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Objective:To analyze the external quality control assessment results of urinary iodine, salt iodine and water iodine in iodine deficiency disorders laboratories in Qinghai Province, to evaluate the testing capacity of provincial, municipal and county-level laboratories and the operation of external quality control network, so as to provide quality assurance for consolidating and eliminating iodine deficiency disorders.Methods:In 2021, 1 provincial, 8 municipal, and 43 county-level laboratories in Qinghai Province had participated in the assessment of urinary iodine and salt iodine, while 1 provincial and 8 municipal-level laboratories had participated in the assessment of water iodine. The assessment results were evaluated using the method of reference value ± uncertainty of external quality control samples.Results:All laboratories that participated in the assessment had provided feedback. One provincial-level laboratory passed the assessment of urinary iodine, salt iodine, and water iodine. Among 8 municipal-level laboratories, 2 laboratories failed the urinary iodine assessment, with a pass rate of 6/8; the assessment of salt iodine and water iodine in 8 laboratories were all qualified. Among 43 county-level laboratories, 7 laboratories failed the urinary iodine assessment, with a pass rate of 83.7% (36/43); the assessment of salt iodine in 43 laboratories were all qualified.Conclusions:The external quality control network of iodine deficiency disorders laboratories in Qinghai Province has fully covered all municipal and county-level laboratories. The testing capability of provincial-level laboratory is stable and maintains a high level; the testing quality of some municipal and county-level laboratories is still unstable and needs to be further strengthened.
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Objective:To study the phenotype and genotype distribution of Yersinia pestis ( Y. pestis) in different natural foci of plague in China, so as to provide scientific basis for plague prevention and control. Methods:A total of 2 184 strains of Y. pestis isolated from different time periods, regions, hosts and vectors in 11 plague natural foci of China since 1943 were selected for biochemical type identification, glycolysis test, virulence factor test [capsule antigen (F1), pesticin Ⅰ (Pst Ⅰ), virulence antigen factor (VWa), pigmentation factor (Pgm)], different region (DFR) typing and clustered regularly interspaced short palindromic repeats (CRISPR) typing. Results:There were 16 biochemical types of Y. pestis in the natural foci of plague in China, and each biochemical type showed obvious regional distribution in each foci. Most strains were positive for ass hide glue glycolysis (89.79%, 1 961/2 184), maltose (80.13%, 1 750/2 184), glycerol (94.23%, 2 058/2 184), and denitrification (82.78%, 1 808/2 184), and negative for rhamnose (88.78%, 1 939/2 184) and melibiose (85.62%, 1 870/2 184). Virulence factor test results showed that 99.95% (2 183/2 184) of Y. pestis were F1 positive; 99.73% (2 178/2 184) of Y. pestis can produce Pst Ⅰ; 73.31% (1 601/2 184) of Y. pestis were VWa positive and 26.69% (583/2 184) were VWa negative; Pgm positive strains accounted for 72.62% (1 586/2 184), Pgm negative strains accounted for 21.52% (470/2 184), and Pgm mixed type strains accounted for 5.86% (128/2 184). According to DFR typing results, there were 52 genotypes in 2 184 strains of Y. pestis, of which 19 were major genotypes and 33 were minor genotypes. CRISPR typing revealed 16 major genotypes, of which 7 were newly discovered. Conclusion:The phenotypes and genotypes of Y. pestis in various natural foci of plague in China are diverse and have geographical distribution characteristics.
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Objective:To learn about the epidemic situation and trend of human brucellosis in Menyuan Hui Autonomous County (referred to as Menyuan County) of Qinghai Province, and to provide reference for formulating brucellosis prevention and control measures in Menyuan County.Methods:Data on human brucellosis in Menyuan County reported by the Infectious Disease Reporting Information Management System of China Disease Control and Prevention Information System from 2013 to 2020 were collected and analyzed by descriptive epidemiological analysis (three distribution).Results:A total of 186 cases of brucellosis were confirmed from 2013 to 2020, with an average annual incidence of 14.553/100 000. The annual incidence rate was increasing year by year(χ 2trend = 22.08, P = 0.002). The cases were distributed in 67 villages of 12 towns; cases were more common in the age group of 15-< 65 years old (96.24%, 179/186), and there were more men than women cases (sex ratio was 3.89∶1.00, 148/38). Conclusions:The incidence rate of brucellosis cases in Menyuan County is increasing year by year, and the scope of its impact is constantly expanding. A multi-sectoral joint prevention and control mechanism should be established to strengthen management, increase the prevention and control of brucellosis, and stop the spread of the epidemic to surrounding counties and cities.
