[Determination of dimethyl oxalate and diethyl oxalate in workplace air by high performance liquid chromatography].

Objective: To establish a high performance liquid chromatography method for the simultaneous determination of dimethyl oxalate (DMO) and diethyl oxalate (DEO) in workplace air. Methods: From January 2022 to January 2023, air samples were collected by silica gel tubes, desorbed by acetonitrile, separated by C18 chromatographic column, detected by photo-array detector, and retention time was used to characterize and peak area was used to quantify at 210 nm wavelength. Results: The linear relationships of DMO and DEO were good, r>0.999. The detection limits of DMO and DEO were 0.39 and 0.52 µg/ml, respectively. The quantitative limit was 1.28 µg/ml for DMO and 1.72 µg/ml for DEO. Average desorption efficiency for DMO was 82.40%-92.72%, and DEO was 94.13%-97.69%. The intra-assay precision of DMO was 1.87%-6.18%, and DEO was 2.25%-3.31%. Inter-assay precision of DMO was 3.29%-5.73%, and DEO was 1.38%-2.94%. Average sampling efficiencies were 100% for both DMO and DEO. Breakthrough capacity of DMO was 37.61 mg (200 mg solid adsorbent), DEO was >28.11 mg (200 mg solid adsorbent). Samples should be stored at 4 ℃ for at least 7 days. Conclusion: This method is easy to operate and has strong practicability. All indicators meet the requirements of the specification, and it is suitable for the simultaneous determination of DMO and DEO in the workplace air.

[Study on determination of 2-thioxothiazolidine-4-carboxylic Acid in urine by high performance liquid chromatography].

Objective: To establish a high performance liquid chromatography method for the determination of 2-thioxothiazolidine-4-carboxylic acid (TTCA) in urine. Methods: After acidification with hydrochloric acid, TTCA in urine was first extracted by ethyl acetate with excessive sodium chloride, then gradient separated by a symmetry C18 column and then detected by a diode array detector. The quantification was based on a working curve of external standard method. Results: The linear relationship of TTCA in urine was good in the range of 0.03-10.00 mg/L, and the correlation coefficient was 0.9999. The detection limit and minimum quantitative concentration of TTCA in urine were 0.008 mg/L and 0.027 mg/L. The intra-assay precision of the method was 0.9%-1.4%, the inter-assay precision was 1.3%-3.5%, and the average recovery was 85.0%-92.7% while the concentrations of TTCA in urine was 0.8, 2.0 and 8.0 mg/L, respectively (n=6) . Conclusion: The gradient elution high performance liquid chromatography method has simple operation and high sensitivity, and it is suitable for the determination of TTCA on a low level in urine for occupational workers exposure to carbon disulfide.

[Gene polymorphisms of cytochrome B-245 alpha chain (CYBA) and cholesteryl ester transfer protein (CETP) and susceptibility to generalized aggressive periodontitis].

OBJECTIVE: To explore the correlation of cytochrome B-245 alpha chain (CYBA) rs4673 and cholesteryl ester transfer protein (CETP) rs12720922 polymorphisms with the susceptibility of gene-ralized aggressive periodontitis (GAgP). METHODS: The study was a case-control trial. A total of 372 GAgP patients and 133 periodontally healthy controls were recruited. The CYBA rs4673 and CETP rs12720922 polymorphisms were detected by matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). Logistic regression models were used to analyze the correlation of CYBA rs4673 and CETP rs12720922 variants with the susceptibility of GAgP. The interaction between the two gene polymorphisms to the susceptibility of GAgP was analyzed by the likelihood ratio test. The interaction model adopted was the multiplication model. RESULTS: The mean age of GAgP group and control group was (27.5±5.2) years and (28.8±7.1) years respectively. There was significant difference in age between the two groups (P < 0.05). The gender distribution (male/female) was 152/220 and 53/80 respectively, and there was no significant difference between GAgP group and controls (P>0.05). For CYBA rs4673, the frequency of CT/TT genotype in the GAgP group was significantly higher than that in the controls [18.0% (66/366) vs. 10.6% (14/132), P < 0.05]. After adjusting age and gender, the individuals with CT/TT genotype had a higher risk of GAgP (OR=1.86, 95%CI: 1.01-3.45, P < 0.05), compared with CC genotype. There was no statistically significant difference in distributions of the CETP rs12720922 genotypes (GG, AA/AG) between GAgP patients and healthy controls (P>0.05). A significant interaction between CYBA rs4673 and CETP rs12720922 in the susceptibility to GAgP was observed. The GAgP risk of the individuals with CYBA rs4673 CT/TT and CETP rs12720922 GG genotypes was significantly increased (OR=3.25, 95%CI: 1.36-7.75, P < 0.01), compared with those carrying CC and AA/AG genotypes. CONCLUSION: CYBA rs4673 CT/TT genotype is associated with GAgP susceptibility. There is a significant interaction between CYBA rs4673 CT/TT genotype and CETP rs12720922 GG genotype in the susceptibility of GAgP.

