[Clinical features and drug resistance in children with Salmonella infection].

OBJECTIVE: To study the clinical features and drug resistance in children with Salmonella infection. METHODS: A total of 163 children with positive fecal cultures for Salmonella who were hospitalized between 2013 and 2017 were enrolled. A retrospective analysis was performed for their data on clinical features, distribution of Salmonella serotypes, and drug sensitivity test results. RESULTS: Among the 163 children with Salmonella infection, 79 (48.5%) were aged ≤1 year. Main clinical manifestations included fever and diarrhea. Of all the children, 121 (74.2%) reached a body temperature of above 39°C, 52 (31.9%) had diarrhea more than 10 times a day, and 56 (34.4%) had respiratory infection. Salmonella infection often occurred in summer and autumn. Of all the children, 131 (80.4%) had the infection in May to October. Salmonella typhimurium was observed in 100 children (61.3%) and Salmonella enteritidis was observed 15 children (9.2%). All serotypes of Salmonella had a drug resistance rate of >20% to cefotaxime, as well as high sensitivities to ß-lactamase inhibitors (amoxicillin/clavulanic acid and piperacillin/tazobactam). There were no strains resistant to carbapenems including imipenem. CONCLUSIONS: Infants aged ≤1 year are susceptible to Salmonella infection in summer and autumn, and the most common serotype is Salmonella typhimurium. Main clinical manifestations are fever and diarrhea in children with Salmonella infection, and most children also have respiratory infection. Salmonella has an increased rate of drug resistance to third-generation cephalosporins. In clinical treatment, antimicrobial drugs should be used according to the results of drug sensitivity test.

Clinical significance of combined testing of YKL-40 with CEA in Chinese colorectal cancer patients.

BACKGROUND: To investigate the practical value of individual and combined testing of plasma levels of YKL-40, CEA, and CA199 for auxiliary diagnosis and detection of recurrence of colorectal cancer. METHODS: ELISA and ECLIA were used to evaluate levels of YKL-40, CEA, and CA199 in 120 colorectal cancer patients (56 initial-diagnosis, 42 post-operative, and 22 recurrent cases). Forty-three patients with benign colorectal disease and 36 healthy patients were enrolled as controls. The relationship between YKL-40 and clinical indicators of tumor pathology was analyzed. The positive rate and diagnostic efficacy of single and combined YKL-40, CEA, and CA199 testing were assessed in patients with colorectal cancer. RESULTS: Plasma YKL-40 in the cancer group was significantly higher than in the benign control and healthy control group, and the mean values were 145.4 ng/mL, 107.7 ng/mL, and 51.3 ng/mL (p < 0.05), respectively. With 72 ng/mL as the diagnostic threshold, the sensitivity and specificity of YKL-40 in colorectal cancer diagnosis were found to be 73.2% and 66.7%, respectively. Early-stage colorectal cancer patients showed a YKL-40 positive rate (73%) significantly higher than those of CEA and CA199 (50% and 32%, respectively; p < 0.05). When YKL-40 testing was combined with CEA or CA199, the positive rate increased to 82.1% and 80.3%, respectively. Through ROC curve analysis of the post-operative recurrent group against the non-recurrent group, the areas under the curve for YKL-40, CEA, and CA199 were found to be 0.907, 0.714, and 0.759, respectively. Based on the Dukes classification, the mean YKL-40 value for stages A/B, C, and D were 120.1 ng/mL, 131.7 ng/mL, and 226.8 ng/mL (p = 0.008), respectively. The plasma YKL-40 level gradually increased as the disease progressed. Lower degrees of tumor differentiation were correlated with higher YKL-40 levels. The mean YKL-40 values of high, medium, and low tumor differentiation groups were 96.8 ng/mL, 127.5 ng/mL, and 225.7 ng/mL (p = 0.004), respectively. CONCLUSIONS: The benefits of using YKL-40 testing are higher than CEA and CA199 for the monitoring of colorectal cancer recurrence. Combined testing of both YKL-40 and CEA was found to be optimal for auxiliary diagnosis of colorectal cancer. Plasma YKL-40 was found to be suitable for auxiliary diagnosis of colorectal cancer.

Management of refined and personalized newborn blood specimen collection.

