Risk factors and prediction models for bronchiolitis obliterans after severe adenoviral pneumonia.

Severe adenoviral pneumonia (SAP) can cause post-infectious bronchiolitis obliterans (PIBO) in children. We aimed to investigate the relevant risk factors for PIBO and develop a predictive nomogram for PIBO in children with SAP. This prospective study analysed the clinical data of hospitalised children with SAP and categorised them into the PIBO and non-PIBO groups. Least absolute shrinkage and selection operator (LASSO) regressions were applied to variables that exhibited significant intergroup differences. Logistic regression was adopted to analyse the risk factors for PIBO. Additionally, a nomogram was constructed, and its effectiveness was assessed using calibration curves, C-index, and decision curve analysis. A total of 148 hospitalised children with SAP were collected in this study. Among them, 112 achieved favourable recovery, whereas 36 developed PIBO. Multivariable regression after variable selection via LASSO revealed that aged < 1 year (OR, 2.38, 95% CI, 0.82-6.77), admission to PICU (OR, 24.40, 95% CI, 7.16-105.00), long duration of fever (OR, 1.16, 95% CI, 1.04-1.31), and bilateral lung infection (OR, 8.78, 95% CI, 1.32-195.00) were major risk factors for PIBO. The nomogram model included the four risk factors: The C-index of the model was 0.85 (95% CI, 0.71-0.99), and the area under the curve was 0.85 (95% CI, 0.78-0.92). The model showed good calibration with the Hosmer-Lemeshow test (χ2 = 8.52, P = 0.38) and was useful in clinical settings with decision curve analysis. CONCLUSION: Age < 1 year, PICU admission, long fever duration, and bilateral lung infection are independent risk factors for PIBO in children with SAP. The nomogram model may aid clinicians in the early diagnosis and intervention of PIBO. WHAT IS KNOWN: • Adenoviruses are the most common pathogens associated with PIBO. • Wheezing, tachypnoea, hypoxemia, and mechanical ventilation are the risk factors for PIBO. WHAT IS NEW: • Age < 1 year, admission to PICU, long duration of fever days, and bilateral lung infection are independent risk factors for PIBO in children with SAP. • A prediction model presented as a nomogram may help clinicians in the early diagnosis and intervention of PIBO.

Apelin-13 Administration Protects Against LPS-Induced Acute Lung Injury by Inhibiting NF-κB Pathway and NLRP3 Inflammasome Activation.

BACKGROUND/AIMS: Acute lung injury (ALI) is induced by a variety of external and internal factors and leads to acute progressive respiratory failure. Previous studies have shown that apelin-13 can decrease the acute lung injury induced by LPS, but the specific mechanism is unclear. Therefore, a mouse lung injury model and a cell model were designed to explore the mechanism of how apelin-13 alleviates the acute lung injury caused by LPS. METHODS: The effect of apelin-13 on LPS-induced structural damage was determined by H&E staining and by the wet/dry weight ratio. The related inflammatory factors in BALF were examined by ELISA. The apoptotic pathway and the NF-κB and NLRP3 inflammasome pathways were evaluated by using Western blotting and immunofluorescence staining. RESULTS: LPS induced the structural damage and the production of inflammatory cytokines in the lung tissues of mice. These deleterious effects were attenuated by apelin-13 administration. The protective effects of apelin-13 were associated with decreased reactive oxygen species (ROS) formation and the inhibition of the activation of the NF-κB and NLRP3 inflammasome pathways in mice and in Raw264.7 cells. CONCLUSION: Taken together, these data suggest that apelin-13 administration ameliorates LPS-induced acute lung injury by suppressing ROS formation, as well as by inhibiting the NF-κB pathway and the activation of the NLRP3 inflammasome in the lungs.

Early Diagnostic Performance of Heart-Type Fatty Acid Binding Protein in Suspected Acute Myocardial Infarction: Evidence From a Meta-Analysis of Contemporary Studies.

