[Early diagnosis and intervention for prepubertal short stature children]. / å ³æ³¨é’æ˜¥æœŸå‰çŸ®èº«æå„¿ç«¥çš„æ—©æœŸè¯Šæ–­åŠå¹²é¢„.

The prevalence of short stature among prepubertal children in China is relatively high. Early identification of the cause and timely intervention can bring greater benefits to children with short stature. This paper provides an overview of early diagnosis, intervention measures, and personalized medication dosage for prepubertal short stature children, aiming to provide references for clinical doctors.

[Clinical and genetic analysis of two cases with Rubinstein-Taybi syndrome].

OBJECTIVE: To summarize the clinical characteristics and identify gene mutations of 2 probands with Rubinstein-Taybi syndrome (RSTS). METHODS: Clinical characteristics of 2 probands with Rubinstein-Taybi syndrome were summarized. Genomic DNA was extracted from peripheral blood samples from the patients and their parents. Genomic DNA was subjected to whole exome next generation sequencing. Suspected variants were confirmed by Sanger sequencing. RESULTS: The two patients were characterized by typical facial features, broad thumbs and big toes, intellectual disability, and postnatal growth retardation. Two variants of the CREBBP gene, namely c.3779+1G>A and c.5052_c.5053insT, were respectively identified in the 2 patients. Among these, c.3779+1G>A was a previously known pathological mutation, while c.5052_c.5053insT was unreported previously. Both variants were predicted to be pathological. CONCLUSION: Two cases of Rubinstein-Taybi syndrome were diagnosed, which facilitated the diagnosis and genetic counselling.

A Newborn with Congenital Hyperinsulinism.

Objective: Our aim was to describe the molecular alterations in the ABCC8 gene in a child with congenital hyperinsulinism (CHI). Methods: Genetic analysis of the ABCC8 gene of a newborn infant with congenial hyperinsulinism was obtained. Results: There were two mutations in the ABCC8 gene, c.4412delT, and c.3979G > A, indicating a compound heterozygous mutation. The c.4412delT variant is associated with CHI, and the c.3979G > A variant is associated with neonatal diabetes. Treatment with diazoxide was not effective, octreotide treatment with acetate was effective. Conclusion: The combination of a mutation of the ABCC8 gene c.4412delT, associated with CHI, and the mutation of c.3979G > A, associated with neonatal diabetes, resulted in a neonate with hypoglycemia. The mechanism remains unclear.

Metamaterial perfect absorbers with solid and inverse periodic cross structures for optoelectronic applications.

Metamaterial based on a metal/insulator/metal (MIM) tri-layer structure provides an agile platform to realize high absorption efficiency for a variety of applications including semiconductor optoelectronic detectors. In this work, we use the finite time domain difference (FDTD) method and coupled mode theory (CMT) to numerically study metal/semiconductor/metal (MSM) structures and discuss their effective absorption for optoelectronic application. We compare MSM structures with a different top metal layer design and find that cross shaped absorber (CSA) and it's complementary cross shaped absorber (CCSA) exhibit different phase diagrams due to a distinctive dependence of radiation loss on geometrical parameters. Our results show that CSA (CCSA) structures are suitable for thinner (thicker) sandwiched semiconductor with a larger (smaller) imaginary part of its dielectric constant. The necessary condition to realize a maximum figure of merit (FOM) value for effective absorption is discussed in comparison with the perfect absorber condition. Our work may provide guidelines to design the general light-harvesting optoelectronic devices with high efficiencies based on metamaterial-semiconductor hybrid systems.

Design of triple-band metamaterial absorbers with refractive index sensitivity at infrared frequencies.

A triple-band perfect plasmonic metamaterial absorber based on a metal/insulator/metal (MIM) structure is designed. A new freedom through tuning the thicknesses of each ring structures is introduced to realize a quasi-three-dimensional perfect absorber at three extinction wavelengths by using the finite difference time domain method. The physical machine is explained by the time domain field analyses and the coupled mode theory. The characteristics of the absorber make our proposed strategy applicable for the design of more general multiband and broadband perfect absorbers. In addition, these perfect absorbing metamaterials are found to exhibit excellent performance in refractive index sensing.

