Iron chelators reverse organ damage in type 4B hereditary hemochromatosis: Case reports.

RATIONALE: Hereditary hemochromatosis (HH) is a hereditary disorder of iron metabolism. It is classified into 4 main types depending on the underlying genetic mutation: human hemochromatosis protein (HFE) (type 1), hemojuvelin (HJV) (type 2A), HAMP (type 2B), transferrin receptor-2 (TFER2) (type 3), and ferroportin (type 4). Type 4 HH is divided into 2 subtypes according to different mutations: type 4A (classical ferroportin disease) and type 4B (non-classical ferroportin disease). Type 4B HH is a rare autosomal dominant disease that results from mutations in the Solute Carrier Family 40 member 1 (SLC40A1) gene, which encodes the iron transport protein ferroportin. PATIENT CONCERNS: Here we report 2 elderly Chinese Han men, who were brothers, presented with liver cirrhosis, diabetes mellitus, skin hyperpigmentation, hyperferritinaemia as well as high transferrin saturation. DIAGNOSIS: Subsequent genetic analyses identified a heterozygous mutation (p. Cys326Tyr) in the SLC40A1 gene in both patients. INTERVENTIONS: We treated the patient with iron chelator and followed up for 3 years. OUTCOMES: Iron chelator helped to reduce the serum ferritin and improve the condition of target organs, including skin, pancreas, liver as well as pituitary. LESSONS: Type 4B HH is rare but usually tends to cause multiple organ dysfunction and even death. For those patients who have difficulty tolerating phlebotomy, iron chelator might be a good alternative.

Usefulness of controlled attenuation parameter and liver stiffness measurement for detecting increased arterial stiffness in asymptomatic populations in China.

In recent studies, vibration-controlled transient elastography (FibroScan) has been reported as an alternative noninvasive approach for measuring liver steatosis and fibrosis. The present study aimed to investigate the feasibility of FibroScan controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) in the detection of increased arterial stiffness in asymptomatic populations in China.A retrospective cohort recruiting 4747 asymptomatic patients with no underlying causes of liver disease and having FibroScan and brachial-ankle pulse wave velocity (baPWV) during wellness check-up was covered. Nonalcoholic fatty liver disease (NAFLD) was defined as a CAP ≥238 dB/m. NAFLD with significant fibrosis was defined as an LSM ≥7.3 kPa in the presence of NAFLD. Increased arterial stiffness was determined as a BaPWV ≥1.4m/second.Among the 4747 study participants, 1596 subjects (33.6%) suffered from increased arterial stiffness. The prevalence of increased arterial stiffness progressively increased across CAP quartiles and LSM quartiles in NAFLD (23.5%, 30.8%, 38.3%, 43.7%, P < .001 and 33.1%, 36.8%, 40.4%, 48.2%, P < .001, respectively). After conventional cardiovascular risk factors were adjusted (age, sex, overweight, diabetes mellitus, hypertension, hypercholesterolemia, and current smoking habits), multivariate logistic regression analysis revealed that CAP (odd ratio [OR] = 1.005; 95% confidence interval [CI]: 1.003-1.006; P < .001), NAFLD (OR = 1.427; 95% CI: 1.212-1.681; P < .001), LSM in NAFLD (OR = 1.073; 95% CI: 1.023-1.125; P = .003), and significant fibrosis in NAFLD (OR = 1.480; 95% CI: 1.090-2.010; P = .012) were independently associated with increased arterial stiffness. Furthermore, in a multivariate logistic regression analysis, OR (95% CI) for the maximal vs. the minimal quartile of CAP was 1.602 (1.268-2.024), and that of LSM in NAFLD was 1.362 (1.034-1.792) after adjustment for the above-mentioned risk factors. Notably, NAFLD and significant fibrosis in NAFLD were significantly correlated only with increased arterial stiffness in subjects without hypertension or diabetes mellitus after adjustment for the above-mentioned risk factors.CAP-defined NAFLD and LSM-defined significant fibrosis in NAFLD showed significant and independent relationships with increased arterial stiffness even after adjustment for conventional cardiovascular risk factors, which can be conducive to stratifying relative risk of subjects having undergone screening assessment for cardiovascular disease.