BACKGROUND: Although cardiac troponin is the cornerstone in diagnosis of acute myocardial infarction (AMI), the accuracy is still suboptimal in the early hours after chest pain onset. Due to its small size, heart-type fatty acid-binding protein (H-FABP) has been reported accurate in diagnosis of AMI, however, this remains undetermined. The aim is to investigate the diagnostic performance of H-FABP alone and in conjunction with high-sensitivity troponin (hs-Tn) within 6 hours of symptom onset. Furthermore, accuracy in 0h/3h algorithm was also assessed. METHODS: Medline and EMBASE databases were searched; sensitivity, specificity and area under ROC curve (AUC) were used as measures of the diagnostic accuracy. We pooled data on bivariate modelling, threshold effect and publication bias was applied for heterogeneity analysis. RESULTS: Twenty-two studies with 6602 populations were included, pooled sensitivity, specificity and AUC of H-FABP were 0.75 (0.68-0.81), 0.81 (0.75-0.86) and 0.85 (0.82-0.88) within 6 hours. Similar sensitivity (0.76, 0.69-0.82), specificity (0.80, 0.71-0.87) and AUC (0.85, 0.82-0.88) of H-FABP were observed in 4185 (63%) patients in 0h/3h algorithm. The additional use of H-FABP improved the sensitivity of hs-Tn alone but worsened its specificity (all p<0.001), and resulted in no improvement of AUC (p>0.99). There was no threshold effect (p=0.18) and publication bias (p=0.31) in this study. CONCLUSIONS: H-FABP has modest accuracy for early diagnosis of AMI within 3 and 6 hours of symptom onset. The incremental value of H-FABP seemed much smaller and was of uncertain clinical significance in addition to hs-Tn in patients with suspected AMI. Routine use of H-FABP in early presentation does not seem warranted.

TAB3 defect induces augmented cardioprotection loss from ischemic injury.

The transforming growth factor ß-activated kinase-binding protein 3 (TAB3) plays a crucial role in modulating cell apoptosis and proliferation in many diseases, including hepatocellular carcinoma, lung cancer, and intracerebral hemorrhage. However, the functional role of TAB3 in the heart is not well reported. In our study, we first investigated the role of TAB3 in ischemia heart diseases. For in vitro studies, cardiomyocytes (CMs) were isolated from both TAB3 knockout (KO) and wild-type (WT) mice, and the apoptosis ratios were tested after a 48-h ischemic stimulation. A proliferation test and tubeformation assay were underwent at normoxia condition. For in vivo studies, the MI model was completed for both TAB3 KO and WT mice. Echocardiography was evaluated at 3 days and 28 days post-MI, whereas the hemodynamics test was performed 28 days post-MI. The histology results of the apoptosis, proliferation of myocardium, neovasculation of microvessels, and infarct zone assessments were determined using terminal deoxynucleotidyl transferase dUTP nick end labeling staining, Ki67 immunostaining, α-SMA/CD31 immunostaining, and the Masson-Trichrome method, respectively. Expression changes of the related proteins caused by TAB3 deficiency were confirmed using both quantitative real-time polymerase chain reaction and immunoblotting. Our results indicate that the absence of TAB3 induced more CMs apoptosis, decrease cardiomyocyte proliferation, and weaker angiogenesis in vitro and in vivo. Worse cardiac function and enlarged scar formation were detected in TAB3 KO mice, and increased expression of active-caspase-3 and decreased expression of NF-κB/p65, Akt, Bcl-2/Bax, and VEGF occurred. In summary, our findings indicate that the absence of TAB3 plays a harmful role in ischemic heart disease.

Overexpression of stathmin is resistant to paclitaxel treatment in patients with non-small cell lung cancer.