Background: Iatrogenic blood loss is an important cause of neonatal anemia. In this study, a spreadsheet tool was developed to reduce blood collection, providing a new idea for the prevention of iatrogenic blood loss in newborns. Methods: Based on hematocrit, minimum test volume and dead volume, a new tool was to calculate the minimum blood collection volume and the number of containers required for the test portfolio. We collected data from October 2022 to October 2023 from Xiamen Maternal and Child Health Hospital for analysis and validation. Results: During this year, there were 16,434 patients and 13,696 plasma/serological samples in the neonatology department. Among them, there were 8 test combinations of greater than 1%, and 9490 samples in total. According to the hospital manual, the recommended amount of blood collection is 27,534 ml and 9490 containers. Through the analysis of this tool, total blood collection was 8864.77 ml, marked qnantity of upward containers (closest level to the calculated blood collection volume) was 10301 ml, and the amount of containers was 8835, which decreased by 67.8%, 62.58% and 6.9% respectively. Besides, if the hematocrit information cannot be obtained in advance and the high hematocrit is calculated as 0.8, the recommended amount of blood collection is 14334.3 ml, and the marked amount of the upward container markering is 17340 ml, decreasing by 47.9% and 37.02% respectively. Conclusion: We have developed an auxiliary tool that can manage neonatal blood specimen collection in a fine and personalized way and can be applied among different laboratory instruments by parameters modification.

Homologous booster immunization with an inactivated vaccine induced robust antibody response in healthcare workers: A retrospective study.

Coronavirus Disease 2019 (Covid-19) severely impacted the health, society, and economy around the world. With declining protective efficacy of primary vaccination and the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, a Covid-19 booster vaccination is being fully implemented globally. Many people received three doses of BBIBP-CorV inactivated vaccine in China and other developing countries. However, the antibody response and immune persistence of the homologous BBIBP-CorV booster vaccination is yet to be thoroughly evaluated, as previous studies focused within one month after the third dose. In this study, 97 participants were enrolled to analyze the antibody response and immune persistence within 6 months as well as the safety within 7 days after the third-dose of homologous BBIBP-CorV inactivated vaccine. The seroconversion rate for total antibody against the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein were both 100% at month 1 and month 6 after the third dose. The IgG against the RBD of the SARS-CoV-2 S protein seroconversion rate increased from 42.27% before the third dose to 100% 1 month after the third dose and then slightly decreased to 98.97% 5 months later. Positive IgM against the RBD of the SARS-CoV-2 S protein was rare and was observed in only one participant at month 1 after the third dose. The neutralizing antibody levels at month 1 and month 6 after the third dose increased 63.32-fold and 13.16-fold compared with those before the third dose, and the positive rate for neutralizing antibody was still 100% at month 6 after the third dose. Importantly, the antibody responses induced by the vaccine and immune persistence were not affected by sex or age. No serious adverse reactions were reported. Total antibody and IgG against the RBD of the SARS-CoV-2 S protein were highly correlated with neutralizing antibody, suggesting that total antibody and IgG against the RBD of the SARS-CoV-2 S protein could be used as predictors for neutralizing antibody. In conclusion, the third dose of homologous BBIBP-CorV inactivated vaccine induced a robust antibody response and moderate immune persistence. These finding are of great significance for development future vaccination strategies.

[High-dose tirofiban in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention].

OBJECTIVE: To evaluate the clinical outcomes of high-dose tirofiban in patients with ST-elevation myocardial infarction (ASTEMI) undergoing primary percutaneous coronary intervention (PCI). METHODS: A total of 104 consecutive ASTEMI patients undergoing primary PCI were enrolled from January 2010 to February 2011. They were randomized into the high-dose tirofiban group (n = 52) and the normal-dose tirofiban group (n = 52). We measured the sumST-segment resolution of ECG post-PCI respectively and left ventricular ejective fraction (LVEF) at Day 90 post-PCI. RESULTS: After PCI, the sumST-segment resolution of ECG of the high-dose tirofiban group significantly improved than that of the normal-dose tirofiban group (38% ± 12% vs 34% ± 13%, P < 0.05). Before PCI, LVEF of two groups is 50.2% ± 1.4% vs 49.6% ± 1.1% (P > 0.05), but at day 90 post-PCI, LVEF had significant difference between two groups (60.1% ± 1.1% vs 56.0% ± 1.2%, P < 0.05). The rates of major and moderate hemorrhage did not differ significantly between two groups. CONCLUSION: High-dose tirofiban improves myocardial reperfusion and clinical outcome. It re-emphasizes the importance of further platelet aggregation inhibition in ASTEMI patients undergoing primary PCI.

[High maintenance dose of clopidogrel improves long-term clinical outcomes in patients with elective percutaneous coronary intervention].