The associations among Helicobacter pylori infection, white blood cell count and nonalcoholic fatty liver disease in a large Chinese population.

Reported relationships among Helicobacter pylori infection, white blood cell (WBC) count and nonalcoholic fatty liver disease (NAFLD) are inconsistent and controversial. We, therefore, conducted a cross-sectional study to investigate the associations among the presence of NAFLD, WBC count and H pylori infection, as diagnosed using the C-urea breath test (UBT).This study included 20,389 subjects enrolled at the International Health Care Center of the Second Affiliated Hospital of the Zhejiang University School of Medicine from January 2015 to December 2015. All participants underwent a C-UBT for the diagnosis of H pylori infection and ultrasonography for NAFLD as well as a blood test to determine WBC count. Multivariate logistic regression was then performed to evaluate the relationship among H pylori infection, WBC count and NAFLD.H pylori infection was detected in 38.49% (7,848/20,389) of the subjects via the UBT, and NAFLD was present in 37.24% (7,592/20,389) of the subjects. The prevalence of H pylori infection was higher in the NAFLD group than in the control group (41.25% vs 36.85%, P <.001). Significant differences were found between various WBC quartiles and H pylori infection, age, gender, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), high-sensitivity C-reactive protein (HS-CRP), glycosylated hemoglobin (HbA1c), triglyceride (TG), low-density lipoprotein (LDL-C), fasting blood glucose (FPG), homeostasis model assessment of insulin resistance (HOMA-IR), and smoking. Multivariate logistic regression revealed that the combination of H pylori infection and WBC count (odds ratio [OR] = 1.067, 95% confidence interval [CI]: 1.014, 1.093; P = .007; OR = 1.165, 95% CI: 1.023, 1.488; P <.001; OR = 1.183, 95% CI: 1.085, 1.559; P <.001, respectively) was positively associated with NAFLD.H pylori infection and WBC count may contribute to the pathogenesis of NAFLD.

[The association between body mass index and non-alcoholic fatty liver disease].

OBJECTIVE: To investigate the association of body mass index (BMI) with alcoholic fatty liver disease (NAFLD). METHODS: A cohort of 725 adult subjects underwent general health check-up at our hospital in July 2008, then were followed up in 2011. The clinical data including body mass index(BMI), blood pressure, lab testing results and liver ultrasonic findings were retrospectively analyzed. The NAFLD was diagnosed according to the guidelines for management of nonalcoholic fatty liver disease: an updated and revised edition in 2010 based on liver ultrasound results. The risk factors for NAFLD were analyzed with multivariate logistic regression. RESULTS: One hundred and sixty two NAFLD cases and 563 non-NAFLD cases were found in 2008 check-up. Among 563 non-NAFLD subjects, NAFLD was developed in 132 (23.4%) at follow-up in 2011. The incidence of NAFLD was correlated with the baseline BMI (χ²=82.861，P<0.01). Multivariate logistic regression analysis showed that baseline BMI，systolic blood pressure, alanine aminotransferase and the increase of BMI were the independent risk factors, while high density lipoprotein-cholesterol (HDL-C) was the protective factor for the development of NAFLD. Among 162 NAFLD cases, 71 (43.8%) had no evidence of NAFLD at the second check-up in 2011. The remission of NAFLD was negatively correlated with baseline BMI (χ²=22.425，P<0.01). Multivariate logistic regression analysis showed that male sex, baseline BMI and the increase of BMI were negatively associated with remission of NAFLD, while the age was positively associated with the remission of NAFLD. CONCLUSION: The development and remission of NAFLD are frequently encountered in health check-up subjects, which are closely related to baseline BMI and changes of BMI during the follow-up．

Association between non-alcoholic fatty liver disease and arterial stiffness in the non-obese, non-hypertensive, and non-diabetic young and middle-aged Chinese population.

