The health effects associated with environmental pollutants remain one of the major public health issues at present. The research method focusing on the population as the research subjects is limited by reliable cohorts, and the research method targeting individual molecules cannot fully reflect the biological health effects under environmental pollutant stress. Using high-throughput multi-omics, machine learning, and epigenetic detection to conduct targeted research and joint analysis on cells, organoids, organs, animals, and humans in different biological dimensions will help provide data support for the study of potential targets and biological effects of environmental pollutants, providing a theoretical basis for the risk assessment and safety evaluation of environmental pollutants.

The cultivation of graduate students' scientific research ability is an important task of colleges and universities. The evaluation standards of cultivation achievements play an important guiding role. In recent years, quantitative academic evaluation based on the "five-only" has caused some negative effects on the cultivation of talents in colleges and universities. A new evaluation system needs to be established. During the transition period between the old and new academic evaluation systems, the evaluation criteria for the cultivation of graduate students' scientific research capabilities will inevitably need to be reformed. This study attempts to reform the existing evaluation standards by investigating the evaluation standards for the cultivation of scientific research capabilities in various colleges and universities. The aim is to improve the evaluation of the achievements in the cultivation of scientific research ability of graduate students and improve the quality of the cultivation of scientific research ability of graduate students.

Objective:To prepare the control materials of point-of-care(POC) glucose testing and evaluate their homogeneity, stability and matrix effects.Methods:The high, medium and low concentration control materials were prepared from patient leftover whole blood, which was centrifuged, fixed, washed, filtered, and aliquoted. The homogeneity and stability of the control materials were evaluated according to CNAS (China National Accreditation Service for Conformity Assessment, CNAS) GL29:2010"Reference materials-General and statistical principles for certification". The control materials were used to evaluate the matrix effects in POC glucose detection systems by Deming regression, according to the Clinical and Laboratory Standards Institute (CLSI) EP14-A3. Meanwhile, these control materials were used as the internal quality control, and their coefficients of variation ( CV) were calculated. One-way ANOVA and t-Test were used to analyze the results. Results:The homemade materials at three concentrations showed good homogeneity[ F< F0.05(9, 20)]. When the control materials were stored at 2-8 ℃, the stable phases for the opened and closed bottles were 10 days and 15 days, respectively, and there was no statistically significant difference between the results of the first day( P>0.05). The control materials at three concentrations also showed good applicability and there were no matrix effects in 10 POC glucose systems. When the control materials were detected in the internal quality control, the CVs of the high, medium and low concentrations were 0.63%, 0.66% and 1.65%, respectively, which were all below 7.5%. Conclusions:The homemade human control materials of POC glucose testing showed good homogeneity, stability and applicability. They met the requirements of quality control in hospital settings, which provided a good application prospect of the quality management of POC glucose testing.

Postzygotic mutations are acquired in normal tissues throughout an individual's lifetime and hold clues for identifying mutagenic factors.Here,we investigated postzygotic mutation spectra of healthy individuals using optimized ultra-deep exome sequencing of the time-series samples from the same volunteer as well as the samples from different individuals.In blood,sperm,and muscle cells,we resolved three common types of mutational signatures.Signatures A and B represent clock-like mutational processes,and the polymorphisms of epigenetic regulation genes influence the pro-portion of signature B in mutation profiles.Notably,signature C,characterized by C＞T transitions at GpCpN sites,tends to be a feature of diverse normal tissues.Mutations of this type are likely to occur early during embryonic development,supported by their relatively high allelic frequencies,presence in multiple tissues,and decrease in occurrence with age.Almost none of the public datasets for tumors feature this signature,except for 19.6％of samples of clear cell renal cell carcinoma with increased activation of the hypoxia-inducible factor 1(HIF-1)signaling pathway.Moreover,the accumulation of signature C in the mutation profile was accelerated in a human embryonic stem cell line with drug-induced activation of HIF-1α.Thus,embryonic hypoxia may explain this novel signature across multiple normal tissues.Our study suggests that hypoxic condition in an early stage of embryonic development is a crucial factor inducing C＞T transitions at GpCpN sites;and indi-viduals'genetic background may also influence their postzygotic mutation profiles.

