Iron Deficiency Anemia: An Updated Review.

BACKGROUND: Worldwide, iron deficiency anemia is the most prevalent nutritional deficiency disorder and the leading cause of anemia in children, especially in developing countries. When present in early childhood, especially if severe and prolonged, iron deficiency anemia can result in neurodevelopmental and cognitive deficits, which may not always be fully reversible even following the correction of iron deficiency anemia. OBJECTIVE: This article aimed to familiarize physicians with the clinical manifestations, diagnosis, evaluation, prevention, and management of children with iron deficiency anemia. METHODS: A PubMed search was conducted in February 2023 in Clinical Queries using the key term "iron deficiency anemia". The search strategy included all clinical trials (including open trials, non-randomized controlled trials, and randomized controlled trials), observational studies (including case reports and case series), and reviews (including narrative reviews, clinical guidelines, and meta-analyses) published within the past 10 years. Google, UpToDate, and Wikipedia were also searched to enrich the review. Only papers published in the English literature were included in this review. The information retrieved from the search was used in the compilation of the present article. RESULTS: Iron deficiency anemia is most common among children aged nine months to three years and during adolescence. Iron deficiency anemia can result from increased demand for iron, inadequate iron intake, decreased iron absorption (malabsorption), increased blood loss, and rarely, defective plasma iron transport. Most children with mild iron deficiency anemia are asymptomatic. Pallor is the most frequent presenting feature. In mild to moderate iron deficiency anemia, poor appetite, fatigability, lassitude, lethargy, exercise intolerance, irritability, and dizziness may be seen. In severe iron deficiency anemia, tachycardia, shortness of breath, diaphoresis, and poor capillary refilling may occur. When present in early childhood, especially if severe and prolonged, iron deficiency anemia can result in neurodevelopmental and cognitive deficits, which may not always be fully reversible even with the correction of iron deficiency anemia. A low hemoglobin and a peripheral blood film showing hypochromia, microcytosis, and marked anisocytosis, should arouse suspicion of iron deficiency anemia. A low serum ferritin level may confirm the diagnosis. Oral iron therapy is the first-line treatment for iron deficiency anemia. This can be achieved by oral administration of one of the ferrous preparations, which is the most cost-effective medication for the treatment of iron deficiency anemia. The optimal response can be achieved with a dosage of 3 to 6 mg/kg of elemental iron per day. Parenteral iron therapy or red blood cell transfusion is usually not necessary. CONCLUSION: In spite of a decline in prevalence, iron deficiency anemia remains a common cause of anemia in young children and adolescents, especially in developing countries; hence, its prevention is important. Primary prevention can be achieved by supplementary iron or iron fortification of staple foods. The importance of dietary counseling and nutritional education cannot be overemphasized. Secondary prevention involves screening for, diagnosing, and treating iron deficiency anemia. The American Academy of Pediatrics recommends universal laboratory screening for iron deficiency anemia at approximately one year of age for healthy children. Assessment of risk factors associated with iron deficiency anemia should be performed at this time. Selective laboratory screening should be performed at any age when risk factors for iron deficiency anemia have been identified.

Role of hyperbaric oxygen therapy in PDGF-BB-mediated astrogliosis in traumatic brain injury rats associated with ERK1/2 signaling pathway inhibition.

BACKGROUND: Hyperbaric oxygen (HBO) plays positive roles in the therapy of traumatic brain injury (TBI); however, the mechanism underlying its effects on TBI is largely unknown. The study aims to elucidate the molecular mechanism implicated with the interaction between platelet-derived growth factor-BB (PDGF-BB) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway, which may play critical roles during HBO treatment both in the astrocyte scratching model in vitro and rat TBI model in vivo. METHODS: Changes in neurological function and wound healing were evaluated using the neurological severity scores (NSS) scale, immunohistochemistry, western blotting, and qRT-PCR, respectively. RESULTS: The results showed that PDGF-BBi (PDGB interfered with small RNA) dramatically improves neuronal viability in vitro when transfected into the scratched astrocytes derived from the cerebral cortex of neonatal rats. Moreover, in vivo experiments revealed that HBO therapy substantially elevated the NSS scores and simultaneously reduced the mortality in TBI rats, as indicated by the NSS scales. Notably, HBO therapy was found to possess the ability to inhibit glial cell proliferation, promote the regeneration of neurons and synapses, and ultimately facilitate the wound healing, as revealed by immunohistochemistry and glial scar formation found in TBI rats. Importantly, HBO markedly decreased the expression levels of PDGF-BB and ERK1/2. It can clearly be seen that downregulated PDGF-BB and ERK1/2 levels were corresponding with the status of significant amelioration of the therapeutic effect of HBO. Conversely, the upregulation of PDGF-BB and ERK1/2 levels was in line with the opposite effect. CONCLUSION: It has been concluded that HBO therapy may play its active role in TBI treatment dependent on astrogliosis inhibition, which may be achieved by downregulating the ERK1/2 signaling pathway mediated by PDGF-BB.