BACKGROUND AND OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is associated with arterial stiffness in the general population. Age, obesity, hypertension, and diabetics are risk factors for arterial stiffness. In this study, we aimed to investigate the association between NAFLD and arterial stiffness as measured by brachial-ankle pulse wave velocity (baPWV) in the non-obese, non-hypertensive, and non-diabetic young and middle-aged Chinese population. METHODS: A cross-sectional study with 1296 non-obese, non-hypertensive, and non-diabetic young and middle-aged (20-65 years) subjects undergoing routine medical check-ups in the International Health Care Center of the Second Affiliated Hospital of School of Medicine of Zhejiang University was carried out. Fatty liver was diagnosed by ultrasonography, and baPWV was measured using an automatic waveform analyzer. The subjects were classified into two groups according to the presence of NAFLD, and divided into a further two groups according to their baPWV. RESULTS: The overall incidence of NAFLD was 19.0%, and NAFLD patients had a significantly higher level of baPWV than the controls ((1321±158) cm/s vs. (1244±154) cm/s; P<0.001). The incidence of NAFLD was clearly higher in the increased baPWV group than in the normal baPWV group (29.3% vs. 16.9%; P<0.001), and the incidence increased in line with the increase of baPWV quartiles in the normal range as well as with the severity of arterial stiffness (both P for trend <0.001). Multiple linear logistic regression analysis showed that the presence of NAFLD was positively and independently associated with baPWV. CONCLUSIONS: Our results suggest that the presence of NAFLD is associated with arterial stiffness as measured by baPWV in the non-obese, non-hypertensive, and non-diabetic young and middle-aged Chinese population.

Ideal cardiovascular health in Chinese urban population.

BACKGROUND: The American Heart Association's 2020 Strategic Goals define a new concept of cardiovascular health. However, the prevalence of ideal cardiovascular health outside of the United States is unclear, and its relationship with psychological status has not been reported. METHOD: We included 9962 participants (mean age 47.1 years; 44.2% women) from the survey of the Disease Risk Evaluation and Health Management study from October 2009 to Feb 2012. The prevalence of poor, intermediate, and ideal cardiovascular health levels were calculated, and psychological status was assessed using the 21-item Depression Anxiety Stress Scales. RESULTS: After adjusting for sex and age, only 0.5% of the participants met ideal levels of all 7 cardiovascular health metrics, and 26.9% presented with 5 to 7 ideal health metrics. Fasting plasma glucose was the most prevalent ideal metric (71.2%), whereas physical activity was the least prevalent (18.1%). Women had a significantly higher proportion of 5 to 7 ideal health metrics compared with men (40.4% versus 13.4% after adjusting for age), and the proportion of participants who had 5 to 7 ideal health metrics significantly decreased with age (P<0.001 for trend). Furthermore, the scores for depression, anxiety, and stress showed a negative correlation with the number of ideal health metrics, with regression coefficients of -0.07, -0.07, and -0.11, respectively (P<0.05). CONCLUSIONS: Few adults met ideal levels of cardiovascular health. Individuals, communities, and health-care providers in China should be better integrated to pay closer attention to primordial prevention of unhealthy lifestyles and psychological problems.

Age- and gender-specific prevalence of carotid atherosclerosis and its association with metabolic syndrome in Hangzhou, China.

OBJECTIVE: Because of rapid alterations in lifestyle and the incidence of metabolic syndrome (MetS), the prevalence of carotid atherosclerosis (CA) and carotid plaque (CP) may increase in China. We aimed to evaluate the prevalence of CA and CP as well as its relation to MetS in an East Chinese population. METHODS: The study included 6142 subjects who underwent general health screening including carotid ultrasonography in 2009. Diagnoses of MetS were made according to the revised Adult Treatment Panel III criteria. RESULTS: The prevalence of CA and CP increased gradually with age. These conditions were more prevalent in men than in women (CA: 22.1%vs 12.0%, P < 0.001; CP: 12.6%vs 7.2%, P < 0.001). Multivariate logistic regression analysis showed that male gender, age, blood pressure, fasting blood glucose (FBG) and low-density lipoprotein cholesterol were risk factors for CA and CP, while high-density lipoprotein cholesterol was protective for CA. Age ≥ 50 years has the largest impact on CA and CP, followed by elevated blood pressure and elevated blood glucose. Individuals with MetS had a higher prevalence of CA (27.7%vs 20.0% in men, 24.0%vs 10.3% in women; P < 0.001 in both) and CP (16.6%vs 11.2% in men, P < 0.001; 11.8%vs 6.5% in women, P < 0.005) than those without MetS. The prevalence and odds ratios of CA and CP aggregated with an increasing number of MetS components, even in individuals exhibiting only one component. CONCLUSIONS: These results indicate that CA and CP have become a major public health problem in China. MetS and its components were associated with an increased prevalence of CA and CP.

