Identification of a p.Trp403* nonsense variant in PHEX causing X-linked hypophosphatemia by inhibiting p38 MAPK signaling.

X-linked hypophosphatemia (XLH) is the most common hereditary rickets, caused by mutations in PHEX encoding the phosphate regulating endopeptidase homolog X-linked. Here, we report a nonsense variant in exon 11 of PHEX (c.1209G>A p.Trp403*) cosegregating with XLH in a Chinese family with a LOD score of 2.70. Real-time reverse transcription polymerase chain reaction analysis demonstrated that p.Trp403* variant did not cause nonsense-mediated mRNA decay (NMD), but significantly increased the expression level of FGF23 mRNA in the patients. Interestingly, p.Trp403* significantly reduced phosphorylation of p38 mitogen-activated protein kinase (MAPK) but not ERK1/2. Moreover, overexpression of FGF23 significantly decreased phosphorylation of p38 MAPK, whereas knockdown of FGF23 by siRNA significantly increased phosphorylation of p38 MAPK. These data suggest that p.Trp403* may not function via an NMD mechanism, and instead causes XLH via a novel signaling mechanism involving PHEX, FGF23, and p38 MAPK. This finding provides important insights into genetic and molecular mechanisms for the pathogenesis of XLH.

[Pure red cell aplasia in children: a clinical analysis of 16 cases].

OBJECTIVE: To study the clinical features, treatment, and prognosis of pure red cell aplasia (PRCA) in children. METHODS: A retrospective analysis was performed for the clinical data of 16 children with PRCA. The outcome and prognosis of patients treated with prednisone combined with Huaiqihuang granules versus prednisone alone were evaluated. RESULTS: All the 16 children complained of symptoms of anemia including pale or sallow complexion. Of 12 children undergoing pathogen test, 7 (58%) were found to have pathogen infection, among which human cytomegalovirus was the most common. Lymphocyte subsets were measured for 7 children, among whom 5 (71%) had lymphocyte immune disorder. Six children were found to have abnormalities in immunoglobulin and complement. The 8 children treated with prednisone combined with Huaiqihuang granules had a median follow-up time of 21.5 months, among whom 1 was almost cured, 1 was relieved, and 6 were obviously improved; the median onset time of treatment was 1 month, and 2 children had disease recurrence in the course of drug reduction or withdrawal. The 8 children in the prednisone alone treatment group had a median follow-up time of 34 months, among whom 4 were almost cured, and 4 were obviously improved; the median onset time of treatment was 2.5 months, and 4 children had recurrence during drug reduction or withdrawal. CONCLUSIONS: Children with PRCA usually complain of anemia-related symptoms. Laboratory tests show pathogen infection in some children with PRCA, and most of children have immune disorders. Glucocorticoids have a good therapeutic effect, but some children relapse in the course of drug reduction or withdrawal. Combined treatment with prednisone and Huaiqihuang granules may have a faster onset of action and less possibility of recurrence.

Correlation Between HIF1-A Expression and Airway Remodeling in COPD.

Background: Airway remodeling is a significant pathological characteristic of chronic obstructive pulmonary disease (COPD). In recent years, hypoxia-inducible factor 1-α (HIF-1α), a member of the hypoxia-inducible factor protein family, has gained attention. However, the potential correlation between HIF-1α and COPD airway remodeling remains unclear. Objective: This study explored the expression patterns of HIF-1α in patients with COPD and its association with airway remodelling. This investigation aims to furnish novel insights for the clinical identification of prospective therapeutic targets for ameliorating COPD-related airway remodelling. Patients and Methods: A total of 88 subjects were included, consisting of 28 controls and 60 COPD patients. Various staining methods were employed to observe the pathological changes in airway tissues. Immunohistochemistry was utilized to detect the expression of HIF-1α and MMP9 (matrix metalloproteinase 9) in airway tissues. Enzyme-linked immunosorbent assay (ELISA) was used to measure the concentration in serum of HIF-1α and MMP9. Computed tomography (CT) airway parameters were measured in all participants to assess airway remodeling. The relationship between serum HIF-1α and MMP9 concentrations and airway parameters was analyzed. Results: Staining of airway structures in COPD patients revealed significant pathological changes associated with airway remodelling, including mixed cilia and subepithelial fibrosis. The expression of HIF-1α and MMP9 was significantly higher in both human airway tissue and serum compared to controls. Chest CT scans exhibited typical imaging features of airway remodeling and increased airway parameters. Conclusion: The findings suggest a correlation between increased HIF-1α expression and COPD airway remodelling. This study provides novel evidence that HIF-1α may be a potential biomarker for airway remodelling in COPD patients.

