Effect of Tacrolimus Time in Therapeutic Range on Postoperative Recurrence in Patients Undergoing Liver Transplantation for Liver Cancer.

BACKGROUND AND OBJECTIVE: Liver cancer is the second highest cause of cancer-related deaths worldwide. It is commonly treated with liver transplantation, where tacrolimus is typically used as an antirejection immunosuppressant. The purpose of this study was to evaluate the effect of tacrolimus time in therapeutic range (TTR) on liver cancer recurrence in liver transplant recipients and to compare the performance of TTRs calculated according to the target ranges recommended in published guidelines. METHODS: A total of 84 patients who underwent liver transplantation for liver cancer were retrospectively included. Tacrolimus TTR was calculated using linear interpolation from the date of transplantation until recurrence or the last follow-up according to target ranges recommended in the Chinese guideline and international expert consensus. RESULT: Twenty-four recipients developed liver cancer recurrence after liver transplantation. The CTTR (TTR calculated according to the Chinese guideline) for the recurrence group was significantly lower than that of the nonrecurrence group (26.39% vs. 50.27%, P < 0.001), whereas the ITTR (TTR calculated according to the international consensus) was not significantly different between the two groups (47.81% vs. 56.37%, P = 0.165). Multivariate survival analysis revealed that age, microvascular invasion, hepatocellular carcinoma, CTTR, and mean tacrolimus trough concentration were independent predictors of liver cancer recurrence after liver transplantation. CONCLUSIONS: TTR predicts liver cancer recurrence in liver transplant recipients. The range of tacrolimus concentrations recommended in the Chinese guideline was more beneficial than that recommended in the international consensus for Chinese patients undergoing liver transplantation for liver cancer.

Relationship of imipenem therapeutic drug monitoring to clinical outcomes in critically ill patients: a retrospective cohort study.

The primary objective of this study was to evaluate the predictors associated with target concentration (non-)attainment of imipenem in critically ill patients. The secondary objective was to explore the correlation between achieving imipenem target concentrations and clinical outcomes of therapy. A retrospective cohort study was conducted in critically ill patients treated with imipenem. Clinical data were extracted from the patients' electronic medical records. The pharmacokinetic/pharmacodynamic target was defined as free imipenem concentrations above the minimum inhibitory concentration (MIC) of the pathogen at 100% (100%fT>MIC) of the dosing interval. Factors associated with the non-attainment of target concentrations were evaluated using binomial logistic regression. Kaplan-Meier analysis was used to investigate the correlation between (non-)attainment targets and 30-day mortality. A total of 406 patients were included, and 55.4% achieved the target of 100%fT>MIC. Regression analysis identified an initial daily dose of imipenem ≤ 2 g/day, augmented renal clearance, age ≤ 60 years, recent surgery, and absence of positive microbiology culture as risk factors for target non-attainment. Achieving the 100%fT>MIC target was significantly associated with clinical efficacy but not with 30-day mortality. Selective application of therapeutic drug monitoring in the early stages of imipenem treatment for critically ill patients can improve clinical outcomes. Further research should explore the potential benefits of TDM-guided dosing strategies for imipenem in critical care settings.

Metabolic alteration of circulating steroid hormones in women with gestational diabetes mellitus and the related risk factors.

