Objective:To evaluate the effect of necrostatin-1 (Nec-1)pre-treatment on postoperative cognitive function in aged rats with chronic pain due to knee arthritis.Methods:One hundred and twenty healthy male Sprague-Dawley rats, aged 22 months, weighing 550-600 g, were divided into 4 groups ( n=30 each) using a random number table method: chronic pain due to knee arthritis group(group P), chronic pain due to knee arthritis + operation group (group PS), dimethyl sulfoxide (DMSO) + chronic pain due to knee arthritis + operation group (DMSO+ PS group), and necrostatin-1 + chronic pain due to knee arthritis + operation group (Nec-1+ PS group). The inflammation-induced knee arthritis model was developed by injecting monosodium iodoacetate (MIA) into the left joint cavity.The exploratory laparotomy under sevoflurane anesthesia was performed at 12 weeks after intra-articular MIA injection. In Nec-1+ PS group and DMSO+ PS group, necrosstatin-1 6.25 mg/kg and the equal dose of DMSO were intraperitoneally injected at 1 h before surgery, respectively. At 7 days after surgery, the Morris water maze test was used to evaluate the cognitive function, the activation of microglial cells in the dentate gyrus of hippocampus was observed by immunofluorescent staining, and the activation rate of microglia cells was calculated, the necrosis rate of neurons was determined by flow cytometry, the expression of receptor-interacting protein kinase 1 (RIPK1)and phosphorylated mixed lineage kinase domain-like protein (p-MLKL) was determined by Western blot, and the contents of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and IL-6 were determined by enzyme-linked immunosorbent assay. Results:Compared with P group, the escape latency was significantly prolonged, the time of staying at the original platform quadrant was shortened, and the number of crossing the original platform was reduced, the activation rate of microglia cells in the hippocampal dentate gyrus and necrosis rate of hippocampal neurons were increased, the expression of RIPK1 and p-MLKL was up-regulated, and the contents of pro-inflammatory factors TNF-α, IL-1β and IL-6 in hippocampus were increased in PS, DMSO+ PS and Nec-1+ PS groups ( P<0.05). Compared with PS group and DMSO+ PS group, the escape latency was significantly shortened, the time of staying at the original platform quadrant was prolonged, and the number of crossing the original platform was increased, the activation rate of microglia cells in the hippocampal dentate gyrus and necrosis rate of hippocampal neurons were decreased, the expression of RIPK1 and p-MLKL was down-regulated, and the contents of pro-inflammatory factors TNF-α, IL-1β and IL-6 in hippocampus were decreased in Nec-1+ PS group ( P<0.05). Conclusions:Necrostatin-1 pre-treatment can improve postoperative cognitive function in aged rats with chronic pain due to knee arthritis, and the mechanism may be related to inhibition of necrosis in hippocampal neurons and reduction of neuroinflammation.

Objective To analyze the relationship between blood glucose,blood lipid and body mass index (BMI) in elderly patients with hypertension.Methods Form January 2016 to December 2017,376 hypertensive patients over 65 year old in Jinan city were enrolled in this study.The sex,age,BMI,fasting blood glucose and blood lipid were investigated and tested.The prevalence of coronary heart disease and diabetes mellitus in hypertensive patients were investigated,and the relationship between BMI and blood glucose,blood lipid and liver function index were explored.Results Of 376 hypertensive patients,the detection rate of diabetes mellitus was 21.01％ (79/376),221 cases were diagnosed with coronary heart disease,with the detection rate of 58.78％.With the rise of BMI,fasting blood glucose showed an upward trend.Person correlation analysis showed that there was a significant positive correlation between BMI and fasting blood glucose(r =0.167,P =0.003).The difference between TG and TC in different BMI groups was statistically significant(FTG =12.48,P ＜ 0.001;Frc =4.83,P ＜ 0.001).The content of alanine transaminase in the overweight group and obese group was significantly higher than that in the normal body weight group,the difference was statistically significant(F =5.24,P =0.005).Conclusion For elderly hypertensive patients,it is urgent to test blood glucose and coronary heart disease screening.For people over the age of 65,obesity is still an important risk factor for hyperlipidemia and hyperglycemia.Therefore,body weight control is needed in elderly patients with hypertensive.

