OBJECTIVE:To evaluate the effect of deferoxamine (DFO) on bone marrow hematopoietic function in C57 mice exposed to a sublethal dose of X-ray irradiation. METHODS:C57 mice exposed to a sublethal dose (5.4 Gy, 1.0 Gy/min) of total body X-ray irradiation (TBI) were treated with subcutaneous injection of 100 mg/kg DFO, with normal saline as the control, on a daily basis for 10 and 20 consecutive days. Body weight changes of the mice were monitored every 3 days. Five mice were selected from each group at 10 and 20 days for examination of blood cell counts, bone marrow nucleated cell counts, percentage of bone marrow CD34+ cells, bone marrow pathology, and expressions of cleaved PARP-1, cleaved caspase-3, VEGF, GPX4, and SLC7A11 in the nucleated cells. RESULTS:The body weight of the mice decreased significantly on day 3 in TBI and DFO groups (P<0.05), and to the lowest on day 6 in TBI group (P<0.01). Blood cell counts and bone marrow nucleated cell counts of the mice were significantly decreased at 10 and 20 days following TBI (P<0.01). On day 10 following TBI, the mice showed significantly decreased nucleated cells and the presence of adipocytes in the bone marrow, where increased expressions of cleaved PARP-1 and cleaved caspase-3 and lowered expressions of GPX4 and SLC7A11 were detected in the nucleated cells (P<0.05). In the mice exposed to TBI, treatment with DFO significantly increased CD34+ cell percentage (P<0.001), decreased the expressions of cleaved PARP-1 and cleaved caspase-3, and increased the expressions of GPX4, SLC7A11 and VEGF in the bone marrow nucleated cells (P<0.05). DFO treatment significantly increased blood cell counts and bone marrow nucleated cells in mice at 20 days following TBI (P<0.05). CONCLUSION:DFO improves bone marrow hematopoiesis in mice with sublethal-dose TBI by inhibiting apoptosis and ferroptosis of bone marrow nucleated cells and promoting VEGF expression and CD34+ cell proliferation.

Objective:To clarify the definition of severe pulmonary tuberculosis and its inclusion criteria by summarizing and analyzing the studies of severe pulmonary tuberculosis (TB).Methods:A systematic search of Medline (via PubMed), Cochrane Library, Web of Science, Web of Science, Epistemonikos, Embase, CNKI, WanFang database, and CBM database was conducted to collect studies published between 2017 and 2022 on patients with severe pulmonary TB. Searches were performed using a combination of subject terms and free words. The search terms included: tuberculosis, severe, serious, intensive care, critical care, respiratory failure, mechanical ventilation, hospitalization, respiratory distress syndrome, multiple organ failure, pulmonary heart disease, and pneumothorax. The definitions and inclusion criteria for severe pulmonary TB in the included studies were extracted.Results:A total of 19 981 studies were identified and 100 studies were finally included, involving 8 309 patients with severe pulmonary TB. A total of 8 (8.00%) studies explicitly mentioned the definition of severe pulmonary TB, and 53 (53.00%) studies clearly defined the inclusion criteria for patients with severe pulmonary TB. A total of 5 definitions and 30 inclusion criteria were extracted. A total of 132 dichotomous variables and 113 continuous variables were included in the outcome indicators related to patients with severe pulmonary TB of concern in the studies.Conclusions:The definition and diagnostic criteria for severe TB are unclear, and there is an urgent need to develop a clear definition and diagnostic criteria to guide clinical practice.