OBJECTIVE: To evaluate the efficacy of a 300 mg loading dose of clopidogrel followed by 150 mg as maintenance dose in patients with percutaneous coronary intervention (PCI). METHODS: A total of 108 consecutive patients undergoing elective PCI were recruited from our hospital from July 2007 to July 2008. A 300 mg loading dose was administered prior to PCI. Then they were randomized to receive clopidogrel 75 mg (n = 55) or 150 mg (n = 46) daily for 30 days. From Day 30 to Month 6 post-operation, all of them received 75 mg/d clopidogrel and were followed up for a mean period of 6 months. RESULTS: Thirty days after PCI, the platelet inhibition of the 150 mg group was significantly higher than the 75 mg group (64.2% ± 13.3% vs 52.6% ± 14.3%, P = 0.00). The ratios of fatal or non-fatal myocardial infarction (MI) (1(1.8%) vs 3 (6.5%), P = 0.405) and target vessel revascularization (TVR) (4(7.2%) vs 6 (13.0%), P = 0.714) were significantly lower in the 150 mg group than those in the 75 mg group. So the overall incidence of MACE including death, MI and TVR was obviously lower in the 150 mg group than that in the 75 mg group (13.0% vs 20.2%, absolute risk reduction 7.3%). CONCLUSION: A high clopidogrel maintenance dose of 150 mg daily for the first month after PCI reduces the risk of long-term adverse events in patients with elective percutaneous coronary intervention.

[Prognostic significance of admission N-terminal pro-brain natriuretic peptide in predicting angiographic no-reflow phenomenon during percutaneous coronary intervention in patients with acute myocardial infarction].

OBJECTIVE: To determine the relationship between N-terminal pro-brain-type natriuretic peptide (NT-proBNP) and angiographic no-reflow phenomenon in patients with acute myocardial infarction (AMI) after primary percutaneous coronary intervention (PCI). METHODS: The data of 106 consecutive AMI patients undergoing primary PCl were collected and analyzed retrospectively. NT-proBNP was obtained pre-PCI at admission. According to the NT-proBNP level, they were divided into normal and elevated NT-proBNP groups. The no-reflow phenomenon was defined as an angiographic outcome of Thrombolysis In Myocardial Infarction (TIMI) grade < 3 without accompanying mechanical factors. RESULTS: The patients with elevated NT-proBNP on admission had a higher incidence of no-reflow phenomenon than those with NT-proBNP level. Compared to normal reflow counterparts, no-reflow patients had a higher NT-proBNP level [1883 ng/L (484 ∼ 5500 ng/L) vs 220 ng/L (87 ∼ 926 ng/L) P = 0.046]. Multivariate analysis showed that a high NT-proBNP level (NT-proBNP > 1765 ng/L) on admission was an independent predictor of no-reflow. This cut-off value yielded a sensitivity of 60.0% and a specificity of 87.5% respectively. CONCLUSION: The NT-proBNP level on admission may be a prognostic biomarker in the prediction of the development of angiographic "no-reflow" phenomenon after primary PCI for AMI patients.

Molecular Evolution of Attachment Glycoprotein (G) and Fusion Protein (F) Genes of Respiratory Syncytial Virus ON1 and BA9 Strains in Xiamen, China.

Monitoring viral transmission and analyzing the genetic diversity of a virus are imperative to better understand its evolutionary history and the mechanism driving its evolution and spread. Especially, effective monitoring of key antigenic mutations and immune escape variants caused by these mutations has great scientific importance. Thus, to further understand the molecular evolutionary dynamics of respiratory syncytial virus (RSV) circulating in China, we analyzed nasopharyngeal swab specimens derived from hospitalized children ≤5 years old with acute respiratory tract infections (ARIs) in Xiamen during 2016 to 2019. We found that infants under 6 months of age (52.0%) were the main population with RSV infection. The prevalent pattern "BBAA" of RSV was observed during the epidemic seasons. RSV ON1 and BA9 genotypes were the dominant circulating strains in Xiamen. Interestingly, we observed four Xiamen-specific amino acid substitution combinations in the G protein and several amino acid mutations primarily occurring at antigenic sites Ø and V in the F protein. Our analyses suggest that introduction of new viruses and local evolution are shaping the diversification of RSV strains in Xiamen. This study provides new insights on the evolution and spread of the ON1 and BA9 genotypes at local and global scales. IMPORTANCE Monitoring the amino acid diversity of the RSV G and F genes helps us to find the novel genotypes, key antigenic mutations affecting antigenicity, or neutralizing antibody-resistant variants produced by natural evolution. In this study, we analyzed the molecular evolution of G and F genes from RSV strains circulating in Xiamen, China. These data provide new insights on local and global transmission and could inform the development of control measures for RSV infections.