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Objective:To follow up the iodine nutrition and intellectual development of school children aged 8-10 years old in Nangqian County of Qinghai Province after 9 years of the implementation of iodine deficiency disorders intervention measures with iodine supplement as the main measure.Methods:In order to improve the iodine nutritional status of the population in Nangqian County, free iodized salt distribution, health education and other intervention measures for iodine deficiency disorders were implemented for 9 consecutive years since 2013. In May 2012 (before iodine supplementation) and September 2021 (after iodine supplementation), the same 5 townships (towns) were selected, and children aged 8-10 years old (half male and half female, age balanced) born locally in the central primary school of each township (town) were selected as the survey subjects. Household edible salt samples and random urine samples were collected for salt iodine and urinary iodine detection; the second revised version of the Chinese Combined Raven's Test (rural version) was used to assess the intelligence quotient (IQ) of children. The Flynn effect (FE) gain was used to adjust IQ, the corrected IQ = (IQ starting point value - current year's IQ value) - FE gain (calculated by 0.74/year). The differences of salt iodine and urinary iodine related indexes, IQ value and corrected IQ were compared before and after iodine supplementation.Results:After iodine supplementation, the coverage rate of iodized salt reached 100.00% (300/300), and the consumption rate of qualified iodized salt reached95.00% (285/300), the median urinary iodine increased to 157.20 μg/L, and all indexes met the elimination standard of iodine deficiency disorders. The IQ value of children aged 8-10 years old after iodine supplementation was 99.00 ± 14.90, significantly higher than that before iodine supplementation (82.00 ± 13.20, F = 156.82, P < 0.001). The FE gain in 9 years was 6.66, and the actual IQ gain of children aged 8-10 years old after iodine supplementation was 10.34. There were statistically significant differences in IQ value before and after iodine supplementation in male and female children ( F = 78.84, 78.88, P < 0.001). After iodine supplementation, there was a statistically significant difference in IQ value between children in the 8-year-old group and the 10-year-old group ( P = 0.010). There were statistically significant differences in IQ value before and after iodine supplementation in 8, 9 and 10 years old groups ( F = 55.23, 65.79, 36.85, P < 0.001). Conclusion:Intervention measures for iodine deficiency disorders, mainly iodine supplement, can significantly improve the iodine nutrition status of children aged 8-10 years old, and significantly promote the intellectual development of children.
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Objective:To observe multiple locus variable-number tandem repeat analysis (MLVA) typing of Brucella isolated from Himalayan marmot in Qinghai-Tibet Plateau of Qinghai Province, and to explore the relationship between the strains and strains previous isolated from Qinghai Province. Methods:Blood samples of Himalayan marmot were collected in Qinghai-Tibet Plateau of Qinghai Province from March 2019 to October 2020. Pathogens were isolated and cultured from Brucella antibody positive samples identified by using the rose bengal test (RBT). Conventional biological methods and molecular biological methods (BCSP31-PCR and AMOS-PCR) were used for strain identification. At the same time, MLVA method was used to genotype the isolated strains, and cluster analysis was used to analyze the genetic relationships between the strains based on the genotype of 70 Brucella isolated from different hosts in Qinghai Province. Results:A total of 1 466 blood samples of Himalayan marmot were collected from Qinghai-Tibet Plateau. Two strains of Brucella were isolated and cultured from 64 RBT-positive samples, named QH2013054 and QH2013062, respectively. They were identified as Brucella ovis biotype Ⅲ by conventional and molecular biological methods. The MLVA genotyping results showed that QH2013054 and QH2013062 were different at the Bru16 locus, indicating different MLVA genotypes. Cluster analysis showed that strain QH2013054 had the same MLVA genotype as 7 strains, among which 6 strains were from 3 farmers and 3 sheep from the same family in Gonghe County, and 1 strain was from a farmer in Menyuan Hui Autonomous County. The strain QH2013062 had the same MLVA genotype as 4 strains, including 3 strains from 3 farmers in Menyuan Hui Autonomous County and 1 strain from a farmer in Tu Autonomous County of Huzhu. Conclusions:The strains of Brucella isolated from Himalayan marmot in Qinghai-Tibet Plateau of Qinghai Province have the same MLVA genotype as some strains of Brucella isolated from humans and sheep in Qinghai Province. It is speculated that the host humans, sheep and Himalayan marmot in Qinghai-Tibet Plateau may have a common source of infection.