[Attention should be paid to the establishment and management of glaucoma records].

Glaucoma is the world's leading cause of irreversible blindness. As a chronic disease, it requires lifelong follow-up and management. In the long-term follow-up of glaucoma patients, a diagnosis and treatment management system is helpful. Despite the availability of various means of informationalized record management, there remain problems and challenges, like a lack of unified file management standards, data incompatibility, and barriers to inter-hospital data sharing, which lead to the failure to establish a comprehensive and standardized glaucoma record for patients. It is necessary to form a standardized management system so as to improve the efficiency and accuracy of the diagnosis and treatment of glaucoma, better maintain the visual function of patients and reduce the burden on society and family.

[The controversy and value of the combination of hydrocortisone, ascorbic acid and thiamine in treating sepsis].

Sepsis is a common cause of death in intensive care unit. Some retrospective studies had shown the combination of hydrocortisone, ascorbic acid and thiamine (HAT therapy) could lower mortality rate of patients with sepsis or septic shock. Recently, multiple randomized controlled trials(RCTs) related to the efficacy of combination therapy don't reach a consensus. Though one meta-analysis indicated beneficial effect of HAT regimen on decreasing mortality rate of patients with sepsis or septic shock, improving SOFA score and reducing use of vasopressor. However, controversy still exist in the target population, timing, dose and duration of HAT regimen. Thus, the optimized RCTs are needed to provide more definitive evidence.

[Determination of five phenolic compounds in workplace air by composite sampling tube-high performance liquid chromatography].

Objective: To develop a method for simultaneous determination of Dydroquinone, Resorcinol, Pyrocatechol, 4-Nitrophenol and 2, 4-Dinitrophenol in workplace air by high performance liquid chromatography. Methods: Air samples were collected by composite tube (front end glass fiber filter membrane, back section silica gel) , 10% methanol was desorbed, separated by C18 chromatographic column, detected by photo-diode array (PDA) detector, and quantitatively determined by external standard method at the wave-length of 230 nm. Results: The linear relationship of 5 phenolic compounds was good (r>0.999) . The detection limit of glass fiber filtration membrane and silica gel adsorbent were 0.13-0.41 g/ml and 0.16-1.04 g/ml respectively. The quantitative limit of glass fiber filtration membrane was 0.44-1.36 g/ml, and the silica gel adsorbent was 0.52-3.46 g/ml. The average desorption efficiency of glass fiber membrane and silica gel adsorbent were 97.5%-100.1% and 86.9%-100.3%, respectively. In and between batches, the precision glass fiber filtration membrane was 0.71%-4.88%, 0.91%-4.82%, silica gel adsorbent was 0.47%-4.62%, 0.76%-5.52%. Samples can be stored for at least 30 days at -20 ℃. The possible co-existing interferences of aniline, phenol, p-nitrochlorobenzene, o-nitrophenol and trinitrophenyl did not interfere with the determination. Conclusion: The sensitivity, precision, accuracy and linear range of this method all meet the requirements of the specification. The collection and preservation of samples can also meet the requirements of the limits. It is suitable for the simultaneous determination of hydroquinone, resorcinol, hydroquinone, hydroquinone, hydroquinone, p-nitrophenol and 2, 4-dinitrophenol in the air of the workplace.

[Association of low serum indirect bilirubin level with all-cause mortality in maintenance hemodialysis patients].