Objective To grasp the current situation of drinking water-borne endemic fluorosis in Shandong Province,and provide a scientific basis for formulating preventive strategies.Methods In 2016,according to the "National Surveillance Scheme of Drinking Water-Borne Endemic Fluorosis" and "Shandong Provincial Surveillance Scheme of Drinking Water-Borne Endemic Fluorosis",10 counties (cities,districts) were selected in Shandong Province,3-5 villages were selected in each county (city,district),to investigate the operation of water improvement and fluorine reduction project and the water fluorine,and 1 tap water sample in each village was collected to detect water fluorine.At the same time,dental fluorosis examination was performed on all children aged 8-12 years old and fluorosis X-ray examination was performed on adults aged ≥25 years old.Water fluorine was detected by ion selective electrode method;the water fluorine was determined according to "Standards for Drinking Water Quality" (GB 5749-2006);criteria for diagnosis,grading and epidemic intensity of dental fluorosis were based on "Diagnosis of Dental Fluorosis" (WS/T 208-2011);the diagnostic and grading criteria for skeletal fluorosis were based on the "Diagnostic Criteria for Endemic Skeletal Fluorosis" (WS 192-2008).Results All the 32 villages in 10 counties (cities,districts) changed water,water improvement and fluorine reduction project ran normally,24 villages had qualified water fluorine (≤ 1.20 mg/L),and 8 villages had water fluorine exceeding the standard.The detection rate of dental fluorosis in children was 25.75％ (419/1 627),and the difference between 10 counties (cities,districts) was statistically significant (x2 =288.55,P ＜ 0.01);the dental fluorosis index was 0.48,and the defect rate was 2.77％ (45/1 627).The detection rate of skeletal fluorosis in adults was 4.72％ (72/1 525),and the difference between 10 counties (cities,districts) was statistically significant (x2 =18.83,P ＜ 0.01).Conclusions The problem of water fluorine exceeding the standard in water improvement and fluorine reduction project in Shandong Province is still serious.The condition of fluorosis has not been fully controlled,and the prevention and treatment measures need to be further strengthened.

Objective To understand the implementation effects of control measures and the dynamic prevalence of drinking water-borne endemic fluorosis in Shandong Province.Methods From 2013 to 2017 in Shandong Province drinking water-borne endemic fluorosis areas,in accordance with the method of simple random sampling,10 monitored counties were selected,10 water fluorine decreasing projects were investigated of its running effect,and water fluoride was detected.In each monitored county,3 villages in the diseased areas were selected as fixed monitored villages.If the monitored village had changed its water,the operation of the project would be investigated.If the monitored village had not changed the water,one water sample would be collected according to 5 directions of east,west,south,north and middle to determine the water fluorine.All children aged from 8 to 12 in the village were also examined for dental fluorosis.X-ray fluorosis and urinary fluorosis in adults aged over 25 were detected in 2013 and 2017.Results From 2013 to 2017,in monitored counties,the normal operation rate of improved-water defluoridation projects was 99.19％ (368/371),the qualified rate of water fluoride content was 66.85％ (248/371).In 128 improved water projects,the normal operation rate was 100.00％ (128/128),the qualified rate of water fluoride content was 67.19％ (86/128).The average detection rate of dental fluorosis and community fluorosis index (CFI) in children aged 8-12 were 33.92％ (2 608/7 689) and 0.68 in all monitored counties from 2013 to 2017.The detection rate presented a declining trend year by year (x2 =152.47 P ＜ 0.01).The average detection rate and CFI in the villages with normal operation projects and qualified fluoride content were 26.10％ (1 311/5 023) and 0.47.The detection rate presented a declining trend year by year (x2 =207.67 P ＜ 0.01).The detection rate and CFI in the villages with water improvement projects under abnormal operation or excessive fluoride were 48.65％ (1 297/2 666) and 0.90.The detection rate of dental fluorosis in the villages with normal operation projects and qualified fluoride content was lower than the rate of the villages with water improvement projects under abnormal operation or excessive fluoride (x2 =193.98,P ＜ 0.01).In 2013 and 2017,X-ray detection rates of skeletal fluorosis in adults aged over 25 were 8.04％ (119/1 481) and 6.04％ (81/1 342),respectively.The adult urinary fluoride geometric mean values (1.24,1.49 mg/L) were lower than the normal limit of 1.6 mg/L both in qualified villages of water ffuoride content and exceeding-standard villages in 2017.Conclusions In Shandong Province,the effective water improvement has acquired some effects in control of drinking water-borne endemic fluorosis.But the water fluoride content of improved water defluoridation projects exceeds the national standard seriously and fluorosis has not been effectively controlled.

