[Prognostic analysis of patients with acute leukemia and central nervous system involvement undergoing allogeneic hematopoietic stem cell transplantation].

Objective: To investigate the potential of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in mitigating the adverse prognosis associated with central nervous system leukemia (CNSL) and to assess the significance of prophylactic intrathecal injection. Methods: A retrospective cohort analysis was conducted involving 30 patients with acute leukemia who had a history of CNSL who underwent allo-HSCT at Peking University People's Hospital between September 2012 and March 2018 (referred to as the CNSL-positive group). In addition, 90 patients with acute leukemia were selected from the same period who underwent allo-HSCT without a history of CNSL (referred to as the CNSL-negative group) and a rigorous 1∶3 matching was performed based on disease type, disease status, and transplantation type to form the control group. The prognosis between the two groups was compared using Kaplan-Meier analysis and the high-risk factors for CNSL relapse post-transplant were identified through Cox proportional-hazards model. Results: The median age of patients in the CNSL-negative group was significantly higher than that of patients in the CNSL-positive group (32 years vs. 24 years, P=0.014). No significant differences were observed in baseline data, including sex, disease type, disease status at transplantation, donor-recipient relationship, and human leukocyte antigen consistency between the two groups. The median follow-up time was 568 days (range: 21-1 852 days). The 4-year cumulative incidence of relapse (71.4%±20.9% vs. 29.3%±11.5%, P=0.005) and the cumulative incidence of CNSL post-transplant (33.6%±9.2% vs. 1.2%±1.2%, P<0.001) were significantly higher in the CNSL-positive group than in the CNSL-negative group. Furthermore, the 4-year leukemia-free survival rate in the CNSL-positive group was significantly lower than that in the CNSL-negative group (23.1%±17.0% vs. 71.5%±11.6%, P<0.001). However, no significant differences were observed in the 4-year cumulative transplant-related mortality and overall survival rates between the two groups (both P>0.05). Multivariate analysis revealed that a history of CNSL before transplantation (HR=25.050, 95%CI 3.072-204.300, P=0.003) was identified as high-risk factors for CNSL relapse post-transplant. Conversely, haploidentical transplantation was associated with a reduced risk of CNSL relapse post-transplant (HR=0.260, 95%CI 0.073-0.900, P=0.034). Within the CNSL-positive group, seven patients received prophylactic intrathecal therapy after transplantation, and their CNSL relapse rate was significantly lower than that of the 23 patients who did not receive intrathecal therapy after transplantation (0/7 vs. 9/23, P=0.048). Conclusions: Patients with a history of CNSL have a higher risk of relapse and experience poorer leukemia-free survival following transplantation. The use of prophylactic intrathecal injection shows promise in mitigating CNSL relapse rates, although further validation through prospective studies is necessary to substantiate these observations.

[Comparison of three dimensional CT venography and ascending phlebography based on propensity score matching in the evaluation of recurrent varicose veins].

Objective: To compare the efficacy of lower extremity three dimensional CT venography (CTV) and lower extremity ascending phlebography in evaluating recurrent varicose veins. Methods: A retrospective analysis was conducted on clinical data from 235 patients with unilateral recurrent varicose veins who were treated at the Department of Vascular Surgery,Beijing Shijitan Hospital,Capital Medical University, between January 2015 and December 2020.There were 112 males and 123 females, with an age of (62.5±11.4)years (range:24 to 75 years).Patients were stratified into two groups based on preoperative imaging examination:the CTV group (utilizing lower extremity venous ultrasound+lower extremity CTV) and the control group (employing lower extremity venous ultrasound+lower extremity ascending phlebography).The two groups were matched in a 1∶1 ratio using propensity score matching, resulting in 43 cases per group.Comparative analyses between the groups at the one-year postoperative follow-up were performed using independent sample t tests, Wilcoxon rank-sum tests, χ2 tests, and linear regression analysis. Results: One year post-surgery,the CTV group exhibited a lower venous clinical severity score (VCSS) compared to the control group(M(IQR),3.0(4.3) vs.4.0(5.8),Z=-2.038,P=0.040).Additionally, the chronic venous insufficiency patients' quality of life questionnaire (CIVIQ-20) scores were significantly higher in the CTV group than in the control group (89.0(8.0) vs.82.5(17.0), Z=-2.627, P=0.010).Patients in the CTV group also experienced a shorter ulcer healing time compared to the control group (4.0(4.0) weeks vs.12.0(7.0) weeks, Z=-3.217,P<0.01).Both groups showed no clinically symptomatic recurrent varicose veins or ulcers.However, they exhibited ultrasound-detectable varicose vein recurrence, with no statistically significant difference (χ2=0.453,P=0.500).The number of diseased vessels requiring management based on ultrasound supplemented by CTV was 16, while the number supplemented by ascending phlebography was 7,with a statistically significant difference (χ2=4.800,P=0.030).Linear regression analysis demonstrated that clinical-etiology-anatomy-pathology clinical grading and the preoperative imaging examination method exerted independent influences on VCSS and CIVIQ-20 during the one-year postoperative assessment. Conclusions: CTV-assisted ultrasound enables a direct and comprehensive evaluation and localization of diseased veins in patients with recurrent varicose veins.The utilization of lower extremity vein ultrasound combined with CTV-guided management of lower extremity vessels in minimally invasive treatment significantly improves patient prognosis, surpassing the assessment provided by ascending phlebography.

