Efficacy and safety of human chorionic gonadotropin combined with human menopausal gonadotropin and a gonadotropin-releasing hormone pump for male adolescents with congenital hypogonadotropic hypogonadism.

BACKGROUND: Compared to adult studies, studies which involve the treatment of pediatric congenital hypogonadotropic hypogonadism (CHH) are limited and no universal treatment regimen is available. The aim of this study was to evaluate the feasibility of human chorionic gonadotropin (hCG)/human menopausal gonadotropin (hMG) therapy for treating male adolescents with CHH. METHODS: Male adolescent CHH patients were treated with hCG/hMG (n = 20) or a gonadotropin-releasing hormone (GnRH) pump (n = 21). The treatment was divided into a study phase (0-3 months) and a follow-up phase (3-12 months). The testicular volume (TV), penile length (PL), penis diameter (PD), and sex hormone levels were compared between the two groups. The TV and other indicators between the groups were analyzed using a t-test (equal variance) or a rank sum test (unequal variance). RESULTS: Before treatment, there was no statistical difference between the two groups in terms of the biochemistry, hormones, and other demographic indicators. After 3 months of treatment, the TV of the hCG/hMG and GnRH groups increased to 5.1 ±â€Š2.3 mL and 4.1 ±â€Š1.8 mL, respectively; however, the difference was not statistically significant (P > 0.05, t = 1.394). The PL reached 6.9 ±â€Š1.8 cm and 5.1 ±â€Š1.6 cm (P < 0.05, t = 3.083), the PD reached 2.4 ±â€Š0.5 cm and 2.0 ±â€Š0.6 cm (P < 0.05, t = 2.224), respectively, in the two groups. At the end of 6 months of treatment, biomarkers were in normal range in the two groups. Compared with the GnRH group, the testosterone (T) level and growth of PL and PD were significantly greater in the hCG/hMG group (all P < 0.05). While the TV of both groups increased, the difference was not statistically significant (P > 0.05, t = 0.314). After 9 to 12 months of treatment, the T level was higher in the hCG/hMG group. Other parameters did not exhibit a statistical difference. CONCLUSIONS: The hCG/hMG regimen is feasible and effective for treating male adolescents with CHH. The initial 3 months of treatment may be a window to optimally observe the strongest effects of therapy. Furthermore, results from the extended time-period showed positive outcomes at the 1-year mark; however, the long-term effectiveness, strengths, and weaknesses of the hCG/hMG regimen require further research. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02880280; https://clinicaltrials.gov/ct2/show/NCT02880280.

Cosinor-rhythmometry for 24-h urinary sodium, potassium, creatinine excretion in the Chinese adult population.

BACKGROUND: The low accuracy of equations predicting 24-h urinary sodium excretion using a single spot urine sample contributed to the misclassification of individual sodium intake levels. The application of single spot urine sample is limited by a lack of representativity of urinary sodium excretion, possibly due to the circadian rhythm in urinary excretion. This study aimed to explore the circadian rhythm, characteristics, and parameters in a healthy young adult Chinese population as a theoretical foundation for developing new approaches. METHODS: Eighty-five participants (mean age 32.4 years) completed the 24-h urine collection by successively collecting each of the single-voided specimens within 24 h. The concentrations of the urinary sodium, potassium, and creatinine for each voided specimen were measured. Cosinor analysis was applied to explore the circadian rhythm of the urinary sodium, potassium, and creatinine excretion. The excretion per hour was computed for analyzing the change over time with repeated-measures analysis of variance and a cubic spline model. RESULTS: The metabolism of urinary sodium, potassium, and creatinine showed different patterns of circadian rhythm, although the urinary sodium excretion showed non-significant parameters in the cosinor model. A significant circadian rhythm of urinary creatinine excretion was observed, while the circadian rhythm of sodium was less significant than that of potassium. The circadian rhythm of urinary sodium and creatinine excretion showed synchronization to some extent, which had a nocturnal peak and fell to the lowest around noon to afternoon. In contrast, the peak of potassium was observed in the morning and dropped to the lowest point in the evening. The hourly urinary excretion followed a similar circadian rhythm. CONCLUSION: It is necessary to consider the circadian rhythm of urinary sodium, potassium, and creatinine excretion in adults while exploring the estimation model for 24-h urinary sodium excretion using spot urine.

Age-dependent changes of total and differential white blood cell counts in children.