Objective To evaluate the CT enterography(CTE)of Crohn's disease (CD)in active state and catabatic state by using the Logistic regression analysis.Methods 6 2 patients with CD diagnosed by clinic,imaging,endoscopy,surgery or pathology were analyzed retrospectively.The CTE features of CD in active state and catabatic state were recorded and compared by using single factor and multiple stepwise Logistic regression analysis,and the Logistic regression model was established.Results There were 62 patients with CD, including 40 in active state and 22 in catabatic state.There were significant differences between the bowel wall thickness,the CT value in arterial phase as well as in portal venous phase,the type of enhancement pattern,pseudodiverticulum of free margin,increased mesenteric fat density,comb sign,enlarged abdominal lymph nodes and cellulitis in active state and those in catabatic state of CD by using single factor analysis (P<0.05).The bowel wall thickness (OR=4.589,95%CI:1.689-11.822),bowel wall uniformity enhancement (OR=0.006, 95%CI:0.001-0.067 )and comb sign(OR=23.112,95%CI:1.707-312.997)were significant features by using Logistic regression analysis. Conclusion The bowel wall thickness,bowel wall uniformity enhancement and comb sign are the independent characteristic CTE features to predict the CD in active state or in catabatic state.The Logistic regression model is helpful in demonstrating the state of CD.

Chronic heart failure(CHF)is the performance of end-stage cardiovascular disease and the leading cause of death in recent years.With the rapid development of medical care,the mortality rate of heart failure is still high.This is one in the two major challenges in the cardiovascular field in the 21st century.The new drug LCZ696 is a dual inhibitors of angiotensin receptor blockers(ARB)and neprilysin(NEP),which may lead to new hope for patients with heart failure.In order to determine the efficacy and safety of LCZ696 in the treatment of heart failure,foreign countries have carried out some large-scale trials,such as PARAMOUT, PARADIGM,TITRATION and so on.The results of these studies reflected the superiority of LCZ696 compared with enalapril,valsartan and other drugs in the treatment of chronic heart failure.ARB/antiotensin converting enzyme inhibitors(ACEI)targets the angiotensin receptor to dilate blood vessels and inhibits the sympathetic nerve,but their effects on sodium withdrawal and diuresis are weak.The sacubitril in LCZ696 prevents natriuretic peptide from degrading,strengthens the natriuretic diuretic and further expansion of blood vessels.Thereby it improves water and sodium retention and cardiac function.It can play a better synergistic role combined with valsartan.

Objective To evaluate the health-related quality of life (HRQOL) for prostate cancer patients receiving androgen deprivation therapy (ADT).Methods We studied 200 patients with prostate cancer who were treated with primary ADT in Peking University People's Hospital from June 2014 to June 2015.The patients'average age was 73.9 years.The mean PSA level was 21.57 ng/ml when they were diagnosed with prostate cancer.Of these 200 patients,79％ (158/200) were localized and seclected ADT therapy due to age,body condition,basic diseases or individual will.21％ (42/200) were locally advanced or metastasic,which accord with the indication of ADT therapy.The scales,including the MOS item short from health survey (SF-36),Functional Assessment of Cancer Therapy-General module (FACT-G),Functional Assessment of Cancer Therapy-Prostate instrument (FACT-P),Self-Rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS) were used to evaluate their HRQOL.Results According to results of SF36,the physical health component score and mental health component score was 67.41 ± 16.39 and 64.81 ± 17.51,respectively.They indicated that the overall quality of life of these patients was at an acceptable level.And the average score of all domains exceeded 60 except general health domain,which the score was only 40.03 ± 21.89.When it comes to FACT-P,the sum score,emotional well-being score and prostate cancer component score were 8.15 ± 3.72,12.30 ± 4.04 and 77.41 ± 9.95,respectively,which were less than half of their respective top score.However the physical well-being score was 20.41 ±4.29,which was a relatively satisfactory value.In addition,61％ (121/200) patient selected not at all in item I am able to have and keep an erection.The score of SDS and SAS was 46.76 ± 8.29 and 43.25 ±9.69,respectively.And there were 23.0％ (46/200) and 21.5％ (43/200) patiens exhibited depression and anxiety,respectively.Conclusion In the present study,the prostate cancer patients receiving ADT showed acceptable HRQOL,but some patients sufferd from depression,anxiety and erectile dysfunction.

