Red blood cell count and risk of adverse outcomes in patients with mildly reduced left ventricular ejection fraction.

BACKGROUND: Anemia is associated with increased rates of heart failure (HF)-related mortality and hospitalization. No studies have focused on the association between the red blood cell (RBC) count and the prognosis of patients with HF with mildly reduced left ventricular ejection fraction (HFmrEF). We retrospectively analyzed the effect of the RBC count on outcome events in patients with HFmrEF. METHODS: We investigated the association of the RBC count with outcome events in 1691 patients with HFmrEF (mean age: 68 years; 35% female) in Xiangtan Central Hospital. Using Cox proportional hazards models, the RBC count was assessed as both a continuous and categorical variable. RESULTS: During follow-up (median: 33 months), cardiovascular death occurred in 168 patients (114 men and 54 women). After adjusting for established risk factors, each 1.0 × 1012 cell/L increase in the RBC count was associated with a 28% lower risk of cardiovascular death in men and a 43% lower risk in women. Patients with low RBC counts had a 0.5-fold higher risk of cardiovascular death than those with normal RBC counts. The hazard ratio for men was 1.42 (95% confidence interval [CI]: 1.07-1.89), and the hazard ratio for women was 1.79 (95% CI: 1.20-2.67). The RBC count was not significantly associated with the composite endpoint of cardiovascular death and HF readmission (cardiovascular events) (p > .05). CONCLUSIONS: A decreased RBC count is associated with increased cardiovascular mortality in patients with HFmrEF. Correcting a low RBC count might potentially reduce the risk of cardiovascular death in patients with HFmrEF.

Impact of atrial fibrillation on cerebro-cardiovascular outcome of heart failure with mildly-reduced ejection fraction.

AIMS: Atrial fibrillation (AF) and heart failure (HF) often co-exist and are closely intertwined. The impact of AF on the outcome of patients with heart failure with mildly-reduced ejection fraction (HFmrEF) is not fully clear. This study aimed to investigate the impact of AF on the outcomes of hospitalized HFmrEF patients. METHODS AND RESULTS: The study included 1691 consecutive patients with HFmrEF (mean 68.2 years, 64.8% male) including 296 AF patients. Patients completed 1 year and mean of 33 month clinical follow-up after discharge by telephone interview, clinical visit, or community visit. The primary endpoint was cerebro-cardiovascular events (CCE, composite of HF rehospitalization, stroke, or cardiovascular death). After propensity score matching, 296 patients were included into the AF group (mean 71.5 years) and 592 patients into the non-AF group (mean 70.6 years). After propensity score matching, CCE at 1 year (59.1% vs. 48.5%, P = 0.003) and at a mean of 33 month (77.0% vs. 70.6%, P = 0.043). AF was independently associated with increased CCE within 1 year (HR = 1.31, 95% CI 1.07 to 1.61, P = 0.010) and at 33 months (HR = 1.20, 95% CI 1.00 to 1.43, P = 0.050) post-discharge after adjusted for other clinical confounders including discharge heart rate, NT-proBNP, haemoglobin, and uric acid. CONCLUSIONS: AF is independently associated with an increased risk of CCE in HFmrEF patients within 1 year and at a mean of 33 months after discharge.

Sex differences in patients with heart failure and mildly reduced left ventricular ejection fraction.

Clinical studies on heart failure with mildly reduced left ventricular ejection fraction (HFmrEF) have gradually increased. However, studies on the prognostic differences between men and women among patients with HFmrEF are few, and no evidence on sex differences in such patients exists. Therefore, we retrospectively assessed the data of patients with HFmrEF using propensity score-matched analysis (PSMA). A total of 1691 patients with HFmrEF were enrolled in the Outcome of Discharged HFmrEF Patients study (OUDI-HF study), which included 1095 men and 596 women. After propensity score matching, we compared the difference in cardiovascular (CV) events (cardiovascular death or heart failure readmission) and all-cause mortality at 90 days and 1 year after discharge between men and women using Kaplan-Meier analysis and Cox regression. After PSMA, men with HFmrEF were 2.2 times more likely to die at 90 days than women with HFmrEF [hazard ratio (HR) 1.88; 95% confidence interval (95% CI) 1.03-3.46; P = 0.041]. However, there was no difference in the 90-day CV events (HR 0.96; 95% CI 0.75-1.22; P = 0.718). Similarly, there was no difference in all-cause mortality (HR 1.16; 95% CI 0.81-1.65; P = 0.417) and CV events (HR 0.98; 95% CI 0.83-1.16; P = 0.817) between men and women after 1 year. Among the patients with HFmrEF, men had a higher 90-day risk of all-cause mortality than women after hospital discharge, and this risk disappeared after 1 year.Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT05240118 (ESC Heart Failure. (2022). doi: https://doi.org/10.1002/ehf2.14044 ).