Health inequalities during 20 years of rapid economic development in China (1980-2000): a mortality analysis.

OBJECTIVE: To examine the influence of China's economic reforms on population health and regional mortality rates. METHODS: Longitudinal study measuring the mortality trends and their regional variations. Using data from the three most recent national censuses, we used the model life table to adjust the mortality levels within the population for each census, and to calculate life expectancy. We then examined the variation in patterns of mortality and population health by economic status, region and gender from 1980-2000. RESULTS: Life expectancy varied with economic status, province, and gender. Results showed that, although life expectancy in China had increased overall since the early 1980s, regional differences became more pronounced. Life expectancy for populations who live in the eastern coastal provinces are greater than those in the western regions. CONCLUSION: Differences in life expectancy are primarily related to differences in regional economic development, which in turn exacerbate regional health inequalities. Therefore, it is necessary to improve economic development in less developed regions and to improve health policies and the public health system that address the needs of everyone.

Elevated Interleukin-6 Levels within 72 Hours Post Admission Are Associated with Disease Progression in Nonseptic Critically Ill Children.

It has been established that the innate and adaptive immune suppression was heterogeneous in septic and nonseptic critically ill patients, while the value of immune function in pediatric patients with nonseptic critical illness is limited. We conducted a single-center retrospective study to explore this issue. A total of 65 children with nonseptic illnesses were studied for lymphocyte subpopulations, immunoglobulin concentrations, complement concentrations, and cytokines in peripheral blood in the next 72 hours after admission to our Pediatric Intensive Care Unit (PICU). When compared to clinically recovered patients, patients with disease progression had a numerically lower but not significantly different median pediatric critical illness score and longer PICU median stays. The analysis of serum immunoglobulin (IgG, IgM, and IgA), serum complement (C3, C4) concentrations, and lymphocyte subpopulations showed no significantly difference between patients with and without relieved clinical symptoms by day 4. For the cytokine analysis, the level of IL-6 was significantly higher in patients with disease progression than that in patients who clinically recovered (p = 0.046). In the univariate Cox regression analysis, plasma IL-6 levels were associated with outcome. Multivariate analysis evidenced that the level of plasma IL-6 was one of the factors determining the length of hospital stays. In conclusions, our results demonstrate that increased IL-6 levels in the initial 72 hours post admission are associated with prolonged stays and disease progression in nonseptic critically ill children in the PICU.

Multitarget and promising role of dihydromyricetin in the treatment of metabolic diseases.

Dihydromyricetin (DMY or DHM), also known as ampelopsin, is the main natural flavonol compound extracted from the plant Ampelopsis grossedentata (Hand. -Mazz) W.T. Wang. In recent years, accumulating studies have been conducted to explore the extensive biological functions of DMY, including antitumor, anti-inflammation, organ-protective, and metabolic regulation effects. DMY acts as a potential preventive or therapeutic agent in treating multiple diseases, such as diabetes mellitus, atherosclerosis, nonalcoholic fatty liver disease and osteoporosis. This review article summarizes the preventive and therapeutic potential of DMY in multiple metabolic diseases and the main signaling pathways in which DMY participates to offer a comprehensive understanding and guidance for future studies.