BACKGROUND: Total and differential white blood cell counts are important for the diagnostic evaluation of suspected diseases. To facilitate the interpretation of total and differential white blood cell counts in pediatric patients, the present study investigated age-dependent changes in total and differential white blood cell counts in healthy reference children. METHODS: Data were obtained from the Pediatric Reference Intervals in China study (PRINCE), which aims to establish and verify pediatric reference intervals for Chinese children based on a nationwide multicenter cross-sectional study from January 2017 to December 2018. Quantile curves were calculated using the generalized additive models for location, shape, and scale method. The 2.5th, 50th, and 97.5th quantile curves were calculated for both total and differential white blood counts. Percents of stacked area charts were used to demonstrate the proportions of differential white blood cells. All statistical analyses were performed using R software. RESULTS: Both 50th and 97.5th quantiles of total white blood cell count and monocyte count were highest at birth, then rapidly decreased in the first 6 months of life; relatively slow reduction continued until 2 years of age. The lymphocyte count was low during infancy and increased to its highest level at 6 months of age; it then exhibited moderate and continuous reduction until approximately 9 years of age. The pattern of neutrophil count changed with age in a manner opposite to that of lymphocyte count. Besides, there were two inter-sections of lymphocyte count and neutrophil count during infancy and at approximately 5 years of age, based on locally weighted regression (LOESS) analysis. There were no apparent age-related changes in eosinophil or basophil counts. CONCLUSION: These data regarding age-related changes in total and differential white blood cell counts can be used to assess the health of pediatric patients and guide clinical decisions.

Final adult height of children with idiopathic short stature: a multicenter study on GH therapy alone started during peri-puberty.

BACKGROUND: To evaluate the efficacy of GH in improving FAH in ISS children in a multicenter study. METHODS: A real-world observation was carried out. Children with ISS in seven hospitals in China were enrolled. The height gains standard deviation score and the height gain over the target height were evaluated. RESULTS: There were 344 ISS patients (217 boys and 127 girls). The baseline average age of boys and girls was 12.7 and 11.7 years, with bone age of 11.7 and 10.1 years, respectively. The baseline height SDS of boys and girls was - 3.07 and - 2.74, and the FAH SDS was - 1.91 and - 1.38, respectively. Compared with the baseline height SDS, the FAH SDS was significantly increased in both boys and girls (both P = 0.0000). The FAH SDS was the highest (gain by 1.54 SD) in the ≥2y treatment course group. Two hundred eighteen patients (218/344, 63.4%) had a FAH SDS > - 2 SD. Among these patients, girls in the 1-2y treatment course group and ≥ 2y group had a FAH SDS higher than TH SDS. Even in the control group, a spontaneous catch-up growth of 1.16 SD was observed. A multivariate linear regression model was used to analyze the results, with FAH SDS as the dependent variable. It was found that the treatment course and baseline height SDS in the boys' model were statistically significant (P < 0.05), whereas the baseline height SDS and baseline bone age significantly affected the girls' FAH SDS (P < 0.05). CONCLUSIONS: Both girls and boys of ISS improved FAH by GH therapy even if treatments begin over 10 years old and majority of them reached TH. Some peri-puberty ISS will have a spontaneous height gain. We recommend the course of GH treatment more than 2 years for girls, and longer courses for boys.

Wedelolactone suppresses cell proliferation and migration through AKT and AMPK signaling in melanoma.

Purpose: Melanoma is a malignant tumor with high degree of malignancy, metastasis and high mortality. As melanoma is not sensitive to treatments, searching for new therapeutic agent is the priority. Wedelolactone (WDL) is a natural compound which has antiproliferation activities. In the current study, the effects of WDL on melanoma are evaluated and the underlying mechanisms are explored. Materials and methods: We treated melanoma cell line MV3 cells with WDL and monitored the cell proliferation, invasion and migration, the mRNA and protein levels of Bax and Bcl-2, expression of cell-cycle regulators including cyclin D, proliferating cell nuclear antigen (PCNA) and p21. We detected the effect of WDL on AKT and AMPK signaling pathways activations. Finally, we evaluated the inhibitory effect of WDL in xenograft nude mice model in vivo. Results: WDL inhibited MV3 cell proliferation, migration and invasion. WDL induced pro-apoptotic protein Bax expression but inhibited antiapoptotic protein Bcl-2 expression. WDL inhibited cyclin D expression while increased p21 expression. WDL inhibited AKT activation but induced AMPK activation. The induction of p21expression by WDL depended on AMPK signaling pathway. WDL inhibited melanoma in xenograft nude mice. Conclusion: WDL suppressed cell proliferation and regulated MV3 cell-cycle proteins through AKT and AMPK signaling in melanoma.