Objective: To understand the current situation regarding pediatric off-label use of drugs recommendations in Chinese clinical practice guidelines and to make recommendations for standardized reporting format regarding off-label use of drugs for children. Methods: This cross-sectional study was carried out by systematically searching the databases for Chinese guideline consensus articles published in journals between 2018 and 2020 and extracting recommendations regarding off-label use of drugs from those articles. The essential characteristics of the included guidelines, the ranking of off-label drug types, the order of drug information, the type of off-label drug use, and the percentage of citation studies on which the recommendations were based were analyzed. Results: Among 108 studies that included Chinese off-label guidelines and consensus, 364 recommendations on pediatric off-label use of drugs were included. The Chinese Medical Association published the most, 48 out of the 108 studies (44.4%), and of those 14 studies (13.0%) were on infectious and parasitic diseases. Of the 364 recommendations on off-label use of drugs, the most commonly addressed drugs were 16 recommendations (4.4%) for cyclosporine A, 11 recommendations (3.0%) for methotrexate , and 11 recommendations (3.0%) for fentanyl. The most commonly addressed drug categories were as follows: 68 recommendations (18.6%) were immune system drugs, 66 recommendations (18.1%) were anti-infectives, and 56 recommendations (15.4%) were oncology drugs. The most commonly addressed drug information accounts were as follows: 364 recommendations (100.0%) were indications, 204 recommendations (56.0%) were dosages, and 198 recommendations (54.4%) were the route of administration. Based on the instructions approved by the Chinese Food and Drug Administration, the main forms of the off-label drug were as follows: 175 recommendations (48.1%) were unapproved indications, 127 recommendations (34.9%) were unapproved populations, and 72 recommendations (19.8%) were unapproved ages. Only 129 recommendations (35.4%) were cited, mainly including clinical guidelines (48 studies, 23.4%), reviews (22 studies, 10.7%), and pediatric randomized controlled trials (22 studies, 10.7%). Conclusions: Off-label use of drugs is commonly recommended in pediatric guidelines and consensus documents written by Chinese authors. However, the reporting of the recommendations varies widely, and the quality of the supporting evidence is poor.

Metallic additive manufacturing (AM) techniques have substantially liberated the architectural design philosophy of macro/mesoscale functional structures from ease of manufacturing to optimization of performance. However, the application of most metallic AM strategies is limited by their low adaptability and high costs in fabricating micro/nanoscale structures that are increasingly demanded in the electronics field. As an emerging and promising metallic AM technology, electrohydrodynamic (EHD) printing relies on the electrostatic force to facilitate the precise deposition of ultrafine droplets or fibers derived from different metallic materials, providing a revolutionary and versatile strategy to fabricate micro/nanoscale metallic architectures. Here we focus on the state-of-the-art developments of metallic EHD printing for micro/nanoscale functional architectures as well as their potential applications. The basic principles, typical setups, working modes, and critical process parameters of micro/nanoscale metallic EHD printing are analyzed. Various metallic inks including nanoparticles and precursors for micro/nanoscale EHD printing are surveyed in terms of ink compositions, minimum feature sizes, as well as post-treatment strategies to achieve specific functionalities. More importantly, we highlight the unique capabilities of micro/nanoscale metallic EHD printing in fabricating minuscule 3D electronic structures, high-resolution multimaterial architectures, high-performance sensing structures, multi-functional optoelectronic components, etc. Finally, major challenges and future perspectives are discussed to translate micro/nanoscale EHD printing into a mature AM technology for the fabrication of 3D functional metallic architectures.

1. A better understanding of intestinal development is essential for the intestinal health of poultry. Intestinal villification starts on embryo day E15 and is generally completed before hatching (E21). The development of lymphoid organs in the intestine starts during embryogenesis. However, transcriptional information on the processing of intestinal morphogenesis and immune development during chick embryogenesis is limited.2. In this work, RNA-sequencing was performed using 12 biological replicates to investigate Hy-Line brown chick embryonic small intestinal transcription at E15 and E21. Differentially expressed genes (DEGs) between E15 and E21 were identified. GO and KEGG enrichment analyses, based on the DEGs, were performed to identify key GO terms in the biological process category and key KEGG pathways. PPI networks were constructed based on the DEGs in the key pathways to screen hub genes. The embryonic small intestinal morphology and IgA distribution were observed by histological processing. The serum levels of IgA and lysozyme were measured by ELISA.3. A total of 76.38 Gb of high-quality RNA-sequencing data were generated and uploaded. A total of 2,676 DEGs, between E15 and E21, were identified. Structural development and villification of the small intestine at E15 tended to proceed via the expression of nervous system development-related genes. A combination of the histological and serological results with the transcriptome data indicated that the identified genes and pathways may be strong candidates for intestinal morphogenesis-regulation.4. The small intestine appears to have developed a relatively complete morphology and transport, metabolism, digestion and immunity functions by E21. This work provided a transcriptome profile of the chick embryonic small intestine and provided insights into the intestinal development and health of poultry.