[General characteristics and clinical practices of Chinese patients with non-alcoholic fatty liver disease].

OBJECTIVE: To assess the characteristics and daily treatment compliance of non-alcoholic fatty liver disease (NAFLD) patients in China. METHODS: NAFLD adult patients from 21 clinics of 12 cities in China were enrolled in this registry. Physical examination such as demographic characteristics (height, weight, waist circumference measurement), blood pressure and clinical laboratory and ultrasonographic examination of liver were undertaken. Daily practice including life style and medication were recorded and assessed in accordance with 2006 Chinese NAFLD treatment guidelines. RESULTS: A total of 1656 patients were enrolled (1146 male and 510 female), mean of 45.8 ± 12.6 years old, mean duration of NAFLD history was (47.2 ± 47.7) months. 44.9% of NAFLD were suffering from metabolic syndromes. Patients with central obesity have higher incidence of hypertension and lower level of high-density lipoprotein cholesterol (HDL-C) than those without central obesity, P < 0.05. Body mass index (BMI), waist circumference, triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) in ALT abnormal group were higher than those in ALT normal group (P < 0.05), HDL-C was lower in ALT abnormal group (P < 0.05). Significant differences existed between the BMI, female waist circumference, TG, fast insulin, HOMA index, ALT, AST and HDL-C among subgroups with mild, moderate and severe steatosis. Majority of the patients did not follow recommendations of NAFLD treatment guidelines. Among targeted population only 15.3% of patients used insulin sensitizers and 23.8% took lipid lowering medicine according to the guideline. CONCLUSION: Data indicated that nearly half of NAFLD patients co-morbid with metabolic disorders. Therapy compliance was unsatisfactory and the gap between current practice and Chinese NAFLD treatment guidelines was not optimal.

[Probe into sleep quality in the patients with irritable bowel syndrome].

OBJECTIVE: To investigate the sleep features in the patients with irritable bowel syndrome (IBS) and compare the sleep quality between those IBS patients who were with and without anxiety and depression. METHODS: Pittsburgh sleep quality index questionnaire (PSQI), self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were measured in the 145 IBS patients and 59 regular physical examination volunteers. IBS patients were also divided into two subgroups--patients with or without anxiety and depression based on cutoff scores of SAS and SDS. Comparisons of sleep quality were made between subgroups, and between IBS patients and volunteer controls. RESULTS: Compared with the controls, the SAS raw score, SDS raw score and SAS positive incidence in IBS patients were shown statistically significant differences (P<0.05), while the SDS positive incidence had no statistically significant difference (P>0.05). PSQI total scores were significantly higher in the IBS patients without anxiety and depression (P<0.05), 3 domains (sleep quality, sleep disturbances and daytime function disorder) were also found statistically significant differences (P<0.05), compared with the controls. The IBS patients with anxiety and depression were statistically significantly different from the controls (P<0.05) in 6 domains (sleep quality, sleep latency, sleep efficiency, sleep disturbances, sleep time and daytime function disorder) and significantly higher PSQI total scores (P<0.05). Statistically significant differences (P<0.05) were also found in all 7 domains and with higher PSQI total scores in IBS patients with anxiety and depression, compared with IBS patients without anxiety and depression. CONCLUSIONS: IBS patients were more likely to have sleep abnormality, mainly in sleep quality, sleep disturbances and daytime function disorder and PSQI total scores. The abnormalities of these factors were independent of emotional disorder. However, emotional disorder worsened the sleep disorder in IBS patients.