[Effect of Huaier Aqueous Extract Combined with Routine Chemo-therapeutic Drugs on Human Acute Lymphoblastic Leukemia Cells Nalm-6 and Sup-B15].

OBJECTIVE: To investigate the proliferation inhibition and pro-apoptotic effect of Huaier aqueous extract combined with routine chemotherapeutic drugs including Vincristine (VCR), Daunorubicin (DNR), L-aspartase (L-Asp) on human acute lymphoblastic leukemia cell lines Nalm-6 and Sup-B15. METHODS: Nalm-6 and Sup-B15 cell lines were treated with different concentrations of Huaier aqueous extract and chemotherapeutics including VCR, DNR, L-Asp alone or in combination for 48 h, and the growth inhibitory effect and IC50 values (the half maximal inhibitory concentration) were detected by CCK-8. Jin's formula was used to estimated the synergistic effect of these combinations. Apoptosis rates of Nalm-6 and Sup-B15 cells and expression of apoptosis-related proteins BAX, BCL-2, cleaved Caspase-3 were determined by flow cytometry and Western blot respectivcly. RESULTS: Huaier aqueous extract, VCR, DNR and L-Asp had inhibition effect on Nalm-6 and Sup-B15 cell lines. The inhibition rate of Huaier aqueous extract combined with VCR, DNR and L-Asp were all higher than those of each dug alone (P＜0.05) and the combination index (q) was between 0.85 and 1.15 or greater than 1.15. The two kinds of drugs showed had additive or synergistic effects. The results of flow cytometry showed that the cell apoptosis rates in combined treatment group were higher than those of each drug alone (P＜0.05). The results of Western blot revealed that Huaier aqueous extract and VCR all decreased protein expression of BCL-2 (P＜0.05) and increase protein expression of BAX (P＜0.05) and cleaved Caspase-3 (P＜0.05) in Nalm-6 and Sup-B15 cells. Compared with Huaier aqueous extract or VCR alone, the effect of two drug combination were more significant. DNR down-regulated protein expression of BCL-2 (P＜0.05) and up-regulated cleaved Caspase-3 (P＜0.05). However, it had no effect on the expression of BAX in Nalm-6 and Sup-B15 cells. When it was combined with Huaier aqueous extract, the expression of cleaved Caspase-3 and BCL-2 showed more significant changes. The expression of BAX in combined treated group did not show significant difference, compared with group treated with Huaier aqueous extract in Nalm-6 and Sup-B15 cells. L-Asp did not show significant effect on the three apoptosis-related proteins and there was no significant difference between the combination group and the Huaier aqueous extract group. CONCLUSION: the combination of Huaier aqueous extract and VCR, DNR, L-Asp shows additive or synergistic effects on human acute lymphoblastic leukemia cell lines Nalm-6 and Sup-B15.

Family Management Style Improves Family Quality of Life in Children With Epilepsy: A Randomized Controlled Trial.

INTRODUCTION: Epilepsy is a common chronic disease with transient brain dysfunction and critically influences the quality of patients' family life. The aim of this study was to analyze the effectiveness of family management style on family quality of life in children. METHODS: We randomized 130 children to either the intervention group (n = 65) or the control group (n = 65). Family management style combined with routine care was applied in the intervention group within the first 24 hours after admission, whereas only routine care was applied in the control group. Family management style contains 3 steps: involve families into the intervention group and determine treatment plan, educate parents on how to manage their family, and monitor quality of home management. Scores on the Beach Center Family Quality of Life Scale (FQOL) of 2 groups were collected at 3 time points: within the first 24 hours after admission (T1), 6 months after discharge (T2), and 12 months after discharge (T3). Repeated-measures analysis of variance of FQOL scores was used to evaluate difference. RESULTS: Full scores and each subscale's scores on FQOL in the control group and the intervention group at T1 had no statistical significance (P > .05). Scores on FQOL at T2 and T3 increased in the intervention group, but there was almost no change in the control group, with statistical significance between the intervention group and the control group (P < .05). Scores on FQOL at T1, T2, and T3 showed that score of subscale except parenting FQOL improved in the intervention group (P < .05), but no difference was shown in the control group (P > .05). There was no difference shown among the control group and the intervention group that interacted with time (P > .05). CONCLUSION: The family management style can effectively improve the family quality of life in children with epilepsy, especially at the satisfaction level of family emotional well-being and disability-related support.

