Update on the Epidemiology, Pathogenesis, and Biomarkers of Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic disorder of the cerebral small blood vessels. It is caused by mutations in the NOTCH3 gene on chromosome 19, and more than 280 distinct pathogenic mutations have been reported to date. CADASIL was once considered a very rare disease with an estimated prevalence of 1.3–4.1 per 100,000 adults. However, recent large-scale genomic studies have revealed a high prevalence of pathogenic NOTCH3 variants among the general population, with the highest risk being among Asians. The disease severity and age at onset vary significantly even among individuals who carry the same NOTCH3 mutations. It is still unclear whether a significant genotype–phenotype correlation is present in CADASIL. The accumulation of granular osmiophilic material in the vasculature is a characteristic feature of CADASIL. However, the exact pathogenesis of CADASIL remains largely unclear despite various laboratory and clinical observations being made. Major hypotheses proposed so far have included aberrant NOTCH3 signaling, toxic aggregation, and abnormal matrisomes. Several characteristic features have been observed in the brain magnetic resonance images of patients with CADASIL, including subcortical lacunar lesions and white matter hyperintensities in the anterior temporal lobe or external capsule, which were useful in differentiating CADASIL from sporadic stroke in patients. The number of lacunes and the degree of brain atrophy were useful in predicting the clinical outcomes of patients with CADASIL. Several promising blood biomarkers have also recently been discovered for CADASIL, which require further research for validation.

Determination of Serum Unbound Bilirubin and Its Clinical Application Value in Neonates / 中山大学学报(医学科学版)

ObjectiveTo investigate the clinical appropriateness and application value of the peroxidase （POD） method for the detection of unbound bilirubin （UB） in neonatal serum. MethodsHydrogen peroxide （0.33 mol/L） and three different final concentrations （0.019， 0.038， 0.075 μg/mL） of horseradish peroxidase （HRP） were added to standard bilirubin solution （1， 2， 3 μmol/L） to obtain a standardized HRP primary rate constant Kp. Then 25 μL of neonatal serum was diluted by 41.6 fold， and measured with 2.4 and 4.8 μg/mL HRP at 37 ℃ under the dark， to determine the UB concentration. The accuracy， precision， and stability of the methodology were validated. The clinical characteristics of 33 jaundiced neonates were collected， including total serum bilirubin （TSB）， indirect bilirubin （IDB）， albumin （ALB）， bilirubin to albumin molar ratio （BAMR）， etc. The experimental data were analyzed by Graphpad Prism 8.0. ResultsA standardized Kp of （7.20±1.08） mL·μg-1·min-1 was determined at pH 7.4±0.2， 37 ℃ in the dark. The HRP activity and UB concentrations remained stable at -20 ℃ for 3 weeks and a week， respectively. The mean intra-day and inter-day coefficients of variation of the serum samples with different UB concentrations were less than 10%. In this study， the UB concentrations in 33 jaundiced neonates （gestational age ≥35 weeks） were measured by the POD method in the range of （0.32～1.20） μg/dL， which was positively correlated with TSB， IDB and BAMR. Of the five infants whose UB concentrations measured more than 1 μg/dL， three received intensive phototherapy （60%）. ConclusionsThe POD method combined with a standard equipment spectrophotometer to detect serum UB concentrations in neonates is easy to operate， rapid to detect， and low cost. This method has good accuracy and precision， which is convenient for clinical implementation. Moreover， the measurement of serum UB may assist us in better management of neonatal jaundice in clinical practice.

Management and prognosis of extremely preterm infants with gestational age ≤25+6 weeks / 中华儿科杂志

