The practice of social protection policies in China: a systematic review on how left-behind children's mental health can be optimised.

AIMS: By discussing the mental health challenges faced by left-behind children, this article recommends or comments on existing social protection policies that can affect left-behind children's mental health at the micro-, meso- and macro-levels to holistically understand how a range of parties can jointly socially include left-behind children, a process which is conducive to the latter's mental health development. METHODS: J.H. carried out a systematic review by searching through the English bibliographical databases Google Scholar, Web of Science and Scopus, in addition to Chinese bibliographic databases CNKI, Wanfang Data and VIP Chinese Science and Technology Periodicals. Here J.H. searched for the words ('social protection' OR 'socially protected') AND ('mental health' OR 'psychological wellbeing' OR 'mental problems' OR 'psychological problems') AND ('left-behind children' OR 'LBC' OR 'leftover children') AND ('China' OR 'Chinese'). Publication dates of the search results were limited to between 2010 and 2022. RESULTS: One of the primary problems encountered by left-behind children is their inadequate home supervision. A further study indicates that parental migration serves as a crucial risk factor for child depression. State-level provision of insurance programmes helps curtail these children's encounters of mental health challenges. Moreover, an improvement in family and school protection is essential when optimising the protection system for left-behind rural Chinese children from poor villages. It is necessary for upper-level government units to re-structure their lower-level counterparts to improve the local administration. This allows lower-level government units to exploit preferential policies, refine relevant regulations and policies on child protection, and facilitate the establishment of social organisations where local policies can be successfully implemented to socially include and protect left-behind children in villages. CONCLUSIONS: At the meso-level, community environment construction should be emphasised. At macro- and meso-levels, government authorities and social organisations should encourage the marketisation of hiring professional surrogate parents. At the micro-level, migrant parents should proactively take an initiative to contact their left-behind children via telecommunications.

Developing a Data Integrated COVID-19 Tracking System for Decision-Making and Public Use.

INTRODUCTION: The unprecedented COVID-19 pandemic unveiled a strong need for advanced and informative surveillance tools. The Centre for Health Informatics (CHI) at the University of Calgary took action to develop a surveillance dashboard, which would facilitate the education of the public, and answer critical questions posed by local and national government. OBJECTIVES: The objective of this study was to create an interactive method of surveillance, or a "COVID-19 Tracker" for Canadian use. The Tracker offers user-friendly graphics characterizing various aspects of the current pandemic (e.g. case count, testing, hospitalizations, and policy interventions). METHODS: Six publicly available data sources were used, and were selected based on the frequency of updates, accuracy and types of data, and data presentation. The datasets have different levels of granularity for different provinces, which limits the information that we are able to show. Additionally, some datasets have missing entries, for which the "last observation carried forward" method was used. The website was created and hosted online, with a backend server, which is updated on a daily basis. The Tracker development followed an iterative process, as new figures were added to meet the changing needs of policy-makers. RESULTS: The resulting Tracker is a dashboard that visualizes real-time data, along with policy interventions from various countries, via user-friendly graphs with a hover option that reveals detailed information. The interactive features allow the user to customize the figures by jurisdiction, country/region, and the type of data shown. Data is displayed at the national and provincial level, as well as by health regions. CONCLUSION: The COVID-19 Tracker offers real-time, detailed, and interactive visualizations that have the potential to shape crucial decision-making and inform Albertans and Canadians of the current pandemic.

[Synchronous multifocal laryngeal squamous carcinoma a case report].

An aged female complained intermittent hoarse 10 years, without swallowing and breathing difficulties. A month ago, this patient's voice hoarse became worse, she also had sore throat and pharyngeal foreign body sensation at the same time. There are visible lesions on the right side of the vocal cords, anterior commissure and on the left side of the ventricular bands. Laryngeal CT: the right side of the vocal cords has increased thickness, and hyper density with mild enhancement.

Effects of the combined arginase and canavanine treatment on leukemic cells in vitro and in vivo.