Background: Abnormally changed steroid hormones during pregnancy are closely related to the pathological process of gestational diabetes mellitus (GDM). Our aim was to systematically profile the metabolic alteration of circulating steroid hormones in GDM women and screen for risk factors. Methods: This study was a case-control study with data measured from 40 GDM women and 70 healthy pregnant women during their 24-28 gestational weeks. 36 kinds of steroid hormones, including 3 kinds of corticosteroids, 2 kinds of progestins, 5 kinds of androgens and 26 kinds of downstream estrogens in serum were systematically measured using a combined sensitive UPLC-MS/MS method. The flux of different metabolic pathways of steroid hormones was analyzed. Logistic regression and ROC curve model analyses were performed to identify potential steroid markers closely associated with GDM development. Results: Serum corticosteroids, progestins and almost all the estrogen metabolites via 16-pathway from parent estrogens were higher in GDM women compared with healthy controls. Most of the estrogen metabolites via 4-pathway and more than half of the metabolites via 2-pathway were not significantly different. 16α-hydroxyestrone (16OHE1), estrone-glucuronide/sulfate (E1-G/S) and the ratio of total 2-pathway estrogens to total estrogens were screened as three indicators closely related to the risk of GDM development. The adjusted odds ratios of GDM for the highest quartile compared with the lowest were 72.22 (95% CI 11.27-462.71, P trend <0.001) for 16OHE1 and 6.28 (95% CI 1.74-22.71, P trend <0.05) for E1-G/S. The ratio of 2-pathway estrogens to total estrogens was negatively associated with the risk of GDM. Conclusion: The whole metabolic flux from cholesterol to downstream steroid hormones increased in GDM condition. The most significant changes were observed in the 16-pathway metabolism of estrogens, rather than the 2- or 4-pathway or other types of steroid hormones. 16OHE1 may be a strong marker associated with the risk for GDM.

Insight into Nephrotoxicity and Processing Mechanism of Arisaema erubescens (Wall.) Schott by Metabolomics and Network Analysis.

Background: Arisaematis Rhizome (AR) has been used as a damp-drying, phlegm-resolving, wind-expelling, pain-alleviating, and swelling-relieving drug for thousands of years. However, the toxicity limits its clinical applications. Therefore, AR is usually processed (Paozhi in Chinese) prior to clinical use. In this study, the integration of ultra-high performance liquid chromatography-quadrupole/ time-of-flight mass spectrometry-based metabolomics and network analysis was adopted to investigate the metabolic shifts induced by AR and explore the processing mechanism. Materials and Methods: Extracts of crude and processed AR products (1g/kg) were intragastrically administered to rats once daily for four consecutive weeks. The renal function was evaluated by blood urea nitrogen, creatinine, interleukin-1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), super oxide dismutase (SOD), the ratio of glutathione/glutathione disulfide (GSH/GSSH), glutathione peroxidase (GSH-Px) and histopathological examination. Furthermore, the chemical composition of AR was clarified by ultra-high performance liquid chromatography-quadrupole/ time-of-flight mass spectrometry, after which the integration of metabolomics and network analysis was adopted to investigate the metabolic shifts induced by AR and explore the processing mechanism. Results: Crude AR caused renal damage by stimulating inflammation and oxidative stress, as confirmed by the increased production of IL-1ß, TNF-α and MDA, and decreased levels of SOD, GSH/GSSH and GSH-Px. Processing with ginger juice, alumen and bile juice alleviated the damage to kidney. Metabolomics results showed that a total of 35 potential biomarkers enriched in amino acid metabolism, glycerophospholipid metabolism, fatty acid-related pathways, etc. were deduced to be responsible for the nephrotoxicity of AR and the toxicity-reducing effect of processing. Conclusion: This work provided theoretical and data support for the in-depth study of the processing mechanism, showing that processing reduces AR nephrotoxicity through multiple metabolic pathways.

Optimal dosing regimen of biapenem based on population pharmacokinetic/pharmacodynamic modelling and Monte Carlo simulation in patients with febrile neutropenia and haematological malignancies.

In the current study, a population pharmacokinetic (PPK) model was developed for biapenem in patients with febrile neutropenia (FN) and haematological malignancies. Through Monte Carlo simulation, optimal administration regimens were suggested based on the developed PPK model. In a prospective, single-centre, open-label study, 174 plasma samples from 120 Chinese patients with FN and haematological malignancies were analysed by chromatography, and PK parameters were analysed by NONMEM. The drug clearance process was influenced by crucial covariates, namely creatinine clearance (CLCR) and concomitant posaconazole (POS). The ultimate PPK model was as follows: CL (L/h)=29.81 × (CLCR/121.38)0.806 × (1-POS × 0.297); volume of distribution (L)=114. For the target of ≥40% fT>minimum inhibitory concentration (MIC) (duration that the plasma level exceeds the MIC of the causative pathogen) and achieving the probability of target attainment ≥90%, the PK/pharmacodynamic breakpoint was 2 mg/L for the 2.4 g/day dosing regimen consisting of 600 mg q6h and 800 mg q8h. The breakpoint was 1 mg/L for the 1.2 g/day dosing regimen consisting of 300 mg q6h and 600 mg q12h. Empirical therapy would benefit from utilizing higher dosages and extended infusion durations. Therefore, it is suggested that patients with symptoms that are strongly suggestive of Pseudomonas aeruginosa or Acinetobacter baumannii infection may be suitable for combined treatment with other antibacterial drugs.