[Insulin-like growth factor-1 alleviates hepatocyte senescence by regulating intranuclear p53-progerin pathway].

To construct cellular senescence model by stimulating primary hepatocytes with hydrogen peroxide (H(2)O(2)). Primary hepatocytes were transfected with p53 siRNA, progerin siRNA or IGF-1 adenovirus vector. The number of SA-ß-Gal stained positive cells and the expression of p53 and progerin were detected. The results showed that p53 siRNA and progerin siRNA had knocked-down the expression of p53 and progerin, and had alleviated the hepatocyte senescence. Transfection of insulin-like growth factor (IGF)-1 adenovirus vector into primary hepatocytes had overexpressed IGF-1, and had alleviated the number of SA-ß-Gal-positive cells. The expression of p53 and progerin was down-regulated in the nucleus, while the expression of p53 was up-regulated in the cytoplasm. The co-precipitation and co-localization of p53 and progerin was decreased in the nuclear region of hepatocytes. IGF-1 overexpression can inhibit intranuclear p53 translocation, alleviate the interaction between p53-progerin, and alleviate hepatocyte senescence.

[Long-term efficacy of radiofrequency closure in the treatment of great saphenous vein varicose].

Objective: To examine the long-term efficacy of radiofrequency closure in the treatment of great saphenous vein varicose. Methods: The clinic data of 185 patients with varicose veins of lower limbs treated with radiofrequency closure admitted at Department of Vascular Surgery, Beijing Shijitan Hospital, Capital Medical University from July 2016 to January 2017 was analyzed retrospectively. A total of 203 limbs were treated by radiofrequency closure. The long-term efficacy of radiofrequency closure was evaluated by analyzing the closure rate, clinical-etiology- anatomy-pathophysiology (CEAP) grading, venous clinical severity score (VCSS), chronic venous insufficiency questionnaire (CIVIQ) score, and complications, using repeated measures analysis of variance. Results: All procedures were successful. The closure rate was 98.0% (199/203) at one year and two years postoperative, which was still maintained at 97.5% (198/203) at 3 years of follow-up. Postoperative CEAP grading was significantly downgraded compared with that before the operation. Totally 88.4% (76/86) of C5 to C6 grade patients downgraded to C2 to C4 grade at 6 months, and 95.3% (82/86) downgraded to C0 to C2 garde at 3 years postoperative. VCSS and CIVIQ score in both groups significantly improved at all follow-up time points compared to preoperative scores (VCSS: F=1 064.7, P=0.003; CIVIQ score: F=2 984.3, P=0.001). The most common complication was subcutaneous blood stasis (10.8%), most of which disappeared within 1 month after the surgery. Other complications included pigmentation and thrombophlebitis (5.9% and 3.9%, respectively). Conclusion: The long-term efficacy of radiofrequency closure of the great saphenous vein is satisfactory.

[The study of nomogram based on Ishak inflammation score for recurrence of hepatocellular carcinoma after curative resection].