Self-Rolled-Up Aluminum Nitride-Based 3D Architectures Enabled by Record-High Differential Stress.

Aluminum nitride (AlN) continues to kindle considerable interest in various microelectromechanical system (MEMS)-related fields because of its superior optical, mechanical, thermal, and piezoelectric properties. In this study, we use magnetron sputtering to tailor intrinsic stress in AlN thin films from highly compressive (-1200 MPa) to highly tensile (+700 MPa), with a differential stress of 1900 MPa. By monolithically combining the compressive and tensile ultrathin AlN bilayer membranes (20-60 nm) during deposition, perfectly curved three-dimensional (3D) architectures are spontaneously formed upon dry-releasing from the substrate via a 3D MEMS approach: the complementary metal-oxide-semiconductor (CMOS)-compatible strain-induced self-rolled-up membrane (S-RuM) method. The thermal stability of the AlN 3D architectures is examined, and the curvature of S-RuM microtubes and helical structures as a function of the cumulative membrane thickness and stress are characterized experimentally and simulated using a finite-element physiomechanic method. By combining AlN with various materials such as metal (Cu) and silicon nitride (SiNx), AlN-based hybrid S-RuM microtubes with diameters as small as ∼6 µm are demonstrated with a near-unity yield (∼99%). Compared with other stressed thin films for S-RuMs, including PECVD SiNx, magnetron-sputtered AlN-based S-RuMs show better structural controllability and versatility, probably due to the high Young's modulus and stress uniformity. This work establishes the sputtered AlN thin film as a superior stress-configurable S-RuM shell material for high-performance applications in miniaturizing and integrating electronic components beyond those based on other materials such as SiNx. In addition, for the first time, a single-crystal Al1-xScxN/AlN bilayer grown by molecular beam epitaxy is successfully rolled-up with the diameter varying from ∼9 to 14 µm, paving the way for 3D tubular Al1-xScxN piezoelectric devices.

Acupuncture effects on in-vitro fertilization pregnancy outcomes: A meta-analysis.

BACKGROUND: The effects of acupuncture on in-vitro fertilization outcomes remain controversial. This study aimed to perform a meta-analysis to assess the effectiveness of acupuncture as an adjuvant therapy to embryo transfer compared to sham-controls or no adjuvant therapy controls on improving pregnancy outcomes in women undergoing in-vitro fertilization. METHODS: A systematic literature search up to January 2021 was performed and 29 studies included 6623 individuals undergoing in-vitro fertilization at the baseline of the study; 3091 of them were using acupuncture as an adjuvant therapy to embryo transfer, 1559 of them were using sham-controls, and 1441 of them were using no adjuvant therapy controls. They reported a comparison between the effectiveness of acupuncture as an adjuvant therapy to embryo transfer compared to sham-controls or no adjuvant therapy controls on improving pregnancy outcomes in women undergoing in-vitro fertilization. Odds ratio (OR) with 95% confidence intervals (CIs) were calculated assessing the effectiveness of acupuncture as an adjuvant therapy to embryo transfer compared to sham-controls or no adjuvant therapy controls using the dichotomous method with a random or fixed-effect model. RESULTS: Significantly higher outcomes with acupuncture were observed in biochemical pregnancy (OR, 1.98; 95% CI, 1.55-2.53, p < 0.001); clinical pregnancy (OR, 1.70; 95% CI, 1.46-1.98, p < 0.001); ongoing pregnancy (OR, 1.78; 95% CI, 1.41-2.26, p < 0.001); and live birth (OR, 1.58; 95% CI, 1.15-2.18, p = 0.005) compared to no adjuvant therapy controls. However, no significant difference were found between acupuncture and no adjuvant therapy controls in miscarriage (OR, 0.96; 95% CI, 0.48-1.92, p = 0.91). No significant difference was observed with acupuncture in biochemical pregnancy (OR, 1.16; 95% CI, 0.65-2.08, p = 0.62); clinical pregnancy (OR, 1.13; 95% CI, 0.83-1.54, p = 0.43); ongoing pregnancy (OR, 1.04; 95% CI, 0.66-1.62, p = 0.87); live birth (OR, 1.02; 95% CI, 0.73-1.42, p = 0.90), and miscarriage (OR, 1.16; 95% CI, 0.86-1.55, p = 0.34) compared to sham-controls. CONCLUSIONS: Using acupuncture as an adjuvant therapy to embryo transfer may improve the biochemical pregnancy, clinical pregnancy, ongoing pregnancy, and live birth outcomes compared to no adjuvant therapy controls. However, no significant difference was found between acupuncture as an adjuvant therapy to embryo transfer and sham-controls in any of the measured outcomes. This relationship forces us to recommend the use of acupuncture as adjuvant therapy in women undergoing in-vitro fertilization and inquire further studies comparing acupuncture and sham-controls to reach the best procedure.