Baohuoside-I suppresses cell proliferation and migration by up-regulating miR-144 in melanoma.

CONTEXT: Baohuoside-I was reported to induce apoptosis in non-small-cell lung cancer and inhibit the growth of multiple myeloma cells. The antitumour potential of baohuoside-I has not been demonstrated in melanoma yet. OBJECTIVE: To investigate the potential antitumour activity of baohuoside-I against melanoma and elucidate its underlying molecular mechanism. MATERIALS AND METHODS: Cell viability was evaluated by MTT assay. The malignant invasion capacity was measured with trans-well assay. The relative expression change of microRNAs was profiled with microarray. TargetScan was utilized for prediction of target gene of miR-144. Regulatory effect of miR-144 on SMAD1 was determined by dual luciferase reporter assay. Endogenous SMAD1 protein in response to ectopic expression of miR-144 was determined by immunoblotting. Xenograft mice were employed to evaluate antitumour potential of baohuoside-I (25 mg/kg by tail intravenous injection every two days) in vivo. RESULTS: Baohuoside-I significantly inhibited proliferation (45 ± 4% reduction in M14 and 35 ± 3% reduction in MV3 at 24 h) and migration (70 ± 4% reduction in M14 and 72 ± 3% reduction in MV3) in melanoma cells. Mechanistically, baohuoside-I up-regulated miR-144 expression levels (3 ± 0.2-fold). Silence of miR-144 reversed the inhibition of baohuoside-I in melanoma. We have identified that SMAD1 was the novel target of miR-144. Moreover, baohuoside-I suppressed melanoma in vivo (52 ± 8% reduction in xenograft tumour size at day 20). CONCLUSIONS: Our data suggested significant antitumour potential of baohuoside-I against melanoma both in vitro and in vivo, which warrants further laboratory investigation and clinical trial.

Effects of salt substitutes on blood pressure: a meta-analysis of randomized controlled trials.

BACKGROUND: Clinical trials assessing the effects of salt substitutes on blood pressure (BP) have reported mixed results. OBJECTIVES: A meta-analysis of randomized controlled trials was conducted to evaluate the effect of salt substitutes on BP, including systolic BP (SBP) and diastolic BP (DBP). DESIGN: Studies were identified via systematic searches of the PubMed, Embase, Cochrane Library, Wanfang Data, and the China National Knowledge Infrastructure databases through December 2013. Random-effects models were used to estimate pooled mean differences in SBP and DBP. RESULTS: Six cohorts from 5 articles (1 trial enrolled 2 cohorts for independent intervention) consisting of 1974 participants were included. Pooled results showed that salt substitutes had a significant effect on SBP (mean difference: -4.9 mm Hg; 95% CI: -7.3, -2.5 mm Hg; P < 0.001) and DBP (mean difference: -1.5 mm Hg; 95% CI: -2.7, -0.3 mm Hg; P = 0.013). Significant heterogeneity was found for both SBP (I(2) = 76.7%) and DBP (I(2) = 65.8%). The sensitivity analysis indicated that the pooled effects of salt substitutes on SBP and DBP were robust to systematically dropping each trial. Furthermore, no evidence of significant publication bias from funnel plots or Egger's tests (P = 0.17 and 0.22 for SBP and DBP, respectively) was found. CONCLUSION: This meta-analysis showed that salt-substitution strategies are effective at lowering SBP and DBP, which supports a nutritional approach to preventing hypertension.

Factors associated with prehospital delay in patients with ST-segment elevation acute myocardial infarction in China.