Sensitive colorimetric sensing of glutathione and H2O2 based on enhanced peroxidase mimetic activity of MXene@Fe3O4.

The peroxidase-like activity of MXene@Fe3O4 nanocomposites and the relevant colorimetric application have been investigated for the first time. According to a kinetic study, MXene@Fe3O4 nanocomposites displayed higher peroxidase activity than their individual components, and the catalytic process followed a ping-pong mechanism. The improved peroxidase-like activity of the MXene@Fe3O4 nanocomposites was obtained due to the synergetic impact of the Fe3O4 and MXene phases, the huge ion-accessible interface, and quick electron transfer channels in the nanocomposites. In the presence of hydrogen peroxide (H2O2), the MXene@Fe3O4 nanocomposites can catalyze the reaction of the colorless substrate 3, 3, 5, 5-tetramethylbenzidine (TMB) into oxidized TMB which revealed a blue color at 652 nm. After the introduction of glutathione (GSH), the blue color was gradually fading owing to the hydroxyl radical scavenging effect of glutathione. A colorimetric detection platform based on the peroxidase-like activity of the MXene@Fe3O4 nanocomposites was developed for H2O2 and GSH with a detection limit of 0.4 µM and 0.5 µM, respectively. The calibration plot for glutathione detection is calculated by absorbance difference at 652 nm, which ranged from 0.5 to 10 µM with a detection limit of 0.2 µM. The recoveries of GSH with different concentrations ranged from 93.76 to 108.50% and the relative standard deviation from 0.30 to 5.96%. This work significantly extends the application of MXene@Fe3O4 nanocomposites in the construction of colorimetric sensors and reveals a satisfactory result in real sample analysis.

Establishment and validation of a sensitive LC-MS/MS method for quantification of urinary estrogens in women with gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is not only a threat to the health of pregnant women, but also has profound effects on the health of offspring. Studies have shown that the imbalance of estrogen metabolism is associated with an increased risk of GDM. In this study, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established and validated for simultaneous quantification of thirteen estrogens in the urine of GDM women, including estrone (E1), estradiol (E2), estriol (E3), and their hydroxylated and methylated metabolites. The method was achieved on a Waters CORTECS C18 column (2.1 mm × 150 mm, 1.6 µm) within 8.5 min. The linear range of thirteen estrogens in urine was 2-1000 pg·mL-1. Both intra- and inter-day precision for each analyte were less than 15%, with accuracies ranging from 8.3% to 7.3%. The extraction recoveries rate were between 86% and 111%, and stability verification results met the requirements for determination of biological samples. The results suggested that the concentrations of estrogens in all urine samples range from 0.08 to 134.06 (pg·mg-1 creatinine). The mean levels of E1, E2 and most estrogen metabolites in the urine of GDM women were higher than those in healthy pregnant women. Notably, the mean level of 2-hydroxyestrone (2-OHE1) in GDM women was 13.2-fold lower than that in healthy pregnant women. The types of estrogens with the highest mean levels in the urine of GDM and healthy pregnant women were obviously different, which are 2-methoxyestrone (2MeOE1) and E3, respectively. Our results demonstrated that this specific and sensitive method is suitable for quantifying estrogens in human urine and could provide support for further research on estrogen-related pathological mechanisms in GDM and other diseases.

Steroid Hormone Profiling in Hyperandrogenism and Non-hyperandrogenism Women with Polycystic Ovary Syndrome.