It was previously demonstrated in in vitro experiments that canavanine (Cav), a natural toxic arginine analogue of plant origin, is a promising candidate for augmenting the antineoplastic effects of arginine starvation. We demonstrated herein that recombinant human arginase, an arginine degrading enzyme, abrogated growth and significantly increased Cav cytotoxicity toward cultured L1210 murine leukemic cells. Cav co-treatment further reduced cells viability in a time-dependent manner and significantly promoted apoptosis induction. In the pilot study we also evaluated for the first time the potential toxicity of the combined arginine deprivation and Cav treatment in healthy mice. Administration of Cav alone or in combination with pegylated cobalt-containing human arginase (Co-hARG) did not evoke any apparent toxic effects in these animals, with no significant behavioural and survival changes after several weeks of the treatment. The therapeutic effects of the combination of Co-hARG and Cav were provisionally evaluated on the highly aggressive murine L1210 leukemia, which is semi-sensitive to arginine deprivation as a monotreatment. Combination of two drugs did not result in significant prolongation of the survival of leukemia-bearing mice. Thus, we have shown that the proposed combinational treatment is rather non-toxic for the animals. It has to be further evaluated in animal studies with alternative tumor models and/or drug doses and treatment modalities.

Effect of curcumin on p38MAPK expression in DSS-induced murine ulcerative colitis.

The aim of this study was to determine the therapeutic effect of curcumin on dextran sulfate sodium-induced ulcerative colitis (UC) and to explore the related mechanism. Sixty mice were randomly divided into 6 groups. A group was the normal control group; B group was the model group; C group was the 1.5 mg/kg dexamethasone group based on the B group; and D, E and F groups were 15, 30, and 60 mg/kg curcumin groups, respectively, based on the B group. The mice were killed 7 days after treatment; the expression of TNF-α and MPO in colon tissue was determined with ELISA, and colon p-p38MAPK and p38MAPK mRNA expression was evaluated by immunohistochemistry and RT-PCR, respectively. In the C, D, E, and F groups, TNF-α and MPO levels significantly decreased (P < 0.05), and the expression of p-p38MAPK also significantly decreased (P < 0.01). The expression of p38MAPK mRNA in the C, D, E, and F groups decreased (P < 0.01), and there was a statistically significant difference between the E and F groups (P < 0.01). Curcumin had a therapeutic effect, which probably played a role in UC treatment by inhibiting the p38MAPK signaling pathway, thereby reducing the release of TNF-α.

Henoch Schonlein Purpura in children: clinical analysis of 120 cases.

BACKGROUND: Henoch Schonlein Purpura (HSP) is a systemic vasculitic disease which is common in children. It is very important to understand the clinical features of this disease for doctors and nurses. OBJECTIVES: To study the clinical characteristics of HSP in children. METHODS: Collect the clinical data of the HSP children, and analyze the clinical characteristics of these HSP patients. RESULTS: The ratio of M:F was 1.9:1. The mean age was 6.6 ± 1.6 years. The typical onset seasons were spring, winter and autumn. Infection and food allergy were the main etiological factors. The first symptom was skin purpura and these purpura mainly concentrated the lower extremities and buttocks. The dominant digestive clinical features were abdominal pains and vomiting. The knee joint and ankle joint were most frequently affected. The typical kidney symptoms were microscopic hematuria and albuminuria. An increased ESR was reported in 68 patients (56.7%). Serum C3 decreased in 13 cases (10.8%). ASO titer was higher in 57 children (47.5%). CONCLUSION: There were gender, season and area differences for the HSP patients. The etiological factors were diverse. HSP patients could have various clinical symptoms and rare complications.

Medical methods for cervical ripening before the removal of intrauterine devices in postmenopausal women: a systematic review.