BACKGROUND: Prehospital delay is the most critical factor to prognosis of ST-elevation myocardial infarction (STEMI). Few study had examined a series of predictors of prehospital delay by multivariate analysis of sociodemographic and clinical characteristics, onset features, and symptom condition of STEMI in China. METHODS: A total of 1088 hospitalized STEMI participants were screened to collect sociodemographic data, medical history information, and symptom onset status from clinical medical records. Factors associated with prehospital delay were examined using bivariate and multivariate analysis method. RESULTS: The median prehospital delay time (PDT) was 130 minutes in STEMI participants. Multivariate regression models examining 8 predictors were associated with prehospital delay, including senior high school or above educational level, myocardial infarction (MI) history, vertigo onset symptom, ambulance transportation, onset in daytime (6:00-18:00), onset at home, anterior wall MI, and posterior wall MI. Mortality in PDT more than 120 minutes group was 5.5%, whereas it was 4.3% in PDT 120 minutes of less group without significant statistically difference (P > .05). CONCLUSIONS: Multivariate analysis results found that symptom onset-related variables strongly influenced PDT. Onset-related status of STEMI needed to be combined into interventions of participants, and more emergency education should be recommended to both participants and their relatives. Most importantly, more efforts should be taken to educate the public about the symptoms and signs to increase the recognition of STEMI.

[The optimal cut-off value of waist-to-height ratio for detecting severe central obesity and low body weight adult Chinese population].

OBJECTIVE: To explore the optimal cut-off values of waist-to-height ratio (WHtR) for detecting the severe central obesity and low body weight in adult Chinese population. METHODS: A total of 30 630 participants aged 35-59 years from different areas in mainland China were surveyed for cardiovascular diseases risk factors in two independent cross-sectional studies that carried out in 1992-1994 and 1998, respectively. Indices, such as sensitivity, specificity for hypertension, abnormal glucose, high serum total cholesterol, low serum high density lipoprotein cholesterol and clustering of risk factors (number ≥ 2) were calculated to evaluate the efficacy individual cut-off point of WHtR. The cut-off point value for obvious central obesity was fixed on the point whose specificity of the point was gathered more than 90%. And the cut-off point value to indicate low weight was determined by the percentile distribution of WHtR, at which the 5th percentile of point, both in male and female population. Based on the principle of convenient and practical for use, the optimal cut-off point values of WHtR for low weight and obvious central obesity were determined. RESULTS: The cut-off values of WHtR to detect severe central obesity were 0.54 and 0.57 for men and women, respectively. Additionally, the cut-off points of WHtR for each of the 4 cardiovascular risk factors to evaluate the severity separately ranged from 0.54 to 0.55 in male, and ranged from 0.57 to 0.58 in female. The 5th percentile of WHtR, which was the point value of WHtR to indicate low body weight, was 0.40 in both male and female population. CONCLUSION: Our data suggest that the optimal cut-off value of WHtR for defining severe central obesity and low body weight should be 0.57 and 0.40, respectively.

[Contrast and efficacy of waist circumference and waist-to-height ratio in predicting central obesity].

OBJECTIVE: To study the efficacy of waist circumference (WC) and waist-to-height ratio (WHtR) in predicting central obesity among the Chinese adult population. METHODS: A total of 30 630 participants aged 35 - 59 from different areas in mainland China were surveyed for the risk factors of cardiovascular diseases (CVD) in two independent cross-sectional studies that were carried out in 1992 - 1994 and 1998, respectively. In subgroups with different heights, consistency analysis for central obesity diagnosed by WHtR (≥ 0.50) and WC (≥ 85 cm for men, ≥ 80 cm for women) were conducted. Sensitivity and specificity for predicting the clustering of risk factors (number ≥ 2) would include hypertension, abnormal glucose, high serum total cholesterol and low serum high density lipoprotein cholesterol and they were also calculated to evaluate the efficacy of prediction, with the two indices in the different height subgroups as well. RESULTS: The consistency of diagnosis on central obesity by WC and WHtR was good in the whole population (the Kappa value was 0.805 in men and 0.816 in women), but poor (all Kappa values ≤ 0.6) for those with tall (men's height ≥ 180 cm and women's height ≥ 170 cm) or with short statures (men's height < 160 cm, and women's height < 150 cm). Sensitivity in the shorty subgroups and specificity in the tall subgroups appeared poor in both genders, by using WC criteria to predict the clustering of risk factors. However, the sensitivity (ranged from 56.1% to 64.1% for men and 64.7% to 73.2% for women) and specificity (from 70.0% to 74.5% for men, 59.2% to 75.9% for women) seemed good and stable in all the subgroups as well as in both genders by using the WHtR criteria. CONCLUSION: WC and WHtR could both be applied in predicting the clustering of risk factors of CVD and in evaluating the central obesity in the whole population. With satisfactory efficacy, WHtR seemed to be better than WC in the prediction of central obesity, both in men or women with tall or short statures.