Objective: To investigate the correlation between Ishak inflammation score and the clinicopathological characteristics and recurrence of patients with hepatocellular carcinoma (HCC) after curative resection, and then set up a recurrence nomogram for HCC. Methods: A total of 326 patients with HCC after curative resection from January 2006 to December 2009 were studied retrospectively as training cohort and 110 HCC patients after surgery from January 2010 to December 2012 were used as validation cohort.Clinical follow-up data and peritumoral Ishak inflammation score in training cohort were used to set up a nomogram predicting recurrence of HCC, which was verified by validation cohort. Kaplan-Meier and Cox proportional hazard regression model were used to analyzed accuracy of model prediction. Results: According to Ishak inflammation score, patients were divided into four subgroups: Grade Ⅰ(1-4 scores), Grade Ⅱ(5-8 scores), Grade Ⅲ (9-12 scores) and Grade Ⅳ(13-18 scores). Ishak inflammation score were associated with aspartate transaminase(median 36.0 U/L, P=0.011), γ-glutamyl transpeptidase(median 54.5 U/L, P=0.005), HBV-DNA load(20.5%>10(6) copies/ml, P=0.015) and microvascular invasion(26.7% positive, P=0.021). Multivariate analysis showed that Ishak inflammation score(P=0.007), HBV-DNA load(P<0.01), tumor size(P=0.001) and microvascular invasion(P=0.001) were related with the recurrence of HCC patients.These four risk factors were incorporated into the nomogram.Calibration curves of the nomogram had good agreement between prediction and observation in the probability of recurrence.Both C-indexes and receiver operating characteristic curve analyses revealed that this nomogram had better predictive abilities than those of the AJCC and Barcelona Clinic Liver Cancer (BCLC) stage systems.These results were verified by the validation cohort. Conclusion: A nomogram based on Ishak inflammation score could accurately predict the recurrence of HCC and contribute to HCC relapse surveillance after curative hepatectomy.

[Validation of the Caprini risk assessment model for venous thromboembolism in Chinese hospitalized patients in a general hospital].

Objective: To assess the validity of Caprini risk assessment model in prediction of venous thromboembolism in Chinese hospitalized patients in a general hospital. Methods: Medical record review was performed in Beijing Shijitan Hosital for all eligible hospitalized patients who underwent screening for venous thromboembolism between January and December 2015. The Caprini score of patients with or without venous thromboemboilism and incidence of venous thromboembolism in patients with various Caprini risk levels, surgery and medical patients was compared. Results: A total of 6 966 inpatients were enrolled. Three hundred and ninety-six patients developed venous thromboembolism. The Caprini median score of patients with venous thromboemboilism was 5 (3-7), which higher than 3(2-5) of patients without venous thromboembolism(Z=-13.68, P<0.01). Incidence of venous thromboembolism of patients in low, moderate, high, highest risk level was 1.0%, 1.8%, 5.7%, 10.6%, respectively. There was no statistically significant difference of incidence between low and moderate risk patients (OR=1.88, 95%CI: 0.89-3.99, P>0.05), but significant difference between moderate and high risk (OR=3.23, 95%CI: 2.06-5.06, P<0.01), high and highest risk patients (OR=1.97, 95%CI: 1.59-2.45, P<0.01). There was no incidence difference of venous thromboembolism between surgery and medical patients in the same Caprini level of low (χ(2)=3.58 , P>0.05), moderate(χ(2)=2.89, P>0.05), high(χ(2)=0.46, P>0.05), highest risk(χ(2)=1.61, P>0.05). Conclusion: Caprini risk assessment model can effectively predict the occurence of venous thromboembolism in Chinese hospitalized patients with high risk of VTE(Caprini score >2)in a general hospital.

[Expression of Brain Natriuretic Peptide in Myocardial Tissue of Sudden Cardiac Death and Non-sudden Cardiac Death].