First report of Nigrospora musae causing white leaf spot of Basella alba L in China.

Basella alba L, an edible annual twining herb of the genus Basella and the family Basella, has been widely introduced and cultivated in China. Basella alba L. as a leaf vegetable, is rich in vitamins A and C, iron, and calcium (FAO 1988). In May 2022, severe white leaf spots were observed in plantation located in Shuangfeng County (27°41'36" N, 111°56'60" E), Hunan Province, China. More than 50 Basella alba L plants were surveyed with over 80% disease incidence in an area of 300 square meters of greenhouse. The symptoms on leaves were initially small purplish-brown lesions from leaf margins or tips, with lesions expanded, the middle of the lesions was yellowish-white to yellowish-brown, slightly dented. The edge of lesions was purplish-brown, with obvious boundary between the diseased parts and the non-diseased ones. A total of 20 symptomatic samples were randomly collected. Lesion margins were surface sterilized in 2% sodium hypochlorite for 1 min, rinsed with sterile distilled water for three times, dried, placed on potato dextrose agar (PDA), and incubated at 25°C and 60% relative humidity in the dark for 3 days. Hyphal sections from colony edges were transferred to new PDA plates. Six isolates were obtained. Colonies were fast-growing, massive sparse aerial hyphae, initially white, turning gray and black after 7 days. Hyphae were branched, septa, and transparent. To induce sporulation, colonies were transferred to sodium carboxymethyl cellulose (CMC) plates (Z. M. Wen., & X. Y. Luo 1991). Conidia were single-celled, dark black, oblate, or nearly spherical, and measured 10.2 to 15.1 µm × 9.7 to 16.0 µm in diameter (n=50). For molecular identification, the rDNA internal transcribed spacer (ITS), the ß-tubulin gene (TUB), and the translation elongation factor 1-alpha gene (TEF1) were amplified from genomic DNA by primers ITS1/ITS4 (White et al. 1990), Bt2a/Bt2b (Glass & Donaldson. 1995), and EF1-728F/EF1-986R (Carbone & Kohn, 1999). The sequences of six isolates (L1, L2, L7, L10, L11, L12) were deposited in GenBank with accession numbers OP703335, OP703336, OP703337, OP703338, OP703339, OP703340 (ITS), OP784252, OP784157, OP784253, OP784254, OP784255, OP784256 (TEF-1α), and OP724156, OP724158, OP779771, OP779772, OP779773, OP779774 (TUB2). A blast search of sequences showed the ITS, TEF-1α, and TUB2 sequences had >98% identity with homologue sequences from Nigrospora musae isolates BRJ2 (OP451019.1), CBS 319.34 (KY019419.1) and LC6385 (KY019567.1), respectively. These morphological features and molecular identification indicated that the pathogen possessed identical characteristics as Nigrospora musae (Wang, 2017). Pathogenicity test was carried out in plants. Strains were cultured on CMC plates for 14 days, then the mycelium was scraped to make conidial suspension (1×106 conidia/mL). After 5-6 leaves of the Basella alba L were sprouted, conidial suspension was sprayed directly on the leaves, with leaves sprayed by sterile distilled water as the control. All plants were kept in the greenhouse with temperature at 25/30°C (night/day) and 75% relative humidity. After 7 days, symptoms were observed on inoculated leaves of plants, which were the same as previously described samples, while the control plants showed no symptoms. The test was repeated three times with similar results. The strains reisolated from the inoculated leaves were morphologically identical to Nigrospora musae, conforming to Koch's postulates. symptoms of Nigrospora musae is similar to that of the other leaf diseases of Basella alba L reported in China. (H. P. Jiang.2000; S. Tan.1996). To our knowledge, this is the first report of Nigrospora musae causing white leaf spot of Basella alba L in China. The pathogen may severely threat the production of Basella alba L. The information on identification of this fungus may be helpful to the control and prevention of the disease. References: 1. FAO. 1988. Page 103 in: Traditional Food Plants: A Resource Book for Promoting the Exploitation and Consumption of Food Plants in Arid, Semi-arid and Sub-humid Lands of Eastern Africa. FAO Food and Nutrition Paper 42. FAO, Rome, Italy. 2. Z. M. Wen., & X. Y. Luo. Fusarium graminearum spore production medium filtering [J]. Chinese journal of food hygiene, 1991 (04): 11-13. 3. White, T. J., et al. 1990. Page 315 in: PCR Protocols: A Guide to Methods and Applications. Academic Press, San Diego, CA. 4. Carbone, I., et al. 1999. Mycologia. 91: 553-556. 5. Glass, N. L., and Donaldson, G. C. 1995. Appl. Environ. Microbiol. 61: 1323. 6. Wang, 2017. Phylogenetic reassessment of Nigrospora: Ubiquitous endophytes, plant, and human pathogens. 7. H. P. Jiang., et al. Occurrence and comprehensive control of white leaf spot of Basella alba L [J]. Plant Protection Technology and Extension, 2000(02):19. 8. S. Tan. The symptoms and control measures of white leaf spot of Basella alba L [J]. Anhui Agricultural, 1996(08):15. *Indicates the corresponding author. Kaifa Guo, E-mail: andygkf@126.com.