Objective: To investigate the outcomes including major complications and prognosis of extremely preterm infants with gestational age ≤25+6 weeks. Methods: The cross-sectional study enrolled 233 extremely preterm infants with gestational age ≤25+6 weeks who were admitted to the Department of Neonatology of Shenzhen Maternity and Child Healthcare Hospital from January 2015 to December 2021. The clinical data including perinatal factors, treatments, complications, and prognosis were extracted and analyzed. These extremely preterm infants were also grouped according to gestational age and year of admission to further analyze their survival rate, major complications, causes of death, and long-term outcomes. The comparisons between the groups were performed with Chi-square test and Kruskal-Wallis. Results: Among these 233 extremely preterm infants, 134 (57.5%) were males and 99 (42.5%) females. The gestational age was (24.6±0.9) weeks, the birth weight was 710.0 (605.0,784.5) g, and the overall survival rate was 61.8% (144/233). Among the surviving extremely preterm infants, the earliest gestational age was 22+2 weeks and the lowest birth weight was 390 g. There were 17.6% (41/233) of extremely preterm infants had treatment withdrawn and were discharged in line with the will of guardians. Among the rest 192 extremely preterm infants managed with aggressive treatments, 14 (7.3%) died in hospital and 34 (17.7%) had treatment withdrawn later due to severe complications. Of the 192 extremely preterm infants, 144 (75.0%) survived, and the survival rate increased year by year (χ2=26.28, P<0.001) while the mortality decreased year by year (χ2=14.09, P=0.027). Among the survivors, 20.8%(30/144) had no major complications, and the incidence of complications was also negatively related with the gestational age (χ2=7.24, P=0.044), and the length of invasive ventilation was negatively related to the gestational age (χ2=29.14, P<0.001). In the group of less than 23+6 weeks, all extremely preterm infants had one or more major complications. The follow-up were completed in 122 infants and revealed that delayed motor development, language retardation, and hearing and vision impairment accounted for 17.2% (21/122), 8.2% (10/122) and 17.2% (21/122), respectively. Conclusions: Extremely preterm infants with gestational age ≤25+6 weeks are difficult to treat, but the survival rate of infants undergoing aggressive treatments increases year by year. Although the prevalence of major complications is still high, most extremely preterm infants have acceptable prognosis during follow-up.

The value of real-time shear wave elastography in evaluating the severity of liver fibrosis in hepatitis B / 中国热带医学

@#Abstract: Objective　To explore the value of real-time shear wave elastography in evaluating the severity of liver fibrosis in hepatitis B, and to analyze the factors that affecting its accuracy. Methods　A total of 196 chronic hepatitis B patients, who admitted to the Third Affiliated Hospital of Chengdu Medical College from February 2018 to October 2020, were selected for retrospective analysis. Demographic indicators such as gender, age, body mass index(BMI), and laboratory indicators such as fasting blood glucose, liver function, and blood lipid composition were collected. The patients were detected by real-time shear wave elastography. Taking the pathological test results as the gold standard, the diagnostic value of real-time shear wave elastography in the severity of liver fibrosis in chronic hepatitis B was analyzed, and the comprehensive effect of various factors on the diagnostic accuracy of real-time shear wave elastography was evaluated by Logistic regression analysis. Results　The differences in real-time shear wave elastography of patients with different severity of liver fibrosis in hepatitis B were statistically significant, and F0 grade <F1 grade <F2 grade <F3 grade <F4 grade (all P<0.05). ROC analysis showed that the cut-off values of real-time shear wave elastography for patients with liver fibrosis in hepatitis B ≥ F1, ≥ F2, ≥ F3 and F4 were 6.15 kPa, 7.03 kPa, 8.15 kPa and 10.09 kPa respectively; the area under the curve (AUC) was 0.759, 0.806, 0.900 and 0.930 respectively (P<0.05). Results of multivariate Logistic regression analysis based on univariate analysis showed that glutamic alanine transaminase (ALT), glutamic oxalacetic transaminase (AST), fatty liver and inflammation levels were independent factors affecting the accuracy of real-time shear wave elastography in evaluating the severity of liver fibrosis in hepatitis B (P<0.05). Conclusions　Real-time shear wave elastography technology can be used to evaluate the severity of liver fibrosis in hepatitis B, and its accuracy is mainly affected by ALT, AST, inflammation levels and fatty liver.

Development and validation of a deep learning model to screen hypokalemia from electrocardiogram in emergency patients / 中华医学杂志(英文版)

BACKGROUND@#A deep learning model (DLM) that enables non-invasive hypokalemia screening from an electrocardiogram (ECG) may improve the detection of this life-threatening condition. This study aimed to develop and evaluate the performance of a DLM for the detection of hypokalemia from the ECGs of emergency patients.@*METHODS@#We used a total of 9908 ECG data from emergency patients who were admitted at the Second Affiliated Hospital of Nanchang University, Jiangxi, China, from September 2017 to October 2020. The DLM was trained using 12 ECG leads (lead I, II, III, aVR, aVL, aVF, and V1-6) to detect patients with serum potassium concentrations <3.5 mmol/L and was validated using retrospective data from the Jiangling branch of the Second Affiliated Hospital of Nanchang University. The blood draw was completed within 10 min before and after the ECG examination, and there was no new or ongoing infusion during this period.@*RESULTS@#We used 6904 ECGs and 1726 ECGs as development and internal validation data sets, respectively. In addition, 1278 ECGs from the Jiangling branch of the Second Affiliated Hospital of Nanchang University were used as external validation data sets. Using 12 ECG leads (leads I, II, III, aVR, aVL, aVF, and V1-6), the area under the receiver operating characteristic curve (AUC) of the DLM was 0.80 (95% confidence interval [CI]: 0.77-0.82) for the internal validation data set. Using an optimal operating point yielded a sensitivity of 71.4% and a specificity of 77.1%. Using the same 12 ECG leads, the external validation data set resulted in an AUC for the DLM of 0.77 (95% CI: 0.75-0.79). Using an optimal operating point yielded a sensitivity of 70.0% and a specificity of 69.1%.@*CONCLUSIONS@#In this study, using 12 ECG leads, a DLM detected hypokalemia in emergency patients with an AUC of 0.77 to 0.80. Artificial intelligence could be used to analyze an ECG to quickly screen for hypokalemia.