Objective To explore the CRP harmonization by calibration using commutable trueness verification materials. Methods High and low level of CRP concentrations trueness verification materials(H and L) were prepared by Beijing center for clinical laboratories. Thesetrueness verification materials were diluted to 5 calibration points(5L, 4L+1H, 3L+2H, 1L+4H, 5H) by weighing method, respectively. These 5 points were used to calibrate four different brands of CRP detection system (Diasys, Leadman, Siemens and Roche) instead of the original procedure. Sera from 21 patients and the international standard ERM DA-474/IFCC were used to compare harmonization and trueness after calibration. Each sample above was measured twice. Results After calibration, the median of CV was reduced from 19.33％ to 2.92％ among 21 patient samples, less than the optimal CV based on biological variability (CV=10.6％). Compared with Desai, the slopes were closer to 1 from 0.90-1.09 to 0.93-0.96 after calibration. Meanwhile, if ERM-DA474/IFCC was used as the trueness verification materials, the absolute bias wasreduced from 3.08-11.07 mg/L to 0.52-2.97 mg/L which was close to theuncertainty of itself (2.5 mg/L). Conclusions Afterthe calibration which contained five linear concentration points of CRP trueness verification materials by weighing method, both harmonization and trueness of CRP were improved.

Objective To prepare the trueness verification materials of C-reactive protein (CRP) and evaluate its homogeneity, stability and commutability. Methods The high and low CRP concentrations trueness verification materials were from patient leftover sera which were pooled, mixed thoroughly, filtered and aliquoted. The homogeneity, stability and commutability of these materials were evaluated according to CNAS(China National Accreditation Service for Conformity Assessment, CNAS)-GL29:2010 "Reference materials-General and statistical principles for certification (ISO Guide35:2006)"and the Clinical and Laboratory Standards Institute (CLSI) EP30A. The trueness verification materials were used to evaluate the commutability in 10 clinical CRP detection systems, using forty-five patients' leftover sera with different CRP concentration evaluated by Deming regression in EP30A of CLSI. Meanwhile, the commutability of dilution series of ERM DA-474/IFCC were evaluated using the same method. Results A total of two CRP concentration level trueness verification materials were prepared, with high and low concentration levels of 754 and 743 vials, 1 ml each, respectively. The preparation showed good homogeneity (F

Objective To evaluate the effect of anti-myosin monoclonal antibodies-nuclear factor kappa B (NF-κB) decoy oligodeoxynucleotides-lipofectamine compound (mAb2G4-ODN-lip) on myocardial ischemia-reperfusion (I/R) injury in rats.Methods Forty clean-grade healthy adult male Sprague-Dawley rats,aged 8-10 weeks,weighing 240-260 g,were divided into 4 groups (n=10 each) using a random number table:sham operation group (group S),myocardial I/R group (group I/R),ODN-lip group (group ODN) and mAb2G4-ODN-lip group (group mAb2G4).Myocardial I/R was induced by occlusion of the left anterior descending branch of coronary artery for 30 min followed by 120 min reperfusion.In ODN and mAb2G4 groups,ODN-lip (100 μg ODN) and mAb2G4-ODN-lip (100 μg ODN) compounds were injected via the femoral vein,respectively,immediately after onset of ischemia.The left anterior descending branch of coronary artery was only occluded but not ligated in group S.The animals were sacrificed at 120 min of reperfusion and myocardial specimens of the left ventricle on the ischemic side were obtained for examination of the pathological changes (using haematoxylin and eosin staining) and for determination of the expression of NF-κB (by Western blot) and contents of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) (by enzyme-linked immunosorbent assay).Results Compared with group S,the expression of NF-κB was significantly up-regulated,and the contents of TNF-α and IL-6 were increased in I/R,ODN and mAb2G4 groups (P＜ 0.05).Compared with group I/R,the expression of NF-κB was significantly down-regulated,and the contents of TNF-α and IL-6 were decreased in ODN and mAb2G4 groups (P＜0.05).Compared with group ODN,the expression of NF-κB was significantly down-regulated,and the contents of TNF-α and IL-6 were decreased in group mAb2G4 (P＜0.05).The pathological changes of myocardial tissues were significantly attenuated in group I/R,group ODN and group mAb2G4 in turn.Conclusion mAb2G4-ODN-lip can mitigate myocardial I/R injury in rats.