Obesity increases cardiovascular mortality in patients with HFmrEF.

Background: High body mass index increases the risk of heart failure morbidity and mortality. It is unclear whether a high body mass index is associated with prognosis in patients with heart failure with mildly reduced left ventricular ejection fraction (HFmrEF). We retrospectively analyzed the effect of a high body mass index on the prognosis of patients with HFmrEF. Methods: We investigated the association between body mass index and cardiovascular death (death from any cardiovascular mechanism) in 1,691 HFmrEF patients (mean age, 68 years; 35% female) in Xiangtan Central Hospital. Using Cox proportional hazards models, body mass index was assessed as a continuous and a categorical variable. Results: Cardiovascular death occurred in 133 patients (82 males and 51 females) after 1 year of follow-up. After adjustment for established risk factors, there was a 7.5% increase in the risk of cardiovascular death for females for each increment of 1 in BMI. In contrast, changes in male body mass index were not significantly associated with cardiovascular death (P = 0.097). Obese subjects had a 1.8-fold increased risk of cardiovascular death compared with subjects with a normal body mass index. The hazard ratio for females was 2.163 (95% confidence interval: 1.150-4.066). Obesity was not significantly associated with cardiovascular death in males (P = 0.085). Conclusion: An increased body mass index is associated with an increased risk of cardiovascular death in patients with HFmrEF; however, this risk was mainly associated with female patients with HFmrEF and less with male patients with HFmrEF.

Effect of Body Surface Area on Severe Osteoporotic Fractures: A Study of Osteoporosis in Changsha China.

Clinical vertebral fractures and femoral neck fractures are severe osteoporotic fractures that increase morbidity and mortality. Anthropometric variables are associated with an increased risk of osteoporotic fractures, but it is not clear whether body surface area (BSA) has an effect on clinically severe osteoporotic fractures. The study included total of 3,694 cases of clinical vertebral fractures and femoral neck fractures (2,670 females and 1,024 males) and 3,694 controls without fractures who were matched with the cases by sex and age. There was a significant positive correlation between BSA and bone mineral density (BMD) in female and male fracture patients (females: r = 0.430-0.471, P < 0.001; males: r = 0.338-0.414, P < 0.001). There was a significant systematic increase in BMD in both genders at various skeletal sites, grouped by BSA quartile. The osteoporosis rates of the lumbar spine (97.9%), femoral neck (92.4%) and total hip (87.1%) in the female Q1 group were significantly higher than those in the Q4 group (P < 0.001), which were 80.0%, 57.9% and 36.9%, respectively, in the Q4 group; the osteoporosis rates of the lumbar spine, femoral neck, and total hip were 53.9%, 59.4%, and 36.3% in the male Q1 group, and 15.2%, 21.9%, and 7.03% in the Q4 group, which were significantly lower than those in the Q1 group (P < 0.001). In age-adjusted Cox regression models, the risk of fracture in the remaining three groups (Q2, Q3, and Q4) for weight, BMI, and BSA for both genders, compared with the highest quartile (Q1 by descending quartile stratification) were significantly higher. In models adjusted for age and BMD, only men in the BSA Q3 (HR = 1.55, 95% CI = 1.09-2.19) and BSA Q4 groups (HR = 1.41, 95% CI = 1.05-1.87) had significantly higher fracture risks. In models adjusted for age, height, weight, BMI, and BSA, low BMD was the greatest fracture risks for both sexes. Our results showed that BSA was closely related to BMD, prevalence of osteoporosis, and fracture risk, and that a decline in BSA may be a new potential risk factor for osteoporotic fractures in Chinese men.