Body mass index, waist circumference, and cardiometabolic risk factors in young and middle-aged Chinese women.

OBJECTIVE: To assess the associations between body mass index (BMI), waist circumference (WC), and cardiometabolic risk factors in young and middle-aged Chinese women. METHODS: A total of 3011 women (1938 young women, 1073 middle-aged women), who visited our health care center for a related health checkup, were eligible for study. BMI and WC were measured. The subjects were divided into normal and overweight/obesity groups based on BMI, and normal and abdominal obesity groups based on WC. Cardiometabolic variables included triglyceride (TG), high density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), homeostasis model assessment of insulin resistance (HOMA-IR), and blood pressure (BP). RESULTS: The prevalence of overweight/obesity was significantly higher in middle-aged women (32.4%) than in young women (12.0%). The prevalence of abdominal obesity was also higher in middle-aged women (60.3%) than in young women (36.2%). There were significant differences in the comparison of all related cardiometabolic variables between different BMI (or WC) categories in young and middle- aged women groups, respectively. After adjustment for age, partial correlation analysis indicated that both BMI and WC were correlated significantly with all related cardiometabolic variables. After adjustment for age and WC, although the correlation coefficient r' was attenuated, BMI was still correlated significantly with all related cardiometabolic variables in young and middle-aged women. After adjustment for age and BMI, partial correlation analysis showed that WC was correlated significantly with TG, FBG, HOMA-IR, and HDL-C in young women and significantly with TG, HOMA-IR, and HDL-C in middle-aged women. CONCLUSIONS: The prevalence of overweight/obesity and abdominal obesity was high in Chinese young and middle-aged women. BMI was a better predictor of cardiovascular disease and diabetes than WC in young and middle-aged women, and moreover, measurement of both WC and BMI may be a better predictor of cardiovascular disease and diabetes mellitus than BMI or WC alone.

Novel blood-based, five-gene biomarker set for the detection of colorectal cancer.

PURPOSE: We applied a unique method to identify genes expressed in whole blood that can serve as biomarkers to detect colorectal cancer (CRC). EXPERIMENTAL DESIGN: Total RNA was isolated from 211 blood samples (110 non-CRC, 101 CRC). Microarray and quantitative real-time PCR were used for biomarker screening and validation, respectively. RESULTS: From a set of 31 RNA samples (16 CRC, 15 controls), we selected 37 genes from analyzed microarray data that differed significantly between CRC samples and controls (P < 0.05). We tested these genes with a second set of 115 samples (58 CRC, 57 controls) using quantitative real-time PCR, validating 17 genes as differentially expressed. Five of these genes were selected for logistic regression analysis, of which two were the most up-regulated (CDA and MGC20553) and three were the most down-regulated (BANK1, BCNP1, and MS4A1) in CRC patients. Logit (P) of the five-gene panel had an area under the curve of 0.88 (95% confidence interval, 0.81-0.94). At a cutoff of logit (P) >+0.5 as disease (high risk), <-0.5 as control (low risk), and in between as an intermediate zone, the five-gene biomarker combination yielded a sensitivity of 94% (47 of 50) and a specificity of 77% (33 of 43). The intermediate zone contained 22 samples. We validated the predictive power of these five genes with a novel third set of 92 samples, correctly identifying 88% (30 of 34) of CRC samples and 64% (27 of 42) of non-CRC samples. The intermediate zone contained 16 samples. CONCLUSION: Our results indicate that the five-gene biomarker panel can be used as a novel blood-based test for CRC.

[Harmine induces apoptosis in human SGC-7901 cells].

OBJECTIVE: [corrected] To investigate the effect of apoptosis induced in human SGC-7901 cells by Harmine. METHODS: The effect of Harmine on human SGC-7901 cell survival and apoptosis was determined by MTT assay, light microscopy and flow cytometry. Cell genomic DNA was detected by agarose electrophoresis. RESULTS: The survival of human SGC-7901 cells decreased; Apoptotic cells were observed by fluorescent microscope; FCM analysis showed that the peak of apoptosis increased. Typical DNA Ladder were detected in DNA agarose gel electrophoresis. CONCLUSION: HM can induce apoptosis in human SGC-7901 cells.