Provider-controlled or user-dependent contraceptive methods: Levels and pattern among married women of reproductive age in China, 1988-2006.

OBJECTIVES: To explore levels and patterns in contraceptive use since the introduction of informed choice in reproductive health services in China since 1994, and to assess the implications of reproductive health service needs among married women of reproductive age in China. MATERIAL AND METHODS: Data from Chinese nationwide surveys of family planning and reproductive health undertaken in 1988, 1997, 2001, and 2006 were analyzed to assess levels and trends in patterns of contraceptive use among married women by age, residence, and number of children. Contraceptive methods were classified into two categories: provider-controlled and user-dependent methods. RESULTS: The provider-controlled pattern for contraceptive use was predominant regardless of whether women were free to choose their own contraceptives. Older, rural women, and those with more than one child preferred provider-controlled contraceptive methods; this trend has changed little after 1997. In contrast, the user-controlled methods were preferred by young, urban women, strikingly with no or only one child, and geographically in more affluent areas in north or southwest China. CONCLUSION: A preference for user-dependent methods is noted in the urban areas but inclination towards provider-controlled contraceptive methods is still prevalent in rural areas in China.

The changing patterns of abortion among married women in China, 1984-2005.

OBJECTIVE: To identify changing levels and patterns of abortion in China among married women, and the determinants of these changes. STUDY DESIGN: Based on data from four nationwide surveys conducted by the Chinese National Population and Family Planning Commission in 1988, 1997, 2001 and 2006, this paper analyzed abortion rates by age, residence, and education. To minimize recall error, only the pregnancy history of the 5-10 years before the survey was used. RESULTS: Overall abortion levels in China fluctuated in the period 1970-1990, but declined markedly after 1991. The profile of women resorting to abortion has shifted from older, rural, less educated women, toward younger, urban, more educated women, at a rate beyond the change in composition of the population as a whole. Young, urban, educated women are also the demographic group more likely to employ "user controlled", short term methods. CONCLUSION: The findings are consistent with a gradual shift in the Chinese family planning programme, increasingly meeting the principles of the International Conference on Population and Development, which calls for making contraception accessible, and thereby helping women avoid recourse to abortion. Future reproductive health programmes should allow women more autonomy in socio-economic factors affecting their reproductive health.

Trends in contraceptive patterns and behaviors during a period of fertility transition in China: 1988-2006.

BACKGROUND: This paper explores how contraceptive patterns and behaviors changed during the course of China's population transition and a period of low fertility from 1988 to 2006. STUDY DESIGN: Based on data from Chinese nationwide surveys of family planning and reproductive health undertaken in 1988, 1997, 2001 and 2006, this study uses a multinomial logit model to analyze changes in, regional differences in and determinants of contraceptive behaviors during this period. RESULTS: The overall prevalence of contraceptive use among married women aged 15-49 years changed little during these 20 years, holding steady at about 90%. However, there were notable changes in the method mix: the predominant methods used were the long-term methods of the intrauterine device (IUD) and female sterilization, and contraceptive use gradually shifted from sterilization to IUDs and condoms. There existed a close relationship between contraceptive methods used and sociodemographic characteristics. Hans, rural, old and less educated women are more likely to use sterilization, while minorities, urban, young and educated women are more likely to use IUDs. CONCLUSION: There are marked changes in the method mix among different demographic groups during the course of China's population transition and a period of low fertility. The findings indicate that future works aimed at promoting reproductive health should be diverse among different populations.