Pitavastatin Combined with Ezetimibe Treatment was an Effective Approach to Non-IRA Lesion of ST-segment Elevation Myocardial Infarction Patients with Primary Percutaneous Coronary Intervention.

OBJECTIVE: ST-Segment Elevation Myocardial Infarction (STEMI) patients with the multivessel disease have distinctive plaque characteristics in non-IRA lesions. Intensive statin therapy was a potential approach to treat STEMI patients with the non-IRA disease. However, there is still poor evidence about the therapeutic effect. In this study, we have evaluated the detailed therapeutic effect of statin plus ezetimibe intensive therapy. METHODS: For STEMI patients with non-IRA disease undergoing primary Percutaneous Coronary Intervention (PCI), 183 control STEMI patients without non-IRA disease undergoing primary PCI, and 200 STEMI patients with non-IRA disease undergoing primary PCI were introduced into this study. 200 STEMI patients with non-IRA disease undergoing primary PCI were divided into Normal group, Intensive group, Normal & Combined group, and Intensive & Combined group. The baseline information for each participant was recorded. Meanwhile, the physiological and biochemical indicators of each member with different treatments were collected after one-year follow-up. RESULTS: For STEMI patients with non-IRA disease undergoing primary PCI, no differences could be detected in multiple indexes such as OCT examination results, age, stroke, etc. However, diabetes mellitus, smoking, and coronary Gensini score were different between different groups (P<0.05). After one year follow-up, cholesterol, low-density lipoprotein, coronary Gensini score, thin-cap fibroatheroma, length of non-infarcted arterial lesions, non-infarct artery lesion range, myocardial infarction again, and revascularization again were significantly different between different groups (P<0.05). CONCLUSION: The results mentioned above suggested that pitavastatin combined with ezetimibe was an effective approach for STEMI patients with non-IRA disease undergoing primary PCI. The results obtained in this study have provided a novel method for the treatment of STEMI patients with non-IRA disease undergoing primary PCI.

Schizandrin B attenuates hypoxia/reoxygenation injury in H9c2 cells by activating the AMPK/Nrf2 signaling pathway.

Schizandrin B exhibits prominent antioxidant and anti-inflammatory effects, and plays an important role in ameliorating myocardial ischemia/reperfusion injury. However, the underlying protective mechanisms remain to be elucidated. The aim of the present study was to explore the cardioprotective effects of schizandrin B against hypoxia/reoxygenation (H/R)-induced H9c2 cell injury, focusing on the role of the adenosine monophosphate-activated protein kinase (AMPK)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in this process. The results showed that schizandrin B attenuated the H/R-induced decrease in cell viability and the increase in lactate dehydrogenase release, as well as the apoptosis rate in H9c2 cells. Schizandrin B also mitigated H/R-induced oxidative stress, as illustrated by the decrease in intracellular reactive oxygen species generation, malondialdehyde content and NADPH oxidase 2 expression, and the increase in antioxidant enzyme superoxide dismutase and glutathione peroxidase activities. In addition, schizandrin B reversed the H/R-induced upregulation of pro-inflammatory cytokines [interleukin (IL)-1ß (IL-1ß) tumor necrosis factor-α, IL-6 and IL-8] and the downregulation of anti-inflammatory cytokines (transforming growth factor-ß and IL-10) in the culture supernatant. Notably, schizandrin B increased the expression of Nrf2, NAD(P)H: Quinone oxidoreductase (NQO-1) and heme oxygenase-1 (HO-1) in H/R-treated H9c2 cells, activating the Nrf2 signaling pathway. The cardioprotection of schizandrin B against H/R injury was inhibited by Nrf2 knockdown induced byNrf-2-specific small interfering RNA (siRNA; si-Nrf2) transfection. Furthermore, schizandrin B enhanced phosphorylated (p)-AMPK expression, while AMPK knockdown induced by AMPK-specific siRNA(si-AMPK) transfection remarkably eliminated schizandrin B-induced cardioprotection and reduced Nrf2 expression in H/R-treated H9c2 cells. Taken together, these results suggested that schizandrin B exerts cardioprotection on H/R injury in H9c2 cells due to its antioxidant and anti-inflammatory activities via activation of the AMPK/Nrf2 pathway.