Novel protein kinase C phosphorylated kinase inhibitor-matrine suppresses replication of hepatitis B virus via modulating the mitogen-activated protein kinase signal.

HBV (hepatitis B virus) infection still threatens human health. Therefore, it is essential to find new effective anti-HBV compounds. Here, we identified matrine as a novel inhibitor of PKC (protein kinase C) phosphorylated kinase by screening a natural compound library. After HepG2.215 cells were treated with matrine, we carried out a phosphorylated proteomics sequence study and analyzed the prediction of related kinase expression level. In the case of HBV infection, it was found that PKC kinase mediates the activation of mitogen-activated protein kinase (MAPK) signaling pathway known as son of sevenless (SOS) activation. It was also found that PKC kinase inhibits the expression of C-X-C Motif Chemokine Ligand 8 (CXCL8) by inhibiting the activity of activating transcription factor 2/ cAMP response element binding protein (ATF2/CREB), and this effect is independent of its activated MAPK signaling pathway. Finally, Western blot was used to detect the expression of MAPK, ATF2, CREB3 phosphorylation and nonphosphorylation in matrine-treated cells and PKC-treated cells. PKC phosphorylated kinase inhibitor-matrine suppresses the replication of HBV via modulating the MAPK/ATF2 signal. Matrine is a good clinical drug to enhance the autoimmunity in the adjuvant treatment of chronic HBV infection.

Effect of Huangqin decoction on regulating intestinal flora in colitis mice characterized as inhibition of the NOD2-dependent pathway.

CONTEXT: Chinese herb Huangqin decoction (HQD) can regulate intestinal flora in ulcerative colitis (UC) mice. OBJECTIVE: Our study clarifies the mechanism of HQD in regulating the intestinal flora of UC mice. MATERIALS AND METHODS: Male C57BL/6 mice were randomly divided into six groups: Control, Model (3% DSS), Sulfasalazine (500 mg/kg), HQD-L (250 mg/kg), HQD-M (500 mg/kg), and HQD-H (1000 mg/kg) groups. Measurement of body weight, colon length, DAI, and haematoxylin-eosin staining were conducted. FISH and 16S rDNA detected colonic bacterial infiltration and intestinal flora changes. The expression of RegIIIγ and PRRs (NOD2, TLR5, TLR4) were detected by FCM and WB, respectively. In addition, WB, qPCR, or IHC were used to detect the expression of NOD2, MyD88, RIP2, and NF-κB p65 in the colon. ELISA was used to determine cytokines. RESULTS: Compared with the model group (DAI score, 2.38 ± 0.05; histological score, 4.08 ± 0.54), HQD treatment significantly reduced the DAI score (L, 2.16 ± 0.09; M, 1.45 ± 0.05; H, 1.18 ± 0.05) and histological score (L, 3.16 ± 0.82; M, 2.50 ± 0.81; H, 1.51 ± 0.76); restored the weight, the colonic length (p < 0.05). 16S rDNA identification showed HQD regulated the balance of intestinal flora. Moreover, HQD suppressed the expression of RegIIIγ (p < 0.05) and prevented colonic bacterial infiltration. Furthermore, WB results showed NOD2, and TLR4 were inhibited by HQD, especially NOD2 (p < 0.01). The data of WB, qPCR, and IHC demonstrated that the NOD2-dependent pathway was inhibited by HQD (p < 0.01). DISCUSSION AND CONCLUSIONS: HQD (1000 mg/kg) regulates the intestinal flora of colitis mice, mainly characterized as inhibition of the NOD2-dependent pathway. These results indicate that HQD has potential.