Mesenchymal-to-epithelial transition (MET) is a therapeutic target in non-small cell lung cancer (NSCLC), which has a variety of genomic variants. MET amplification and MET exon 14 skipping (MET ex14) have been notable for meaningful clinical response to MET inhibitor therapy. However, comprehensive molecular characteristics of MET variants of Chinese NSCLC patients are not well understood. FFPE tumor and matched blood samples from 3433 Chinese NSCLC patients were collected for targeted next generation sequencing (NGS). Genomic variants including single nucleotide variations (SNV), short/long insertion/deletions (Indel), copy number alterations and gene rearrangements were analyzed. MET amplification, MET ex14 skipping and gene fusion were defined as MET druggable variations. Tumor mutational burden (TMB) was analyzed in all patients. In total, MET variations were identified in 3.3% (115/3433) of Chinese NSCLC patients. Mutation rates varied in different histological types: 3.3% (N=95) in adenocarcinoma, 1.7% (N=7) in squamous cell carcinoma, 10.1% (N=7) in adenosquamous carcinoma and 15.0% (N=3) in sarcomatoid carcinoma. MET druggable variations had been found enriched at an advanced clinical stage accounted for 3.8% of stage IV cases while only 1.2% of cases at earlier stages. Consistent to the previous studies, MET amplification and MET ex14 skipping were identified in 1.5% and 0.8% of NSCLC patients respectively. MET rearrangement was identified in seven patients in this cohort with partner genes as CD47, ST7, TMEM168, MYTKL and FOXP2. Moreover, 39.5% of MET point mutations resulting in pathway activation (D1010, D1228 and H1094) in this cohort could then be potential targets for MET inhibitors. Twenty six percent of all MET variations co-mutated with EGFR sensitive mutations, which may be a resistance mechanism for EGFR-TKI therapy. The median TMB of patients with MET variations was 6.1 muts/Mb. Cases with MET SNV/Indel alterations had higher median TMB than wild type MET (8.1 vs. 4.6 muts/Mb, respectively, P = 0.03). In particular, a newly acquired MET fusion was detected in a 60-year old female NSCLC patient when disease progressed on TKI against the original EGFR L858R-mutant. She achieved a partial response to crizotinib plus osimertinib treatment. Our study revealed that MET variations occurred in 3.3% of Chinese NSCLC patients. Besides MET amplification and MET ex14 skipping, MET rearrangements and targetable point mutations we identified might be potential therapeutic targets for these patients.

Chicken is bred all over the world and has significant economic value as one of the major agricultural commercial animals. The behavior of growth, reproduction and disease resistance varies among different chicken breeds. Deciphering the genetic basis of these differences has great value in both biological science and agricultural economy. In this study, we used next-generation sequencing technique to study the genetic mechanism of MAFbx (muscle atrophy F-box) varied expression in different chicken breeds. Ubiquitin E3 ligase–MAFbx/Atrogin-1 plays an important role in muscle protein degradation. In our previous study, we found that the expression of MAFbx/Atrogin-1 was significantly higher in wild chicken than in broiler, which implied the importance of MAFbx/Atrogin-1 in muscle development. Thus, we sought to unveil the molecular mechanism of how the MAFbx/Atrogin-1 affects the development of muscle. Our study may help to shorten the period of chicken breeding and improve the productivity. We proved that the expression of MAFbx/Atrogin-1 was higher in Red Jungle Fowl (RJF) and Chahua than in broiler chicken. HE staining of skeleton results demonstrated that the myofiber was thinner in RJF. The MAFbx/Atrogin-1 expression profile in differential development stages showed that the gene expression divergence had emerged at Day 4 after born. The sequencing results of MAFbx/Atrogin-1 gene region in eight different domestic chicken breeds performed that heterogeneity reduced in broiler chicken. We presumed that a causative mutation occurred in MAFbx/Atrogin-1 gene region. In vitro, luciferase and gel shift assay of candidate SNPs confirmed that a single base mutation of gene’s intron 4 reduced the enhancer activity and inhibited the binding of transcription regulator in broiler chicken. Our results suggested that MAFbx/Atrogin-1 expression variance was probably caused by the mutation.