OBJECTIVES: To study the expression pattern of brain natriuretic peptide （BNP） in myocardial tissue from forensic routine cases and to explore its application value in the forensic determination of sudden cardiac death （SCD）. METHODS: The data of 96 autopsy cases accepted by the center of Medico-legal Investigation of China Medical University between December 2008 to May 2014 were collected. There were 62 cases in SCD group cardiac and 34 cases in non-SCD group. The myocardial tissues were taken from left and right ventricular wall, respectively. The expressions of BNP protein and BNP mRNA in myocardial tissue were detected by HE staining, immunohistochemical staining, Western blotting and quantitative real-time reverse transcription-polymerase chain reaction （RT-qPCR）, etc. RESULTS: The immunohistochemical staining of myocardial tissue showed diffusely positive staining in SCD group, and patchily or diffusely positive staining in non-SCD group with lighter degree. The result of Western blotting showed that the expression of BNP protein elevated in left ventricular wall of SCD group. The result of RT-qPCR showed a positive correlation between the BNP mRNA expressions in bilateral ventricular walls and the heart weight, bilateral lung weight, and N-terminal prohormone of brain natriuretic peptide （NT-proBNP） concentration. There were large differences between the BNP mRNA concentrations in SCD group and non-SCD group, and the former was statistically higher （P<0.05）. CONCLUSIONS: The expressions of BNP protein and BNP mRNA in myocardial tissue are related to the causes of death. Combined with pathological changes, the expressions of BNP protein and BNP mRNA in myocardial tissue have certainly practical significance for the determination of SCD and the analysis of the death mechanism in the cases related to forensic pathology.

[The Changes of HIF-1α and VEGF-A in Myocardial Tissue of Rats with Arrhythmias].

OBJECTIVES: To observe the expression changes of hypoxia inducible factor-1α（HIF-1α） and vascular endothelial growth factor-A （VEGF-A） in rats with arrhythmias, and to explore the differences of the expression pattern in the two indicators of acute myocardial ischemia caused by arrhythmias and coronary insufficiency. METHODS: The arrhythmia was induced by CaCl2, and the expression changes of HIF-1α and VEGF-A were detected by immunohistochemistry, Western blotting and real-time PCR within 6 h after the arrhythmia in rats. RESULTS: The expression of HIF-1α and VEGF-A showed diffuse in the myocardial tissue of rats died from arrhythmias. Both of them increased in the early arrhythmia, then decreased. Extensive myocardial ischemia happened at the beginning of arrhythmia occurrence and its range didn't expand with time. CONCLUSIONS: The expressions of HIF-1α and VEGF-A in myocardium of the rats with arrhythmia can provide evidence for the differential diagnosis of acute myocardial ischemia caused by fatal arrhythmia and coronary insufficiency.

Expression of IL-21 in rats with inflammatory bowel disease.

The purpose of this study was to investigate the expression of interleukin (IL)-21 in rats with inflammatory bowel disease (IBD). Fifty adult Wistar rats were randomly divided into two groups: DSS, in which IBD was induced by giving the rats 7% DSS for seven days in their water, and a water control. Blood samples were collected and the concentration of IL-21 in serum was detected by enzyme-linked immunosorbent assay. Colon tissue of rats was examined by immunohistochemical staining. Rats in the DSS group were lethargic, with matte coat color and decreasing body weight. In the DSS group, brown loss stool appeared after four days, and blood appeared in the stool along with dark red hematocele in the intestinal cavity after ten days. Rats in the control group were active and body weight increased regularly. Their stool was black and granular and the color of the intestinal canal was pink. The original body weight of all rats in both groups was similar but seven days after induction of IBD, the weight of the DSS rats dropped significantly compared to the control group (P < 0.05). Serum IL-21 levels were 1.37 ± 0.43 pg/mL in the control group and 3.86 ± 1.27 pg/mL in the DSS group (P < 0.05). More IL-21 positive cells were detected in the intestinal mucosal epithelial cell layer and the lamina propria of the submucosa in the DSS group than in the control group. In conclusion, IL-21 is involved in the pathological process of IBD.

Characterization and significance of MUC1 and c-myc expression in elderly patients with papillary thyroid carcinoma.

The aim of this study was to examine the expression of mucin 1 (MUC1) and c-myc and the significance thereof in elderly patients with papillary thyroid carcinoma. The expression levels of MUC1 and c-myc were examined by immunohistochemical methods in 58 patients with papillary thyroid carcinoma, 35 with nodular goiter, and 30 subjects with normal thyroid tissue. The positive rate of MUC1 detection in papillary thyroid carcinoma was 77.6% (45/58), while it was 90.0% (9/10) in those with infiltration and 88.2% (15/17) in those with lymphatic metastasis. The positive rate of c-myc was 81.0% (47/58) in those with papillary thyroid carcinoma and 100.0% (17/17) in those with lymphatic metastasis. These results demonstrated that there were differences in MUC1 and c-myc expression in benign and papillary thyroid carcinoma and that these differences were related to thyroid cancer lymphatic metastasis.