Objective: To investigate the association of low serum indirect bilirubin (IBIL) level with all-cause mortality in maintenance hemodialysis (MHD) patients. Methods: A multicenter retrospective cohort study was conducted in seven hemodialysis centers of Guizhou province. The adult outpatients who underwent hemodialysis for more than 3 months were included between June 2015 and June 2016. Demographics, baseline clinical and laboratory test results were collected. Patients were divided into 4 groups according to their baseline serum IBIL levels (interquartile range), and followed up until June 30, 2018. Kaplan-Meier method was used to compare the survival rate of each group. Cox regression model was used to analyze the association of IBIL with all-cause mortality. Results: A total of 885 hemodialysis dialysis patients with baseline IBIL data were enrolled in this study, with age of (55.4±16.2) years old, among whom 57.9% (512/885) were male. Median IBIL was 4.8 µmol/L and interquartile range was 3.3-7.0 µmol/L. The comparison between IBIL quartile groups showed that the differences in proportion of diabetics, hemoglobin, serum albumin, platelet, serum calcium, alanine aminotransferase (ALT), uric acid and urea nitrogen were statistically significant (all P<0.05). After a median follow-up of 24 months, 210 patients died, and 96 cases became lost to follow-up. Kaplan-Meier curves showed higher all-cause mortality in patients with IBIL≤3.3 µmol/L (Q1 group) (65/219, P=0.015). After adjusting for age, gender, comorbidities, and biochemical indicators, taking baseline IBIL Q2 level (IBIL 3.4~4.8 µmol/L) as a reference, the hazard ratio for all-cause death in patients with IBIL≤3.3 µmol/L was 1.661 (95%CI: 1.114-2.476, P=0.013). Kaplan-Meier survival curve showed that there was no significant difference in mortality between the quartile groups according to total bilirubin (TBIL) or direct bilirubin (DBIL) (P=0.167, 0.156). Conclusion: Baseline low serum IBIL in maintenance hemodialysis patients is associated with all-cause mortality.

[Short-term clinical efficacy of a collagen matrix and free gingival graft in augmenting keratinized mucosa around dental implants].

Objective: To compare the short-term outcomes of a collagen matrix (CM) and free gingival graft (FGG) in augmenting keratinized mucosa around dental implants. Methods: Nineteen partially edentulous patients who had undergone implant surgery or implant review from June 2017 to June 2018 at Department of Periodontology, Peking University School and Hospital of Stomatology with lack of keratinized mucosa at buccal aspect of implants (<2 mm) were recruited in this study. According to the width of keratinized mucosa (KW) pre-operation, 9 patients including 5 males and 4 females were assigned into control group (KW<0.5 mm) which performed free gingival graft (17 implants) and 10 patients including 3 males and 7 females were assigned into experimental group (KW≥0.5 mm) which used collagen matrix as the grafts (15 implants). The KW at buccal aspect of each implant were measured pre-operation and 2 weeks, 1 month, 2 months, 3 months after surgery respectively. Each of the patients was required to fill out a questionnaire using a visual analogue scale to assess the postoperative morbidity. Results: The KWs around implants were increased significantly during the 3 months follow-up period in both groups (P<0.01). At 3 months after surgery, KW gain in control group was (3.44±1.64) mm, in experimental group was (2.30±0.82) mm, the difference between two groups was statistically significant (P<0.05). Meantime, the total shrinkage of KW in control group [(34±25)%] and experimental group [(51±11)%] also showed a statistically significant difference (P<0.01). However, by using collagen matrix as the grafts, augmented tissues had a much more comparable appearance with adjacent tissues than that in control group. And the patients of experimental group experienced much less postoperative bleeding than those of control group. Conclusions: Both collagen matrix and free gingival graft can significantly increase the KW around implants within the 3 months post-surgery follow-up period. There were more KW gain and less shrinkage in group FGG than that in group CM. However, surgery time were reduced and the postoperative bleeding were less in group CM than in group FGG as no harvesting procedure was needed.

Clinical application of kelp micro gelation (KMG) in partial splenic embolization.

OBJECTIVE: We aimed to compare and analyze the long-term efficacy and safety between kelp micro gelation (KMG) and gelfoam particles in partial splenic embolization (PSE). PATIENTS AND METHODS: This study retrospectively included 65 liver cirrhosis patients with comorbidity of hypersplenism who were admitted in Nanfang Hospital from July 2008 to May 2012. Among the included patients, 33 patients were in KMG-PSE group, and 32 cases were included in Gelfoam-PSE group. According to the Child-Pugh criteria, all cases were divided into grade A, B, and C, respectively. All eligible subjects received CT or MR examination and laboratory examination. RESULTS: Our results showed that both KMG and gelfoam particles could substantially improve the short-term efficacy of thrombocytopenia leukopenia. However, the efficacy of KMG is superior to that of gelfoam. Due to the characteristic of KMG as a permanent agent, KMG may result in an obvious pain in the spleen after PSE, especially in patients with megalosplenia. KMG was more expensive than gelfoam particles. The complication rate in patents with great embolization was much higher than that with less embolization. CONCLUSIONS: The efficacy of KMG is superior to that of gelfoam in both short-term and long-term. To effectively control the occurrence of severe complication, the embolization should be controlled less than 70% regardless of the embolization agents.