Pancreatic and duodenal homeobox-1 in pancreatic ductal adenocarcinoma and diabetes mellitus / 中华医学杂志(英文版)

Diabetes mellitus and pancreatic ductal adenocarcinoma are two common diseases worldwidely which are both derived from different components of pancreas. The pancreatic and duodenal homeobox-1 (PDX1) is an essential transcription factor for the early development of pancreas that is required for the differentiation of all pancreatic cell lineages. Current evidence suggests an important role of PDX1 in both the origin and progression of pancreatic diseases. In this review, we discussed recent studies of PDX1 in diabetes mellitus and pancreatic cancer, and the therapeutic strategies derived from this transcription factor.

Extracorporeal shock wave therapy in cubital tunnel syndrome: A pilot study

@# To investigate the clinical therapeutic effect of extracorporeal shock wave therapy in the treatment of cubital tunnel syndrome. Methods: Seven patients (10 elbows) with moderate cubital tunnel syndrome participated in this study. Three sessions of radial extracorporeal shock wave therapy (2,000 shots, 4 Bar, 5 Hz) (once a week) were administered to the ulnar nerve at the proximal cubital tunnel region. The primary and secondary outcomes were assessed using the Visual Analog Scale (VAS) and the shortened Disabilities of the Arm, Shoulder and Hand questionnaire (Quick DASH), respectively, at the 4th, 8th, and 12th week, following the 3rd session of shock wave therapy. Results: The VAS and Quick DASH scores demonstrated improvements at all follow-up time points, in all treated elbows. The mean VAS and Quick DASH score improved from 4.7±0.3(mean±SE) to2.2±0.2 and 16.6±2.1to 6.8±1.6 respectively during 12 weeks follow up (all p <0.01). Conclusion: This pilot study revealed the safety and efficacy of extracorporeal shock wave therapy in patients with moderate cubital tunnel syndrome.

The tyrosine kinase inhibitor nintedanib activates SHP-1 and induces apoptosis in triple-negative breast cancer cells

Triple-negative breast cancer (TNBC) remains difficult to treat and urgently needs new therapeutic options. Nintedanib, a multikinase inhibitor, has exhibited efficacy in early clinical trials for HER2-negative breast cancer. In this study, we examined a new molecular mechanism of nintedanib in TNBC. The results demonstrated that nintedanib enhanced TNBC cell apoptosis, which was accompanied by a reduction of p-STAT3 and its downstream proteins. STAT3 overexpression suppressed nintedanib-mediated apoptosis and further increased the activity of purified SHP-1 protein. Moreover, treatment with either a specific inhibitor of SHP-1 or SHP-1-targeted siRNA reduced the apoptotic effects of nintedanib, which validates the role of SHP-1 in nintedanib-mediated apoptosis. Furthermore, nintedanib-induced apoptosis was attenuated in TNBC cells expressing SHP-1 mutants with constantly open conformations, suggesting that the autoinhibitory mechanism of SHP-1 attenuated the effects of nintedanib. Importantly, nintedanib significantly inhibited tumor growth via the SHP-1/p-STAT3 pathway. Clinically, SHP-1 levels were downregulated, whereas p-STAT3 was upregulated in tumor tissues, and SHP-1 transcripts were associated with improved disease-free survival in TNBC patients. Our findings revealed that nintedanib induces TNBC apoptosis by acting as a SHP-1 agonist, suggesting that targeting STAT3 by enhancing SHP-1 expression could be a viable therapeutic strategy against TNBC.