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Objective:To understand the water iodine content in Qinghai Province and draw a distribution map of water iodine, so as to provide a basis for scientific supplementation of iodine and continuous elimination of iodine deficiency hazards.Methods:In 2017, in all counties (cities, districts) in Qinghai Province, with townships (towns, streets, referred to as townships) as the unit, the residents' drinking water samples were collected, water iodine content was tested, the median water iodine was calculated, and the water iodine distribution map of Qinghai Province was drew.Results:Totally 1 836 drinking water samples were collected in 392 townships, the median water iodine was 1.7 μg/L. Townships that had the median water iodine < 5 μg/L, in the range of 5 to 10 μg/L and > 10 μg/L accounted for 80.6% (316/392), 17.1% (67/392) and 2.3% (9/392), respectively. Among all townships, the highest of the median water iodine was 24.8 μg/L. Based on the results, water iodine distribution map of Qinghai Province, water iodine distribution map of Xining City and water iodine distribution map of Haidong City were compiled.Conclusions:Iodine deficiency is widespread throughout natural environment in Qinghai Province. Hence, salt iodization measures to prevent iodine deficiency disorders should be implemented continuously. According to the water iodine distribution map, the people should be guided to supplement iodine scientifically.
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Objective:To investigate the dietary iodine intake of people in different areas of Qinghai Province, and to provide the basis for scientific iodine supplementation and continuous elimination of iodine deficiency hazards.Methods:From 2018 to 2019, according to administrative division, natural geographical regions, population distribution and economic development level of Qinghai Province, a total of 14 survey sites were selected. One village was selected from each survey site, and 20 households were selected from each village, the salt samples and 24 h urine samples of all family members were collected to detect salt iodine and urinary iodine. One drinking water sample was collected at the five directions of east, west, south, north and middle of each village to detect water iodine. Salt iodine was detected by direct titration, urinary iodine and water iodine were detected by arsenic-cerium catalytic spectrophotometry. At the same time, the 3-day weighing method was used to investigate the diet, the daily dietary iodine intake per capita (the result was expressed as average) and the proportion of dietary iodine in urinary iodine were calculated, the daily dietary iodine intake per capita of different production modes (agricultural region and pastoral region), different geographical environment (Hehuang Valley, Qaidam Basin, Qilian Mountain and Qingnan Plateau), different nationalities (Han, Tibetan, Hui, Mongolian, Tu, Salar) and different economic levels (< 8 000, 8 000 -, 10 000 -, ≥12 000 Yuan) were compared.Results:A total of 999 people from 280 families were surveyed, including 511 males and 488 females. The median water iodine of each survey site was less than 10 μg/L, all of which were environmentally iodine-deficient areas. A total of 280 salt samples were collected, the median salt iodine was 26.0 mg/kg, and the consumption rate of qualified iodized salt was 100% (280/280). A total of 999 urine samples were tested, and the median urinary iodine of people was 192.5 μg/L, which was at an appropriate level of iodine. There was no statistically significant difference ( t =-1.599, P > 0.05) in the daily dietary iodine intake per capita (28.53, 33.44 μg) of people in agricultural region ( n = 643) and pastoral region ( n = 356). The daily dietary iodine intake per capita (25.38, 33.30, 32.98, 34.79 μg) of people in Hehuang Valley ( n = 448), Qaidam Basin ( n = 125), Qilian Mountain ( n = 157), and Qingnan Plateau ( n = 269) were compared, the difference was statistically significant ( F = 2.883, P < 0.05); among them, the daily dietary iodine intake per capita in Hehuang Valley was lower than that