Relationship between vitamin D receptor (VDR) polymorphisms and the efficacy of recombinant human growth hormone (rhGH) treatment in children with idiopathic short stature.

Polymorphisms in the vitamin D receptor (VDR) gene are associated with idiopathic short stature (ISS) in several countries. This study aimed to identify a possible correlation between polymorphisms in the VDR promoter in Chinese children with ISS and the efficacy of the recombinant human growth hormone (rhGH) treatment. Pre-pubertal children with ISS and healthy age- and gender-matched children (N = 95 each) were enrolled in this study. Two single nucleotide polymorphisms (SNPs) in the VDR promoter (rs11568820 at the Cdx-2-binding site upstream of exon 1e and rs4516035 at -1012 upstream of exon 1a) were typed. The growth velocity, standard deviation score (SDS) of height for chronological age, height SDS for bone age, predicted adult height, and serum insulin-like growth factor 1 (IGF-1) and IGF-binding protein 3 (IGFBP-3) levels of the ISS patients were determined before and 6 months after rhGH treatment. No significant differences were observed in the genotype frequencies between the ISS cases and controls. After rhGH treatment, the growth velocity of the A/G genotype at the Cdx-2-binding site SNP locus was significantly higher than that of the G/G genotype; the IGF-1 and IGFBP-3 levels were also higher in the treated group than the untreated group. However, these changes were independent of the VDR-promoter genotype. Polymorphisms in the VDR promoter may not result in the pathogenesis of ISS in Chinese children. The A/G genotype showed a significantly higher growth velocity than the G/G genotype, and may represent a short-term marker of growth potential.

Dosage assessment of valnemulin in pigs based on population pharmacokinetic and Monte Carlo simulation.

To estimate the valnemulin pharmacokinetic profile in a swine population and to assess a dosage regimen for increasing the likelihood of optimization. This study was, respectively, performed in 22 sows culled by p.o. administration and in 80 growing-finishing pigs by i.v. administration at a single dose of 10 mg/kg to develop a population pharmacokinetic model and Monte Carlo simulation. The relationships among the plasma concentration, dose, and time of valnemulin in pigs were illustrated as C(i,v) = X(0 )(8.4191 × 10(-4) × e(-0.2371t) + 1.2788 × 10(-5) × e(-0.0069t)) after i.v. and C(p.o) = X(0) (-8.4964 × 10(-4) × e(-0.5840t) + 8.4195 × e(-0.2371t) + 7.6869 × 10(-6) × e(-0.0069t)) after p.o. Monte Carlo simulation showed that T(>MIC) was more than 24 h when a single daily dosage at 13.5 mg/kg BW in pigs was administrated by p.o., and MIC was 0.031 mg/L. It was concluded that the current dosage regimen at 10-12 mg/kg BW led to valnemulin underexposure if the MIC was more than 0.031 mg/L and could increase the risk of treatment failure and/or drug resistance.

Diagnostic accuracy of atopy patch tests for food allergy in children with atopic dermatitis aged less than two years.

BACKGROUND: Atopy patch tests (APT) have been introduced as a valuable tool for the diagnosis of food allergy. However, interpretation of the readout of APT requires further clarification. OBJECTIVE: To investigate the accuracy of APT in identifying atopic sensitisation to hen's eggs (HE), cow's milk (CM), soybean and wheat in Chinese children with atopic dermatitis (AD) aged less than two years and to evaluate skin signs of APT for accurate diagnosis of food allergy. METHODS: APT was performed and food allergy confirmed by open oral food challenges with HE, CM, soybean and wheat in 150 Chinese AD children aged less than two years. The sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, positive (LR+) and negative likelihood ratio (LR-) of APT were calculated. RESULTS: Erythema and infiltration were not sufficiently indicative of a positive APT. The PPV increased with the appearance of indurations and the number of papules. The true positive APT rate increased from scores of + to +++. The PPV and specificity were 100% while APT scores of +++ were obtained with HE, CM and wheat. The sensitivity of APT with HE, CM, soybean and wheat allergy ranged from 59.6% to 90.5%, while the specificity ranged from 82.1% to 92.4%. CONCLUSION: The APT is a suitable method for the diagnosis of AD in Chinese children aged less than two years with food allergies. Erythema and infiltration are not sufficient indicators of APT positivity. The PPV increases with indurations and the number of papules.