Risk factors of short-term, intermediate-term, and long-term cardiac events in patients hospitalized for HFmrEF.

AIMS: Clinical data on the prognostic determinants over varying periods within the same cohort of heart failure with mid-range or mildly reduced ejection fraction (HFmrEF) remain scarce. This study aimed to identify the short-term, intermediate-term, and long-term risk factors of adverse cardiovascular (CV) outcomes in patients hospitalized for HFmrEF. METHODS AND RESULTS: This retrospective study included 1691 consecutive HFmrEF patients admitted to our hospital between January 2015 and August 2020. Baseline data including clinical characteristics, laboratory and cardiac imaging examinations were obtained. Patients completed at least 1 year clinical follow-up after discharge by telephone interview, clinical visit, or community visit. The primary endpoint was defined as a composite of CV death or rehospitalization for heart failure (CV events) at 3, 12, and 33 months after the diagnosis of HFmrEF. Mean age of the whole cohort was 69 (61-77) years and 64.8% were male. The median clinical follow-up was 33 (20-50) months. CV events were 17.5%, 28.2%, and 57.8% at 3, 12, and 33 months after discharge, respectively. Independent risk factors for CV events were uric acid >382 µmol/L, creatinine >100 µmol/L, N-terminal pro-B type natriuretic peptide (NT-proBNP) > 3368 pg/mL and haemoglobin <120 g/L for men and <110 g/L for women at 3 and 12 months. Pulmonary artery systolic pressure >35 mmHg and the ratio of early transmitral flow velocity to early mitral annular velocity >18 served as independent risk factors for CV events at 12 months. At 33 months, uric acid > 382 µmol/L, NT-proBNP >3368 pg/mL, and pulmonary artery systolic pressure >35 mmHg were the independent risk factors of CV events. CONCLUSIONS: Higher uric acid, creatinine, NT-proBNP, and lower haemoglobin levels at baseline are valuable serum biomarkers for risk stratification of short-term and long-term CV outcomes of HFmrEF patients. Future studies are needed to verify if intensive heart failure therapy for identified high-risk HFmrEF patients based on these four serum biomarkers could improve their short-term and long-term CV outcomes or not.

Impact of B-lines-guided intensive heart failure management on outcome of discharged heart failure patients with residual B-lines.

AIMS: Pulmonary congestion (PC) expressed by residual lung ultrasound B-lines (LUS-BL) could exist in some discharged heart failure (HF) patients, which is a known determinant of poor outcomes. Detection efficacy for PC is suboptimal with widely used imaging modalities, like X-ray or echocardiography, while lung ultrasound (LUS) can sufficiently detect PC by visualizing LUS-BL. In this trial, we sought to evaluate the impact LUS-BL-guided intensive HF management post-discharge on outcome of HF patients discharged with residual LUS-BL up to 1 year after discharge. IMP-OUTCOME is a prospective, single-centre, single-blinded, randomized cohort study, which is designed to investigate if LUS-BL-guided intensive HF management post-discharge in patients with residual LUS-BL could improve the clinical outcome up to 1 year after discharge or not. METHODS AND RESULTS: After receiving the standardized treatment of HF according to current guidelines, 318 patients with ≥3 LUS-BL assessed by LUS within 48 h before discharge will be randomly divided into the conventional HF management group and the LUS-BL-guided intensive HF management group at 1:1 ratio. Patient-related basic clinical data including sex, age, blood chemistry, imaging examination, and drug utilization will be obtained and analysed. LUS-BL will be assessed at 2 month interval post-discharge in both groups, but LUS-BL results will be enveloped in the conventional HF management group, and diuretics will be adjusted based on symptom and physical examination results with or without knowing the LUS-BL results. Echocardiography examination will be performed for all patients at 12 month post-discharge. The primary endpoint is consisted of the composite of readmission for worsening HF and all-cause death during follow up as indicated. The secondary endpoints consisted of the change in the New York Heart Association classification, Duke Activity Status Index, N terminal pro brain natriuretic peptide value, malignant arrhythmia event and 6 min walk distance at each designed follow up, echocardiography-derived left ventricular ejection fraction, and number of LUS-BL at 12 month post-discharge. Safety profile will be recorded and managed accordingly for all patients. CONCLUSIONS: This trial will explore the impact of LUS-BL-guided intensive HF management on the outcome of discharged HF patients with residual LUS-BL up to 1 year after discharge in the era of sodium-glucose cotransporter-2 inhibitors and angiotensin receptor blocker-neprilysin inhibitor. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05035459.