Transcriptome Analysis of Effects of Folic Acid Supplement on Gene Expression in Liver of Broiler Chickens.

Folic acid is a water-soluble B vitamin, and plays an important role in regulating gene expression and methylation. The liver is the major site of lipid biosynthesis in the chicken. Nevertheless, how gene expression and regulatory networks are affected by folic acid in liver of broilers are poorly understood. This paper conducted the RNA-seq technology on the liver of broilers under folic acid challenge investigation. First, 405 differentially expressed genes (DEGs), including 157 significantly upregulated and 248 downregulated, were detected between the control group (C) and the 5 mg folic acid group (M). Second, 68 upregulated DEGs and 142 downregulated DEGs were determined between C group and 10 mg folic acid group (H). Third, there were 165 upregulated genes and 179 downregulated genes between M and H groups. Of these DEGs, 903 DEGs were successfully annotated in the public databases. The functional classification based on GO and KEEGG showed that "general function prediction only" represented the largest functional classes, "cell cycle" (C vs. M; M vs. H), and "neuroactive ligand-receptor interaction" (C vs. H) were the highest unique sequences among three groups. SNP analysis indicated that numbers of C, M and H groups were 145,450, 146,131, and 123,004, respectively. Total new predicted alternative splicing events in C, M, and H groups were 9,521, 9,328, and 8,929, respectively. A protein-protein interaction (PPI) network was constructed, and the top 10 hub genes were evaluated among three groups. The results of real time PCR indicated that mRNA abundance of PPARγ and FAS in abdominal fat of M and H groups were reduced compared with the C group (P < 0.05). Ultramicroscopy results showed that folic acid could reduce lipid droplets in livers from chickens. Finally, contents of LPL, PPARγ, and FAS in abdominal fat were decreased with the folic acid supplmented diets (P < 0.01). These findings reveal the effects of folic acid supplemention on gene expression in liver of broilers, which can provide information for understanding the molecular mechanisms of folic acid regulating liver lipid metabolism.

Comprehensive O-Glycosylation Analysis of the SARS-CoV-2 Spike Protein with Biomimetic Trp-Arg Materials.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a serious public health threat. Most vaccines against SARS-CoV-2 target the highly glycosylated spike protein (S). A good knowledge of the glycosylation profile of this protein is key to successful vaccine development. Unlike the 22 confirmed N-glycosylation sites on SARS-CoV-2 S, only a few O-glycosylation sites on this protein have been reported. This difference is mainly ascribed to the extremely low stoichiometry of O-glycosylation. Herein, we designed the biomimetic materials, Trp-Arg (WR) monomer-grafted silica microspheres (designated as WR-SiO2), and these biomimetic materials can enrich N- and O-linked glycopeptides with high selectivity. And WR-SiO2 can resist the nonglycopeptides' interference with the 100 molar fold of BSA during O-linked glycopeptide enrichment. We utilized WR-SiO2 to comprehensively analyze the O-glycosylation profile of recombinant SARS-CoV-2 S. Twenty-seven O-glycosylation sites including 18 unambiguous sites are identified on SARS-CoV-2 S. Our study demonstrates that the biomimetic polymer can offer specific selectivity for O-linked glycopeptides and pave the way for O-glycosylation research in biological fields. The O-glycosylation profile of SARS-CoV-2 S might supplement the comprehensive glycosylation in addition to N-glycosylation of SARS-CoV-2 S.

Self-Anchored Catalyst Interface Enables Ordered Via Array Formation from Submicrometer to Millimeter Scale for Polycrystalline and Single-Crystalline Silicon.