Plasmonic focusing of infrared SNOM tip patterned with asymmetric structures.

Several scattering type metal tips patterned with asymmetric metal/dielectric bump gratings are studied and proved to be efficient in focusing light energy into nano 'hot spot'. The dielectric bump tip shows complex mechanisms including local geometric resonance, surface plasmon polariton (SPP) standing wave resonance and Fano effect in the near-field enhancement. Additionally, considering the practical situation, we also demonstrate that, for the case of bending tip surface, the grating coupling method for plasmonic nano-focusing is still applicable if the intervals between neighboring bumps are well designed according to the surface bending curvature. With practical realizations, our results could benefit not only infrared scanning near-field optical microscopes (SNOMs) but also many other applications in nanotechnology such as sensing and lithography.

Assessing size shifts amidst a warming climate in lakes recharged by the Asian Water Tower through satellite imagery.

Recent studies indicate that the Asian Water Tower (AWT) is at risk due to climate change, which can negatively impact water and food security in Asia. However, there is a lack of comprehensive information on lakes' spatial and temporal changes in this region. This information is crucial for understanding the risk magnitude and designing strategies. To fill this research gap, we analyzed 89,480 Landsat images from 1977 ± 2 to 2020 ± 2 to investigate the changes in the size of lakes recharged by the AWT. Our findings showed that out of the 209 lakes larger than 50 km2, 176 (84 %) grew during the wet season and 167 (81 %) during the dry season. 74 % of expanded lakes are located in the Inner Tibetan Plateau (TP) and Tarim basins. The lakes that shrank are found mainly in the Helmand, Indus, and Yangtze basins. Over the entire period, the area of shrinkage (55,077.028 km2 in wet season, 53,986.796 km2 in dry) markedly exceeded expansion (13,000.267 km2 in wet, 11,038.805 km2 in dry), with the drastic decline of the Aral Sea being a major contributor to shrinkage, accounting for 90 % of the total loss. From 1990 ± 2 to 2020 ± 2, alpine lakes mostly expanded, plain lakes mostly shrank, with the opposite trend from 1977 ± 2 to 1990 ± 2. Glacial loss and permafrost thawing under global warming in the Inner TP, Tarim Interior, Syr Darya, and Mekong basins were strongly correlated with lake expansion. However, permafrost discontinuities may prevent significant growth of lakes in the Indus and Ganges basins despite increased recharge. Our findings point to the prominence of the risk the lakes recharged by AWT face. Taking immediate action to manage these risks and adaptation is crucial as the AWT retreats and lake recharges are slowed.

Clinical evaluation, accurate diagnosis and treatment of four pedigrees with Fabry's disease.

Objective: This article analyzes the data of four families with mutations of the GLA (galactosidase) gene with a special focus on the clinical presentation, diagnosis, and interdisciplinary clinical management of Fabry disease (FD) and enzyme replacement therapy (ERT) treatment, and has the aim to assess more accurate prevention and treatment strategy. Methods: The MSSI (Mainz Severity Score Index) scale was used to evaluate the clinical data of five children diagnosed in our hospital, and the genotypes of all the patients with FD were collected. Two of the male children started ERT. We summarize the clinical effect and the evaluation of globotriaosylsphingosine (Lyso-GL-3) before and after treatment. Results: Five children were confirmed as having FD using the family histories, clinical manifestations, α-galactosidase A (a-Gal A) activity, and genetic test results. Two children used agalsidase α every 2 weeks regularly, after ERT. Their clinical symptoms improved, their pain intensity was significantly relieved, and upon re-examination their Lyso-GL-3 decreased conspicuously and no serious adverse reactions occurred. We report for the first time four families with children with FD. The youngest child was only 1 year old. The four families included one girl which is rare in X-linked lysosomal storage diseases. Conclusion: The clinical phenotype of FD in childhood is nonspecific, and the misdiagnosis rate is high. Most children with FD have a delayed diagnosis, and their organs are often seriously damaged in adulthood. Pediatricians must improve their diagnosis and treatment awareness, screen high-risk groups, and emphasize multidisciplinary cooperation and holistic lifestyle management after diagnosis. The diagnosis of the proband is also conducive to the mining of other cases of FD families and has important guiding significance for prenatal diagnosis.