[Clinical analysis of 39 cases of heterotopic gastric mucosa in the upper esophagus].

OBJECTIVE: To determine accurately the incidence of heterotopic gastric mucosa in the upper esophagus (HGMUE) in China, and to study the macroscopic and microscopic aspects of the lesions and to evaluate the clinical importance of HGMUE. METHODS: A prospective study was made among a total of 15,228 consecutive patients, 8,573 male and 6,655 female, aged 54 (8-95), undergoing gastroscopy. Disease histories of all patients were carefully inquired, especially those regarding possible complaints including discomfort of throat and swallowing pain and so on. Special care was taken in the upper esophageal sphincter area to make sure whether the area was adequately inspected. Biopsy specimens from aberrant mucosa were obtained and the sections were stained with haematoxylin and eosin, and Giemsa stain for Helicobacter pylori. RESULTS: HGMUE was found in 39 patients (0.26%) with an average age of 50. Five patients with H. pylori infection in heterotopic gastric mucosa also presented the infection in the stomach. The gastric mucosa was gastric body type in 8 patients, transitional type in 11 patients, and antral pattern in 7 patients. Intestinal metaplasia was found in 5 patients, and mild atypical hyperplasia in 2 patients. An impressive finding was coexistent erosive gastritis in 14 patients (35.9%), Barrett's esophagus in one patient (2.6%), peptic ulcer in 8 patients (20.5%), and a patient had the complication of constriction in the upper esophagus. CONCLUSION: HGMUE is not rare in China. The presence of inlet patches is possibly correlated with specific symptoms. There are some severe complications in HGMUE, especially esophageal constriction. Close surveillance should be taken for rare cases with metaplasia or dysplasia in HGMUE.

Significance of vascular endothelial growth factor expression and its correlation with inducible nitric oxide synthase in gastric cancer.

AIM: To investigate the clinical significance of the expression of VEGF165mRNA and the correlation with vascular endothelial growth factor (VEGF) protein and inducible nitric oxide synthase (iNO) in human gastric cancer. METHODS: We tested VEGF165mRNA expression in 31 cases of resected gastric cancer specimens and normal paired gastric mucosae by RT-PCR. Total RNA was extracted with TRIzol reagents, transcribed into cDNA with oligo (dT15) priming, inner controlled with beta-actin expression and agarose gel isolated after PCR. VEGF expression was quantitated with IS1000 imaging system. Meanwhile we also examined expression levels of VEGF protein and iNOS in 85 cases of gastric cancer. All paraffin-embedded samples were immunohistochemically stained by streptavidin -peroxidase method (SP). RESULTS: The mean expression of VEGF165mRNA in gastric cancer was 1.125+/-0.356, significantly higher than that of normal paired mucosae, which was 0.760+/-0.278. The data indicated that the expression level of VEGF165mRNA was well related to lymph node metastasis and TNM stages of UICC. The expression levels in patients with lymph node metastasis and without lymph node metastasis were 1.219+/-0.377 and 0.927+/-0.205 respectively (P<0.05). The expression in stages I, II, III, IV was 0.934+/-0.194, 1.262+/-0.386 respectively (P<0.01). Further analysis showed the lymph node metastasis rate in the group with over-expression of VEGF was higher than that in the group with low expression of VEGF (83.3% vs 46.2%), and the ratio of stage III+IV in the group with over-expression of VEGF was also higher than that in the group with low expression with VEGF (77.8% vs 33.8%) (P<0.05). The positive rates of expression of VEGF protein and iNOS in 85 cases of gastric cancer were 75.4% and 58.8% respectively, and 50.1% of the patients showed positive staining both for iNOS and VEGF, the correlation with the two factors was significant (P=0.018). But more intensive analysis showed the immunoreactive grades of VEGF were not associated with that of iNOS. CONCLUSIONS: The expression of VEGF165mRNA is well related with lymph node metastasis and TNM stages of UICC in gastric cancer, and is concerned with the invasiveness and metastasis of gastric cancer. The relationship can be observed between the expression of VEGF and iNOS in gastric cancer.