Defying text definitions of wet etching, metal-assisted chemical etching (MacEtch), a solution-based, damage-free semiconductor etching method, is directional, where the metal catalyst film sinks with the semiconductor etching front, producing 3D semiconductor structures that are complementary to the metal catalyst film pattern. The same recipe that works perfectly to produce ordered array of nanostructures for single-crystalline Si (c-Si) fails completely when applied to polycrystalline Si (poly-Si) with the same doping type and level. Another long-standing challenge for MacEtch is the difficulty of uniformly etching across feature sizes larger than a few micrometers because of the nature of lateral etching. The issue of interface control between the catalyst and the semiconductor in both lateral and vertical directions over time and over distance needs to be systematically addressed. Here, we present a self-anchored catalyst (SAC) MacEtch method, where a nanoporous catalyst film is used to produce nanowires through the pinholes, which in turn physically anchor the catalyst film from detouring as it descends. The systematic vertical etch rate study as a function of porous catalyst diameter from 200 to 900 nm shows that the SAC-MacEtch not only confines the etching direction but also enhances the etch rate due to the increased liquid access path, significantly delaying the onset of the mass-transport-limited critical diameter compared to nonporous catalyst c-Si counterpart. With this enhanced mass transport approach, vias on multistacks of poly-Si/SiO2 are also formed with excellent vertical registry through the polystack, even though they are separated by SiO2 which is readily removed by HF alone with no anisotropy. In addition, 320 µm square through-Si-via (TSV) arrays in 550 µm thick c-Si are realized. The ability of SAC-MacEtch to etch through poly/oxide/poly stack as well as more than half millimeter thick silicon with excellent site specificity for a wide range of feature sizes has significant implications for 2.5D/3D photonic and electronic device applications.

LC-MS/MS determination of naringin, hesperidin and neohesperidin in rat serum after orally administrating the decoction of Bulpleurum falcatum L. and Fractus aurantii.

To identify and quantify biologically active components in rat serum after orally administrating the decoction of Bulpleurum falcatum L. and Fractus aurantii, one of traditional Chinese medicines (TCMs), high-performance liquid chromatography (HPLC)-tandem mass spectrometry method was developed and validated. The HPLC separation was carried out on a Waters Nova Pak C(18) column using acetonitrile and water as mobile phase after the sample of rat serum was cleaned up with solid-phase extraction. Atmospheric pressure chemical ionization in the negative ion mode and selected reaction monitoring (SRM) method was developed to determine the active components. Three flavonoids of hesperidin, neohesperidin and naringin were identified in the serum by comparing their retention times and three independent SRM precursor/product ion transitions with those of corresponding reference standards. The concentrations of naringin, hesperidin and neohesperidin in rat serum determined by SRM measurement were 16.3, 11.9 and 14.3 ng/ml, respectively, after orally administrating the decoction of B. falcatum L. and F. aurantii. This method was validated in terms of recovery, linearity, accuracy and precision (intra- and interday variation). The recoveries from spiked control samples were 93.0, 89.3 and 91.2% for hesperidin, neohesperidin and naringin, respectively. Linearity in rat serum was observed over the range of 2.0-50.0 ng/ml. Percent bias (accuracy) and precision were well within the acceptable range and the relative standard deviation (R.S.D.) of the measured rat serum samples was less than 10% (n=5).

Characterization of phthalides in Ligusticum chuanxiong by liquid chromatographic-atmospheric pressure chemical ionization-mass spectrometry.

High-performance liquid chromatography (HPLC) with diode-array detection interfaced to atmospheric pressure chemical ionization (APCI)-mass spectrometry (MS) is applied to analyze phthalides from Chuanxiong (the rhizome of Ligusticum chuanxiong). This herb material, containing plenty of phthalide compositions, is selected as the analytical target in this paper for its hematological activity. Some of the phthalides are not stable and are difficult to analyze by gas chromatography-MS. Under optimized LC-MS-MS conditions, six phthalides in the methanol extract of Chuanxiong are unambiguously identified, and characteristic fragments are obtained using homemade reference standards. Ten other phthalides in the extract are confirmed by means of LC-APCI-MS with positive-negative ion mode and collision-induced dissociation in combination with UV spectrophotometry. The results show that LC-MS-MS is a method of choice for fast detection and detailed structural analysis of such mixtures in the crude extract of Chuanxiong.

[Determination of hesperidin and naringin in Fructus Aurantii Immaturus and Fructus Aurantii by reversed-phase high performance liquid chromatography].

An HPLC method was established for the determination of hesperidin and naringin in the Fructus Aurantii Immaturus and Fructus Aurantii from different places. Hesperidin and narigin were separated on a Hypersil ODS1 column with acetonitrile-0.5% acetic acid (volume ratio of 22:78) as the mobile phase and detected at 283 nm. The flow rate was 1.0 mL/min. The column temperature was set at 35 degrees C. The calibration curves were linear in the ranges of 0.060 g/L-0.604 g/L and 0.0125 g/L-0.125 g/L for naringin and hesperidin respectively. The average recoveries were 97.1% for naringin and 95.3% for hesperidin. The method is simple, rapid, accurate and reliable.