BACKGROUND: Electromagnetic pulse (EMP) radiation can affect the learning and memory function of experimental rats and induce injury of hippocampal issues and change of ultrastructure of rats.OBJECTIVE: To observe the effects of EMP on injury of hippocampal neurons cultured in vitro and [Ca2+]i, and analyze deeply possible mechanism of cerebral injury induced by EMP.DESIGN: Randomized controlled animal experiment.SETTING: Department of Pathology, Chengde Medical College.MATERIALS: Several Wistar neonate rats, of either sex (half and half),were selected. Source of EMP radiation was high intensity EMP dummy source.METHODS: The experiment was performed from March to December 2004 at the Academy of Military Medical Science and Chengde Medical College, respectively. Several Wistar neonate rats were decapitated to take out the brains under narcotization. Hippocampal tissues were isolated. The cell suspension was adjusted to 5×108 L-1 for inoculation. Grouping: ①Cultured cells were assigned into control group and radiation group. Cells were collected immediately after radiation to perform observation of morphology and determination of free calcium ion concentration. ②Other cultured cells were divided into control group, 0-hour radiation group and 12-hour radiation group. Cell apoptosis rate and necrosis rate were determined. (Dosage of cultured cells: one culture flask of each group was checked in each item for 3 times). EMP radiation was in 6×104 V/m, with pulse rise time of 20 ns,pulse width of 30 μs, frequency of 2.5 pulses/min, totally for 2 minutes.EMP radiation was performed in primary cultured hippocampal neurons,and then morphological change of neurons was observed under inverted phase contrast microscope before and after radiation. Cell apoptosis and necrosis were measured with FACS method; Free [Ca2+]i concentration in neurons was measured with Fluo-3-AM fluorescent probe loading and laser confocal microscopy scanning.MAIN OUTCOME MEASURES: Morphological change of neuron, cell apoptosis rate and necrosis rate and free [Ca2+]i concentration.RESULTS: ①Immediately after EMP radiation, the onset of colliquation appeared in nerval cells gradually, and neurite was recovery and degeneration. ②Apoptosis rate after 12-hour EMP radiation recovered as compared with that at hour 0 after radiation, but significantly increased as compared with the control group [(59.27±1.27)%, (72.17±6.21)%, (17.45±5.63)%,P＜0.05]. ③Necrosis rate at hour 0 and hour 12 after radiation increased as compared with the control group, but there was no statistical significant difference [(13.71±2.31)%, ( 11.96±1.04)%, (8.45±0.67)% ,P ＞ 0.05].④[Ca2+]i fluorescence intensity at hour 0 after EMP radiation was higher obviously than that in the control group (107.34±26.14,54.93±16.08,P ＜ 0.05).CONCLUSION: EMP induces morphological injury, necrosis and increase of apoptosis rate in hippocampal neurons, and Ca2+ fluorescence intensity increases markedly in neurons.

Objective To evaluate the clinical effect of CEREC chairside on atypical porcelain inlay restoring class [[cavity.Methods 30 patients that required re-treatment because of resin restoration failure and early posterior proximal caries were selected randomly.The original fillings,secondary carious tissues and undercut parts were removed.The clear and round edge lines were prepared.With Sirona CEREC Blocs,35 atypical ceramic inlays were produced in accordance with CEREC AC CAD/CAM standard procedures.After clinical trial and modification,the inlays were bonded with 3M Veneer resin adhesive cement.Evaluation was done immediately and 3,6,12 and 24 months after restoration.Two senior prosthodontists did the evaluation according to the modified USPHS criteria.Results The evaluation results were all A when estimated immediately after restoration.None inlay falled off during the first two years.However,3 inlay were found to be damaged when reviewed at the 24th month.There exsited two patients having mild symptoms of dentine hypersensitivity which appeared at the beginning and died out gradually.Generally speaking,more than 90％ of inlay restorations had reached the USPHS criteria A.Color match and retention represented better effects.Conclusions CEREC atypical ceramic inlays can effectively restore Class Ⅱ cavity,short-term effect is good,but long-term effect still needs further observations.