[Data distribution and transformation in population based sampling survey of viral load in HIV positive men who have sex with men in China].

Objective: To understand the distribution of population viral load (PVL) data in HIV infected men who have sex with men (MSM), fit distribution function and explore the appropriate estimating parameter of PVL. Methods: The detection limit of viral load (VL) was ≤ 50 copies/ml. Box-Cox transformation and normal distribution tests were used to describe the general distribution characteristics of the original and transformed data of PVL, then the stable distribution function was fitted with test of goodness of fit. Results: The original PVL data fitted a skewed distribution with the variation coefficient of 622.24%, and had a multimodal distribution after Box-Cox transformation with optimal parameter (λ) of-0.11. The distribution of PVL data over the detection limit was skewed and heavy tailed when transformed by Box-Cox with optimal λ=0. By fitting the distribution function of the transformed data over the detection limit, it matched the stable distribution (SD) function (α=1.70, ß=-1.00, γ=0.78, δ=4.03). Conclusions: The original PVL data had some censored data below the detection limit, and the data over the detection limit had abnormal distribution with large degree of variation. When proportion of the censored data was large, it was inappropriate to use half-value of detection limit to replace the censored ones. The log-transformed data over the detection limit fitted the SD. The median (M) and inter-quartile ranger (IQR) of log-transformed data can be used to describe the centralized tendency and dispersion tendency of the data over the detection limit.

[Comparison of different methods in dealing with HIV viral load data with diversified missing value mechanism on HIV positive MSM].

Objective: To compare results of different methods: in organizing HIV viral load (VL) data with missing values mechanism. Methods We used software SPSS 17.0 to simulate complete and missing data with different missing value mechanism from HIV viral loading data collected from MSM in 16 cities in China in 2013. Maximum Likelihood Methods Using the Expectation and Maximization Algorithm (EM), regressive method, mean imputation, delete method, and Markov Chain Monte Carlo (MCMC) were used to supplement missing data respectively. The results: of different methods were compared according to distribution characteristics, accuracy and precision. Results HIV VL data could not be transferred into a normal distribution. All the methods showed good results in iterating data which is Missing Completely at Random Mechanism (MCAR). For the other types of missing data, regressive and MCMC methods were used to keep the main characteristic of the original data. The means of iterating database with different methods were all close to the original one. The EM, regressive method, mean imputation, and delete method under-estimate VL while MCMC overestimates it. Conclusion: MCMC can be used as the main imputation method for HIV virus loading missing data. The iterated data can be used as a reference for mean HIV VL estimation among the investigated population.

[Development of HIV infection risk assessment tool for men who have sex with men based on Delphi method].

Objective: To develop a HIV infection risk assessment tool for men who have sex with men (MSM) based on Delphi method. Methods: After an exhaustive literature review, we used Delphi method to determine the specific items and relative risk scores of the assessment tool through two rounds of specialist consultation and overall consideration of the opinions and suggestions of 17 specialists. Results: The positivity coefficient through first and second round specialist consultation was 100.0% and 94.1%, respectively. The mean of authority coefficients (Cr) was 0.86. Kendall's W coefficient of the specialist consultation was 0.55 for the first round consultation (χ(2)=84.426, P<0.001) and 0.46 for the second round consultation (χ(2)=65.734, P<0.001), respectively, suggesting that the specialists had similar opinions. The final HIV infection risk assessment tool for MSM has 8 items. Conclusions: The HIV infection risk assessment tool for MSM, developed under the Delphi method, can be used in the evaluation of HIV infection risk in MSM and individualized prevention and intervention. However, the reliability and validity of this risk assessment tool need to be further evaluated.

[Effect of data missing on population based viral load survey in HIV infected men who have sex with men sampled in 16 large cities, China].