The purpose of this study is to explore the differences in the steroid metabolic network between hyperandrogenic and non-hyperandrogenic women with polycystic ovary syndrome (PCOS). A sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed for the quantification of 36 kinds of serum steroids in 80 PCOS women during their follicular phase. Compared with those in non-hyperandrogenemia PCOS women (NA-PCOS), the levels of 17-hydroprogesterone (P = 0.009), androstenedione (P < 0.001), total testosterone (P < 0.001), dihydrotestosterone (P = 0.025), estrone (P = 0.007), and estradiol (P < 0.001) were increased in hyperandrogenemia PCOS (HA-PCOS) women. It was suggested that HA-PCOS may have increased activity of P450c17 (17-hydropregnenolone/pregnenolone, P = 0.008), 3ßHSD2 (androstenedione/dehydroepiandrosterone, P = 0.004), and 17ßHSD3 (testosterone/dehydroepiandrosterone, P = 0.01) and decreased activity of 5α reductase (dihydrotestosterone/testosterone, P = 0.008). Moreover, the ratio of luteinizing hormone (LH) to follicle stimulating hormone (FSH) was found to be related to these increased steroids and enzyme activities. In conclusion, the HA-PCOS and the NA-PCOS women showed different steroid profiles, and the different enzyme activities in steroidogenic pathway may be the main reason for the difference.

Prognostic value of protein biomarkers in liver transplantation: A systematic review.

Liver transplantation is currently the preferred method for the treatment of advanced liver disease and early-stage hepatocellular carcinoma (HCC). Although advances in surgical techniques, immunosuppressive drugs and postoperative management have reduced the incidence of postoperative complications, how to effectively predict or diagnose postoperative complications earlier and reduce their incidence is still a clinical concern. We performed a comprehensive proteomics literature research to identified protein biomarkers in complications after liver transplantation. Seventeen studies met the inclusion criteria including ischemia reperfusion injury (IRI) (n = 4), acute rejection (AR) (n = 4), renal dysfunction (n = 4), HCC recurrence (n = 2), primary graft dysfunction (PGD) (n = 1), infection (n = 1), and liver fibrosis (n = 1). A total of 625 differentially expressed proteins (DEPs) have been reported between postoperative complications and controls, of which 63 have been validated by quantitative protein expression and 26 have been reported by at least two studies and showed consistently changes. The results of the bioinformation analysis show that the immune system, especially the innate immune system and cytokine signaling in immune system, is an important protein-mediated pathway that affects the prognosis of liver transplantation.

Potentially inappropriate medications in Chinese older adults: a comparison of two updated Beers criteria.

Background Beers criteria have been into the mainstay to characterize the potentially inappropriate medication since its first publication, but the recent version, Beers 2019, is yet to be validated by clinical studies nationally. Objective To identify the prevalence and the predictors of potentially inappropriate medications in hospitalized geriatric patients based on the Beers 2019 and 2015 criteria. Setting Nanjing Drum Tower Hospital, a 3000-bed tertiary care teaching hospital in China. Method We conducted a cross-sectional study from July 1, 2018 to December 31, 2018. Data from all hospitalized patients aged ≥ 65 years were collected from the hospital database. Inappropriate prescriptions were identified using the Beers 2019 criteria and the Beers 2015 criteria. Main outcome measure Prevalence Ratio (PR) and predictors of potentially inappropriate medications. Results The prevalence of inappropriate prescriptions based on the Beers 2019 criteria was 64.80%. This result was slightly higher than that of the Beers 2015 criteria (64.31%). The most commonly encountered inappropriate prescriptions identified using the two criteria were proton-pump inhibitors. The kappa coefficient was 0.826 (p < 0.001) indicating a strong coherence between the two criteria. The most important factor associated with inappropriate medications use was the number of prescribed drugs (PR 5.17, 95% CI 2.89-8.43; PR 4.58, 95% CI 1.93-7.25). Conclusion This study showed a high prevalence of potentially inappropriate medication in the Chinese geriatric population, which was associated with the number of prescribed drugs. The predictors identified in this research might help pharmacists to detect high-risk drugs and intervene in time.

Prognostic value of endogenous and exogenous metabolites in liver transplantation.