in Qingnan Plateau ( P < 0.05). The daily dietary iodine intake per capita of different nationalities were compared, the difference was statistically significant ( F = 3.647, P < 0.05), Salar ( n = 68) and Tibetan ( n = 239) were higher (37.21 and 32.21 μg). The daily dietary iodine intake per capita (38.97, 17.01, 30.86, 33.14 μg) of annual per capita disposable income < 8 000 ( n = 194), 8 000-( n = 221), 10 000-( n = 302), ≥12 000 Yuan ( n = 282) were compared, the difference was statistically significant ( F = 9.407, P < 0.05). The proportions of dietary iodine in urinary iodine of various population ranged from 5.35% to 15.54%. Conclusions:The iodine nutrition of people in Qinghai Province is suitable, the dietary iodine intake of people is closely related to geographical environment, nationality and economic level. But the proportion of dietary iodine in urinary iodine is relatively low, the consumption of iodized salt is still the main way for people to intake iodine, and it is also the main measure to continuously eliminate the harm of iodine deficiency in Qinghai Province.
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Objective:To establish the minimum inhibitory concentration (MIC) detection method of Yersinia pestis by determining MIC of 11 kinds of antibiotics against Yersinia pestis, to master the inhibition range of common antibiotics on Yersinia pestis, and provide baseline data for clinical treatment of plague. Methods:According to Clinical Labor Standard Institution (CLSI), the agar plate dilution method was used to determine the MIC of 11 kinds of antibiotics against 118 strains of Yersinia pestis, including ofloxacin, ciprofloxacin, trimethoprim-sulfamethoxazole, kanamycin, streptomycin, ceftriaxone, ampicillin, chloramphenicol, spectinomycin, cefuroxime and tetracycline. MIC 50 and MIC 90 (the minimum concentration of drug which could inhibit 50% and 90% of bacterial growth) were calculated. The consistency was observed by comparing the results with those of the disk diffusion method. One hundred and eighteen strains of Yersinia pestis were isolated from natural plague foci of Qinghai Province and preserved by Qinghai Institute for Endemic Disease Prevention and Control. Results:Among 118 strains of Yersinia pestis tested, no single or multiple strains of Yersinia pestis resistant to 11 kinds of antibiotics were found, which was consistent with the results of the disk diffusion method. The MIC 50 and MIC 90 of 11 kinds of antibiotics against 118 strains of Yersinia pestis were obtained. Conclusions:The MIC detection method of Yersinia pestis is successfully established. This method can be used to measure the MIC of antibiotics against Yersinia pestis in high throughput and evaluate the sensitivity of Yersinia pestis to antibiotics. It is an efficient, economical and practical experimental method.
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Objective:To investigate the efficacy of Da Vinci robot-assisted surgery for mediastinal tumor, and summarize the value of Da Vinci system in mediastinal surgery.Methods:The clinical data of 339 cases of robot-assisted mediastinal mass in Shanghai Chest Hospital from April 2015 to September 2020 were retrospectively analyzed, to compare perioperative outcomes of robotic surgery and conventional video-assisted thoracoscopic surgery 2 949 cases.Results:All the operations were successfully completed as planned. No residual lesions, conversion or second operation was observed in the consecutive cohort. The operating time[(81.8±36.8)min vs.(95.6±58.3)min, P=0.015]and post-operation stay[(3.1±1.9)days vs.(3.8±2.3)days, P=0.002] were statistically shorter in robotic group than those inconventional thoracoscopic group. Intraoperative blood loss in two groups was similar[(43.2±22.6)ml vs.(44.0±33.4)ml, P>0.05]. Conclusion:The Da Vinci robot system in mediastinal surgery is safe and feasible with great perspective in the new age of minimally invasive thoracic surgery. Compared with thoracoscopic surgery, it can shorten the operation time and reduce the postoperative hospital stay. It has certain advantages in operator experience and patient recovery.