Spatiotemporal distribution characteristics of ecosystem health and the synergetic impact of its driving factors in the Yangtze River Delta, China.

In recent years, . the rapid development of the Yangtze River Delta in China has led to increasingly serious regional eco-environmental problems. Therefore, it is of great significance for the construction of ecological civilization to study the ecosystem health in the Yangtze River Delta. In this paper, the assessment framework of "Vigor-Organization-Resilience" was used to assess the ecosystem health index (EHI) of the Yangtze River Delta from 2000 to 2020, and then the spatial autocorrelation method was used to analyze the agglomeration of EHI in 314 counties in this region. Finally, the eXtreme Gradient Boosting (XGBoost) model and the SHapley Additive exPlanation (SHAP) model were combined to explore the synergistic impact of EHI driving factors. The results show that (1) from 2000 to 2020, the EHI in the Yangtze River Delta is at the level of ordinary health, and gradually decreased; (2) the EHI has significant spatial positive correlation and aggregation; (3) the driving factors in descending order of importance are urbanization level (UL), precipitation (PRE), PM2.5 (PM), normalized difference vegetation index (NDVI), and temperature (TEMP); and (4) the relationship between UL and EHI is logarithmic; PRE and EHI are quartic polynomial; PM, NDVI, TEMP, and EHI are quadratic polynomial. The results of this paper are of great significance to the management and restoration of the ecosystem in this region.

Reconstruction of all-weather land surface temperature based on a combined physical and data-driven model.

At present, the remote sensing (RS) thermal infrared (TIR) images that are commonly used to obtain land surface temperature (LST) are contaminated by clouds and thus cannot obtain spatiotemporal integrity of LST. To solve this problem, this study combined a physical model with strong interpretability with a data-driven model with high data adaptability. First, the physical model (Weather Research and Forecast (WRF) model) was used to generate LST source data. Then, combined with multisource RS data, a data-driven method (random forest (RF)) was used to improve the accuracy of the LST, and a model framework for a data-driven auxiliary physical model was formed. Finally, all-weather MODIS-like data with a spatial resolution of 1 km were generated. Beijing, China, was used as the study area. The results showed that in cases of more clouds and fewer clouds, the reconstructed all-weather LST had a high spatial continuity and could restore the spatial distribution details of the LST well. The mean absolute error (MAE), root mean square error (RMSE), and correlation coefficient (ρ) in the case of more (fewer) clouds were ranked as follows: MAE < 1 K (< 2 K), RMSE < 2 K (< 2 K), and ρ > 0.9. The errors obeyed an approximately normal distribution. The total MAE, RMSE, and ρ were 0.80 K, 1.09 K, and 0.94 K, respectively. Generally, the LST reconstructed in this paper had a high accuracy, and the model could provide all-weather MODIS-like LST to compensate for the disadvantages of satellite TIR images (i.e., contamination by clouds and inability to obtain complete LST values).

A Real-World Study of Recombinant Human Growth Hormone in the Treatment of Idiopathic Short Stature and Growth Hormone Deficiency.