2,3,7,8-Tetrachlorodibezo-p-dioxin exposure and prostate cancer: a meta-analysis of cohort studies.

OBJECTIVE: To perform a meta-analysis of cohort studies and evaluate the association between exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and prostate cancer quantitatively. STUDY DESIGN: Publications before April 2012 about populations exposed to TCDD were searched in PubMed. Only cohort studies were included. Extraction and quality assessment of included articles was performed independently by two authors using the MOOSE guidelines. METHODS: A total of 17 cohort studies on prostate cancer with information about standardized mortality ratios (SMR), risk ratio (RR), standardized incidence ratios (SIR) and TCDD exposure were included. SMRs and RRs were pooled separately after weighing each study by calculating the inverse of the estimated variance. RESULTS: Based on the 13 reported SMRs or SIRs, the meta-analysis yielded a meta-SMR of 1.26 (95% confidence interval 1.00-1.57, P = 0.046). The meta-RR, based on four reported RR from four cohorts, was 1.04 (95% confidence interval 0.85-1.28). Begg's funnel plot showed little evidence of publication bias (Egger's test P-value = 0.817). CONCLUSION: This meta-analysis suggests that exposure to TCDD is associated with increased risk of prostate cancer.

A discrete-to-continuum model for the human cornea with application to keratoconus.

We introduce a discrete mathematical model for the mechanical behaviour of a planar slice of human corneal tissue, in equilibrium under the action of physiological intraocular pressure (IOP). The model considers a regular (two-dimensional) network of structural elements mimicking a discrete number of parallel collagen lamellae connected by proteoglycan-based chemical bonds (crosslinks). Since the thickness of each collagen lamella is small compared to the overall corneal thickness, we upscale the discrete force balance into a continuum system of partial differential equations and deduce the corresponding macroscopic stress tensor and strain energy function for the micro-structured corneal tissue. We demonstrate that, for physiological values of the IOP, the predictions of the discrete model converge to those of the continuum model. We use the continuum model to simulate the progression of the degenerative disease known as keratoconus, characterized by a localized bulging of the corneal shell. We assign a spatial distribution of damage (i.e. reduction of the stiffness) to the mechanical properties of the structural elements and predict the resulting macroscopic shape of the cornea, showing that a large reduction in the element stiffness results in substantial corneal thinning and a significant increase in the curvature of both the anterior and posterior surfaces.

Anti-erythropoietin receptor antibodies in systemic lupus erythematosus patients with anemia.

Anemia is a common hematologic abnormality in systemic lupus erythematosus (SLE). An inadequate erythropoietin (EPO) response in SLE patients with anemia has been described that may be due to the presence of antibodies to EPO in SLE patients. However, whether anemia in patients with SLE is related to antibodies to EPO receptor (EPOR) has not yet been investigated. We enlisted 169 consecutive patients with SLE and 45 normal individuals to investigate the existence and importance of circulating autoantibodies to EPOR in sera from patients with SLE. In all patients with SLE, the disease activity was evaluated by using the SLE disease activity index SLEDAI. Anti-EPOR antibodies were detected by using an enzyme-linked immunosorbent assay (ELISA). A higher frequency of anti-EPOR antibodies was observed in SLE patients than in healthy controls (18.3% vs 2.2%, p = 0.007). Moreover, anti-EPOR antibodies were detected in 22 of 69 (31.9%) SLE patients with anemia and in only nine of 100 (9.0%, p < 0.001) in those without. Furthermore, the patients with anti-EPOR antibodies exhibited more severe anemia and often presented as microcytic anemia (p = 0.001). Finally, anti-EPOR antibodies seemed more likely to occur in patients with rash (p = 0.008), lower levels of C(3) component (p = 0.01), higher titer of anti-dsDNA antibodies (p < 0.001) and higher disease activity scores (p = 0.024). The results of this study suggest that anti-EPOR antibodies might play a vital role in SLE patients developing anemia because of the higher incidence of antibodies to EPOR found in SLE patients with anemia. Thus, there might be clinical value in detecting anti-EPOR antibodies in SLE patients with anemia. Therefore, the pathologic role of the antibodies in inducing anemia needs to be established in future studies.