Study on inhibitory effects of Triperygium Wilfordii Polyglucoside on Dipeptidyl peptidase I and regulatory mechanism / 中国免疫学杂志

Objective:Dipeptidyl peptidase I(DPPI),a lysosomal cysteine protease for serine proteases activation,highly expressed in granule immune cells.This study used collagen induced arthritis(CIA) rat model to investigate the effects of Triperygium Wilfordii Polyglucoside(TWP) on DPPI activity and the pharmacological mechanism in RA treatment.Methods:Rats were divided into four groups randomly,the blank control group,the CIA model group,the high dose (5.0 mg/100 g body-weight) and low dose(2.5 mg/100 g body-weight)treatment group.Bovine collagen-Ⅱ plus complete Freund′s adjuvant injected twice in rats.Physical assessments were carried out.12 days post-injections,the rats of treatment group were intragastric administered with TWP every day.The rats were killed after two week administrations.Serum and synovial membrane homogenates were collected and DPPI activity was detected by fluorescence substrate.Joint HE staining and cell counting were carried out,Zymography was used to detect the MMP-2/9 activity in synovial fluids.Total protein in synovial membrane homogenates were measured by BCA method.Results:TWP could reduce the number of CIA synovial tissue mast cells,inhibited DPPI activity in the synovial fluids and in serum.The expression levels of MMP-2/9 activity and synovium total protein content were also reduced by TWP.Conclusion:Triperygium Wilfordii Polyglucoside has inhibitory effects on DPPI activity on CIA rats,which might be the one of the pharmacological mechanisms in RA treatment.

Effect of concentrated growth factors on the treatment of degree Ⅱ furcation involvements of mandibular molars / 北京大学学报(医学版)

Objective:Concentrated growth factors (CGF),a new generation of platelet concentrate products,appears to have more abundant growth factors because of its special centrifugation process.However,there are few studies supporting this.This study was designed to evaluate the effect of CGFs in the treatment of Ⅱ ° furcations of mandibular molars.Methods:In the present study,thirty-one Ⅱ ° furcation involvements in twenty mandiblular molars were included and randomly divided into two groups.The furcation involvements in the experimental group were treated with bone graft therapy combined with CGFs,and the furcation involvements in the control group were treated with bone graft therapy alone.The clinical examination and cone beam computed tomography (CBCT) were performed at baseline and 1 year post-surgery for the two groups.The changes of clinical and CBCT data at baseline and 1 year postsurgery were compared between the experimental group and the control group.Results:At baseline,there were no significant differences between the two groups in the probing depth (PD),vertical clinical attachment loss (CAL-V) and horizontal clinical attachment loss (CAL-H):PD (7.36 ± 2.32) mm (the experimental group) vs.(7.53 ±2.06) mm (the control group);CAL-V (8.69 ± 1.65) mm (the experimental group) vs.(8.81 ±1.53) mm (the control group);CAL-H (5.24 ±2.01) mm (the experimental group) vs.(5.35 ±2.14) mm (the control group).At the end of 1 year post-surgery,the clinical parameters of both groups were significantly improved (P ＜ 0.001).For the experimental group,the average vertical attachment gain was (2.78 ± 1.66) mm,and the vertical attachment loss was improved significantly compared with the baseline (P ＜ 0.001);the average horizontal attachment gain was (2.10 ± 1.89) mm,and the horizontal attachment loss were improved significantly compared with the baseline (P ＜ 0.001).Furthermore,the improvement degree of the experimental group was significantly higher than that of the control group (P ＜ 0.001).At baseline,there were no statistical differences in the vertical bone loss (BL-V) or horizontal bone loss (BL-H) between the two groups (P ＞ 0.05):BL-V (5.08 ± 2.17) mm (the experimental group) vs.(5.84 ± 2.65) mm (the control group);BL-H (5.85 ±2.13) mm (the experimental group) vs.(6.01 ±2.27) mm (the control group).At 1 year post-surgery,both groups showed significant radiographic bone gain at vertical and horizontal directions compared with baseline (P ＜ 0.001).For the experimental group,the average vertical radiographic bone gain was (2.20 ± 1.98) mm,the horizontal radiographic bone gain was (2.51 ±2.18) mm,the vertical and horizontal radiographic bone loss were both significantly reduced compared with the baseline (P ＜ 0.001).For the control group,the average vertical radiographic bone gain was (1.89 ± 2.15) mm,the horizontal radiographic bone gain was (1.30 ± 2.47) mm,the vertical and horizontal radiographic bone losses were both significantly reduced compared with the baseline (P ＜ 0.001).And the experimental group showed significantly higher bone gain at vertical and horizontal directions compared with the control group (P ＜ 0.001).Conclusion:Within the limitation of the present study,CGFs showed positive role in the treatment of Ⅱ° furcation involvements of mandibular molars.