Objective: This study aimed to evaluate the clinical efficacy of recombinant human growth hormone (rhGH) in the treatment of children with idiopathic short stature (ISS) and growth hormone deficiency (GHD) and to explore the related factors affecting treatment efficacy. Methods: The current research reflects a real-world study. A total of 79 patients with ISS and 95 patients with GHD (both groups pre-puberty) who had been treated with rhGH for more than one year from January 2010 to September 2019 were included in this study. The patients were divided into two groups, ie, an ISS and a GHD group, respectively. The growth indexes, such as chronological age (CA), bone age (BA), height standard deviation score (HtSDS), insulin-like growth factor-1 (IGF-1) SDS, and body mass index were recorded and compared between the two groups before and after treatment. The treatment efficacy was evaluated according to changes in HtSDS before and after treatment, and the influencing factors of clinical efficacy were analyzed using a multivariate regression model. Results: At the start of treatment, the differences in CA, BA, height, weight, sexual development stage, HtSDS, mid-parental height SDS, and IGF-1 SDS between the two groups were not statistically significant (P > 0.05). However, the initial dose of rhGH in the GHD group was significantly lower than in the ISS group (P < 0.001). Following rhGH treatment, the differences in CA, BA, BA/CA ratio, and IGF-1 SDS measured at 6, 12, 18, and 24 months between the ISS and GHD groups were not statistically significant, while the difference in HtSDS measured at 6 months was statistically significant. With the extension of rhGH treatment time, the annual growth rate (GV) gradually decreased, and the difference between HtSDS and the baseline gradually increased; however, the differences between the ISS and GHD groups were not statistically significant. The most important factor affecting the treatment efficacy for patients with ISS was age at the start of treatment; the most important factors affecting the treatment efficacy for patients with GHD were age and IGF-1 SDS. Conclusion: Recombinant human growth hormone treatment can significantly improve the height of patients with ISS and GHD. There was no significant difference in growth rate between patients with ISS and those with GHD at relatively high doses. The common factor affecting the treatment efficacy of the two groups was the age at the start of treatment. During treatment, monitored data indicated that rhGH treatment of GHD and ISS thyroid function showed a clinical phenomenon in the form of increased free triiodothyronine, rather than hypothyroidism, which was rarely reported in existing studies.

Effect of rainfall-runoff process on sources and transformations of nitrate using a combined approach of dual isotopes, hydrochemical and Bayesian model in the Dagang River basin.

The control of agricultural nitrogen through inflow rivers is crucial for lake aquatic environment conservation, while nitrate is the main form of non-point source pollution of agricultural nitrogen in watersheds. Therefore, understanding the nitrate sources and transformation in the intensive-agricultural region was particularly concerned. Nitrate sources and transformation varied largely during some crucial periods or events. However, low-resolution sampling campaigns increased some uncertainties due to without considering the effect of key driving factors for identifying nitrate transformations and sources. In our study, high-frequency sampling and analysis of nitrogen and oxygen isotope, hydrochemical and Bayesian model was conducted at the Dagang River to capture nitrate sources and transformations and identify its response to rainfall-runoff process at the event scale. In addition, the N cycle process was refined by comparing the variation and relationship of water quality factors and isotopes before, during, and after rainfall. We found that nitrate and major ions derived from similar agricultural activities caused by anthropogenic factors, such as domestic sewage from rural residents and livestock waste, through field survey and principal component analysis. The δ15N-NO3- and δ18O-NO3- in Dagang River ranged from +0.05‰ to +9.94‰ and + 1.49‰ to +11.64‰, respectively. The spatio-temporal variations of nitrate isotopes and hydrochemical compositions of river water suggested that nitrification was the dominant nitrate transformation process although the mixing effect occurred in some periods, especially during, and after the rainfall. The relationship between NO3-/Cl- and Cl- ratios suggested the occurrence of denitrification in downstream of the river basin after the rainfall. The results of Bayesian model showed that livestock manure and groundwater contributed to the most (66.4 ± 31.9%) nitrate, which indicated the necessity to establish its regulatory policy to avoid the overuse of livestock manure and groundwater in Dagang River. This study benefit for developing concrete and legible management and conservation strategies for decreasing the effect of anthropogenic nitrogen loading on lake eutrophication.

Clinical and genetic characteristics of two cases with Williams-Beuren syndrome.

Herein, we describe 2 cases of Williams-Beuren syndrome (WBS). In both cases, the patients exhibited mental retardation, characteristic facial features, and indirect inguinal hernia. Case 1, a girl aged 2 years and 5 months old, presented with hypercalcemia, and in case 2, a boy aged 4 years and 11 months old, the disorder manifested as infantile spasms, supravalvular aortic stenosis, and pulmonary stenosis. Brain MRI revealed no abnormalities in either case. The electroencephalogram of case 2 showed hypsarrhythmia. Case 1 was treated with bisphosphonates and somatropin for hypercalcemia and short stature. Case 2 received antiepileptic drug and ketogenic diet therapy. In both cases, a 7q11.23 deletion including fragment deletion of the GTF21 gene was found, which may be associated with mental retardation. Notably, in case 2, a 921.1kb deletion in Yq11.23 was detected, which has not been reported in WBS before. The deletion of Yq11.23 is located in the AZFc region, which is an important factor in male infertility with primary azoospermia and oligozoospermia. The occurrence of hypercalcemia in case 1 may be related to the deletion of BAZ1B, while the supravalvular aortic stenosis and pulmonary stenosis were associated with deletion of the ELN gene. We explored the clinical and genetic characteristics of WBS to better understand disease.