Magnetotelluric Signal-Noise Identification and Separation Based on ApEn-MSE and StOMP.

Natural magnetotelluric signals are extremely weak and susceptible to various types of noise pollution. To obtain more useful magnetotelluric data for further analysis and research, effective signal-noise identification and separation is critical. To this end, we propose a novel method of magnetotelluric signal-noise identification and separation based on ApEn-MSE and Stagewise orthogonal matching pursuit (StOMP). Parameters with good irregularity metrics are introduced: Approximate entropy (ApEn) and multiscale entropy (MSE), in combination with k-means clustering, can be used to accurately identify the data segments that are disturbed by noise. Stagewise orthogonal matching pursuit (StOMP) is used for noise suppression only in data segments identified as containing strong interference. Finally, we reconstructed the signal. The results show that the proposed method can better preserve the low-frequency slow-change information of the magnetotelluric signal compared with just using StOMP, thus avoiding the loss of useful information due to over-processing, while producing a smoother and more continuous apparent resistivity curve. Moreover, the results more accurately reflect the inherent electrical structure information of the measured site itself.

Oestrogen Inhibits Arterial Calcification by Promoting Autophagy.

Arterial calcification is a major complication of cardiovascular disease. Oestrogen replacement therapy in postmenopausal women is associated with lower levels of coronary artery calcification, but its mechanism of action remains unclear. Here, we show that oestrogen inhibits the osteoblastic differentiation of vascular smooth muscle cells (VSMCs) in vitro and arterial calcification in vivo by promoting autophagy. Through electron microscopy, GFP-LC3 redistribution, and immunofluorescence analyses as well as measurement of the expression of the autophagosome marker light-chain I/II (LC3I/II) and autophagy protein 5 (Atg5), we show that autophagy is increased in VSMCs by oestrogen in vitro and in vivo. The inhibitory effect of oestrogen on arterial calcification was counteracted by 3-methyladenine (3MA) or knockdown of Atg5 and was increased by rapamycin. Furthermore, the inhibitory effect of oestrogen on arterial calcification and the degree of autophagy induced by oestrogen were blocked by a nonselective oestrogen receptor (ER) antagonist (ICI 182780), a selective oestrogen receptor alpha (ERα) antagonist (MPP), and ERα-specific siRNA. Our data indicate that oestrogen inhibits the osteoblastic differentiation of VSMCs by promoting autophagy through the ERα signalling pathway in vitro and arterial calcification in vivo by increasing autophagy. Our findings provide new insights into the mechanism by which oestrogen contributes to vascular calcification in vitro and in vivo.

Gender differences in a reference database of age-related femoral neck geometric parameters for Chinese population and their association with femoral neck fractures.

Femoral neck geometric parameters (FNGPs) are closely related to the strength of the femoral neck and the risk of fragility fractures. No reference database is available for FNGPs for Chinese population, and gender-related differences in FNGPs as well as their association with the risk of femoral neck fractures are unknown. This investigation aimed to set up reference databases for FNGPs, understand gender-related differences in FNGPs, and examine the association between FNGPs and the risk of osteoporotic fractures of the femoral neck. This study included 5268 females and 2156 males (aged 15-91years) from Chinese population. A total of 384 patients (282 females and 102 males) had sustained femoral neck fractures; 384 age- and sex-matched individuals without any fractures served as controls. Femoral neck DXA images were used to measure bone mineral density (BMD) and eight FNGPs. Our results showed that the age-related trends of FNGPs were fitted with the best goodness-of-fit by applying the cubic regression model. The trends shown by FNGPs were significantly different between male and female subjects, and the fitting curves were significantly higher in male subjects. After adjustments were made for age, height, weight, and body mass index, Cox regression analysis showed that changes in all FNGPs were related to increased hazard ratios (HRs) of femoral neck fractures. After further adjustment was made for BMD of the femoral neck, the HRs related to a cortical thickness (CT) decrease and buckling ratio (BR) increase in females went up by 3.35-folds (95% CI: 2.75-4.07) and 1.86-folds (95% CI: 1.33-2.60), respectively. In males, the HRs related to the decrease in CT and cross-sectional area (CSA) increased by 3.21-folds (95% CI: 2.32-4.45) and 1.88-folds (95% CI: 1.03-3.44), respectively. In conclusions, the reference databases of FNGPs established in this study will assist in the evaluation and prediction of femoral neck fracture risk in the clinic. The decrease in CT and increase in BR of the femoral neck were independent risk factors for osteoporotic fractures of the femoral neck in females from mainland China, while a decrease in CT and CSA were risk factors in male.