Accuracy of partial-mouth examination protocols in periodontal epidemiological surveys: a systemic review / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To evaluate the accuracy of partial- mouth periodontal examination (PMPE) protocols frequently used in epidemiological periodontal surveys.</p><p><b>METHODS</b>Articles in English or Chinese published before Jan 31st 2014 were searched, which compared the results of PMPE protocols with those of gold-standard protocol, i.e.full-mouthmesialbuccal-midbuccal-distobuccal-mesiolingual-midlingual-distolingual (MB-B-DB-ML-L-DL) protocol.</p><p><b>RESULTS</b>Twelve articles were included and nine that frequently used PMPE protocols were evaluated. All these protocols underestimated the prevalence scores. For prevalence of probing depth (PD) ≥ 4 mm, 6 mm and attachment loss (AL) ≥ 4 mm, 6 mm, smaller amount of underestimation was observed in community periodontal index of treatment needs (CPITN) teeth (-12.6%--3.5%), full-mouth MB-B-DB (-16.1%--3.5%), full-mouth MB-B-DL (-10.8%--6.1%) and half-mouth MB-B-DB-ML-L-DL (-23.6%--2.0%) protocols. For severity and extent estimates, half-mouth MB-B-DB-ML- L-DL provided lowest biased results (relative bias: -1.0%- 1.1% for severity and -6.7%-0.1% for extent). Full-and half-mouth MB-B-DB also performed well, with relative bias within ± 5.0% in most cases. CPITN overestimated the severity and extent of periodontal disease, the relative bias of which amounted to 42.3% and 38.1%, respectively.</p><p><b>CONCLUSIONS</b>Half-mouth MB-B-DB-ML-L-DL and full-mouth MB-B-DB protocols caused lower biased results in prevalence, severity and extent estimates of PD and AL.</p>

Effect of dangua recipe on glycolipid metabolism and VCAM-1 and its mRNA expression level in Apo E(-/-) mice with diabetes mellitus / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of Dangua Recipe (DGR) on glycolipid metabolism, vascular cell adhesion molecule-1 (VCAM-1) and its mRNA expression level of transgenic Apo E(-/-) mouse with spontaneous atherosclerosis, thus revealing its partial mechanism for curing diabetes mellitus (DM) with angiopathy.</p><p><b>METHODS</b>Diabetic model was prepared by peritoneally injecting streptozotocin (STZ) to Apo E(-/-) mouse. Totally 32 modeled mice were stratified by body weight, and then divided into 4 groups referring to blood glucose levels from low to high by random digit table, i.e., the model group (MOD, fed with sterile water, at the daily dose of 15 mL/kg), the DGR group (fed with DGR at the daily dose of 15 mL/kg), the combination group (COM, fed with DGR at the daily dose of 15 mL/kg and pioglitazone at the daily dose of 4.3 mg/kg), and the pioglitazone group (PIO, at the daily dose of 4.3 mg/kg), 8 in each group. Another 8 normal glucose C57 mouse of the same age and strain were recruited as the control group. All interventions lasted for 12 weeks by gastrogavage. The fasting blood glucose (FBG), body weight, food intake, water intake, skin temperature, the length of tail, and the degree of fatty liver were monitored. The hemoglobin A1c (HbA1c), total cholesterol (TC), and LDL-C were determined. Endothelin-1 (ET-1) was determined by radioimmunoassay. Nitrogen monoxidum (NO) was determined by nitrate reductase. The kidney tissue VCAM-1 level was analyzed with ELISA. The expression of VCAM-1 mRNA in the kidney tissue was detected with real time quantitative PCR.</p><p><b>RESULTS</b>Compared with the control group, the body weight and food intake decreased, water intake increased in all the other model groups (P < 0.05). Besides, the curve of blood glucose was higher in all the other model groups than in the control group (P < 0.01). Compared with the model group, the body weight increased; levels of HbAlc, TC, LDL-C, ET-1, and VCAM-1 were significantly lower; and skin temperature was higher in the DGR group (P < 0.05, P < 0.01). Compared with the PIO group, body weight, the increment of body weight, FBG, TC, and LDL-C were lower (P < 0.05, P < 0.01); food intake and water intake increased more and the tail length was longer in the DRG group (P < 0.01). There was no statistical difference in the level of NO among groups. The degree of fatty liver in the model group was significantly severer than that in the control group (P < 0.05). It was obviously alleviated in the DGR group (P < 0.05) when compared with the model group and the PIO group (P < 0.05, P < 0.01). But it was severer in the PIO group than in the model group (P < 0.01). The degree of fatty liver in the combination group ranged between that of the DGR group and the PIO group (P < 0.05). The level of VCAM-1 mRNA expression was significantly lower in the DGR group than in the model group, the PIO group, and the combination group (P < 0.05).</p><p><b>CONCLUSIONS</b>DGR had effect in lowering blood glucose and blood lipids, and fighting against fatty liver of transgenic Apo E(-/-) mouse with spontaneous atherosclerosis. DGR played an effective role in preventing and treating DM with angiopathy by comprehensively regulating glycolipid metabolism and promoting the vascular function.</p>