Liver transplantation has been widely accepted as an effective intervention for end-stage liver diseases and early hepatocellular carcinomas. However, a variety of postoperative complications and adverse reactions have baffled medical staff and patients. Currently, transplantation monitoring relies primarily on nonspecific biochemical tests, whereas diagnosis of multiple complications depends on invasive pathological examination. Therefore, a noninvasive monitoring method with high selectivity and specificity is desperately needed. This review summarized the potential of endogenous small-molecule metabolites as biomarkers for assessing graft function, ischemia-reperfusion injury and liver rejection. Exogenous metabolites, mainly those immunosuppressive agents with high intra- and inter-individual variability, were also discussed for transplantation monitoring.

Response to the Comments on "Determining Allele-Specific Protein Expression (ASPE) Using a Novel Quantitative Concatamer Proteomics Method".

Russell and colleagues deserve credit for being the first to use a QconCAT standard to simultaneously quantify both the wild-type and mutant peptides of a protein (i.e., CYP2B6) ( J. Proteome Res. 2013, 12 (12), 5934-5942. DOI: 10.1021/pr400279u). However, the rationale of their study was entirely different from ours ( J. Proteome Res. 2018, 17 (10), 3606-3612. DOI: 10.1021/acs.jproteome.8b00620). Their study focused on the quantification of individual drug-metabolizing enzymes and transporters, whereas ours developed a targeted proteomics method to determine the allele-specific protein expression (ASPE) of a gene and advocated the use of the ASPE imbalance as the phenotype for identifying cis-regulatory genetic variants of the gene. More importantly, the digestion enzyme trypsin interacts with three to four amino acid residues around scissile bonds, and certain residues, such as negatively charged amino acids, can significantly affect the digestion efficiency. The QconCAT standard reported in our study differs from conventional QconCAT standards such as that used by Russell et al. in that at least 15 native flanking amino acids were included to ensure accurate measurement of ASPE ratios.

Determining Allele-Specific Protein Expression (ASPE) Using a Novel Quantitative Concatamer Based Proteomics Method.

Measuring allele-specific expression (ASE) is a powerful approach for identifying cis-regulatory genetic variants. Here, we developed a novel targeted proteomics method for the quantification of allele-specific protein expression (ASPE) based on scheduled parallel reaction monitoring (PRM) with a heavy stable isotope-labeled quantitative concatamer (QconCAT) internal protein standard. This strategy was applied to the determination of the ASPE of UGT2B15 in human livers using the common UGT2B15 nonsynonymous variant rs1902023 (i.e., Y85D) as the marker to differentiate expressions from the two alleles. The QconCAT standard contains both the wild-type tryptic peptide and the Y85D mutant peptide at a ratio of 1:1 to ensure accurate measurement of the ASPE of UGT2B15. The results from 18 UGT2B15 Y85D heterozygotes revealed that the ratios between the wild-type Y allele and the mutant D allele varied from 0.60 to 1.46, indicating the presence of cis-regulatory variants. In addition, we observed no significant correlations between the ASPE and mRNA ASE of UGT2B15, suggesting the involvement of different cis-acting variants in regulating the transcription and translation processes of the gene. This novel ASPE approach provides a powerful tool for capturing cis-genetic variants involved in post-transcription processes, an important yet understudied area of research.

Characterizing ceftriaxone-induced urolithiasis and its associated acute kidney injury: an animal study and Chinese clinical systematic review.