SS-31 Protects Liver from Ischemia-Reperfusion Injury via Modulating Macrophage Polarization.

Ischemia-reperfusion injury (IRI) is a common complication in liver surgeries. It is a focus to discover effective treatments to reduce ischemia-reperfusion injury. Previous studies show that oxidative stress and inflammation response contribute to the liver damage during IRI. SS-31 is an innovated mitochondrial-targeted antioxidant peptide shown to scavenge reactive oxygen species and decrease oxidative stress, but the protective effects of SS-31 against hepatic IRI are not well understood. The aim of our study is to investigate whether SS-31 could protect the liver from damages induced by IRI and understand the protective mechanism. The results showed that SS-31 treatment can significantly attenuate liver injury during IRI, proved by HE staining, serum ALT/AST, and TUNEL staining which can assess the degree of liver damage. Meanwhile, we find that oxidative stress and inflammation were significantly suppressed after SS-31 administration. Furthermore, the mechanism revealed that SS-31 can directly decrease ROS production and regulate STAT1/STAT3 signaling in macrophages, thus inhibiting macrophage M1 polarization. The proinflammation cytokines are then significantly reduced, which suppress inflammation response in the liver. Taken together, our study discovered that SS-31 can regulate macrophage polarization through ROS scavenging and STAT1/STAT3 signaling to ameliorate liver injury; the protective effects against hepatic IRI suggest that SS-31 may be an appropriate treatment for liver IRI in the clinic.

Vertebral Collapse Prevented Following Teriparatide Treatment in Postmenopausal Kümmell's Disease Patients with Severe Osteoporosis.

OBJECTIVE: To compare the preventive effects of teriparatide and alendronate on the progression of vertebral body collapse in postmenopausal single-level Kümmell's disease (KD). METHODS: From March 2013 to December 2020, the medical records for 53 postmenopausal single-level KD patients who received conservative treatment with teriparatide (25 patients, teriparatide group) or alendronate (28 patients, alendronate group) were retrospectively reviewed. Midsagittal computed tomography (CT) images were analyzed by ImageJ to assess the intravertebral bone formation (mineralized bone) by calculating the ratio of area of intravertebral mineralized bone (AIMB) to the area of fractured vertebral body (AFVB). The changes in radiological parameters of the fractured vertebral body including kyphosis angle (KA), anterior and posterior border heights (ABH and PBH) and spinal canal diameter (SCD), bone turnover biomarkers (BTMs), and bone mineral density (BMD) were analyzed to evaluate the therapeutic effect. RESULTS: At month 12, the ratio of AIMB to AFVB was significantly greater in teriparatide group (54.28% ± 15.30%) than in alendronate group (35.57% ± 17.61%) (P < 0.001). Sagittal CT substantiated the formation of bone bridge in 16 patients in teriparatide group. No bone bridge was detected in alendronate group. The KA was significantly smaller and the ABH, PBH, and SCD was greater in teriparatide group than in alendronate group (all P < 0.001). The KA increments were significantly smaller in teriparatide group (3.98° ± 1.30°) than in alendronate group (11.43° ± 3.73°) (P < 0.001). The ABH and PBH decrement were significantly lower in teriparatide group (11.96% ± 1.93% and 2.80% ± 2.52%) than in alendronate group (37.04% ± 8.00% and 19.50% ± 8.22%) (both P < 0.001). The BTMs and BMD were significantly greater in the teriparatide group than in the alendronate group. In teriparatide group, KA increment was negatively correlated with the change in PINP (r = -0.781, P < 0.001) and the ratio of AIMB to AFVB (r = -0.592, P = 0.002) from baseline to month 12. The ABH decrement was negatively correlated with the change in PINP (r = -0.612, P = 0.001) and the ratio of AIMB to AFVB (r = -0.806, P < 0.001) from baseline to month 12. CONCLUSIONS: In postmenopausal single-level KD patients, conservative treatment with teriparatide was better than alendronate at preventing the progressive vertebral collapse.