Objective To evaluate the role of classⅠhistone deacetylase (HDAC) in myocardial ischemia-reperfusion (I∕R) injury in diabetic rats and the relationship with adenosine monophosphate-acti- vated protein kinase (AMPK)∕mammalian target of rapamycin (mTOR) signaling pathway. Methods SPF healthy adult male Sprague-Dawley rats, weighing 210-220 g, were used in this study. Type I diabetes mellitus was induced by single intraperitoneal injection of streptozotocin dissolved in citrate buffer 60 mg∕kg, and 8 weeks later the rats with type I diabetes mellitus were used for experiment. Forty-eight diabetic rats were divided into 4 groups (n＝12 each) by using a random number table method: sham operation group (group S), myocardial I∕R group (group I∕R), myocardial I∕R plus class I HDAC inhibitor MS-275 group (group I∕R+MS) and myocardial I∕R plus MS-275 plus AMPK inhibitor Compound C group ( group I∕R+MS+CC). Myocardial I∕R was induced by ligation of the left anterior descending branch of the coronary ar-tery for 45 min followed by 180 min of reperfusion in anesthetized rats. In group I∕R+MS, MS-275 10 mg∕kg was intraperitoneally injected once a day for 7 consecutive days, and myocardial I∕R was produced after the end of administration. AMPK inhibitor Compound C 0. 5 mg∕kg was intravenously injected at 30 min before ischemia in group I∕R+MS+CC. Six rats were sacrificed at the end of reperfusion for determina-tion of myocardial infarct size. Another 6 rats were selected at the end of reperfusion and sacrificed for deter-mination of the level of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) in serum (by en-zyme-linked immunosorbent assay), expression of AMPK, phosphorylated AMPK ( p-AMPK), mTOR, phosphorylated mTOR (p-mTOR), ubiquitin-binding protein P62 (P62), microtubule-associated protein 1 light chain 3 Ⅰ(LC3 Ⅰ) and LC3Ⅱ in myocardial tissues (by Western blot). The ratios of p-AMPK∕AMPK, p-mTOR∕mTOR and LC3Ⅱ∕Ⅰwere calculated. Results Compared with group S, the myocardial infarct size and levels of serum CK-MB and LDH were significantly increased in I∕R, I∕R+MS and I∕R+M+CC groups, the ratios of p-AMPK∕AMPK and LC3Ⅱ∕Ⅰwere significantly increased, p-mTOR∕mTOR ratio was decreased, and P62 expression was down-regulated in group I∕R+MS (P＜0. 05), and no significant change was found in p-AMPK∕AMPK ratio, p-mTOR∕mTOR ratio, LC3Ⅱ∕Ⅰ ratio or P62 expression in I∕R and I∕R+M+CC groups (P＞0. 05). Compared with group I∕R, the myocardial infarct size and levels of serum CK-MB and LDH were significantly decreased, the ratios of p-AMPK∕AMPK and LC3Ⅱ∕Ⅰwere in-creased, p-mTOR∕mTOR ratio was decreased, and P62 expression was down-regulated in group I∕R+MS (P＜0. 05), and no significant change was found in the parameters mentioned above in group I∕R+M+CC (P＞0. 05). Compared with group I∕R+MS, the myocardial infarct size and levels of serum CK-MB and LDH were significantly increased, the ratios of p-AMPK∕AMPK and LC3Ⅱ∕Ⅰ were decreased, p-mTOR∕mTOR ratio was increased, and P62 expression was up-regulated in group I∕R+M+CC ( P＜0. 05). Con-clusion Class Ⅰ HDAC is involved in myocardial I∕R injury through enhancing AMPK∕mTOR signaling pathway-regulated level of autophagy in diabetic rats.