Paclitaxel can exert therapeutic effects by interacting with microtubules. Stathmin and ß-III-tubulin, which have impact on microtubule activity, are believed to be involved in the chemotherapy. The purpose of the present study was to evaluate the associations between stathmin and ß-III-tubulin expression and treatment response and survivals in patients with non-small cell lung cancer (NSCLC). Two hundred thirty-eight patients who were treated by platinum-based chemotherapy were enrolled in this study, among them, 111 patients also received paclitaxel treatment. Formalin-fixed and paraffin-embedded tumor tissues were collected for messenger RNA (mRNA) and protein detection. We assessed the associations of the two molecules with treatment response and survival outcome. High level of stathmin exhibited poor response to chemotherapy (for mRNA, P = 0.041; for protein, P = 0.017). Overexpression of stathmin was associated with shorter overall survival (for mRNA, P = 0.012; for protein, P = 0.014) and progression-free survival (for mRNA, P = 0.039; for protein, P = 0.022). Of note, this association was only observed in patients who were treated by both platinum and paclitaxel. Similar effects were not observed for ß-III-tubulin. The findings demonstrated that paclitaxel effect may be interfered with stathmin; overexpression of stathmin is a predictive marker for a worse prognosis in patients with NSCLC who were treated by both platinum and paclitaxel chemotherapy.

Modulating luminescence through anion variation in lead-free Cs2NaInX6 (X = Cl, Br, and I) perovskites: a first-principles study.

The A2B+B'3+X6-type lead-free halide perovskite Cs2NaInCl6 has demonstrated limited luminescence performance attributed to parity-forbidden transitions in its intrinsic form. While extensive exploration has been dedicated to partial cation substitution in Cs2NaInCl6, there is a noticeable gap in understanding the impact of anion composition on this material. In this study, we investigated the influence of anion composition on the luminescence performance of Cs2NaInX6 using first-principles calculations. We first conducted calculations on Cs2NaInX6 in its intrinsic state and on Cs2NaInCl6 with cation substitution to establish the reliability of the transition dipole moment (TDM) as a luminescence descriptor in this system. Following this, we systematically assessed the formation energies, octahedral distortions, and luminescence properties of Cs2NaInX6 with diverse anion compositions. Despite sharing similar stability, closely aligned with the experimentally accessible Cs2NaInCl6, all mixed halide structures exhibited significant octahedral distortions. Additionally, most of these structures displayed considerably enhanced TDM compared to their single halide counterparts. Notably, the structures Cs2NaInX4X'2-b and Cs2NaInX3X'3-b demonstrated superior luminescence performance compared to other structures. The absorption spectra calculated for selected structures revealed the enhancement of their photo-absorbance in the presence of iodine, particularly in the low energy region. This observation provides additional evidence that light absorbance in different energy regions can be effectively regulated in this way. Finally, we also investigated other optical properties that impact luminescence performances, such as the energy loss spectrum L(ω), the reflectivity spectrum R(ω) and the refractivity index n(ω). The findings offer insights into optimizing the luminescence performance of lead-free halide perovskites through anion composition variation.

[Association of chemokines and their receptors genes polymorphisms with risk of myocardial infarction].

OBJECTIVE: To assess the association of variations in chemokines (CCL5, CCL2), chemokine receptor (CCR5 and CCR2) genes with susceptibility to myocardial infarction (MI) through a case-control study. METHODS: Genotypes of patients with MI (n = 634) were compared with those of controls (n = 601). Genetic polymorphisms of CCL5 rs2107538 (-403G > A), CCL2 rs1024611 (-2518A > G), CCR5 rs333 ( δ 32 ins or del) and CCR2 rs1799864 (190G > A) of 1235 individuals were determined with polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Particular genotypes were confirmed with DNA sequencing. RESULTS: No subject was found to carry the CCR5 - δ 32 allele. No association was found between CCL2 rs1024611 and CCR2 rs1799864 polymorphisms and MI. For CCL5 rs2107538 polymorphism, the A allele has occurred at a higher frequency in MI patients than controls, and its AA genotype has been associated with a significantly increased risk of MI independent of conventional risk factors (OR = 3.346, 95%CI = 1.938-5.775, P < 0.01, AA vs. GG). Further analysis indicated that MI patients had significantly more A-403 - A-2518 haplotype (CCL5 -403G > A and CCL2 -2518A > G, 21.8% vs. 26.6%, OR = 1.229, 95%CI = 1.012-1.493, P = 0.038) and AA or AA genotype (CCL5 -403G > A - CCL2 -2518A > G, 5.0% vs. 12.1%, OR = 3.245, 95%CI = 1.780-5.914, P < 0.01). CONCLUSION: Although our data dose not support an association between CCL2 rs1024611, CCR2 rs1799864 and CCR5 rs333 polymorphisms and MI, genetic variation in CCL5 gene may still be a useful marker for assessing susceptibility to MI in ethnic Han Chinese population.