In China, most women with intrauterine devices (IUDs) ask to have them removed following the menopause. As the cervix is stenotic after the menopause and most IUDs do not have a thread attached, various medical methods are used for cervical ripening prior to IUD removal. A systematic review of the relevant literature was conducted to compare different medical methods for cervical priming with no treatment, or with other methods, prior to IUD removal in postmenopausal women. Multiple electronic databases including the Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE, the WHO Reproductive Health Library (2011) and the Chinese Biomedical Literature Database were searched systematically. Reference lists of articles published in English or Chinese between 1980 and 2011 were searched. All randomized controlled trials (RCTs) on IUD removal following the menopause using medical agents compared with no treatment, or with other treatments, were included. Outcomes were the ease of IUD removal, need for forced cervical dilatation, cervical width, procedure time, severe pain and any side-effects. Data were processed using RevMan 5 software. Thirty original RCTs were eligible for inclusion. Most medical agents such as oestrogens, mifepristone, misoprostol and methyl carboprost were highly effective for facilitating IUD removal, and reduced the need for further dilatation during the procedure. In particular, treatment with mifepristone or misoprostol prior to IUD removal was found to increase the width of the cervical canal and reduce the procedure time. Mifepristone was more effective than vaginal misoprostol for cervical dilatation, but it showed similar effectiveness to misoprostol and nilestriol in terms of the ease of IUD removal. Sublingual misoprostol was superior to oral misoprostol for facilitating IUD removal. A dose of misoprostol as low as 200µg was effective for cervical priming. For vaginal and oral misoprostol, the optimum times of application were 2-3h and 1 day prior to the procedure, respectively. All the prophylactic medical methods were able to alleviate pain during IUD removal, and vaginal misoprostol was more effective than nilestriol. Uterine injury was more common with no treatment and with nilestriol. Gastrointestinal side-effects such as nausea and diarrhoea were common with oral misoprostol and vaginal misoprostol, respectively. Therefore, mifepristone or sublingual misoprostol should be the medical treatments of choice. Oestrogen regimens might be alternatives when mifepristone or misoprostol are contraindicated, and there is a need for further study on combined regimens for cervical priming.

Characterization of the expression of macrophage inflammatory protein-1α (MIP-1α) and C-C chemokine receptor 5 (CCR5) after kainic acid-induced status epilepticus (SE) in juvenile rats.

AIMS: To identify the potential role of macrophage inflammatory protein-1α (MIP-1α) with its C-C chemokine receptor 5 (CCR5) in epileptogenic brain injury, we examined their expression in juvenile rat hippocampus and explored the potential link between MIP-1α, CCR5 and neuropathological alterations after status epilepticus (SE) induced by intracerebroventricular (i.c.v.) kainic acid (KA) injection. METHODS: Based on the determination of the development of spontaneous seizures initiated by SE in developing rat brain, we firstly examined hippocampal neurone damage through Nissl and Fluoro-Jade B staining, and evaluated microglial reaction during the early phase following KA-induced SE in 21-day-old rats. MIP-1α and CCR5 protein were quantified by ELISA and Western blot respectively following mRNA by real-time PCR. We also mapped MIP-1α and CCR5 expression in the hippocampus by immunohistochemistry and identified their cellular sources using double-labelling immunofluorescence. RESULTS: In juvenile rats, KA caused characteristic neurone damage in the hippocampal subfields, with accompanying microglial accumulation. In parallel with mRNA expression, MIP-1α protein in hippocampus was transiently increased after KA treatment, and peaked from 16 to 72 h. Double-labelling immunofluorescence revealed that MIP-1α was localized to microglia. Up-regulated CCR5 remained prominent at 24 and 72 h and was mainly localized to activated microglia. Further immunohistochemistry revealed that MIP-1α and CCR5 expression were closely consistent with microglial accumulation in corresponding hippocampal subfields undergoing degenerative changes. CONCLUSIONS: Our data indicated that MIP-1α as a regulator, linking with the CCR5 receptor, may be involved within the early stages of the epileptogenic process following SE by i.c.v. KA injection.

Imbalance of interleukin-18 and interleukin-18 binding protein in children with Henoch-Schönlein purpura.

The balance between interleukin-18 (IL-18) and its endogenous antagonist, IL-18 binding protein (IL-18BP), was evaluated in children with Henoch-Schönlein purpura (HSP). Plasma IL-18 and IL-18BP levels and peripheral blood mononuclear cell IL-18 mRNA expression were significantly higher in patients with active HSP (n = 30) than in healthy controls (n = 20); IL-18BP mRNA expression was similar in active HSP and controls. Plasma levels and mRNA expression of IL-18 and IL-18BP in patients in remission (n = 19) were similar to those in controls. The ratios of IL-18 / IL-18BP plasma levels and IL-18 / IL-18BP mRNA levels in active HSP were significantly higher than in patients in remission and healthy controls. Thus, adequate IL-18BP to block the proinflammatory activity of IL-18 may not be present in active HSP and regulation of the IL-18 / IL-18BP balance might provide a potential therapeutic strategy.