Gated Myocardial Perfusion Imaging Quantitative Analysis Technique in Evaluation of Left Ventricular Remodeling and Its Effect on Cardiac Function After Myocardial Infarction / 中国医学影像学杂志

Purpose To investigate the clinical value of gated myocardial perfusion imaging (GMPI) quantitative analysis technique in evaluating left ventricular remodeling and its effects on left ventricular function in patients with myocardial infarction (MI). Materials and Methods Seventy-six cases of MI patients were retrospectively analyzed, including pure left anterior descending artery (LAD) disease in 21 cases , left circumlfex artery (LCX) or right coronary branch (RCA) disease in 23 patients and multivessel disease in 32 cases. Seventy-four healthy people were additionally selected as control group. GMPI was performed on all subjects. Reconstruction images were automatically analyzed by using cardiac software QGS 2009 to obtain left ventricular remodeling index, including diastolic sphericity index (SIED) and end-systolic sphericity index (SIES). Cardiac function parameters were also obtained, including left ventricular end-diastolic volume (EDV), end-systolic volume (ESV), left ventricular ejection fraction (LVEF), and peak iflling rate (PFR). Differences of the left ventricular remodeling index and cardiac function parameters between the MI group and the control group were compared to analyze the relationship between left ventricular remodeling after myocardial infarction and coronary artery lesions. Results SIED, SIES and EDV, ESV in MI group were signiifcantly higher than those in the normal group (P0.05). Linear regression analysis showed that LVEF and PFR in group of left ventricular remodeling was signiifcantly lower with the increase of SIED (F=43.231 and 15.642, P<0.01). SIED and SIES analysis resulted in high correlation for both intra-observer and inter-observer (r=0.881-0.926, P<0.01). Conclusion Left ventricular remodeling after myocardial infarction can be accurately evaluated by GMPI. Patients with myocardial infarction due to LAD or multi-vessel coronary artery diseases may have left ventricular remodeling easier and more severe. Left ventricular remodeling will seriously affect the myocardial contraction and diastolic function, resulting in the entire left ventricular dysfunction.

IL-13 R110Q, a Naturally Occurring IL-13 Polymorphism, Confers Enhanced Functional Activity in Cultured Human Bronchial Smooth Muscle Cells

PURPOSE: Interleukin (IL)-13, a Th2-type cytokine, plays a pivotal role in the pathogenesis of asthma through its direct effects on airway smooth muscles. A naturally occurring IL-13 polymorphism, R110Q, is strongly associated with increased total serum IgE levels and asthma. In the present study, we aimed to determine whether the IL-13 R110Q variant would display different biochemical properties or altered functions in comparison with wild-type (WT) IL-13 in cultured human bronchial smooth muscle cells (hBSMCs). METHODS: Culture supernatants and cell proteins were collected from cultured hBSMCs that were treated with 50 ng/mL IL-13 or IL-13 R110Q for 24 hours. Eotaxin released into hBSMC culture medium was determined by ELISA. The expression levels of the high-affinity IgE receptor (FcepsilonRI) alpha-chain, smooth muscle-specific actin alpha chain (alpha-SMA), smooth muscle myosin heavy chain (SmMHC), and calreticulin in the cells were measured on Western blots. RESULTS: Compared with WT IL-13, treatment with the IL-13 R110Q variant resulted in a significant increase in eotaxin release as well as significant, although modest, increases in the expression levels of alpha-SMA, SmMHC, calreticulin, and FcepsilonRI alpha-chain. CONCLUSIONS: The results of the present study suggenst that the IL-13 R110Q variant may enhance enhanced functional activities in hBSMCs.