Several FDA-Approved Drugs Effectively Inhibit SARS-CoV-2 Infection in vitro.

To identify drugs that are potentially used for the treatment of COVID-19, the potency of 1403 FDA-approved drugs were evaluated using a robust pseudovirus assay and the candidates were further confirmed by authentic SARS-CoV-2 assay. Four compounds, Clomiphene (citrate), Vortioxetine, Vortioxetine (hydrobromide) and Asenapine (hydrochloride), showed potent inhibitory effects in both pseudovirus and authentic virus assay. The combination of Clomiphene (citrate), Vortioxetine and Asenapine (hydrochloride) is much more potent than used alone, with IC50 of 0.34 µM.

[Effect of tirofiban in acute anterior myocardial infarction patients without ST segment resolution after primary percutaneous coronary intervention].

OBJECTIVE: To observe the effect of glycoprotein receptor blockade tirofiban in acute anterior myocardial infarction patients without ST segment resolution after primary percutaneous coronary intervention (PCI). METHODS: From April 2006 to April 2008, 157 acute anterior myocardial infarction patients without ST segment resolution after PCI were randomly allocated to tirofiban (intravenous bolus 10 microg/kg followed by intravenous infusion of 0.15 microgxkg(-1)xmin(-1) for 48 h, n = 80) or equal volume saline (control group, n = 77). Baseline characteristics, PCI features and clinical outcomes during hospitalization, left ventricular ejection fractions (LVEF) and major adverse cardiac events (MACE, including death, re-infarction and target vessel revascularization) at 30 and 180 days after discharge were compared between the two groups. RESULTS: The baseline clinical characteristics were comparable between the two groups. Compared to control group, the MACE rates and re-infarction rates at 30 days (6.3% vs.18.2%, P < 0.05; 1.3% vs.9.1%, P < 0.05, respectively) and 180 days (10.0% vs.23.4%, P < 0.05; 2.5% vs.10.4%, P < 0.05, respectively) were significantly reduced in tirofiban group. LVEF value was significantly higher in tirofiban group at 30 days and 180 days compared with those in control group [(51 +/- 6)% vs. (46 +/- 8)%, P < 0.05; (57 +/- 7)% vs. (50 +/- 9)%, P < 0.05]. Hemorrhagic complications were similar between the two groups. CONCLUSION: Use of tirofiban for acute anterior myocardial infarction patients without ST segment resolution after PCI is safe and can significantly improve 30 and 180 days clinical outcomes after discharge.

The Associations of PMF1, ICAM1, AGT, TRIM65, FBF1, and ACOX1 Variants With Leukoaraiosis in Chinese Population.

Background: Leukoaraiosis (LA) is shown as white matter hyperintensities on T2-weighted magnetic resonance imaging brain scans. Together with candidate gene association studies (CGAS), multiple genome-wide association studies (GWAS) have reported large numbers of single nucleotide polymorphisms (SNPs) to be associated with LA in European populations. To date, no replication studies have been reported in independent Chinese samples. Methods: Here, we performed a candidate gene association study comprising 220 Chinese subjects with LA and 50 controls. Thirty-nine polymorphisms on 32 risk genes were selected from previous studies, and they were genotyped through matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Genetic association analysis was firstly performed in all subjects with LA. Then, the same analysis was conducted in the six random sampling cohorts of 50 LA patients, respectively. Data analyses on the associations of SNPs with LA risk were evaluated through Pearson's χ2 and multivariate logistic regression tests. Results: We found that eight polymorphisms in six genes (PMF1, ICAM1, TRIM65, AGT, FBF1, and ACOX1) were significantly associated with LA in the genetic association tests. Except for those eight gene variants, 24 other polymorphisms were not found to be significantly associated with LA in general genetic model, dominant model, recessive model, or multiplicative model. Among those eight polymorphisms, rs2984613 in PMF1 showed significant association with LA in the cohort of 220 LA subjects, and such significant association remained in both general genetic model (OR: 0.262, 95% CI: 0.091-0.752, p adj = 0.030) and recessive model (OR: 0.323, 95% CI: 0.119-0.881, p adj = 0.038) when controlling for clinical variables. Seven other significant variants (rs5498 in ICAM1, rs699 in AGT, rs2305913 in FBF1, rs1135640 in ACOX1, and rs3760128, rs7214628, and rs7222757 in TRIM65) were identified in those six random sampling tests that were conducted in the adjusted cohorts of 50 LA patients. In addition, except for rs699 which showed detrimental effect and represented a risk variant for LA, seven other polymorphisms seemed to exert protective effects on LA and to reduce the risk of LA. It is necessary to confirm these associations in an independent cohort. Conclusions: This first replication study on multiple genes in an independent Chinese population did not replicate any risk polymorphisms for LA other than rs 699 in AGT but revealed the significantly negative associations of PMF1, ICAM1, TRIM65, FBF1, and ACOX1 polymorphisms with LA. It not only supported the strong ethnic differences in the genetics of LA but also indicated that those six identified genes may be involved in Chinese white matter lesions. Larger scales of CGAS and GWAS are necessary to confirm and decipher those ethnic-Han specific risk genes for LA in China.