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Thymic epithelial tumors are the most common tumors in anterior mediastinum. They are used to be considered rare in incidence, with an indolent nature of biological behaviors, which led to the lack of high level evidence obtained from prospective randomized controlled trials to guide the clinical treatment. At present, the experience of diagnosis and treatment of thymic tumors varies greatly in different regions. And there are still many problems remain to be solved. This paper aims to establish a standardized surgical treatment based on the latest researches in surgical indications, resection extent, surgical approach, lymph node dissection and postoperative management of thymic tumors.
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Objective To observe the effects of total enteral nutrition ( TEN) and early combined parenteral nutrition ( PEN+TEN) in patients with esophageal cancer after operation .Methods The prospective,random, controlled clinical trial was adopted.One hundred patients receiving esophageal cancer operation were randomly assigned to the TEN group (50 cases) and the PEN+TEN group(50 cases).The differences in nutritional status, inflammatory response, immune status and postop-erative complications were compared in the two groups before and after operation.Results The levels of total serum protein, albumin or retinol binding protein were higher in the PEN group than the TEN group at the 10th day after operation, respective-ly[(60.1 ±6.2)g/L vs(55.3 ±9.3)g/L,(36.4 ±4.2)g/L vs(34.6 ±1.6)g/L,(43.3 ±5.9)g/L vs(34.9 ±3.3)g/L, P<0.05] .The levels of ESR or CRP were higher in PEN +TEN group than the TEN group at the 10th day after operation, re-spectively [(54.9 ±25.8)mm/h vs(31.8 ±14.2)mm/h,(30.9 ±13.2)g/L vs(15.8 ±6.1)g/L, P<0.01] .The levels of CD3+, CD4 +, or CD8 +were higher at the 10 th day after operation than at the day before surgery in TEN group [(59.6 ±9.8)％vs(68.3 ±4.4)％,(41.7 ±7.8)％vs(46.5 ±5.5)％,(23.2 ±5.5)％vs(20.0 ±2.7)％, P<0.05], but not in PEN+TEN group.The levels of IgA or IgG were significant higher in the TEN group than the PEN +TEN group at the 10th day after operation[(1.9 ±0.5)g/L vs(1.6 ±0.3)g/L,(11.9 ±3.3)g/L vs(9.4 ±2.2)g/L, P<0.01].Con-clusion The inflammatory reaction and immune function in TEN group are better than those in PEN +TEN group.Although the nutritional status is worse in the TEN group than that in the PEN group , but the rate of postoperative complications has not increased.
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BACKGROUND@#So far there's no tumor maker applied in diagnosis and treatment of thymic epithelial tumors. This study is to assess the correlation between serum cytokine 19 fragment (Cyfra 21-1) and clinicopathological features and prognosis of thymic epithelial tumors (TETs).@*METHODS@#The clinical data of 159 patients with TETs in Shanghai Chest Hospital was retrospectively analysed. Patients were divided into groups according to different tumor stages and histotypes. Serum Cyfra 21-1 was thus compared. In addition, the possible relationship between perioperative serum Cyfra 21-1 level and the recurrent status was carrid out.@*RESULTS@#Preoperative Cyfra 21-1 serum concentrations in patiants with advanced stage (T4) and thymic carcinomas were significantly higher than that in others (P<0.001, P<0.001, respectively). When the preoperative serum level exceeds the out-off of 1.66 ng/mL, it possibly indicates the recurrence during follow up. Furthermore, the sensitivity, specificity, and positive as well as negative predictive value (PPV and NPV) of postoperative Cyfra 21-1 to predict tumor recurrence were evaluated. At a cut-off of Cyfra 21-1 of 2.66 ng/mL, the sensitivity was 0.7, the specificity was 0.925, the PPV was 0.5 and the NPV was 0.966.@*CONCLUSIONS@#The elevated level of preoperative serum Cyfra 21-1 indicates an advanced stage of tumor or a more malignant histotype (thymic carcinoma). It also probably suggests a higher risk of tumor recurrence. During the oncological follow up, in addition to regular imaging examinations, the blood test of serum Cyfra 21-1 is also suggested to improve the diagnosis of tumor recurrence in order to improve the prognosis.