Objective:To investigate the expression of MEK/ERK signaling pathways in renal cell car-cinoma with bone metastasis,and to analyze the differences of expressions of VEGFR-2,MEK,ERK on the primary and metastasis tissue and its mechanism.Methods:The tissue samples were obtained from 7 renal cell carcinoma patients kindly provided by Department of Urology,Peking University People’s Hos-pital from January 1,2009 to January 1,2010.The expression of MEK/ERK signaling pathways was de-tected in the 7 renal cell carcinoma patients`primary and matched metastatic tissues with ICH,The anti-body concentrations were 1 ∶200,1 ∶25,and 1 ∶250,respectively.The mutation of the twentieth exon of the PDGFRA gene,the second exon of the K-ras gene,the fifteenth exon of the Brafgene and the se-cond exon of the MEK1 gene were detected with PCR.Results:The expression intensities of VEGFR-2, MEK,and ERK were measured by H-score [intensity (1,2,3,or 4)multiplied by the distribution (%)].VEGFR-2,MEK,and ERK expressions were divided into 3 groups according to the positive dis-tribution of the tumor cells:1,0 -5%;2,6% -50%;and 3,>50%,To assess intratumor heteroge-neity,three distinct microscopic fields (×200)from each specimen were used to evaluate the expres-sions,Subsequently,the scores were averaged to obtain a single concatenated score for each tissue. VEGFR-2,MEK,and ERK expressions were assessed by 2 independent pathologists who were blinded to the clinicopathological data.The data were expressed as the mean value of the triplicate experiments.The expressions of MEK,and ERK were higher in the metastatic tissues than in the matched RCC tissues (6.10 ±4.10 vs.1.33 ±0.51,P =0.015;9.10 ±2.24 vs.4.43 ±2.84,P =0.021 )while the ex-pression of VEGFR-2 was not different between the primary and metastatic tissues (P =0.901).No mu-tation was detected on the twentieth exon of the PDGFRA gene,the second exon of the K-ras gene,the fifteenth exon of the Brafgene and the second exon of the MEK1 gene.Conclusion:MEK/ERK signa-ling pathways may play an important role in the metastasis and the resistance of sunitinib in RCC patients with bone metastasis.

Objective To investigate the effects of low frequency repetitive transcranial magnetic stimulation (rTMS) on non-fluent aphasia in patients after stroke.Methods Forty stroke patients displaying non-fluent aphasia were randomly assigned to an rTMS group and a control group using a random number table.Both groups were treated with conventional language therapy,while the rTMS group was additionally given 0.5 Hz rTMS over the Broca's homologues of the unaffected hemisphere 5 days a week for 3 weeks.The patients were stimulated at 90％ of the motor threshold (MT),with 16 second trains and intervals of 3 seconds 48 times (384 pulses) in a session.Before and after the 3 weeks of treatment,the Western Aphasia Battery (WAB) and the Communicative Abilities in Daily Living (CADL) test were conducted in both groups to evaluate their language function and communication ability.Results Only spontaneous speech improved significantly (P＜0.05) in the control group after 3 weeks of treatment.In the rTMS group,the spontaneous speech,auditory comprehension,repetition,naming and aphasia quotient (AQ) had all improved significantly (P＜0.05).Moreover,after the treatment,the average score of the auditory comprehension (153.90± 31.79),repetition (82.65± 15.14),naming(81.28±22.12) and AQ (63.66± 13.64) of the rTMS group were significantly higher than those of the control group (P＜0.05).Conclusion rTMS applied to the Broca's homologues of the unaffected hemisphere can significantly improve language function in those exhibiting non-fluent aphasia after stroke.

Objective To study the neurobehavioral manifestations of pilocarpine-induced temporal lobe epilepsy (TLE) rats in different kinds of learning and memory ability tests at chronic stage.Methods Thirty SD rats were randomized into TLE group (n=20) and control group (n=10).Intraperitoneal injection of lithium-pilocarpine (LIP) was performed in rats of the TLE group,and saline was given to the control group.Six weeks after modeling,rats were investigated in spatial,object,time and space combined episodic memory tests,and received 7.0 T MR imaging for structural images.Results Immediately after LIP treatment,13 rats in the TLE group exhibited status epilepticus.Six weeks later,11 of the 13 rats in the TLE group were observed spontaneous seizures.T2 images from MR imaging implied gray matter damage in the hippocampus in the TLE group and intact structure in the control group.The ranges of motion in the spatial memory,object memory and episodic memory in the control group were (90.56±19.9) m/min,(92.58±14.83) m/min and (94.20±30.99) m/min,respectively;those in the TLE group were (95.09±21.51) m/min,(117.10±44.38) m/min and (104.90±35.22) m/min;no significant differences were noted between the two groups (P＞0.05).In the control group,more exploration time on novel location in the spatial test,novel object in the object test,familiar location-familiar object and novel location-novel object in the episodic test were showed than that on the other objects,with significant difference (P＜0.05).In all the tests,there were no significant differences in the exploration times between/among the objects in the TLE group (P＞0.05).Conclusion All spatial,object and episodic memory are impaired in chronic LIP-TLE rats.