Epidemiology and management of osteoporosis in the People's Republic of China: current perspectives.

With the progressive aging of the population, osteoporosis has gradually grown into a global health problem for men and women aged 50 years and older because of its consequences in terms of disabilities and fragility fractures. This is especially true in the People's Republic of China, which has the largest population and an increasing proportion of elderly people, as osteoporosis has become a serious challenge to the Chinese government, society, and family. Apart from the fact that all osteoporotic fractures can increase the patient's morbidity, they can also result in fractures of the hip and vertebrae, which are associated with a significantly higher mortality. The cost of osteoporotic fractures, moreover, is a heavy burden on families, society, and even the country, which is likely to increase in the future due, in part, to the improvement in average life expectancy. Therefore, understanding the epidemiology of osteoporosis is essential and is significant for developing strategies to help reduce this problem. In this review, we will summarize the epidemiology of osteoporosis in the People's Republic of China, including the epidemiology of osteoporotic fractures, focusing on preventive methods and the management of osteoporosis, which consist of basic measures and pharmacological treatments.

Age-related bone turnover markers and osteoporotic risk in native Chinese women.

BACKGROUND: The rate of bone turnover is closely related to osteoporosis risk. We investigated the correlation between bone turnover markers and BMD at various skeletal sites in healthy native Chinese women, and to study the effect of changes in the levels of bone turnover markers on the risk of osteoporosis. METHODS: A cross-section study of 891 healthy Chinese women aged 20-80 years was conducted. The levels of serum osteocalcin (OC), bone-specific alkaline phosphatase (BAP), serum cross-linked N-terminal telopeptides of type I collagen (sNTX), cross-linked C-terminal telopeptides of type I collagen (sCTX), urinary NTX (uNTX), urinary CTX (uCTX) and total urinary deoxypyridinoline (uDPD) were determined. BMD at the posteroanterior spine and the hip was measured using DXA. RESULTS: Pearson's correlation coefficient found significant negative correlation between bone turnover marker and BMD T-score at different skeletal sites (r = -0.08 to -0.52, all P = 0.038-0.000). After adjustments for age and body mass index, the partial correlation coefficients between the OC, BAP, sNTX, sCTX and uCTX, and the T-scores at various skeletal sites were still significant. After adjustment of height and weight, the correlation coefficients between most BTMs and PA lumbar spine BMD were also significant. Multiple linear regression analysis showed that bone turnover markers were negative determinants of T-scores. BAP and OC accounted for 33.1% and 7.8% of the variations in the T-scores of the PA spine, respectively. Serum OC, BAP, uDPD, and sNTX accounted for 0.4-21.9% of the variations in the femoral neck and total hip T-scores. The bone turnover marker levels were grouped as per quartile intervals, and the T-scores, osteoporosis prevalence and risk were found to markedly and increase with increase in bone turnover marker levels. CONCLUSIONS: This study clarified the relationship between bone turnover markers and osteoporosis risk in native Chinese women. Bone turnover marker levels were found to be important determinants of BMD T-scores. Furthermore, osteoporotic risk significantly increased with increase in the levels of bone turnover markers.

Relationships between age-related biochemical markers of bone turnover and OPG, TGF-ß1 and TGF-ß2 in native Chinese women.

Osteoprotegerin (OPG), transforming growth factor-ß1 (TGF-ß1) and TGF-ß2 are cytokines closely associated with bone metabolism. However, their association with bone turnover markers in native Chinese women remains unknown. The study aims to investigate the relationship between bone metabolism related cytokines including OPG, TGF-ß1, TGF-ß2 and bone turnover markers in native Chinese women. The cross-sectional study was conducted on 691 healthy Chinese women (20-80 years old). Levels of OPG, TGF-ß1, TGF-ß2, serum bone-specific alkaline phosphatase (BAP), osteocalcin (OC), cross-linked N-terminal telopeptides of type I collagen (sNTX), cross-linked C-terminal telopeptides of type I collagen (sCTX), urinary NTX (uNTX), urinary CTX (uCTX) and total urinary deoxypyridinoline (uDPD) were determined. The present study showed that OPG and TGF-ß2 had positive correlation with BAP, OC, uNTX, uCTX and uDPD, while TGF-ß1 showed negative correlation with BAP, OC, sCTX, uNTX and uCTX, and most of the coefficients of partial correlation remained significant after adjustments for age and body mass index (BMI). Multiple linear regression stepwise analysis showed that OPG and TGF-ß2 were positive determinative factors for BAP, sCTX, uNTX and uCTX, which could explain 0.6-16.6% of the variation in these markers. TGF-ß1 was a negative determinative factor for BAP, OC, sCTX and uCTX, which could explain 0.7-7.3% of the variation in these markers. This study suggested that measuring bone turnover indicators and serum cytokines simultaneously might help evaluating changes in bone turnover rate caused by aging or menopause in women.