Objective To value C-reactive protein ( CRP ) trueness verification materials and to perform the CRP trueness verification program in Beijing .Methods The CRP value of trueness verification materials were assigned by the international reference material ERM DA-474/IFCC, using 10 clinical routine detection systems at departments of clinical laboratory of Beijing Chaoyang and Luhe Hospital Affiliated to Capital Medical University .The calibration curves with 4 ERM DA-474/IFCC dilutions were established and used for value transfer for trueness verification materials of two levels .The uncertainty was also assessed during the process.Then, the trueness verification was performed in the EQA at Beijing Center for Clinical Laboratories ( BCCL ) among 42 clinical laboratories.The samples were distributed according to BCCL standard operating procedure .The Microsoft Excel 2007 and SPSS 17.0 were used to process the results and the function of efficiency ( En) was calculated to verify the difference between the value and the overall mean of all participating laboratories .Results The values and uncertainties of two trueness verification materials of CRP were (109.9 ±9.4) mg/L and (27.1 ±2.4) mg/L respectively.The results of trial application of two level trueness verification materials in the EQA at Beijing Center for Clinical Laboratories (BCCL) were satisfied.There were no significant difference between the transfer values from our study and the values from means of all laboratories in Beijing .The function of efficiency ( En ) was less than 1.Conclusions The valueswhich were established by using multiple detection platforms for CRP trueness verification materialswere accurate and the uncertainties were small .This method is a preferably method for CRP value assignment because there was no suitable reference method for CRP measurement till now .Thematerialswere suitable for the trueness verification program for clinical laboratories in Beijing .

Objective To evaluate the effects of sevoflurane on the expression of early growth response gene 1 (Egr-1) and Egr-2 in the suprachiasmatic nuclei (SCN) of sleep-deprived rats.Methods Forty-eight pathogen-free healthy male Sprague-Dawley rats,were divided into 4 groups (n =12 each) using a random number table:control group (group C),sleep deprivation group (group SD),sevoflurane group (group SEV) and sleep deprivation plus sevoflurane group (group SD+SEV).The rats were subjected to sleep deprivation for 96 h in group SD.The rats inhaled 2.5％ sevoflurane for 3 h in group SEV.The rats inhaled 2.5％ sevoflurane for 3 h after being subjected to sleep deprivation for 96 h in group SD+SEV.The mechanical paw withdrawal threshold (MWT) was measured at 12 h,3 days and 7 days after emergence from anesthesia (T1-3).The animals were sacrificed after blood samples were obtained from the external carotid artery,and the cerebral SCN was removed for determination of Egr-1 and Egr-2 expression by Western blot.Results Compared with group C,the MWT was significantly decreased at T1-3 in SD,SEV and SD+SEV groups,the expression of Egr-1 and Egr-2 in SCN was significantly up-regulated at T1-3 in SD and SD+SEV groups,and the expression of Egr-1 in SCN was significantly up-regulated at T1-3,and the expression of Egr-2 in SCN was up-regulated at T1 in group SEV (P＜0.05).Compared with SD and SEV groups,the MWT was significantly decreased at T1-3 in group SD+SEV,and the expression of Egr-1 and Egr-2 in SCN was significantly up-regulated at T1-3 in group SD+SEV (P＜0.05).Conclusion The mechanism by which sevoflurane aggravates hyperalgesia is related to up-regulation of Egr-1 and Egr-2 expression in SCN of sleepdeprived rats.