1,25-Dihydroxyvitamin D3 affects gastric cancer progression by repressing BMP3 promoter methylation.

BACKGROUND: Vitamin D3 has been known to have an anticancer effect, but the mechanisms underlying this is poorly explored. The present study aimed to investigate the antitumor role of vitamin D3 on gastric cancer and mechanisms. METHODS: The Roche Elecsys platform was applied in retrospective studies to detect the role of 25-hydroxylvitamin D3 in adenocarcinoma and colony formation assay was conducted to verify the effect of 1, 25-dihydroxyvitamin D3 on the proliferation of gastric cancer cells. After the identification of hypermethylation of BMP3 CpG islands by bisulfite genomic sequencing (BGS), we further investigated the relationship of BMP3 expression and gastric carcinogenesis by Western blot analysis and gel electrophoresis mobility shift assay (EMSA). RESULTS: Here we show that low concentration of 1, 25-dihydroxyvitamin D3 links to can-cerization and significantly inhibits proliferation of undifferentiated gastric cancer cell lines SGC-7901 and BGC-823. BMP3 promoter hypermethylation was highly correlated with gastric tumor. Moreover, BMP3 expression was regulated by its promoter methylation in gastric cells. The further exploration of the relationship between 1, 25-dihydroxyvitamin D3 and BMP3 by EMSA results that 1, 25-dihydroxyvitamin D3 stimulates BMP3 expression by the inhibition of BMP3 promoter methylation in gastric tumor cells. CONCLUSION: In combination with the data from clinical research, bioinformatics analysis and experimental verification, we propose that 1, 25-hydroxylvitamin D3 affects gastric cancer progression by repressing BMP3 promoter methylation.

[Reasons and complications of pacemaker replacement operation: clinical analysis of 69 case-times].

OBJECTIVE: To analyze the reasons of cardiac permanent pacemaker replacement and the strategies to prevent relevant complications. METHODS: The clinical data of 57 patients, 38 males and 19 females, aged 74 +/- 8 (56-94), 31 with sick sinus syndrome, 26 with II or III degree atrioventricular block, who underwent 63 times of cardiac permanent pacemaker replacement, including 13 times of lead replacement, were analyzed. RESULTS: The reason of replacement included battery normal exhaustion for 57 case-times, battery exhaustion before the defined schedule for 2 case-times, lead electrodes incompletely fractured for 2 case-times, and infection of pacemaker pocket for 2 case-times. There were 9 cases of placement-related complications: pacemaker pocket hematoma (n=4), lead dislocation (n=3), and abandoned leads falling into the right ventricle (n=2). The average lifetime of old pacemakers was 9. 25 years (2 -15 years). The pacing threshold of ventricular leads after pacemaker replacement was (0.77 +/- 0. 40)V, significantly higher than the initial pacing threshold [(0.60 +/- 0.21)V, P < 0.01]. There were no significant differences in the lead impedance and R wave amplitude between the pacemaker replacement and initial implantation [(854 +/- 136)omega vs. (828 +/- 176)omega, and (12 +/- 4)mV vs. (12 +/- 4)mV, both P > 0.05]. CONCLUSION: The main reason of pacemaker replacement is battery exhaustion. Most implanted ventricular leads still can be used. A rare serious complication of cardiac pacemaker replacement operation is abandoned lead falling into the right ventricle, and correct disposing of initial leads help avoid this complication .

The Impact of Gene Polymorphisms on Anticoagulation Control With Warfarin.