Comparison of APF activity and epithelial growth factor levels in urine from Chinese, African-American, and white American patients with interstitial cystitis.

OBJECTIVES: Interstitial cystitis (IC) is a chronic bladder disorder for which the etiology is unknown. We have previously shown that antiproliferative factor (APF), heparin-binding epidermal growth factor-like growth factor (HB-EGF), and epidermal growth factor (EGF) are sensitive and specific biomarkers for IC in white American patients. Because little is known about the epidemiology of this disorder, it is unclear whether these factors would also be useful biomarkers for IC in patients from different racial groups and/or geographic locations. METHODS: Urine specimens were collected from Chinese, white American, and African-American women with IC and age and race-matched asymptomatic normal control women. APF activity was determined by (3)H-thymidine incorporation into primary normal adult human bladder epithelial cells in vitro. The HB-EGF and EGF urine levels were determined by enzyme-linked immunosorbent assay. RESULTS: The Chinese, African-American, and white American women with IC had significantly greater urine APF activity (P <0.000001, P = 0.0008, and P <0.000001, respectively), lower urine HB-EGF levels (P <0.000001, P = 0.02, and P <0.000001, respectively), and greater urine EGF levels (P <0.000001, P = 0.002, and P <0.000001, respectively), than their matched asymptomatic controls. CONCLUSIONS: These findings confirm the utility of APF, HB-EGF, and EGF as biomarkers for IC in patients from three different racial groups and two different countries.

YFH1-mediated iron homeostasis is independent of mitochondrial respiration.

The human gene frataxin and its yeast homolog YFH1 affect mitochondrial function. Deficits in frataxin result in Friedreich ataxia, while deletion of YFH1 results in respiratory incompetence. We determined that as long as respiratory incompetent yeast express Yfh1p they do not accumulate excessive mitochondrial iron. Deletion of YFH1 in respiratory incompetent yeast results in mitochondrial iron accumulation, while the reintroduction of Yfh1p results in mitochondrial iron export. Further, overexpression of Yfh1p has no effect on oxygen consumption in wild-type yeast grown in either fermentative or respiratory carbon sources. We conclude that the effect of Yfh1p on mitochondrial iron metabolism is independent of respiratory activity.

CCC1 is a transporter that mediates vacuolar iron storage in yeast.

The budding yeast Saccharomyces cerevisiae can grow for generations in the absence of exogenous iron, indicating a capacity to store intracellular iron. As cells can accumulate iron by endocytosis we studied iron metabolism in yeast that were defective in endocytosis. We demonstrated that endocytosis-defective yeast (Delta end4) can store iron in the vacuole, indicating a transfer of iron from the cytosol to the vacuole. Using several different criteria we demonstrated that CCC1 encodes a transporter that effects the accumulation of iron and Mn(2+) in vacuoles. Overexpression of CCC1, which is localized to the vacuole, lowers cytosolic iron and increases vacuolar iron content. Conversely, deletion of CCC1 results in decreased vacuolar iron content and decreased iron stores, which affect cytosolic iron levels and cell growth. Furthermore Delta ccc1 cells show increased sensitivity to external iron. The sensitivity to iron is exacerbated by ectopic expression of the iron transporter FET4. These results indicate that yeast can store iron in the vacuole and that CCC1 is involved in the transfer of iron from the cytosol to the vacuole.

CCC1 suppresses mitochondrial damage in the yeast model of Friedreich's ataxia by limiting mitochondrial iron accumulation.

Deletion of YFH1 in Saccharomyces cerevisiae leads to a loss of respiratory competence due to excessive mitochondrial iron accumulation. A suppressor screen identified a gene, CCC1, that maintained respiratory function in a Deltayfh1 yeast strain regardless of extracellular iron concentration. CCC1 expression prevented excessive mitochondrial iron accumulation by limiting mitochondrial iron uptake rather than by increasing mitochondrial iron egress. Expression of CCC1 did not result in sequestration of iron in membranous compartments or cellular iron export. CCC1 expression in wild type cells resulted in increased expression of the high affinity iron transport system composed of FET3 and FTR1, suggesting that intracellular iron is not sensed by the iron-dependent transcription factor Aft1p. Introduction of AFT1(up), a constitutive allele of the iron transcription factor, AFT1, that also leads to increased high affinity iron transport did not prevent Deltayfh1 cells from becoming respiratory-incompetent. Although the mechanism by which CCC1 expression affects cytosolic iron is not known, the data suggest that excessive mitochondrial iron accumulation only occurs when cytosolic free iron levels are high.