OBJECTIVE: To investigate the pathophysiological process of ceftriaxone-induced urolithiasis and its associated acute kidney injury (AKI) based on an animal study and summarize the main clinical characteristics based on a Chinese clinical systematic review. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomly divided into five groups of six each according to different treatments including control; ceftriaxone; ceftriaxone with calcium; calcium; and ceftriaxone, calcium with citrate, respectively. The 24-h urine volume, serum creatinine (Scr) and blood urea nitrogen (BUN) were measured; kidney histological examination and stone analysis were performed. Systematic searches of the Chinese Knowledge Database were conducted for reports on ceftriaxone-induced urolithiasis and AKI. The eligibility of each full-text publication was accessed, and qualified data were extracted and reviewed. RESULTS: Kidney stones and a significantly low 24-h urine volume with increased high Scr and BUN levels were found in the group that received ceftriaxone combined with calcium. Citrate was able to inhibit these biochemical changes and stone formations. A total of 161 qualified patients were included in the Chinese clinical systematic review: The proportion of ceftriaxone-induced urolithiasis was 21.1, 19.3, 19.3, 39.1 and 1.2 % for ages <3, 3-6, 7-17, 18-60 and >60 years. 72.7 % developed acute kidney injury eventually. CONCLUSION: Ceftriaxone-induced urolithiasis was associated with a high risk of AKI. The pathophysiological process may be related to urinary obstruction and crystalline nephropathy. Citrate was able to inhibit stone formation and prevent further kidney injury.

Comparison of renal function and metabolic abnormalities of cystine stone patients and calcium oxalate stone patients in China.

PURPOSE: To compare renal function and metabolic abnormalities of cystine stone patients and calcium oxalate stone patients in China. METHODS: Between 2008 and 2011, thirty cystine stone patients were involved in our study, and an equal number of age- and gender pair-matched patients with calcium oxalate stones. Non-stone forming individuals were elected as controls. The evaluation included blood chemistry studies and 24-h urine collection in both groups of patients. RESULTS: The cystine stone patients had higher mean values of serum blood urea nitrogen, urate and creatinine levels than patients in other two groups. With respect to urine risk factors, cystine stone patients had higher urinary citrate and lower urinary oxalate and creatinine than calcium oxalate stone patients. When compared to non-stone forming individuals, cystine stone patients had higher urinary urate excretion and lower urinary creatinine excretion. Metabolic abnormalities could be demonstrated in 80 % of the cystine stone patients and in 100 % of the calcium oxalate stone patients. We also compared urine risk factors among cystine stone patients with different urine cystine excretion (<1 mmol/24 h, 1-2 mmol/24 h and >2 mmol/24 h). No significant difference was found in urine risk factors among three groups. CONCLUSIONS: This study suggested that cystine stone patients were at greater risk for the loss of renal function than calcium oxalate stone patients, but the risk of the formation of calcium oxalate stones was lower. Our results also indicated that urinary cystine had little or no impact on the excretion of urine chemistries in cystine stone patients.

Infrared spectroscopic analysis of urinary stones (including stones induced by melamine-contaminated milk powder) in 189 Chinese children.

AIM: The aim of the study was to investigate the composition of the stones in Chinese children with urolithiasis, including peculiar stones induced by melamine-contaminated milk powder. MATERIALS AND METHODS: Between 1999 and 2009, 189 urinary stones from children of East China were received at our institution. Among them, 12 stones were received from pediatric stone formers with a history of consuming melamine-contaminated milk powder in 2008; and the remaining stones were defined as "natural" stones. All stones were analyzed by Fourier transform infrared spectroscopy. RESULTS: Among 177 "natural" stones, whewellite stone (49.72%) was observed most frequently followed by weddellite stone (15.25%), uric acid anhydrous stone (9.6%), carbapatite stone (9.04%), cystine stone (9.04%), ammonium acid urate stone (4.52%), struvite stone (2.26%), and sodium urate stone (0.56%). Twelve young children who consumed melamine-contaminated milk powder were younger than 3 years, and their stones were composed of a mixture of uric acid dihydrate and ammonium acid urate based on Fourier transform infrared spectroscopy. In addition, the stones were radiolucent and could be dissolved by urine alkalinization. CONCLUSIONS: Our study emphasizes the relatively high rate of calcium oxalate stones and cystine stones, and the relatively low rate of struvite stones in Chinese children with urolithiasis. The stones caused by melamine-contaminated milk powder are composed of the mixture of uric acid dihydrate and ammonium acid urate.

Infrared spectroscopic analysis of 5,248 urinary stones from Chinese patients presenting with the first stone episode.