Elevated HMGB1 expression induced by hepatitis B virus X protein promotes epithelial-mesenchymal transition and angiogenesis through STAT3/miR-34a/NF-κB in primary liver cancer.

HBV infection plays a crucial role in primary liver cancer development. Also, HBV related liver cancer has higher invasiveness and earlier discovered distant metastasis. HBV-encoded X protein (HBx) exerts various biological functions on liver cancer progression, including proliferation, invasion, and venous metastasis. There is evidence that High-mobility group box 1 (HMGB1) promotes epithelial-mesenchymal transition (EMT) and angiogenesis of tumors, including liver cancer. Therefore, this study investigates whether HMGB1 mediates HBx-induced EMT and angiogenesis in HBV related liver cancer. We collected 76 tumor samples of primary liver cancer patients to analyze the relationship between HMGB1 and portal vein tumor thrombus (PVTT) in HBV related liver cancer. To test the influence of HMGB1 on EMT and angiogenesis, we constructed HBx lentivirus transfected HepG2/Huh7 cell lines and performed invasion assays, tube formation and in vivo metastatic experiments. We evaluated HMGB1 and STAT3/miR-34a/NF-κB pathway in vivo and in vitro by immunoblot, quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence and immunohistochemistry analysis. Subsequent RNA interference (RNAi) and luciferase reporter assay were conducted to detect the functional correlation between HMGB1 and STAT3/miR-34a/NF-κB pathway. Our results showed enhanced expression of HMGB1 in HBV related liver cancer, especially with PVTT, while HMGB1 expression was associated with tumor invasion and metastasis. Further experiments indicated that the activation of STAT3 mediated HBx-induced HMGB1, which is involved in EMT and tumor angiogenesis. Besides, HMGB1 expression stimulated by HBx was dependent on the activation of the NF-κB signaling pathway, which was inhibited by miR-34a, while STAT3 suppressed the expression of miR-34a. Moreover, extracellular HMGB1 induced the IL-6/STAT3/miR-34a axis activation, which indicated a reciprocal relationship between HMGB1 and miR-34a. Collectively, our study provided evidence to reveal that HBx-mediated high expression of HMGB1 accounted for EMT and tumor angiogenesis in HBV related liver cancer, and HMGB1 may be a potential target for predicting venous metastasis.

Synthesis, self-assembly, and drug-loading capacity of well-defined cyclodextrin-centered drug-conjugated amphiphilic A(14)B(7) Miktoarm star copolymers based on poly(epsilon-caprolactone) and poly(ethylene glycol).

Novel drug-conjugated amphiphilic A(14)B(7) miktoarm star copolymers composed of 14 poly(epsilon-caprolactone) (PCL) arms and 7 poly(ethylene glycol) (PEG) arms with beta-cyclodextrin (beta-CD) as core moiety were synthesized by the combination of controlled ring-opening polymerization (CROP) and "click" chemistry. (1)H NMR, FT-IR, and SEC-MALLS analyses confirmed the well-defined A(14)B(7) miktoarm star architecture. These amphiphilic miktoarm star copolymers could self-assemble into multimorphological aggregates in aqueous solution, which were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Moreover, the drug-loading efficiency and drug-encapsulation efficiency of the drug-conjugated miktoarm star copolymers were higher than those of the corresponding non-drug-conjugated miktoarm star copolymers.

Hybrid perfect metamaterial absorber for microwave spin rectification applications.