[Relationship of age-related levels of serum sex hormones with bone mineral density decreasing rate in women].

OBJECTIVE: To explore the relationship between the changes of estrogen, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels and bone mineral density (BMD) decreasing rate (BDR) at different skeletal regions and examine the effects of hormones levels on BDR. METHODS: An age cross-sectional study was conducted in 694 healthy adult women excluded from diseases and drugs affecting bone metabolism. Their age range was 20-80 years. The serum concentrations of FSH, LH and estradiol (E2) were measured with radioimmunoassay. And BDR was measured with a DXA fan-beam bone densitometer at various skeletal regions including lumbar spine, left hip and left forearm. RESULTS: The serum levels of FSH (r = -0.597 to -0.479, all P < 0.01) and LH r = -0.452 to -0.283, all P < 0.01) were significantly negatively correlated with BDR at various skeletal regions. Meanwhile, the serum level of E2 only had slightly positive correlation with hip and distal forearm (r = 0.077 to 0.122, all P < 0.05). After adjusting age and body mass index (BMI), serum FSH still had markedly negative correlation with BDR at various skeletal regions. However, the correlation coefficients became weak. Multiple line regression stepwise analysis revealed that serum FSH was a negative determinant factor of BDR at various skeletal regions: 20%-32% changes in BDR of various skeletal regions were determined by FSH, while LH only produced very small negative effects (0.6%-0.8%) on BDR of lumbar spine. Serum E2 seemed to be a positive determinant factor of skeletal regions and 2.5%-5.4% changes in BDR were determined by E2. The effects of serum FSH on BDR were approximately 3.8-12.8 folds than those of serum E2. CONCLUSIONS: BDR is correlated with increased FSH in women. The most critical factor for aging-related BDR is FSH in women while a decreased level of estrogen may be secondary.

Connective tissue growth factor induces osteogenic differentiation of vascular smooth muscle cells through ERK signaling.

Connective tissue growth factor (CTGF) plays an important role in the pathogenesis of atherosclerosis by promoting vascular smooth muscle cell (VSMC) growth, migration, apoptosis, adhesion and the secretion of matrix components. The osteogenic differentiation of VSMCs is essential in the development of vascular calcification. However, the role of CTGF in the transdifferentiation and calcification of VSMCs is unclear. In the present study, we examined whether CTGF stimulates VSMC transdifferentiation. Primary VSMCs were obtained from mouse thoracic aortas by enzymatic digestion and identified by immunostaining for smooth muscle specific α-actin antibody (α-SMA). VSMC calcification was induced by the addition of CTGF to the osteogenic mediaum containing 5-10% FBS in the presence of 0.25 mM ascorbic acid and 10 mM ß-glycerophosphate for 14 days. Calcified cells were determined by Alizarin Red S staining. Our results revealed that CTGF induced the expression of several bone markers, including alkaline phosphatase (ALP), osteocalcin (OC), osteoprotegerin (OPG) and core-binding factor subunit α1 (Cbfα1)/runt-related transcription factor 2 (Runx2), as well as calcification. However, the inhibition of extracellular signal-regulated kinase (ERK) activity using the ERK-specific inhibitor, PD98059, blocked the induction of these proteins and VSMC calcification. Based on these data, we conclude that CTGF stimulates the transdifferentiation of VSMCs into osteoblasts and that the ERK signaling pathway appears to play a critical role in this process.

Relationship between Serum Levels of OPG and TGF- ß with Decreasing Rate of BMD in Native Chinese Women.

The objective of this study was to investigate the relationship between serum levels of OPG, TGF- ß 1, and TGF- ß 2 and BMD decrease rate (BDR) in native Chinese women. This cross-sectional study was performed on 465 healthy native Chinese women aged 35-80 years. Serum levels of OPG, TGF- ß 1, and TGF- ß 2 were determined. BDR was measured by DXA at the posteroanterior spine, hip, and distal forearm. At all skeletal sites tested, there was a negative correlation between BDR and serum levels of both OPG (r = -0.122 to -0.230, all P = 0.007-0.000) and TGF- ß 2 (r = -0.100 to -0.173, all P = 0.029-0.000) and a positive correlation between BDR and serum TGF- ß 1 (r = 0.245 - 0.365, all P = 0.000). After adjustment for age and BMI, there were no statistically significant correlations between serum levels of OPG or TGF- ß 2 and BDR. However, statistically significant correlations between serum TGF- ß 1 and BDR at the lumbar spine and ultradistal forearm remained. Multiple linear regression stepwise analysis showed that serum OPG could explain 1.4-3.7% of BDR variation. Serum TGF- ß 1 was a positive determinant of BDR and could explain 5.3-13.3% of BDR variation.