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Female , Humans , Male , Middle Aged , Biomarkers, Tumor , Blood , Follow-Up Studies , Keratin-19 , Blood , Chemistry , Neoplasms, Glandular and Epithelial , Blood , Diagnosis , Pathology , Peptide Fragments , Blood , Prognosis , ROC Curve , Retrospective Studies , Thymus Neoplasms , Blood , Diagnosis , PathologyABSTRACT
Objective To investigate the influence of sevoflurane and propofol on postoperative cognitive dysfunction in elderly patients with laparoscopic cholecystectomy.Methods Sixty elderly patients scheduled for elective laparoscopic cholecystectomy in our hospital from March 2016 to September 2016 were selected and divided into the sevoflurane group(S) and propofol group (P),30 cases in each group.Postoperative mini-mental state examination(MMSE) score and occurrence rate of postoperative cognitive dysfunction(POCD) were compared between two groups.Results The MMSE score at T0 had no statistical difference between the two groups;the MMSE score at T1 and T2 in the group S was significantly lower than that in the group P,moreover the occurrence rate of POCD at T1 in the group S was significantly higher than that in the group P;The MMSE score and POCD occurrence rate at T3 had no statistical difference between the two groups(P＞0.05).The MMSE score at T1,T2 and T3 in the group S was significantly decreased compared with that at T0 (P＜0.05);the MMSE score at T1 and T2 in the group P was significantly decreased compared with that at T0 (P＜ 0.05),and which at T3 was gradually recovered.Conclusion Compared with propofol,sevoflurane has more significant and persistent influence on POCD occurrence.
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Objective To investigate the influence of sevoflurane and propofol on postoperative cognitive dysfunction in elderly patients with laparoscopic cholecystectomy.Methods Sixty elderly patients scheduled for elective laparoscopic cholecystectomy in our hospital from March 2016 to September 2016 were selected and divided into the sevoflurane group(S) and propofol group (P),30 cases in each group.Postoperative mini-mental state examination(MMSE) score and occurrence rate of postoperative cognitive dysfunction(POCD) were compared between two groups.Results The MMSE score at T0 had no statistical difference between the two groups;the MMSE score at T1 and T2 in the group S was significantly lower than that in the group P,moreover the occurrence rate of POCD at T1 in the group S was significantly higher than that in the group P;The MMSE score and POCD occurrence rate at T3 had no statistical difference between the two groups(P＞0.05).The MMSE score at T1,T2 and T3 in the group S was significantly decreased compared with that at T0 (P＜0.05);the MMSE score at T1 and T2 in the group P was significantly decreased compared with that at T0 (P＜ 0.05),and which at T3 was gradually recovered.Conclusion Compared with propofol,sevoflurane has more significant and persistent influence on POCD occurrence.
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Objective To observe the antihypertensive effect of compound Yibazhen granules on spontaneous hypertensive rats ( SHR) . Methods Wistar rats were served as normal control group. Sixty SHR were randomly divided into model control group,captopril group,Jane chrysanthemum antihypertension tablet group and compound high dose group,middle dose group and low dose group ( n = 10 each group ) by digital table method. Captopril group was given captopril 30 mg.kg-1 .d-1 ,and Jane chrysanthemum antihypertension tablet group was treated with Jane chrysanthemum antihypertension tablet ( 0. 6 tablet per kg ) , compound Yibazhen granules high dose group, middle dose group and low dose group received compound of 13.18,6.59 and 3.3 mg.kg-1 .d-1 ,respectively. Normal control group and model control group were intragastrically administered with 0.9% sodium chloride solution for 8 weeks. Changes of systolic and diastolic blood pressure of rats and blood urea,creatinine,nitric oxide (NO),nitric oxide synthase (NOS) and angiotensin Ⅱ (Ang Ⅱ) were observed. Results Diastolic pressure of rats in compound Yibazhen granules high dose group, middle dose group and low dose group decreased significantly in 2 weeks. Systolic blood pressure and diastolic blood pressure of compound Yibazhen granules high dose group decreased significantly in 4 weeks,compared with the model control group (P<0.05). Compared with the model control group, concentration of urea and crea in compound Yibazhen granules high dose group, middle dose group and low dose group were significantly lower( P<0.05) . The content of NOS and AngⅡ in rats of compound Yibazhen granules high dose group decreased significantly and the contents of NO increased, which were compared with the model control group ( P<0. 05, P<0. 01 ) . Conclusion The protective effect of compound Yibazhen granules in treating early renal damage in SHR is related to decreasing diastolic blood pressure,concentration of urea,crea and AngⅡ and regulating the levels of NOS and NO.