Investigation on preventive inerting approach of coal spontaneous combustion in gob considering adsorption effect.

Coal spontaneous combustion in the gob poses a significant threat to coal mining operations. Designing optimal process parameters for nitrogen injection to prevent and control fires efficiently is crucial. To achieve this, a multi-field coupling equation was established, considering the adsorption of coal to gas. The model's accuracy was verified on-site, and the effects of nitrogen injection at different locations and flow rates were simulated. The optimal injection parameters were determined by analyzing temperature and inerting time. The results showed that the coal spontaneous combustion hazardous zone in the gob tested on-site was consistent with the simulation from the perspective of physisorption. Nitrogen injection had three stages: gas expansion, rapid oxygen dilution, and complete inerting. The nitrogen injection effect presented a nonlinear change in injection location and flow rate. The optimal nitrogen injection location for the Tingnan Coal Mine in Shaanxi was determined to be 90 m behind the working face on the inlet side, with an optimal flow rate of 800 m3/min. This study focused on gas adsorption and offered valuable insights for creating high-efficiency fire-fighting techniques that involve inserting in the gob.

Three-dimensional distribution and oxidation degree analysis of coal gangue dump fire area: A case study.

Spontaneous combustion of coal gangue dumps poses a significant threat to the health and safety of nearby residents and has adverse effects on the environment. The establishment of measures to extinguish these fires requires information on the three-dimensional characteristics and oxidation degree of the dumps. An acquisition method for the index data was proposed. The temperature and the radon concentration were used as the principal indicators, and the gas concentration was a secondary index for verifying the results. Kriging interpolation was applied to predict the value of the unsampled points. Additionally, the three-dimensional characteristics of the temperature and radon anomalies were determined, thresholds were set, and the changes in the temperature and radon migration were considered to estimate the extent and depth of the fire in the coal gangue dumps. The oxidation degree of the anomalous area was identified according to the critical value of the temperature and radon anomalies. The application of this method in the gangue dump of the Tashan coal mine showed the existence of 17 oxidation areas, covering an area of 31,433 m2, including 4 shallow oxidation areas, 4 deep oxidation areas in coal waste dumps, and 9 medium-deep oxidation areas. According to the decision criterion, 4 areas with relatively high oxidation degree were identified, whereas the remaining sites were low-oxidation areas. Additionally, surface fires and internal fires can be transformed into each other, posing a significant threat. The results obtained from the various data sources were consistent and in agreement with the ground survey results, indicating that the proposed method is effective for the detection of fires in coal gangue dumps.

Pseudomembranous laryngotracheobronchitis due to coinfection with human bocavirus 1 and Mycoplasma pneumoniae: a case report.

Pseudomembranous laryngotracheobronchitis is rarely reported yet potentially life-threatening infectious cause of airway obstruction in children. The causative organisms of this condition are often considered to promote bacterial superinfection following viral infection. We report a case of pseudomembranous laryngotracheobronchitis in a patient caused by human bocavirus 1 and Mycoplasma pneumoniae (M. pneumoniae). A 2-year-old child was admitted to our hospital presenting with cough, hoarseness, and labored breathing. Computed tomography of the chest revealed atelectasis of the right middle lobe of the lung with bronchostenosis and occlusion. Laryngeal edema, pseudomembrane formation and ulceration of the trachea were found during bronchoscopy. Chronic inflammation of the mucosa and local cellulose exudation with acute and chronic inflammatory cell infiltration were confirmed by hematoxylin-eosin staining. Human bocavirus 1 and M. pneumoniae were detected in the bronchoalveolar lavage fluid by next-generation sequencing. The patient tested positive for IgM antibodies against M. pneumoniae. Bronchoscopy was performed three times to clear the secretions in the airway, and azithromycin, ceftriaxone, methylprednisolone, budesonide inhalation, and ambroxol were administered as treatment. The patient's condition improved and she was discharged 21 days after admission. Clinicians should be aware of the potential involvement of human bocavirus 1 and M. pneumoniae in pseudomembranous laryngotracheobronchitis for accurate diagnosis and timely antibiotic administration, and to lower mortality and morbidity rates.