Objective To analyze the effect of stroke duration on the cognitive function in the elderly population in Beijing.Methods Based on the Research Project of Beijing Chronic Disease Combined with Common Elderly Syndrome Community Management Practices,a cross-sectional study was used.From July 2013 to December 2014,the old population in 4 districts and a county (Xicheng District,Fangshan District,Tongzhou District and Yanqing County) in Beijing were sampled with the multi-stage,randomized and stratified sampling.A total of 3 024 subjects were enrolled in the study.The data were obtained from the questionnaires and clinical examinations.Mini-Mental State Examination (MMSE) was used as the evaluation index of cognitive function.The subjects were divided into either a normal cognitive function group (MMSE>26,n=1 878) or a cognitive impairment group (MMSE≤26,n=1 146) according to the MMSE scores.A multiple logistic regression model was used to analyze the effects of hemorrhagic stroke,ischemic stroke,and asymptomatic stroke,as well as disease duration on cognitive function.Results After adjusting for the confounding factors,such as sex,age,educational level,marriage,smoking,and alcohol consumption,the risks of occurring cognitive impairment in patients with hemorrhagic stroke in stroke duration for 1-3,4-10 and >10 years were OR 3.019 (95％CI 0.974-9.361,P=0.056),8.652 (95％CI 2.924-25.601,P<0.01) and 1.104 (95％CI 0.311-3.920,P=0.879) times of those without occurring stroke population;the risks of occurring cognitive impairment in patients with ischemic stroke in stroke duration for 1-3,4-10 and >10 years were 1.000 (95％CI 0.636-1.571,P=1.000),1.874 (95％CI 1.231-2.853,P=0.003),2.439 (95％CI 1.386-4.291,P=0.002) times of those without occurring stroke population.Stroke duration for 4-10 years in patients with hemorrhagic stroke and stroke duration for 4-10 and >10 years in patients with ischemic stroke were all the risk factors for occurring cognitive dysfunction.Conclusion For patients with stroke,stroke duration or long-term effects has a certain impact on cognitive function.

Objective To discuss the relationship between food habits and hyperhomocysteinemia (HHcy), and provide dietary intervention basis for the aged in prevention and cure of HHcy. Methods Participants coming from the cohort of the Beijing Longitudinal Study of Aging in 2009, were asked to complete a food habits questionnaire and underwent laboratory examinations, including total homocysteine and blood biochemical item. According to effects of food on metabolism of Hcy, the commonly used foods were divided into three kinds: (1)Rich in VitB12 or folic acid or betaine:chicken or duck egg, pork or beef or lamb, bean products and vegetables.(2)Rich in VitB6: fish or shrimp, milk and chicken or duck. (3)Rich in antioxidant: fresh fruit, tea and coffee. According to the intake of frequency, each food was divided into"often eat"and"not often eat"or"not eating". HHcy was defined as>15μmol/L, Logistic regression analysis was used to analyze the association between dietary intake and HHcy, after adjusting confounding factors. Results The prevalence of HHcy was 61.9%(902/1458);accordi ng to the results, for the patients who do not often eat or not eat food rich in VitB12 or folic acid or betaine (chicken or duck egg, bean products and pork or beef or lamb) and VitB6 (fish or shrimp and milk), the risk of HHcy was significantly increased. After adjusting for multiple factors, the risk was still significantly increased, P<0.05. Conclusions Not often eating chicken or duck egg(less than once a day), bean products(less than once a week), fish or shrimp(less than twice a month) and not eating pork or beef or lamb or milk, were independtly associated with the increasing risk of HHcy in elderly people.

Objective To investigate the prevalence and risk factors of H-type hypertension among middle-aged and elderly people in Beijing community. Methods A cross-sectional study by recruiting 1 458 middle-aged and elderly people from a cohort of the "Beijing Longitudinal Study of Aging" in 2009 was conducted. All participants were asked to complete a standardized questionnaire, physical examination and laboratory examinations. Hyperhomocysteinemia was defined as homocysteine (Hcy) > 15 μmol/L, and H- type hypertension was defined as having hypertension and hyperhomocysteinemia simultaneously. The prevalence of H-type hypertension was estimated by using the results of 2000 Beijing population census to weight the data. Multivariate Logistic regression analysis was preformed to estimate the associated factors of H-type hypertension. Results The age was (69.48 ± 8.09) years, and the distribution of Hcy was skewed with the median of 16.56 μmol/L. After weight, the prevalence of hyperhomocysteinemia was 57.20% (834/1 458), and the prevalence of H-type hypertension was 35.32% (515/1 458), accounting for 59.47% (515/866) in patients with hypertension. The ageing, male, hyperuricemia, estimated glomerular filtration rate (eGFR) and insufficiency of fishes/ shrimps were independent risk factors of H-type hypertension ( OR = 2.30, 1.04, 1.02, 0.95 and 0.67; 95% CI 1.54-3.44, 1.02-1.06, 1.04-1.06, 0.94-0.97 and 0.46-0.97; P＜0.01 or＜0.05). Conclusions The proportion of H-type hypertension is high in the middle-aged and elderly people in Beijing community. Lowering uric acid, protection of renal function and intake sufficient fishes and shrimps might prevent and control H-type hypertension.