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Microglia play a pivotal role in clearance of Aβ by degrading them in lysosomes, countering amyloid plaque pathogenesis in Alzheimer's disease (AD). Recent evidence suggests that lysosomal dysfunction leads to insufficient elimination of toxic protein aggregates. We tested whether enhancing lysosomal function with transcription factor EB (TFEB), an essential regulator modulating lysosomal pathways, would promote Aβ clearance in microglia. Here we show that microglial expression of TFEB facilitates fibrillar Aβ (fAβ) degradation and reduces deposited amyloid plaques, which are further enhanced by deacetylation of TFEB. Using mass spectrometry analysis, we firstly confirmed acetylation as a previously unreported modification of TFEB and found that SIRT1 directly interacted with and deacetylated TFEB at lysine residue 116. Subsequently, SIRT1 overexpression enhanced lysosomal function and fAβ degradation by upregulating transcriptional levels of TFEB downstream targets, which could be inhibited when TFEB was knocked down. Furthermore, overexpression of deacetylated TFEB at K116R mutant in microglia accelerated intracellular fAβ degradation by stimulating lysosomal biogenesis and greatly reduced the deposited amyloid plaques in the brain slices of APP/PS1 transgenic mice. Our findings reveal that deacetylation of TFEB could regulate lysosomal biogenesis and fAβ degradation, making microglial activation of TFEB a possible strategy for attenuating amyloid plaque deposition in AD.
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Animals , Humans , Mice , Alzheimer Disease , Metabolism , Pathology , Amyloid beta-Peptides , Metabolism , Amyloid beta-Protein Precursor , Genetics , Metabolism , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors , Chemistry , Genetics , Metabolism , Brain , Metabolism , Cells, Cultured , Chloride Channels , Genetics , Metabolism , Disease Models, Animal , HEK293 Cells , Lysosomes , Genetics , Metabolism , Mice, Transgenic , Microglia , Cell Biology , Metabolism , Mutagenesis, Site-Directed , Peptides , Chemistry , Protein Binding , RNA Interference , Sirtuin 1 , Genetics , MetabolismABSTRACT
Objective To observe pathological features of peripheral vessel injury caused by ex-plosion shock wave so as to provide theoretical basis for emergency treatment, prevention and complication reduction of war extremity injuries. Methods A total of 18 rabbits were randomly divided into three groups (six rabbits in each group) and placed respectively at 1, 2 and 3 m away from the explosion cen-ter. The animal model with blast injury was made by using fluid dynamite that electrically exploded at 60 cm above the ground. The physical parameters of blast wave were recorded using pressure transducers (PCB, UAS). After explosion, the femoral arteries were examined grossly, histologically and immunohis-tochemically. Results The results showed that vascular endothelial cells were denudated, the spaces of contractile fiber cells increased and appeared puff, the vassular elastic fibers ruptured, flexed and de-formed visibly. Some parts of the vessel wall ruptured completely or partly, leading to bleeding. TUNEL staining and fluorescence microscope found large number of apoptotic cells in endothelium layer, smooth muscle layer and membrana adventitia layer of the blood vessels. Conclusion Explosion shock wave can result in severe large blood vessel injury, which should be paid much attention during treatment of ex-plosion shock injury.