Differences in warfarin maintenance dosages based on the presence of polymorphisms in VKORC1, CYP2C9, CYP4F2, and ORM1 can be determined through dosage adjustment according to routine guidelines. Little is known about whether routine therapy could provide consensus anticoagulation control for patients with different genotypes. This study was carried out to compare anticoagulant control in patients with different genotypes. Six hundred seventy patients using warfarin according to Chinese guidelines were enrolled. Warfarin dosages and monitored international normalized ratios (INRs) were recorded. Genotypes of VKORC1 rs9923231, CYP4F2 rs2108622, CYP2C9 rs1057910, and ORM1 rs17650 polymorphisms were determined. Warfarin dosages and INR were compared between genotypes. Patients with the AGCC*F*F*1*1 polymorphism took longer than patients with the AACC*F*F*1*1 polymorphism (20 vs 5 days, P < .001) to achieve the targeted INR range. The INR values of patients with AACC*F*F*1*3 were unstable and did not enter the stable state control phase until after 35 days. The peak INR of patients with the AACC*F*F*1*3 polymorphism was exceedingly high, with some values exceeding the control range limit of 3.0. Patients with the AACC*F*S*1*1 or AACT*F*F*1*1 polymorphisms exhibited similar INR values as the patients with the AACC*F*F*1*1 polymorphism. This study found that routine medication with warfarin provides significantly different levels of anticoagulant control between patients with wild-type genotypes and patients with heterozygous polymorphism genotypes of VKORC1 rs9923231 or CYP2C9 rs1057910. Patients with heterozygous polymorphism genotypes of VKORC1 or CYP2C9 require genotype-directed therapy with warfarin to increase efficacy and safety in anticoagulant treatment.

Magnolol suppresses the proliferation and invasion of cholangiocarcinoma cells via inhibiting the NF-κB signaling pathway.

BACKGROUND: Magnolol has shown the potential anticancer properties against a variety of cancers. However, the role of magnolol in cholangiocarcinoma (CCA) cells is unknown. In this study, we assessed the effect of magnolol on the CCA cells. METHODS: CCA cells were treated with magnolol in the absence or presence of TNFα, the activator for NF-κB. After co-incubation with magnolol, cell proliferation and growth were examined by MTT, colony formation and xenograft tumors; cell cycle was analyzed by flow cytometry; cell migration and invasion were detected by wound healing and transwell assays; the expression of PCNA, Ki67, CyclinD1, MMP-2, MMP-7 and MMP-9 and NF-κB pathway were evaluated by using Western blot. RESULTS: Magnolol inhibited the abilities of CCA cell growth, migration and invasion accompanying with a decreased expression of PCNA, Ki67, MMP-2, MMP-7 and MMP-9 (all P<0.05). TREATMENT: with magnolol induced cell cycle arrest in G1 phase with a downregulation of cell cycle protein CyclinD1 (all P<0.05). In addition, magnolol suppressed the expression of p-IκBα and p-P65 and the effect of magnolol on CCA cells could be inhibited by TNFα. CONCLUSIONS: Magnolol could inhibit the growth, migration and invasion of CCA cells through regulation of NF-κB pathway, and these data indicate that magnolol is a potential candidate for treating of CCA.

Identification of two novel genes SLC15A2 and SLCO1B3 associated with maintenance dose variability of warfarin in a Chinese population.

Warfarin is a commonly prescribed and effective oral anticoagulant. Genetic polymorphisms associated with warfarin metabolism and sensitivity have been implicated in the wide inter-individual dose variation that is observed. Several algorithms integrating patients' clinical characteristics and genetic polymorphism information have been explored to predict warfarin dose. However, most of these algorithms could explain only over half of the variation in a warfarin maintenance dose, suggesting that additional genetic factors may exist and need to be identified. Here, a drug absorption, distribution, metabolism and excretion (ADME) Core Panel Kit-based pharmacogenetic study was performed to screen for warfarin dose-associated SNP sites in Han-Chinese population patients taking warfarin therapy, and the screen was followed by pyrosequencing-based validation. Finally, we confirmed that the common variant rs9923231 in VKORC1 and two novel genes, SLC15A2 (rs1143671 and rs1143672) and SLCO1B3 (rs4149117 and rs7311358), are associated with the warfarin maintenance dose. As has been shown for those carriers with the variant rs9923231 in VKORC1, it was suggested that those subjects with homozygous minor alleles in those four SNPs should take a lower warfarin dose than those carrying the wild type alleles. Together with the established predictor rs9923231 in VKORC1, those four novel variants on SLC15A2 and SLCO1B3 should be considered as useful biomarkers for warfarin dose adjustment in clinical practice in Han-Chinese populations.

Analysis of genetic polymorphisms associated with leukoaraiosis in the southern Chinese population: A case-control study.