Dietary iron intake rapidly influences iron regulatory proteins, ferritin subunits and mitochondrial aconitase in rat liver.

Iron regulatory protein 1 (IRP1) and IRP2 are cytoplasmic RNA binding proteins that are central regulators of mammalian iron homeostasis. We investigated the time-dependent effect of dietary iron deficiency on liver IRP activity in relation to the abundance of ferritin and the iron-sulfur protein mitochondrial aconitase (m-acon), which are targets of IRP action. Rats were fed a diet containing 2 or 34 mg iron/kg diet for 1-28 d. Liver IRP activity increased rapidly in rats fed the iron-deficient diet with IRP1 stimulated by d 1 and IRP2 by d 2. The maximal activation of IRP2 was five-fold (d 7) and three-fold (d 4) for IRP1. By d 4, liver ferritin subunits were undetectable and m-acon abundance eventually fell by 50% (P < 0.05) in iron-deficient rats. m-Acon abundance declined most rapidly from d 1 to 11 and in a manner that was suggestive of a cause and effect type of relationship between IRP activity and m-acon abundance. In liver, iron deficiency did not decrease the activity of cytosolic aconitase, catalase or complex I of the electron transport chain nor was there an effect on the maximal rate of mitochondrial oxygen consumption with the use of malate and pyruvate as substrates. Thus, the decline in m-acon abundance in iron deficiency is not reflective of a global decrease in liver iron-sulfur proteins nor does it appear to limit ATP production. Our results suggest a novel role for m-acon in cellular iron metabolism. We conclude that, in liver, iron deficiency preferentially affects the activities of IRPs and the targets of IRP action.

Iron differentially stimulates translation of mitochondrial aconitase and ferritin mRNAs in mammalian cells. Implications for iron regulatory proteins as regulators of mitochondrial citrate utilization.

Utilization of mRNAs containing iron-responsive elements (IREs) is modulated by iron-regulated RNA-binding proteins (iron regulatory proteins). We examine herein whether iron differentially affects translation of ferritin and mitochondrial aconitase (m-Acon) mRNAs because they contain a similar but not identical IRE in their 5'-untranslated regions. First, we demonstrate that m-Acon synthesis is iron-regulated in mammalian cells. In HL-60 cells, hemin (an iron source) stimulated m-Acon synthesis 3-fold after 4 h compared with cells treated with an iron chelator (Desferal). Furthermore, hemin stimulated m-Acon synthesis 2-4-fold in several cell lines. Second, we show that iron modulates the polysomal association of m-Acon mRNA. We observed m-Acon mRNA in both ribonucleoprotein and polyribosomal fractions of HL-60 cells. Hemin significantly increased the polyribosomal association and decreased the ribonucleoprotein abundance of m-Acon mRNA in HL-60 cells. Third, our results indicate that iron differentially regulates translation of m-Acon and ferritin mRNAs. A dose response to hemin in HL-60 cells elicited a 2-2.4-fold increase in m-Acon synthesis within 5 h compared with untreated cells, whereas ferritin synthesis was stimulated 20-100-fold. We conclude that iron modulates m-Acon synthesis at the translational level and that iron regulatory proteins appear to differentially affect translation of IRE-containing mRNAs.

Iron regulatory protein 1 is not required for the modulation of ferritin and transferrin receptor expression by iron in a murine pro-B lymphocyte cell line.