IL-13 R110Q, a Naturally Occurring IL-13 Polymorphism, Confers Enhanced Functional Activity in Cultured Human Bronchial Smooth Muscle Cells

PURPOSE: Interleukin (IL)-13, a Th2-type cytokine, plays a pivotal role in the pathogenesis of asthma through its direct effects on airway smooth muscles. A naturally occurring IL-13 polymorphism, R110Q, is strongly associated with increased total serum IgE levels and asthma. In the present study, we aimed to determine whether the IL-13 R110Q variant would display different biochemical properties or altered functions in comparison with wild-type (WT) IL-13 in cultured human bronchial smooth muscle cells (hBSMCs). METHODS: Culture supernatants and cell proteins were collected from cultured hBSMCs that were treated with 50 ng/mL IL-13 or IL-13 R110Q for 24 hours. Eotaxin released into hBSMC culture medium was determined by ELISA. The expression levels of the high-affinity IgE receptor (FcepsilonRI) alpha-chain, smooth muscle-specific actin alpha chain (alpha-SMA), smooth muscle myosin heavy chain (SmMHC), and calreticulin in the cells were measured on Western blots. RESULTS: Compared with WT IL-13, treatment with the IL-13 R110Q variant resulted in a significant increase in eotaxin release as well as significant, although modest, increases in the expression levels of alpha-SMA, SmMHC, calreticulin, and FcepsilonRI alpha-chain. CONCLUSIONS: The results of the present study suggenst that the IL-13 R110Q variant may enhance enhanced functional activities in hBSMCs.

PEG-mediated covalent binding of VEGF to decellularized aortic valves promotes adhesion and proliferation of endothelial progenitor cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To improve the biological properties of decellularized aortic valves by polyethylene glycol (PEG)-mediated covalent incorporation of vascular endothelial growth factor (VEGF).</p><p><b>METHODS</b>PEG crosslinking of decellularized aortic valves were completed via a Michael-type addition reaction, followed by covalent incorporation of VEGF through another Michael-type addition reaction between the unsaturated propylene acyl of PEG and the thiol groups on cysteine residues of VEGF. The effect of VEGF incorporation was evaluated by enzyme-linked immunosorbent assay (ELISA) and immune fluorescence assay. The endothelial progenitor cells (EPCs) were seeded on decellularized aortic valves with or without these modifications, and after 10 days of culture, the valves were examined for DNA content and by hematoxylin-eosin staining and scanning electron microscopy.</p><p><b>RESULTS</b>Immune fluorescence and ELISA showed that the maximal VEGF incorporation on the decellularized aortic valve reached 908.94∓0.27 pg. Compared with the unmodified valves and the valves with PEG crosslinking, decellularized aortic valves with covalent incorporation of VEGF significantly promoted the adhesion and proliferation of EPCs, which formed a confluent cell monolayer on the valve surface.</p><p><b>CONCLUSIONS</b>PEG-mediated covalent incorporation of VEGF in the decellularized aortic valves improves the adhesion and proliferation of the seeded EPCs to facilitate the construction of tissue-engineered heart valves.</p>

Association of ABCG2 gene C421A polymorphism and susceptibility of primary gout in Han Chinese males / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association between a C421A single nucleotide polymorphism (SNP) in exon 5 of ATP-binding cassette, sub-family G (WHITE), member 2 (ABCG2) gene and susceptibility of primary gout in Han Chinese males.</p><p><b>METHODS</b>For 200 male patients with primary gout and 235 controls, the genotype of C421A locus was analyzed by PCR and direct sequencing. Blood glucose, uric acid, total cholesterol, triglycerides, creatinine and urea nitrogen was measured by an automatic biochemical analyzer.</p><p><b>RESULTS</b>Compared with the controls, there was a higher frequency for AA genotype and A allele of the rs2231142 SNP in gout patients (22.5% vs. 8.5% by genotype; 44.9% vs. 32.3% by allele). The association with gout reached significance (chi-square =15.91, P< 0.001, crude OR=3.02, 95% CI:1.36-4.90 and OR (adjusted by age)=1.80, 95% CI: 1.32-2.45 by dominant mode; chi-square=6.82, P=0.009, OR=1.67, 95% CI: 1.54-2.27 by recessive mode). Blood glucose, uric acid, triglycerides, creatinine and urea nitrogen levels in gout patients were significantly higher than those of controls (P< 0.001).</p><p><b>CONCLUSION</b>The C421A SNP, in particular AA phenotype, may be associated with susceptibility of primary gout in Han Chinese males.</p>

Progress in the association of high affinity IgE receptor with asthma / 国际儿科学杂志

Childhood asthma is one of type Ⅰ allergic diseases,and IgE is indispensable factor in development of asthma.IgE-antigen crosslinking of hish affinity IgE receptor(FcεRⅠ)leads to degranulation of mast cell,leukotriene synthesis and cytokine production.As a re8ult.such changes will bring about inflammation of airway and spasm of airway smooth muscle.Recent researches suggest that Src tyresine kinase play a vital role in their combination.This review discusses the regulation and signaling trannduction of FcεR Ⅰ and the relationship between FcεRⅠ and asthma.