Metamaterials provide compelling capabilities to manipulate electromagnetic waves beyond the natural materials and can dramatically enhance both their electric and magnetic fields. The enhanced magnetic fields, however, are far less utilized than the electric counterparts, despite their great potential in spintronics. In this work, we propose and experimentally demonstrate a hybrid perfect metamaterial absorbers which combine the artificial metal/insulator/metal (MIM) metamaterial with the natural ferromagnetic material permalloy (Py) and realize remarkably larger spin rectification effect. Magnetic hot spot of the MIM metamaterial improves considerably electromagnetic coupling with spins in the embedded Py stripes. With the whole hybridized structure being optimized based on coupled-mode theory, perfect absorption condition is approached and an approximately 190-fold enhancement of spin-rectifying photovoltage is experimentally demonstrated at the ferromagnetic resonance at 7.1 GHz. Our work provides an innovative solution to harvest microwave energy for spintronic applications, and opens the door to hybridized magnetism from artificial and natural magnetic materials for emergent applications such as efficient optospintronics, magnonic metamaterials and wireless energy transfer.

Protective Properties of FOXO1 Inhibition in a Murine Model of Non-alcoholic Fatty Liver Disease Are Associated With Attenuation of ER Stress and Necroptosis.

AIM: The pathogenesis of non-alcoholic fatty liver disease is currently unclear, however, lipid accumulation leading to endoplasmic reticulum stress appears to be pivotal in the process. At present, FOXO1 is known to be involved in NAFLD progression. The relationship between necroptosis and non-alcoholic steatohepatitis has been of great research interest more recently. However, whether FOXO1 regulates ER stress and necroptosis in mice fed with a high fat diet is not clear. Therefore, in this study we analyzed the relationship between non-alcoholic steatohepatitis, ER stress, and necroptosis. MAIN METHODS: Male C57BL/6J mice were fed with an HFD for 14 weeks to induce non-alcoholic steatohepatitis. ER stress and activation of necroptosis in AML12 cells were evaluated after inhibition of FOXO1 in AML12 cells. In addition, mice were fed with AS1842856 for 14 weeks. Liver function and lipid accumulation were measured, and further, ER stress and necroptosis were evaluated by Western Blot and Transmission Electron Microscopy. KEY FINDINGS: Mice fed with a high fat diet showed high levels of FOXO1, accompanying activation of endoplasmic reticulum stress and necroptosis. Further, sustained PA stimulation caused ER stress and necroptosis in AML12 cells. At the same time, protein levels of FOXO1 increased significantly. Inhibition of FOXO1 with AS1842856 alleviated ER stress and necroptosis. Additionally, treatment of mice with a FOXO1 inhibitor ameliorated liver function after they were fed with a high fat diet, displaying better liver condition and lighter necroptosis. SIGNIFICANCE: Inhibition of FOXO1 attenuates ER stress and necroptosis in a mouse model of non-alcoholic steatohepatitis.

Two Chinese Xia-Gibbs syndrome patients with partial growth hormone deficiency.

BACKGROUND: Heterozygous mutations in the AT-hook DNA-binding motif containing one (AHDC1, OMIM * 615790) gene cause an autosomal dominant multisystem developmental disorder known as Xia-Gibbs syndrome (OMIM #615829). Xia-Gibbs syndrome typically presented with global developmental delay, hypotonia, obstructive sleep apnea, seizures, delayed myelination, micrognathia, and other mild dysmorphic features. METHODS: Description of the clinical materials of two Chinese boys who were diagnosed with Xia-Gibbs syndrome based on clinical presentations and next generation sequencing. Review of clinical features and AHDC1 mutations in previously reported Xia-Gibbs syndrome patients together with our two new patients. RESULTS: The Xia-Gibbs syndrome patients exhibited short stature, hypotonia, global developmental delay, speech delay, simian crease, and mild dysmorphic features. Next generation sequencing revealed de novo heterozygous variants in AHDC1 gene. In addition, laboratory test revealed partial growth hormone deficiency. Both patients underwent growth hormone replacement therapy for 24 and 9 months, respectively, and exhibited good response to the treatment. CONCLUSION: This is the first report of Xia-Gibbs syndrome patients to be treated with growth hormone. Review of previously reported Xia-Gibbs syndrome patient indicated that short stature is a frequent feature of this condition, but its underlying cause needs to be further investigated.