Serum total adiponectin level and the risk of cardiovascular disease in general population: a meta-analysis of 17 prospective studies.

OBJECTIVE: Many studies have assessed the association between serum adiponectin and the risk of cardiovascular disease (CVD), yet whether adiponectin is an independent risk factor for CVD remains controversial. We performed a meta-analysis of 17 prospective epidemiologic studies to evaluate this relationship in the general population. METHODS: PubMed and Embase databases were searched through June 2012 to identify studies meeting a priori inclusion criteria, in addition to conducting a secondary reference review. Two principle investigators respectively extracted the information with either fixed-effect model or random-effect model to calculate the relationship between adiponectin and the risk of CVD. RESULTS: We summarized 17 prospective studies with a total of 23,717 participants. Overall, higher serum adiponectin was related to an increased risk of ischemic stroke: pooled risk ratio (RR) of 1.34 [95% confidence intervals (CI): 1.06-1.69] with no heterogeneity (Q = 1.23; P = 0.541). Serum adiponectin was not related to coronary heart disease (CHD) or CVD: pooled RR of 0.96 (95% CI: 0.85-1.08) and 1.00 (95% CI: 0.89-1.13), respectively. CONCLUSIONS: Increased serum adiponectin was related to an elevated risk of ischemic stroke, but there was no clear evidence indicating a positive relationship between adiponectin and the risk of CHD or CVD.

[Clinical characteristics of and related treatments on 1004 patients with acute myocardial infarction from March 2004 to March 2007].

OBJECTIVE: To study the change of baseline clinical characteristics including prehospital delayed time (PDT), modes of transportation and treatment for patients with acute myocardial infarction (AMI) in the past 3 years. METHODS: We used the same questionnaire to accurately collect and retrospectively analyze the data regarding clinical characteristics of all 1004 patients with AMI, who consecutively presented to the Emergency Unit and Emergency Intensive Care Unit (EICU) of Beijing Anzhen Hospital from March 12th 2004 to March 11th 2007. According to the time of onset of the disease, all patients were divided into 3 groups: group A (from Mar. 12th 2004 to Mar. 11th 2005), group B (Mar. 12th 2005 to Mar 11th 2006) and group C (Mar. 12th 2006 to Mar. 11th 2007). Clinical characteristics and treatment were compared. RESULTS: There were significant differences in the number of patients with histories of stroke, coronary artery disease or smoking among the three groups (P < 0.05). No obvious differences in the median of PDT were found among the three groups (P > 0.05). More patients accepted reperfusive therapy in group C compared to group A (P < 0.05), although the mortality rates of AMI among these 3 years were similar. CONCLUSION: Though more people started to have accepted reperfusion therapy, mortality failed to show an obvious decrease. Subject as how to shorten the PDT called for further study.

[Prehospital delay time and mortality in patients with acute myocardial infarction].

OBJECTIVE: To determine the relationship between prehospital delay time (PDT) and other associated factors on mortality in patients with acute myocardial infarction. METHODS: We retrospectively analyzed factors associated with mortality in 580 patients with acute myocardial infarction presented to the Emergency Ward and Emergency Intensive Care Unit (EICU) of Beijing Anzhen Hospital from March 2004 to March 2006 (428 males, average age: 60.7 +/- 12.9 years). The patients were divided to 3 groups according various therapies: thrombolysis, PCI/CABG or symptomatic medication groups. RESULTS: The median PDT was 130 min. Thrombolysis, PCI/CABG and medical therapy were applied in 122 (21.0%), 266 (45.9%) and 192 (33.1%) patients respectively. PDT was significantly longer in patients receiving medical therapy (290.9 min +/- 3.4 min) compared to patients treated with thrombolysis (104.5 min +/- 2.3 min) and PCI/CABG (119.1 min +/- 2.3 min, all P < 0.05). The overall mortality rate was 5.3% (31/580) and all occurred in patients with medical therapy group mostly due to irreversible ventricular fibrillations. Old age (OR = 1.047, P = 0.004), diabetes mellitus (OR = 2.159, P = 0.02) and PDT (OR = 2.159, P = 0.023) are independent predict factors for mortality. CONCLUSION: Coronary Revascularisation by thrombolysis, PCI or CABG early post acute myocardial infarction is the key issue for reducing mortality in patients with acute myocardial infarction.