Borderline clear cell adenofibroma with extensive hemorrhagic necrosis

Borderline clear cell adenofibroma of the ovary is rather rare since most of clear cell tumors are carcinomas. We report a case of ovarian borderline clear cell adenofibroma in a 52-year-old postmenopausal woman. The tumor had the characteristic histologic features of borderline clear cell adenofibroma except for central extensive hemorrhagic necrosis. The prognosis of borderline clear cell adenofibroma is excellent. Because the invasiveness cannot be assessed in the necrotic areas, our patient needed long-term follow-up

Enfermedad tuberculosa entre trabajadores de salud / Tuberculosis disease among health care workers

Introducción: la transmisión de Mycobacterium tuberculosis es un riesgoreconocido en las instituciones de salud. El riesgo varía según el tipo de instalación, la prevalencia de tuberculosis (TB) en la comunidad, el grupo ocupacional de los trabajadores, el área de la instalación en que trabajan y la efectividad del control. Objetivo: describir las características de la enfermedad tuberculosa y los resultados del tratamiento entre los trabajadores de salud atendidos en el Programa de Control de la Tuberculosis del Hospital Nacional Cayetano Heredia. Material y método: estudio descriptivo observacional de casos entre trabajadores de salud (TS) y pacientes (controles) entre que ingresaronal Programa de Control de la Tuberculosis (PCT) del Hospital Nacional Cayetano Heredia (HNCH) entre 1994 al 2007. Resultados: de enero 1994 a diciembre 2007 se atendieron 957 enfermos de tuberculosis de los cuales 159 (16,6 por ciento) fueron TS, con edad promedio de 31,05 ±8,79, siendo 84 (52,8 por ciento) mujeres y 122 (76,7 por ciento) con enfermedad pulmonar. De estos 36,5 por ciento fueron profesionales y 34,6 por ciento estudiantes de ciencias de la salud. Entre los profesionales de la saludhubo 41 médicos (71 por ciento) y de ellos los residentes fueron mayoría (63 por ciento). Entre los estudiantes de ciencias de la salud el grupo mayoritario fue el de los estudiantes de medicina (87 por ciento), y dentro de ellos la mayoría (75 por ciento) externos e internos. De 20 cepas con sensibilidad realizada 11 (55 por ciento) fueron resistentes al menos a un fármaco, 5 (25 por ciento) multidrogoresistentes, 8 (40 por ciento) resistentes a isoniacida, 6 (30 por ciento) a rifampicina, 6 (30 por ciento) a estreptomicina y 4 (20 por ciento) a etambutol. Setenta y cuatro (60,7 por ciento) de los 122 TS con TB pulmonar ingresaron con BK negativo, y sólo 41 (33,6 por ciento) controles (p<0,001). Los TS recibieron el mismo tipo y tiempo de tratamiento (7,2 ± 3,1 meses) que sus controles ...

Introduction: Tuberculosis (TB) transmission is a well-recognized risk in health care facilities. This risk is variable considering to the nature of such facilities (primary, secondary, or tertiary care), the prevalence of TB in the community, occupational groups of healthcare workers (HCW), the particular area in which they work, and the effectiveness of control programs. Objectives: To describe the features of TB and results of therapy for this disease in HCW seen in the TB Control Program in Cayetano Heredia National Hospital in Lima, Peru. Material and methods: A descriptive observational study was performed, including cases (HCWs) and controls (patients) admitted in the TB Control Program in Cayetano Heredia National Hospital in Lima, Peru, between 1994 and 2007. Results: 957 TB cases were seen in the TB Control Program in Cayetano Heredia Hospital from January 1994 to December 2007. One hundred and fifty nine (16,6 per cent) were HCW, their average age was 31,05 ± 8,79 years, 84 (52,8 per cent) were female, and 122 (76,7 per cent) developed pulmonary disease. Of these latter cases, 36,5 per cent were healthcare professionals and 34,6 per cent were medicine, nursing, or health technology students. Amongst healthcare professionals that developed TB, 41 (71 per cent) were physicians, and most of them (63 per cent) were residents in-training. Amongst students, medicine students accounted for most TB cases (87 per cent), and 75 per cent of them were senior medical students (interns and 6th year). Twenty isolated of M. tuberculosis had susceptibility tests performed, 11 (55 per cent) were resistant to at least one antituberculous drug, 5 (25 per cent) were multidrug resistant M. tuberculosis isolates, 8 (40 per cent) were isoniazid-resistant, 6 (30 per cent), were rifampin-resistant, 6 (30 per cent) were streptomycin-resistant, and 4 (20 per cent) were ethambutol-resistant. Seventy four (60,7 per cent) of 122 HCWs with pulmonary TB entered the Program...