing the blood glucose level in diabetic mellitus, while little is known about its effects on vascular complications. This study aimed to observe the effects of phlorizin on the aorta of diabetes db/db mice and explore its mechanism.

METHODSDiabetic db/db mice (n = 16) and age-matched db/m mice (n = 8) were divided into three groups: normal control group (CC group, db/m mice, n = 8), untreated diabetic group (DM group, db/db mice, n = 8) and diabetic group treated by phlorizin (DMT group, db/db mice, n = 8). Phlorizin (20 mg/kg body weight) was given in normal saline solution intragastrically for 10 weeks. Animals were weighed weekly. At the 10th weekend, all mice were fasted overnight and then sacrificed. Fasting blood was collected, and the aortas were dissected. The blood samples were analyzed for fasting blood glucose (FBG), serum advanced glycation end products (AGEs), malondialdehyde (MDA) and superoxide dismutase (SOD) activity, the aortic ultrastructure was studied.

RESULTSThe weight and serum concentration of FBG, AGEs, and MDA in the DM group were higher than that in the CC group (P < 0.01), and they were significantly lower in the DMT group (P < 0.05). Serum SOD activity was lower than that in the CC group (P < 0.01), and it is significantly higher in the DMT group (P < 0.05). The severity of aorta damage in the DMT group was less than that in the DM group.

CONCLUSIONSPhlorizin protected the db/db mice from diabetic macrovascular complications, attributed to the decreasing of blood glucose and AGEs level, and its antioxidant potential. This study may provide a new natural medicine for treating diabetic macrovascular complications.

Animals ; Aorta, Thoracic ; pathology ; Blood Glucose ; analysis ; Diabetic Angiopathies ; drug therapy ; pathology ; Glycation End Products, Advanced ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Phlorhizin ; therapeutic use ; Superoxide Dismutase ; metabolism

AIM:To investigate the expression and localization of autophagy related protein microtublule associated protein 1 light chain 3 (LC3) at various stages of follicular development and atresia in the mice.METHODS:On 0,1,2,3,4 and 5 day after intraperitoneal injection of pregnant mare serum gonadotropin (PMSG),expression and positioning situation of autophagy related protein LC3 and apoptosis related protein cleaved caspase-3 were examined by the method of immunohistochemical staining.The protein levels of cleaved caspase-3 and LC3 were determined by Western blot in cultured mouse granulosa cells after incubation under serum-free conditions in the absence or presence of FSH.LC3 subcellular localization in granulosa cells were studied by the method of immunofluorescence.RESULTS:The LC3 protein expressed in granulosa cells during all developmental stages mainly.Granulosa cells of atretic follicles that showed intense staining of cleaved caspase-3 and LC3.The protein levels of cleaved caspase-3 and LC3-Ⅱ in the granulosa cells significantly decreased at 1 d and 2 d after intraperitoneal injection of PMSG (P ＜ 0.05).The protein levels of cleaved caspase3 and LC3-Ⅱ in the granulosa cells increased in turn on 3,4 and 5 day after intraperitoneal injection of PMSG.The positive correlation between LC3-Ⅱ and cleaved caspase-3 protein levels was observed (r2 =0.8299,P ＜ 0.05).The LC3-Ⅱ protein expressed with punctuate structures in granulosa cell cytoplasm cultured under serum-free conditions in the presence of FSH.CONCLUSION:LC3 is expressed in the follicular granulosa cells with cell specificity and regional specificity.Autophagy is induced mainly in granulosa cells during folliculogenesis and shows positive correlation with apoptosis.Ovarian granulosa cell autophagy and apoptosis are gonadotropic hormone dependent.

OBJECTIVEFactor VIII( FVIII) gene knockout mouse model was established for further study on the treatment of hemophilia A.

METHODSExons 16-19 of the mouse FVIII gene were knocked out by ET clone, ES homologous recombination and tetraploid embryo compensation technology. PCR, reverse transcriptase-PCR(RT-PCR) and immunohistochemistry were used to detect the transcription and translation pattern of FVIII. The phenotype of the knockout mice was analyzed by examining the activated partial thromboplastin time (APTT) and FVIII activity (FVIII:C).

RESULTSPCR, RT-PCR and immunohistochemistry confirmed that FVIII was deficient in the FVIII gene knockout mouse. The APTT results showed that FVIII-deficient mouse plasma had a prolonged clotting time compared to normal mouse plasma. The FVIII:C in heterozygous, hemizygous and homozygous mice was 80%, 8% and 10% of that in normal mice, respectively.

CONCLUSIONThe phenotype of the FVIII gene knockout mouse appears grossly similar to that of human with hemophilia A. Establishment of this model may promote the development of new technologies of treatment to hemophilia A.

Animals ; Disease Models, Animal ; Embryo, Mammalian ; Factor VIII ; genetics ; metabolism ; Female ; Hemophilia A ; genetics ; metabolism ; physiopathology ; Humans ; Male ; Mice ; Mice, Inbred ICR ; Mice, Knockout ; Partial Thromboplastin Time