Developing a system for regulating expression of human hepatocyte growth factor using tetracycline in NRK52E cells.

INTRODUCTION: Hepatocyte growth factor (HGF) is a target of gene therapy for renal fibrosis. The aim of this study was to establish a human HGF gene expression system that is regulated by tetracycline (Tet) in normal rat kidney tubular epithelial cells (NRK52E cells). MATERIALS AND METHODS: The plasmids pTet-on, pBI-L-HGF and pTK-Hyg were transfected sequentially into NRK52E cells using Lipofectamine 2000. The expression of HGF gene was measured, and the activity of expressed HGF was detected. RESULTS: A clone of pBI-L-HGF/NRK52E cells showing strong reaction to doxycycline (Dox) was selected using a luciferase reporter assay system. The expression of both HGF mRNA and protein was significantly higher (both p < 0.01) in the Dox group than that in the control group. Furthermore, the bioactivity of expressed HGF was confirmed in the assay. CONCLUSIONS: A Tet-regulated human HGF gene expression system in NRK52E cells has been established. This cell line may prove useful for gene therapy against renal fibrosis.

Tri-color upconversion luminescence of Rare earth doped BaTiO3 nanocrystals and lowered color separation.

Upconversion tri-color luminescence of Er(3+)/Tm(3+)/Yb(3+) doped BaTiO3 nanocrystals is observed under the excitation of a 980 nm laser diode. Especially, Er(3+) emission has a considerable contribution to the blue portion of the UC spectra, different from the ever-reported results, in which blue emission originates only from Tm(3+). This realization is beneficial to lower the color separation between blue and green (or red) emissions, in fluorescent labeling. The analysis of excitation power dependence and decay time revealed that blue emission of Er(3+) ion is induced by a dual energy transfer upconversion, while Tm(3+) plays a role of both emitter and activator.

[Spectroscopic properties of Er3+-doped germanium bismuthate glass].

Er(3+)-Doped Germanium Bismuthate Glass was fabricated and characterized. The absorption spectrum and up-conversion spectrum of glass were studied. The Judd-Oflet intensity parameters omega(t) (t = 2, 4, 6), determined based on Judd-Ofelt theory, were found to be omega2 = 3.35 x 10(-20) cm2, omega4 = 1.34 x 10(-20) cm2, omega6 = 0.67 x 10(-20) cm2. Frequency up-conversion of Er(3+)-doped germanium bismuthate glass has been investigated. The up-conversion mechanisms are discussed under 808 nm and 980 nm excitation. Stimulated emission cross-section of 4I(13/2) --> 4I(15/2) transition was calculated by McCumber theory. Compared to other host glasses, the emission property of Er(3+)-doped germanium bismuthate glasses has advantage over those of silicate, phosphate and germinate glasses. Er(3+)-doped germanium bismuth glasses are promising upconversion optical and optic-communication materials.

[Frequency up-conversion properties of Er3+ /Yb3+ co-doped zinc oxide powders].

Er3+ /Yb3+ co-doped ZnO powders were prepared by the high temperature sintering method with starting composition of (mol%) 95ZnF2-4. 8Yb2 O3-0. 2Er2 O3. Microstructure analysis by X-ray diffraction (XRD) showed that the sample consists of two phases, i. e. ZnO and YbF3, which verified that the ZnF2 was oxidized during the high temperatue sintering Composition analysis by scanning electron microscope (SEM) and spectroscopic measurements showed that the Er3+ and Yb3+ ons were successfully used in doping the lattice of ZnO, but most of Yb3+ ions were in the YbF3 phase. These results indicated that the up-conversion luminescence was emitted from ZnO, not from YbF3. Under the excitation of 980 nm diodelaser, four strong up-conversion emissions peaks centered at 658, 538, 522 and 409 nm, corresponding to the transitions 4F9/2 --> 4I15/2, 4S3/2 --> 4I15/2, 2 H11/2 --> 4I15/2 and 2 H9/2 --> I15/2, respectively, were observed. Especially, a strong red up-conversion emission was observed, which is different from that the green up-converted luminescence is dominated in glass and ceramics. Three important cross energy transfer (CRET) processes between Er3+ ions played an important role for this. Under 488 nm Ar+ laser excitation, intense violet (409 nm), weak blue (466, 450 nm) and ultraviolet (379 nm) up-conversion luminescence originating from the transitions 2 H9/2 --> 4I15/2, 2P3/2 --> 4I11/2, 4 F3/2 /4 F5/2 --> 4I15/ 2 and 4G11/2 --> 4 I15/2, respectively, were obtained. The dependence of up-conversion intensities on excitation power indicated that two-photon absorption processes were responsible for the violet luminescence under 488 nm excitation, and the violet up-converted luminescence was achieved through the forward and back energy transfer between Er3+ and Yb3+ ions. Our results show that ZnO as a host material has the potential applications in the up-conversion red phosphors and ultraviolet laser materials.