Vitamin D receptor gene BsmI polymorphism B allele, but not BB genotype, is associated with systemic lupus erythematosus in a Han Chinese population.

The vitamin D receptor (VDR) gene is a candidate gene for susceptibility to autoimmune disorders. Association studies of VDR polymorphisms and risk of systemic lupus erythematosus (SLE) have often produced conflicting results in different ethnic backgrounds. The aim of this study is to test the association between VDR gene BsmI polymorphism and the genetic susceptibility to SLE in a Han Chinese population. Three hundred and thirty-seven patients with SLE and 239 healthy controls were genotyped for the VDR gene BsmI polymorphism (rs1544410) by polymerase chain reaction and restriction fragment length polymorphism analysis in this study, after which the relationship between BsmI polymorphisms and the mRNA expression of VDR, as well as clinical manifestations in patients with SLE, was evaluated. It was found that the frequency of B allele was significantly increased in SLE relative to the control group (χ(2) = 4.681, p = 0.031), although the distribution of VDR BsmI polymorphism genotype frequencies did not differ significantly between patients and controls (χ(2) = 4.098, p = 0.129). Moreover, VDR B allele was found to be associated with lupus nephritis (p = 0.027) and also with production of anti-nucleosome antibodies (p = 0.037). The mRNA of VDR was markedly down-regulated in patients with VDR B allele compared with that in patients without B allele (p = 0.016). Our results indicate a possible role of genetic factors (the VDR B allele) in influencing disease susceptibility in Han Chinese patients. Also, VDR B allele is associated with the development of nephritis and the down-regulation of VDR mRNA expression in SLE.

Association of chemokine CXCL12-3'G801A polymorphism with systemic lupus erythematosus in a Han Chinese population.

CXCL12, also known as stromal cell-derived factor (SDF-1), is a CXC chemokine. Recent reports have shown that CXCL12 might play key roles in a murine model of lupus and in patients with systemic lupus erythematosus (SLE). A common variant at position 801 in 3'-untranslated region in CXCL12 gene (designated CXCL12-3'G801A) has been reported in association with autoimmune diseases, such as type 1 diabetes and systemic sclerosis. We investigated the influence of CXCL12-3'G801A polymorphism on susceptibility to SLE by genotyping this single nucleotide polymorphism in 422 SLE patients and 374 healthy controls. The frequency of G/G homozygote was observed in 60.0% of SLE patients and in 52.7% of healthy individuals (χ(2 )= 4.275, p = 0.039). Compared with patients with G/A and A/A genotype, SLE patients with G/G genotype were also more prone to developing photosensitivity (χ(2 )= 6.778, p = 0.034), renal damage (χ(2 )= 6.388, p = 0.041) and to producing antibodies against nucleosomes (χ(2 )= 8.341, p = 0.015). Moreover, the plasma level of CXCL12α was also significantly increased in patients with G/G homozygote than in healthy controls carrying the same genotype [(4067.0 ± 1092.3) pg/ml vs. (3278.5 ± 547.4) pg/ml, p = 0.002]. Our results suggest that polymorphism in CXCL12-3'G801A might be a genetic risk factor for developing SLE. The association of G/G homozygote with nephritis and skin damage developed in SLE patients might be due to its effects upon the production of auto-antibodies and CXCL12 protein.

A quasi-nonlinear analysis of the anisotropic behaviour of human gallbladder wall.

Estimation of biomechanical parameters of soft tissues from noninvasive measurements has clinical significance in patient-specific modeling and disease diagnosis. In this work, we present a quasi-nonlinear method that is used to estimate the elastic moduli of the human gallbladder wall. A forward approach based on a transversely isotropic membrane material model is used, and an inverse iteration is carried out to determine the elastic moduli in the circumferential and longitudinal directions between two successive ultrasound images of gallbladder. The results demonstrate that the human gallbladder behaves in an anisotropic manner, and constitutive models need to incorporate this. The estimated moduli are also nonlinear and patient dependent. Importantly, the peak stress predicted here differs from the earlier estimate from linear membrane theory. As the peak stress inside the gallbladder wall has been found to strongly correlate with acalculous gallbladder pain, reliable mechanical modeling for gallbladder tissue is crucial if this information is to be used in clinical diagnosis.