[Abstract] Objective: To investigate the expression and clinical significance of PD-1/PD-L1 in gastric cancer (GC) tissues. Methods: Paraffin embedded tumor tissues and clinical data of 82 GC patients who had undergone operation at the Fourth Hospital of Hebei Medical University from January 2007 to December 2007 were collected, and their survival status was followed. The protein expressions of PD-1 and PD-L1 in tumor tissues were detected by immunohistochemistry. Kaplan-Meier analysis and Log-Rank test were adopted to analyze the survival of GC patients, and the ROC curve was plotted. Results: The positive rate of PD-L1 protein expression was 42.68% while the positive rate of PD-1 expression was 13.41% in GC tissues. The positive rate of PD-1 and PD-L1 expression in GC tissues of patients without pre-operative distant metastasis was significantly lower than those patients with pre-operative metastasis (PD1： 3.28% vs 42.86%; PD-L1： 13.11% vs 90.48%; all P<0.01). The positive rate of PD-L1 expression in tumor stroma of patients without pre-operative distant metastasis was significantly lower than those with metastasis (PD-L1: 13.11% v s 47.62%, P<0.01). The resection range of stomach, PD-L1 over-expression and the presence of pre-operative distant metastasis were the adverse factors affecting the prognosis of patients with GC (P<0.05). Conclusion: PD-1 and PD-L1 expressions in GC tissues were closely related to the presence of pre-operative distant metastasis and the depth of tumor infiltration. The postoperative survival of patients who were PD-L1 positive was shorter than the negative ones.

Objective: To explore the treatment effects of domestic auricular orthosis on children born with congenital auricular deformity. Methods: Children born with congenital auricle deformity were treated by "Yi Er" auricle orthosis, included 42 ears of 29 cases.These children were divided into three groups according to the birth age. The age less than 7 days was divided into group 1, 7-42 days for group 2, and more than 42 days for group 3. Compare the therapeutic effect of children in different ages. Results: The therapeutic effect was divided into three grades: markedly effective and cured (basically return to normal appearance); effective (improved, but not reached the normal appearance); invalid (no improvement after treatment). The markedly effective and cured rate in group 1, group 2 and group 3 were 100%, 85.7% and 45.0%, the difference was statistically significant(P<0.05), and the average correction time was(20.75±6.50)d, (32.64±15.40)d, (48.23±17.32) d, the difference was statistically significant(P<0.05). Conclusions The domestic auricle orthosis has a significant effect on the correction of children born with congenital auricular deformity. The better treatment effect and the shorter wearing time can be acquired in the early correction.

The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death (ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment (ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin (DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels (DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful anti-tumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo, via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines.

Aberrant activation of oncogenic signaling pathways in tumors can promote resistance to the antitumor immune response. However, single blockade of these pathways is usually ineffective because of the complex crosstalk and feedback among oncogenic signaling pathways. The enhanced toxicity of free small molecule inhibitor combinations is considered an insurmountable barrier to their clinical applications. To circumvent this issue, we rationally designed an effective tumor microenvironment-activatable prodrug nanomicelle (PNM) for cancer therapy. PNM was engineered by integrating the PI3K/mTOR inhibitor PF-04691502 (PF) and the broad spectrum CDK inhibitor flavopiridol (Flav) into a single nanoplatform, which showed tumor-specific accumulation, activation and deep penetration in response to the high glutathione (GSH) tumoral microenvironment. The codelivery of PF and Flav could trigger gasdermin E (GSDME)-based immunogenic pyroptosis of tumor cells to elicit a robust antitumor immune response. Furthermore, the combination of PNM-induced immunogenic pyroptosis with anti-programmed cell death-1 (αPD-1) immunotherapy further boosted the antitumor effect and prolonged the survival time of mice. Collectively, these results indicated that the pyroptosis-induced nanoplatform codelivery of PI3K/mTOR and CDK inhibitors can reprogram the immunosuppressive tumor microenvironment and efficiently improve checkpoint blockade cancer immunotherapy.