Prognostic value of funisitis and/or chorionic vasculitis compared to histologic chorioamnionitis in full-term infants.

AIM: To compare pathological findings in the placenta and cord with the prognosis of full-term infants in cases of neonatal infection and microbial analyses. METHODS: The pathological findings in the placenta and cord and microbial analyses of amniotic fluid and neonatal samples based on culture or polymerase chain reaction (PCR) were observed in 1208 full-term mother-infant pairs at our center. We also collected neonatal clinical infection data, such as the occurrence of septicemia and other infectious diseases. RESULTS: Neonatal infection and positive identification of microorganisms were more common in the funisitis and/or chorionic vasculitis group than in the histologic chorioamnionitis group. CONCLUSION: Funisitis and/or chorionic vasculitis is a valuable pathological marker for assessing the comparison between intrauterine infection and neonatal inflammatory conditions in infants delivered at full-term.

Associations of deregulation of mir-365 and its target mRNA TTF-1 and survival in patients with NSCLC.

microRNA (mir)-365 exerts tumor suppressor function by targeting thyroid transcription factor-1 (TTF-1) in lung cancer cells. The purpose of the present study was to assess mir-365 and its target mRNA TTF-1 in lung cancer and their correlations with patients' survival. Quantitative real-time PCR was used to examine the expression levels of mir-365 and TTF-1 in tumor tissue and its adjacent noncancerous tissue of 126 patients with non-small cell lung cancer (NSCLC). Our results showed that mir-365 was significantly decreased in tumor tissue than that in normal tissue (P=0.006), however, TTF-1 was significantly increased in tumor tissue than in normal tissue (P<0.001). Besides, significant correlations between decreased mir-365 and advanced tumor-node-metastasis (TNM) stage (P=0.001) and regional lymph node involvement (P=0.037) was observed. The similar result was also found between increased TTF-1 and TNM stage (P=0.003). Furthermore, mir-365 downregulation or TTF-1 upregulation were associated with poor outcome of patients than mir-365 upregulation or TTF-1 downregulation (for mir-365: P<0.001; for TTF-1: P=0.002). Of note, combination of decreased mir-365 and increased TTF-1 had worst overall survival (P<0.001). In conclusion, aberrant expression of mir-365/TTF-1 may be involved in the tumor development in patients with NSCLC. Moreover, mir-365 and TTF-1 could jointly predict the prognosis of patients and their combination may serve as a biomarker to predict risk of poor survival in NSCLC patients. Mir-365/TTF-1 might serve as a potential therapeutic target for clinical treatment of NSCLC.

The recovery of bladder epithelial hyperplasia caused by a melamine diet-induced bladder calculus in mice.