Iron regulatory proteins (IRPs) are cytoplasmic RNA binding proteins that are central components of a sensory and regulatory network that modulates vertebrate iron homeostasis. IRPs regulate iron metabolism by binding to iron responsive element(s) (IREs) in the 5' or 3' untranslated region of ferritin or transferrin receptor (TfR) mRNAs. Two IRPs, IRP1 and IRP2, have been identified previously. IRP1 exhibits two mutually exclusive functions as an RNA binding protein or as the cytosolic isoform of aconitase. We demonstrate that the Ba/F3 family of murine pro-B lymphocytes represents the first example of a mammalian cell line that fails to express IRP1 protein or mRNA. First, all of the IRE binding activity in Ba/F3-gp55 cells is attributable to IRP2. Second, synthesis of IRP2, but not of IRP1, is detectable in Ba/F3-gp55 cells. Third, the Ba/F3 family of cells express IRP2 mRNA at a level similar to other murine cell lines, but IRP1 mRNA is not detectable. In the Ba/F3 family of cells, alterations in iron status modulated ferritin biosynthesis and TfR mRNA level over as much as a 20- and 14-fold range, respectively. We conclude that IRP1 is not essential for regulation of ferritin or TfR expression by iron and that IRP2 can act as the sole IRE-dependent mediator of cellular iron homeostasis.

The iron-sulfur cluster of iron regulatory protein 1 modulates the accessibility of RNA binding and phosphorylation sites.

Iron regulatory protein 1 (IRP1) modulates iron metabolism by binding to mRNAs encoding proteins involved in the uptake, storage, and metabolic utilization of iron. Iron regulates IRP1 function by promoting assembly of an iron-sulfur cluster in the apo or RNA binding form, thereby converting it to the active holo or cytoplasmic aconitase form. In continuing our studies on phosphoregulation of IRP1 by protein kinase C (PKC), we noted that the purified apoprotein was more efficiently phosphorylated than was the form partially purified from liver cytosol by chromatography on DEAE-Sepharose which had characteristics of the [3Fe-4S] form of the protein. RNA binding measurements revealed a 20-fold increase in RNA binding affinity and a 4-5-fold higher rate of phosphorylation after removal of the Fe-S cluster from the highly purified [4Fe-4S] form. Phosphorylation of apo-IRP1 by PKC was specifically inhibited by IRE-containing RNA. The RNA binding form had a more open structure as judged by its much greater sensitivity to limited cleavage by a number of proteases. N-Terminal sequencing of chymotryptic peptides of apo-IRP1 demonstrated an increased accessibility to proteolysis of sites (residues 132 and 504) near or within the putative cleft of the protein, including regions that are thought to be involved in RNA binding (residues 116-151) and phosphoregulation (Ser 138). Enhanced cleavage was also observed in the proposed hinge linker region (residue 623) on the surface of the protein opposite from the cleft. Taken together, our results indicate that significant structural changes occur in IRP1 during cluster insertion or removal that affect the accessibility to RNA binding and phosphorylation sites.

Dietary iron intake modulates the activity of iron regulatory proteins and the abundance of ferritin and mitochondrial aconitase in rat liver.

Iron regulatory protein 1 (IRP1) and IRP2 are cytoplasmic RNA binding proteins that coordinate cellular iron homeostasis in mammals. We investigated the effect of dietary iron intake on rat liver IRP activity in relation to the abundance of two targets of IRP action, ferritin and mitochondrial aconitase (m-aconitase). Rats were fed diets containing 2, 11, 20, 37 (control), 72 or 107 mg iron/kg diet for 3 wk. RNA binding activity of IRP1 and IRP2 was enhanced one- to twofold in rats fed 11 or 2 mg iron/kg diet compared with control rats. IRP RNA binding activity was inversely correlated to blood hemoglobin levels (r = -0.787; P < 0.0001). Compared with control rats, liver ferritin levels were depressed in rats fed 20 mg iron/kg diet and were undetectable in rats ingesting diets with 11 or 2 mg iron/kg diet. Ferritin concentrations were biphasically related to IRP RNA binding activity with the regulation of IRP occurring before the onset of ferritin accumulation. Iron deficiency caused up to a 50% decline in m-aconitase abundance. IRP RNA binding activity and m-aconitase abundance were inversely correlated (r = -0.751; P < 0.0001). Our results indicate that (1) liver IRP activity is responsive to a range of dietary iron levels, (2) there appears to be a differential effect of IRPs on ferritin and m-aconitase abundance, and (3) activation of IRPs may contribute to the alterations in energy metabolism in iron deficiency through an impairment of m-aconitase synthesis.