Objective: To analyze the effect of missing data in population based viral load (PVL) survey in HIV infected men who have sex with men (MSM) sampled in 16 cities in China. Methods: The database of 3 virus load sampling survey conducted consecutively in HIV infected MSM population in 16 large cities (Beijing, Shanghai, Nanjing, Hangzhou, Wuhan, Chongqing, Kunming, Xi'an, Guangzhou, Shenzhen, Nanning, Urumuqi, Harbin, Changchun, Chengdu and Tianjin) during 2013-2015 was used. SPSS 17.0 software was used to describe distribution of the missing data and analyze associated factors. Results: A total of 12 150 HIV infected MSM were randomly selected for the surveys, in whom, 9 141 (75.2%) received virus load tests, while 3 009 (24.8%) received no virus load tests, whose virus load data missed. The virus load data missing rates in MSM with or without access to antiretroviral therapy (ART) were 11.5% (765/6 675) and 39.4% (2 060/5 223) respectively, and the virus load data missing rates were 21.9% (1 866/8 523) and 28.4% (959/3 374), respectively, in local residents and non-local residents (migrants). Conclusions: The analysis indicated that the data missing occurred in the virus load survey in HIV infected MSM population. ART status and census registering status were the main influencing factors. Data missing could influence the accurate evaluation of community viral load (CVL) and population viral load(PVL) levels in HIV infected MSM in China.

[Exploration on the 24 hour intraocular pressure fluctuation in glaucoma patients].

Intraocular pressure is the most important and most easily controlled clinical parameters of glaucoma. It has a fluctuation and circadian rhythm. The 24 hours intraocular pressure measurement can better reflect the changes of intraocular pressure. It is clear that peak IOP is an independent risk factor for the progression of glaucoma, but the effect of IOP on glaucoma progression is worth exploring. This article focuses on whether IOP fluctuation is an independent risk factor for glaucoma progression, how to obtain the 24-hour intraocular pressure curve, the future direction of 24-hour intraocular pressure monitoring and other issues in order to cause clinical concern. (Chin J Ophthalmol, 2017, 53: 85-88).

[Effect of laboratory referencing on data analysis of community viral load in HIV positive MSM from 15 cities, China].

Objective: To compare the community viral load (CVL) among MSM in 15 cities in China using standardized national reference sources. Methods: The study analyzed the existing database of National Major Science and Technology Project of China. The database was established with serial random survey of MSM HIV CVL among MSM in 15 cities from 2013 to 2015. VL tests were conducted in 15 laboratories with different equipment and methods, including RT-PCR, nucleic acid sequence based amplification (NASBA), branched DNA testing (bDNA) and Abbott M2000 RealTime system (M2000). Based on proficiency test for 15 laboratories conducted by National HIV Reference Laboratory, VL test values detected with EasyQ, bDNA and M2000 were converted and standardized into resultant values of TaqMan 2.0. Software SPSS 17.0 was used to produce descriptive statistics for the dataset. Results: From 2014 to 2015, the 15 testing sites were found to use a number of different viral load detection techniques. In 2014, the community viral load values were (2.38±1.47) and (2.99±1.31) in 15 testing sites, while in 2015 these values were found to be (2.07±1.34) and (2.72±1.19). The measurement of community VL was done using standard benchmarks of ≤200 copies/ml, ≤400 copies/ml and ≤1 000 copies/ml, that were used for reference for now. Conclusion: It is necessary to use standard detection method to improve the comparability of annual results. Using a standardized rate of ≤400 copies/ml or ≤1 000 copies/ml for successful control of VL was found with high stability for the result comparison among different areas.

Ductilizing bulk metallic glass composite by tailoring stacking fault energy.

Martensitic transformation was successfully introduced to bulk metallic glasses as the reinforcement micromechanism. In this Letter, it was found that the twinning property of the reinforcing crystals can be dramatically improved by reducing the stacking fault energy through microalloying, which effectively alters the electron charge density redistribution on the slipping plane. The enhanced twinning propensity promotes the martensitic transformation of the reinforcing austenite and, consequently, improves plastic stability and the macroscopic tensile ductility. In addition, a general rule to identify effective microalloying elements based on their electronegativity and atomic size was proposed.

Factors of impact on graft function at 2 years after transplantation in living-donor kidney transplantation: a single-center study in china.