Applying a model of bladder epithelial hyperplasia (BEH) caused by melamine-induced bladder calculus (BC), the recovery of BEH after melamine withdrawal was investigated. One experiment, comprising untreated, melamine and recovery groups, was conducted in Balb/c mice. Each group included 4 subgroups. Mice were fed normal-diet in untreated or a melamine-diet in other groups. The melamine-diet was then substituted with normal-diet in recovery group. Both of BC and BEH were observed after 14 and 56 days of melamine-diet. The BC is relatively uniform at the same melamine-diet durations. The BEH was diffuse with many mitotic figures, 4-7 rows of nuclei, and well-defined umbrella/intermediate cells. No marked differences in BEH degree were observed in the two different melamine-diet durations. On 4-42 days after melamine withdrawal, BC was not found, as the progressive regression with complete regression of BEH was observed, along with well-defined ageing/apoptotic cells in the superficial regions of BEH regression tissue. Conclusion, the melamine-induced BEH is relatively uniform, may be self-limiting in rows of nuclei, and can return to normal. Melamine withdrawal duration is critical for the BEH regression. Tissue of the BEH and its regression is ideal for exploring the renewal as well as growth biology of mammalian urothelium.

Preventive and therapeutic effects of sodium bicarbonate on melamine-induced bladder stones in mice.

The actual preventive and therapeutic effects of alkalinizing urine on melamine-induced bladder stones (cystolith) are not completely known. Using an ideal model, two experiments were conducted in Balb/c mice. The mice were fed a normal diet in controls and a melamine diet in the other groups. The first day was set as experiment-day 1. In "Experiment 1", either low-/mid-/high-dose sodium bicarbonate (SB) or sterile water was administered by intragastric perfusion (once daily) to the mice for 14 days. Relative to the model group, the mean pH of the urine in the SB groups was significantly elevated at 3 h after SB administration, with a significant decrease in cystolith incidence on experiment-day 14. In "Experiment 2", on experiment-day 12, the melamine diet was replaced by a normal diet in 4 groups with melamine withdrawal (MW). Meanwhile, either mid-/high-dose SB or sterile water was administered by intragastric perfusion (once) to the mice in the corresponding groups. On experiment-day 12, after an additional 8 h, the cystolith incidence was significantly reduced in the high-SB, MW + mid-SB and MW + high-SB groups than in the model group. In conclusion, low urinary pH is one of the main determinants of the formation of melamine-associated stones, urinary alkalinization can be achieved by a proper dose of oral SB, and SB acts to prevent and treat melamine-induced cystoliths in mice.

Variations in matrix metalloproteinase-1, -3, and -9 genes and the risk of acute coronary syndrome and coronary artery disease in the Chinese Han population.

OBJECTIVES: Matrix metalloproteinases (MMPs) are a group of endopeptidases involved in the pathogenesis of atherosclerosis, and MMP gene polymorphisms may contribute toward the risk of coronary heart disease. Within this context, our aim was to examine whether MMP1, MMP3, and MMP9 gene polymorphisms are associated with susceptibility to acute coronary syndrome (ACS) or angiographic coronary artery disease (CAD). METHODS: The MMP1 -519 A/G, MMP3 -1171 5A/6A, and MMP9 -1562 C/T polymorphisms were evaluated in 1574 individuals. Genotypes of patients with ACS (n=660) and angiographically defined CAD (n=382) were compared with ACS-free (n=914) and non-CAD controls (n=466). RESULTS: The MMP3 5A allele occurred at a higher frequency in patients with ACS than in ACS-free individuals (P=0.001). Logistic regression analysis showed that the 5A/5A genotype of MMP3 was associated with a significantly increased risk of ACS [adjusted odds ratio (OR)=2.297, 95% confidence interval (CI)=1.105-4.775, P=0.026, 5A/5A vs. 6A/6A]. The CT and TT variant genotypes of MMP9 were associated with the occurrence of CAD (adjusted OR=1.425, 95% CI=1.045-1.943, P=0.025, CT+TT vs. CC). None of the MMP1 -519 A/G polymorphisms was associated with ACS or CAD. Because of linkage disequilibrium, MMP1 and MMP3 polymorphisms were combined on chromosome 11q22.3, and the 5A-1171-G-519 haplotype had a genetic risk factor for ACS (OR=1.505, 95% CI=1.219-1.857, P=0.00013), whereas the 6A-1171-G-519 haplotype had a decreased risk of ACS (OR=0.815, 95% CI=0.677-0.981, P=0.03). CONCLUSION: Taken together, the present findings indicate that genetic variations in MMP3 and MMP9 genes may be useful genetic markers for determining susceptibility to CAD in the Chinese Han population.