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BACKROUND:Corneal hemangiogenesis occurs in 40%-60%patients after keratoplasty.Blood vessel is one of the high risk factors for corneal immunological rejection.To inhibit corneal hemangiogenesis would prolong the survival time of the grafts and promote the successful rate of the keratoplasty.OBJECTIVE:To explore the inhibitive effects of doxycycline on corneal angiogenesis after keratoplasty.DESIGN,TIME AND SETTING:A randomized controlled animal experiment was performed at the State Key Laboratory of Ophthalmology(No.2006DA105054),Zhongshan Ophthalmic Center,Sun Yat-sen University from March to August 2007.MATERIALS:A total of 48 healthy dean Sprague Dawley rats served as recipients(right eye)and 24 Wistar rats as donors(both eyes).CD31-PEfluorescent antibody was obtained from Sigma,USA.Sandwich enzyme-linked immunosorbent assay(ELISA)kit for vascular endothelial growth factor(VEGF)was brought from RapidBio,USA.METHODS:Corneal allogenic transplantation models were established in rats.Recipients were equally and randomly divided into 2 groups:saline control group and doxycycline group.Twenty minutes prior to surgery,mydriasis was performed using 1%atropine,with a diameter of 2.75 mm of implant and 2.5 mm of implant bed.In the saline control group,conjunctiva of the right eye received saline,three times a day,following surgery.In the doxycycline group,conjunctiva of the right eye received 1%doxycycline,three times a day,till 30 days following surgery.MAIN OUTCOME MEASURES:The following parameters were measured:corneal angiogenesis using immunofluorescence,expression of VEGF protein by using ELISA.RESULTS:Compared with the survival time of saline control group[(9.67±2.73)days],the mean survival time of doxycycline group[(20.67±3.01)days]was significantly prolonged(P＜0.01).The mean percentages of neovascularized corneal area in the saline control group were(4.00±1.00)%,(14.33±4.04)%,(31.33±3.51)%at 3,7 and 14 days after keratoplasty,respectively.The mean percentages of neovascularized corneal area in the doxycycline group were(1.67±1.15)%,(4.67±1.53)%,(18.33±1.53)%at the same time point respectively.Compared with the saline control group,the mean percentages of neovascularized corneal area of the doxycycline group was significantly reduced at 7 and 14 days after keratoplasty(P ＜0.05).The expression of VEGF in the saline control group was(541.00±75.44)pg/mg,(960.00±90.14)pg/mg,(976.00±130.41)pg/mg at 3,7 and 14 days after keratoplasty,respectively,while expression of VEGF in the doxycycline group was(115.33±9.29)pg/mg,(239.00±41.62)pg/mg,(361.00±65.20)pg/mg,respectively.The difference of VEGF expression at all time points between the two groups was significant (P＜0.05).CONCLUSION:Doxycycline has a significant effect in inhibiting corneal angiogenesis and prolonging survival time of implants after keratoplasty.
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0.05).[Conclusion]The contents of CRP,IL-1,IL -6,TNF-? are strengthenly expressed within 1 hour and have different expressions in different areas.
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[Objective]To study therapeutic effect of different medicines on motorneuron of spinal cord after explosive injury of spinal cord.[Method]Thirty-six rabbits were randomly divided into model group(group A,n= 12),the dexamethasone experiment group(group B,n= 12) and the methylprednisolone experiment group(group C,n=12),all rabbits were made explosive wound by 0.9 g cyclotrimethylene trinitramine,group A injection NS after blast, group B injection dexamethasone and group C injection methylprednisolone,6 and 24 hours after specimen had been taken out,then morphological change and quantity of the spinal motorneurons be observed under light microscopes.[Result]The reversible change of the neurons of rabbits happened after six hours,after 24 hours,the died motoneuron increase obviously, some rabbits remedied with dexamethasone and methylprednisolone after explosive injury in group B and C,quantity of the died motorneuron marked significant difference than that in the control group(P0.05).[Conclusion]Glycocotical stdroid can protect spinal cord motoneurons after explosive injury of spinal cord.In the experiment,there is no preponderance in early treatment of explosive injury of spinal cord between methylprednisolone and dexamethasone.