A series of 5,248 urinary stones was analyzed by Fourier transform infrared spectroscopy between 1999 and 2008. This study evaluated the percentage of each stone type and the association with sex and age in Chinese stone formers presenting with the first stone episode. The overall sex ratio (male:female) was 2.34:1. Results showed that the preponderant type of stone was calcium oxalate, followed by carbapatite, anhydrous uric acid, struvite and cystine. Struvite stones in this study accounted for a relatively low rate compared to that reported by others. Of 5,248 stones, only 38.1% had one component, 42.5% consisted of two components, and 20.4% consisted of three components. Our results also showed the higher percentage of carbapatite stones in females than in males and the increment of anhydrous uric acid stones with age. In addition, the percentage of calcium oxalate stones decreased with increase in the percentage of carbapatite stones over the period.

Aspirin suppresses growth of human gastric carcinoma cell by inhibiting survivin expression.

Regular use of aspirin (ASA) could reduce the risk of gastric cancer although the precise mechanism remains unclear. Down-regulation of survivin may be one of the cyclooxygenase-independent mechanisms whereby ASA induces apoptosis of gastric cancer cell. In this study, we investigated the effect of ASA on the growth, apoptosis and survivin expression of gastric cancer cell line SGC7901. The survival of cells treated with 3.0 and 10.0 mmol/L ASA for 24 h was decreased by 44.6% and 88.5%, respectively. ASA at 3.0 mmol/L inhibited the viability of SGC7901 cells in a time-dependent manner. Apoptosis analysis showed similar results with MTT assay. ASA at 3.0 and 10.0 mmol/L decreased the mRNA transcript levels of survivin and reduced survivin protein levels in SGC7901 cells also in a time-dependent manner. Our findings indicated that ASA inhibited the proliferation of SGC7901 by suppressing survivin at both the transcriptional and translational level.

[A modified rat model for infection-induced stone formation].

OBJECTIVE: To employ a newly modified rat model for infection-induced bladder stone formation. METHODS: 24 adult male Sprague Dawley rats were divided into 3 groups, model group (n=12), sham operation group (n=8) and control group (n=4). The surgical procedures were performed aseptically under anesthesia (25% Ultane 1.0 g/kg). The bladder in model group was exposed through a short lower midline abdominal incision, the puncture needle (G18) with guideline was inserted aseptically into bladder, a metal wire, which have been contaminated by the Proteus mirabilis, was put into the puncture canal, then implanted into the bladder lumen through the guideline. In the sham operated group the puncture needle (G18) with guideline was inserted into bladder without metal wire implanted into the bladder. There was no any operation in control group. The rats were sacrificed by excessive anesthesia at 21 days post challenge. The bladder were removed aseptically and inspected for evidence of urolithiasis. RESULTS: On Day 2 after surgery, two rats died in model group, no rats died in other groups. Twenty-one days after surgery, all of rats in model group developed various-sized bladder stones. There was no stone formation in sham operation group and control group. All stones were verified by infrared spectroscopy and optical crystallography. These stone were struvite stone. CONCLUSION: This model has a less trauma, faster recovery and excellent stone formation so that it may be used for the study of infection stone.

The association between the survivin C-31G polymorphism and gastric cancer risk in a Chinese population.

INTRODUCTION: The C-31G polymorphism in the survivin promoter could de-repress the cell-cycle-dependent transcription of the human survivin gene, resulting in overexpression of survivin. This survivin mutation has only been studied on cervical carcinoma. However, no study has ever been conducted to evaluate the effect of the polymorphism on other cancers, including gastric cancer. METHODS: In this hospital-based, case-control study, we investigated the association between the survivin C-31G polymorphism and risk of gastric cancer in a Chinese population using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) protocols. RESULTS: No statistically significant association was observed between gastric cancer risk and the variant genotype (GG + GC). However, the variant genotype (GG + GC) was either associated with risk of distal gastric cancer (odds ratios=0.50, 95% confidence interval=0.30-0.83) or with risk of well-differentiated tumor (odds ratios=0.46, 95% confidence interval=0.22-0.97). CONCLUSION: Our results demonstrate that the survivin C-31G polymorphism may be involved in distal gastric carcinogenesis and tumor differentiation in a Chinese population.