OBJECTIVE: The aim was to investigate the factors that affect graft function at 2 years after transplantation in living related-donor kidney transplantation. METHODS: We retrospectively reviewed the clinical data of 144 patients who underwent living related-donor kidney transplantation in our hospital from December 2005 to December 2008. Recipients were divided into 2 groups according to glomerular filtration rate (GFR) at 2 years after transplantation: ≤60 mL/min/1.73 m2 (n=51) and >60 mL/min/1.73 m2 (n=93). Variables which affected graft function were compared between the groups. The significant factors were analyzed using logistic regression. RESULTS: Univariate analysis showed significant differences for donor age, donor GFR, recipient weight, recipient body mass index, donor-to-recipient body weight ratio, and acute rejection episodes (P<.05). Logistic regression analysis revealed the independent factors affecting renal function at 2 years after transplantation to be donor GFR (ß=0.032; odds ratio [OR] 1.032; P=.004) and recipient body weight (ß=-0.069; OR 0.934; P=.001). Receiver operating characteristic (ROC) curve analysis showed cutoff values of donor GFR and recipient body weight to be >111.25 mL/min/1.73 m2, and ≤67 kg, respectively. Areas under the ROC curve of donor GFR and recipient body weight were 0.612 and 0.665, respectively. Sensitivity and specificity of donor GFR were 43.0% and 78.4%, respectively. Sensitivity and specificity of recipient body weight were 82.8% and 45.1%, respectively. CONCLUSIONS: Donor GFR and recipient body weight were the independent factors effecting renal function at 2 years after transplantation.

Effects of celecoxib on major prostaglandins in asthma.

BACKGROUND: Prostaglandin (PG) D(2) is a pro-inflammatory and bronchoconstrictive mediator released from mast cells, and is currently evaluated as a new target for treatment of asthma and rhinitis. It is not known which cyclooxygenase (COX) isoenzyme catalyses its biosynthesis in subjects with asthma. OBJECTIVES: Primarily, to assess whether treatment with the COX-2 selective inhibitor celecoxib inhibited biosynthesis of PGD(2) , monitored as urinary excretion of its major tetranor metabolite (PGDM). Secondarily, to determine the effects of the treatment on biosynthesis of PGE(2) , thromboxane A(2) and PGI(2) , also measured as major urinary metabolites. METHODS: Eighteen subjects with asthma participated in a cross-over study where celecoxib 200mg or placebo were given b.i.d. on 3 consecutive days following 2 untreated baseline days. Six healthy controls received active treatment with the same protocol. Urinary excretion of the eicosanoid metabolites was determined by liquid chromatography/tandem mass spectrometry (LC/MS/MS). Lung function was followed as FEV(1) and airway inflammation as fraction of exhaled nitric oxide (F(E) NO). RESULTS: Celecoxib treatment inhibited urinary excretion of PGEM by 50% or more in subjects with asthma and healthy controls, whereas there was no significant change in the excretion of PGDM. In comparison with the healthy controls, the subjects with asthma had higher baseline levels of urinary PGDM but not of PGEM. The 3-day treatment did not cause significant changes in FEV(1) or F(E) NO. CONCLUSION AND CLINICAL RELEVANCE: Biosynthesis of PGD(2) was increased in subjects with asthma and its formation is catalysed predominantly by COX-1. By contrast, COX-2 contributes substantially to the biosynthesis of PGE(2) . The asymmetric impact of celecoxib on prostanoid formation raises the possibility of long-term adverse consequences of COX-2 inhibition on airway homeostasis by the decreased formation of bronchodilator PGs and maintained production of increased levels of bronchoconstrictor PGs in asthmatics.

Microsomal prostaglandin E synthase-1 inhibition in cardiovascular inflammatory disease.

Prostaglandins (PGs), particularly PGE2 and prostacyclin (PGI2), are potent mediators of pain and inflammation. Both atherosclerosis and aortic aneurysm exhibit the hallmarks of inflammation. However, randomized trials of inhibitors of PG synthesis--nonsteroidal anti-inflammatory drugs--reveal that they predispose to cardiovascular risk. This appears to be consequent to inhibition of PGI2 and PGE2 formed by cyclooxygenase-2 (COX-2). Inhibitors of microsomal PGE synthase-1 (mPGES-1) are being developed for relief of pain and interest has focused on their potential impact on the cardiovascular system. Deletion of mPGES-1 retards atherogenesis and limits aortic aneurysm formation in hyperlipidaemic mice. However, it does not predispose to thrombogenesis and has a limited impact on blood pressure compared to inhibition of COX-2. This occurs despite the potential of the suppressed PGE2 in affording cardioprotection via its EP2 and EP4 receptors. However, deletion of mPGES-1 permits rediversion of the PGH2 substrate to other PG synthases and augmented formation of PGI2 and PGD2 mitigates this effect. However, increased PGI2 may also attenuate relief of pain. Pain relief seems likely to be a nuanced indication for mPGES-1 inhibitors, but they have therapeutic potential in syndromes of cardiovascular inflammation, cancer and perhaps in neurodegenerative disease. However, as the products of substrate rediversion vary according to cell type, these drugs may have contrasting impact amongst individuals at varied stages of disease evolution.