Leukoaraiosis (LA) is a frequent neuroimaging finding commonly observed on brain MRIs of elderly people with prevalence ranging from 50% to 100%. Multiple susceptibility genes or genetic risk factors for LA have been identified in subjects of European descent. Here, we report the first replication study on several common and novel genetic variations in the Chinese population. In this study, a total of 244 subjects (201 LA patients and 43 controls) were enrolled according to our new and strict definition for LA. Subsequently, 6 genetic variants at 5 genes, rs3744028 in TRIM65, rs1055129 in TRIM47, rs1135889 in FBF1, rs1052053 in PMF1, and rs1801133 (C677T) and rs1801131(A1298C) in MTHFR, were selected for genotyping using polymerase chain reaction (PCR)-based pyrosequencing and restriction fragment length polymorphism (RFLP) together with capillary electrophoresis (CE) and agarose gel electrophoresis. Finally, Pearson's χ and multivariate logistic regression tests were used to examine the associations between the genotypes and LA. Among these candidate polymorphisms, except for rs1052053 and rs1801131, rs1135889 (P = 0.012) showed significant associations with LA in the dominant model, and the other 3 SNPs, rs3744028 (P = 0.043), rs1055129 (P = 0.038), and rs1801133 (P = 0.027), showed significant associations with LA in the recessive model. However, these differences no longer remained significant after adjusting for age, gender, hypertension, and diabetes mellitus and applying Bonferroni correction or Sidak correction for multiple testing. These results suggest that the above-mentioned genetic variants are not associated with LA risk. In summary, the study did not replicate the susceptibility of rs3744028, rs1055129, and rs1135889 at the Chr17q25 locus for LA nor did it find any other significant results for rs1052053, rs1801133, and rs1801131 in the Chinese population. It strongly indicated the ethnic differences in the genetics of LA. However, the associations of rs3744028 (TRIM65), rs1055129 (TRIM47), rs1135889 (FBF1), and rs1801133 (MTHFR) with LA before Bonferroni correction and Sidak correction for multiple testing are worth highlighting. Thus, we believe that a genome-wide association study and candidate gene association studies are needed to reassess the previous findings and screen novel risk genes for LA in China.

p62 Expression in primary carcinomas of the digestive system.

AIM: To characterize p62 expression and define the relationship between p62 expression and cell proliferation in primary carcinomas of the digestive system. METHODS: p62 expression was characterized in surgically resected tumor specimens from 60 patients with primary carcinomas of the digestive tract (including 22 esophageal carcinomas, 17 gastric carcinomas, and 21 colorectal carcinomas) and 40 patients with hepatocellular carcinoma (HCC) by immunohistochemistry (IHC). The cell proliferation was determined by IHC of Ki-67 in 40 patients with HCC. RESULTS: Twenty-two cases of esophageal carcinoma were histopathologically diagnosed as squamous cell carcinoma. We combined the gastric and colorectal carcinomas based on the equivalent histology. The 38 tumors in the combined groups, consisted of 17 well-differentiated, eight moderately differentiated, nine poorly differentiated carcinomas, and four mucinous adenocarcinomas. According to the criteria of Edmondson and Steiner, 40 patients with HCC were graded (2 grade I, 17 grade II and 21 grade III). p62 expression in primary carcinomas of the gastrointestinal tract (60/60,100%) was higher than that (27/40, 67.5%) of HCC (P<0.01, chi(2) = 19.63). High expression levels of p62 were positively correlated with histological grades in gastric and colorectal carcinomas (P<0.0001) and inversely associated with those in HCC (P = 0.0322). No significant correlations were observed for esophageal carcinomas (P = 0.8246). p62 expression was also detected in the cytoplasm of morphologically normal columnar epithelial cells adjacent to the cancer foci of gastric and colorectal carcinomas. In 40 HCC specimens, the mean Ki-67 labeling index (LI) was (19.6+/-16.0)%. It was (28.3+/-18.73)% in 12 cases with high p62 expression (+++), (7.53+/-14.83)% in 13 cases without p62 expression(-). Patients with a high p62 expression showed a significantly higher level of Ki-67 staining than those without p62 expression (P<0.05, t = 2.069). CONCLUSION: p62 expression is common in carcinomas of the digestive system and higher in carcinomas of the gastrointestinal tract than in primary HCC. p62 is a cellular differentiation-related protein. Cancer cells with a high p62 expression exhibited highgrowth fractions in HCC.