Early bone mineral density decrease is associated with FSH and LH, not estrogen.

BACKGROUND: It remains unclear whether gonadotropins or estrogen is responsible for early bone mineral density (BMD) decrease in Chinese women. METHODS: A cross-sectional study was conducted on 368 healthy adult women, aged 35-60 years. We measured BMD, calculated BMD decrease rates (BDRs) and assessed serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E(2)) levels. RESULTS: BDR was significantly negatively correlated with serum FSH (r=-0.429 to -0.622, all p=0.000) and LH (r=-0.359 to -0.526, all p=0.000). After adjustment for age and body mass index, the negative correlations of serum FSH and LH with BDR persisted, but there was no overall correlation between serum E(2) and BDR. Multiple linear stepwise regression analysis suggested that serum FSH is a negative determinant of BDR. Serum E(2) seems to be a positive determinant of BDR in a few parts of the skeleton. CONCLUSIONS: The decrease of BMD during the menopause is associated with FSH and LH levels, rather than E(2) in Chinese women.

[Serum retinol binding protein 4 and bone metabolism in patients with type 2 diabetes].

OBJECTIVE: To determine the relation between serum concentration of retinol binding protein (RBP) 4 and markers of bone metabolism, bone mineral density (BMD) in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 82 patients newly diagnosed with T2DM and 46 subjects with normal glucose tolerance (NGT) enrolled in the cross-sectional study. Subset analyses were performed, dividing subjects on the basis of gender into M-T2DM, F-T2DM, M-NGT, and F-NGT. The serum concentrions of RBP4, osteocalcin (OC) and C-terminal telopeptide of collagen type I (CTX) were measured with ELISA. The BMD was measured by dual-energy X-ray absorptiometry (DXA) with a Hologic QDR4500A device. RESULTS: In both the T2DM groups, lnRBP4 showed a positive relationship with lnCTX (M-T2DM, r=0.564, P<0.01; F-T2DM, r=0.386, P=0.018), but no association with lnOC. After adjusting for age, smoking, creatinine clearance rate (CCr), and waist-to-hip ratio (WHR), lnRBP4 still showed a strong association with lnCTX in the M-T2DM group (r'=0.536, P<0.01), but not in F-T2DM (r'=0.317, P=0.072). In the NGT group, there was no relation between lnRBP4 and lnCTX or lnOC. LnRBP4 showed no association with BMD in all groups. CONCLUSION: The level of serum RBP4 may be correlated with the bone metabolism in patients with T2DM.

The relationship between bone turnover markers and BMD decreasing rates in Chinese middle-aged women.

BACKGROUND: The relationship between bone turnover markers (BTMs) and BMD decreasing rate (BDR) in Chinese women is unclear. Wu investigated the relationship between (BTMs) and BDR at various skeletal sites in Chinese middle-aged women. METHODS: A cross-section study of 555 healthy Chinese women over 35-60years of age. BMD at posteroanterior spine, the left hip, and the left forearm were measured with a DXA. Levels of serum osteocalcin (OC), bone-specific alkaline phosphatase (BAP), cross-linked N-terminal telopeptides of type I collagen (sNTX) and total urinary deoxypyridinoline (uDPD) were determined. RESULTS: BDR at various skeletal sites had significant negative correlation with serum OC(r=-0.395 to -0.530), BAP(r=-0.297 to -0.486), and sNTX(r=-0.207 to -0.272). After adjustment of age and weight, serum OC, BAP, and sNTX rather than total uDPD still exhibited significant correlations with BDR. Stepwise regression analyses showed that, serum OC and BAP were the significantly negative determinants of BDR. Between 4.7-27.7% and 1.2-16.1% of the changes in BDR were determined by serum OC and BAP, respectively. However, sNTX and total uDPD had no significant effect on BDR at various skeletal sites. CONCLUSIONS: This study indicated the correlation between BTMs and early-stage BDR in Chinese middle-aged women and suggested that serum OC and BAP, rather than sNTX and total uDPD, are the key determining factors of early BMD decreases.