The plant-specific AWPM-19-domain proteins play important roles in plant development and stress responses. In the current study, OsPM19L1 encoding Oryza sativa AWPM-19-like protein 1 was isolated from rice. Tissue-specific gene expression analysis revealed that OsPM19L1 was highly expressed in the leaf sheath of rice. Interestingly, expression of OsPM19L1 was high at the early stage of panicle development and decreased thereafter. qRT-PCR analysis indicated that OsPM19L1 was dramatically induced by 20% PEG stress (>600-fold), exogenous abscisic acid (>350-fold), salt and cold stress. Subcellular localization assay suggested that the OsPM19L1-GFP (green fluorescent protein) fusion protein was localized in the membrane system in rice cells. Moreover, under stress conditions, OsPM19L1 expression was enhanced in an ABI5-Like1 (ABL1) deficiency rice mutant, abl1, suggesting that ABL1 negatively regulates OsPM19L1 gene expression. Thus, OsPM19L1 appears to be closely associated with stress tolerance through ABA-dependent pathway in rice.

A 30 kW-powered DC Arcjet Plasma enhanced chemical-vapor deposition (CVD) system was applied to grow diamonds which included the nano-crystal free-standing film, the nano-/micro-crystal layered free-standing film, the gradient micro-crystal free-standing film and the millimeter-sized grain. The free-standing film quality, such as the roughness, the sp2 content, the residual stress and the grain morphology, was studied by an atomic force microscope (AFM), Raman spectra, a scanning electron microscope (SEM) and a high resolution electron microscope (HREM). In large-sized grain deposition, as-grown deposit was obtained about 1 × 1 × 1 mm3 in size under the condition of 10 μm/h of the substrate moving speed without Nitrogen enhancement. Characterized by Raman spectra and Laue back reflection X-ray diffraction, the deposit was proven to be single crystal diamond with small grains coving its surfaces. The growth rate was about 30 μm/h. Optical emission spectrum (OES) was utilized to characterize gas phases in the plasma for diamond deposition. The mean electron temperature (Te) in the plasma was calculated based on the value of the emission intensity ratio of IHγ/IHβ. Te varied from 0.33 eV to 0.5 eV depending on the concentration of CH4 in H2 from 1.0% to 25%. C2 radical was found to be the dominant carbon source compared with CH radical. The influence of the radical on the morphology of diamond was discussed. It was found that the nano-crystal could be grown when the ratio of the emission intensity, IC2/ICH, was larger than 8.

Purpose. This study investigated human telomerase RNA gene (TERC) gain and polysomy of chromosome 3 in cervicovaginal liquid-based pap preparations in Guilin, China, and assessed the relationship between FISH findings and clinical diagnoses. Methods. Slides prepared from 63 liquid-based preparations with cytologic diagnoses of negative for squamous intraepithelial lesion or malignancy (NILM n = 9), atypical squamous cells of undetermined significance (ASCUS, n = 18), low-grade squamous intraepithelial lesion (LSIL, n = 14), high-grade squamous intraepithelial lesion (HSIL, n = 9), and cervical squamous cell carcinoma (SCCA, n = 13) were analyzed for TERC gain and polysomy of chromosome 3 using a commercially available two-color FISH probe. The results of the cytologic analysis and those of concurrent or subsequent biopsies, when available, were compared with the FISH findings. The Mann-Whitney test was used to assess associations between FISH findings and diagnoses. Results. TERC gain and polysomy of chromosome 3 were significantly associated with the cytologic diagnosis (p? 0.001). Patients with HSIL or SCCA cytology diagnoses had a significantly higher percentage of cells with TERC gain and polysomy of chromosome 3 than did patients with NILM, ASCUS or LSIL cytologic diagnoses. Those abnormal cases with CIN1 histological diagnosis had a significantly lower percentage of cells with TERC gain and polysomy of chromosome 3 than did patients with a CIN2, CIN3 and SCCA histological diagnosis. Conclusions. TERC gain and polysomy of chromosome 3 may be important associated genetic events in cervical intraepithelial neoplasia and carcinoma. FISH is a potential tool for the diagnoses of uterine cervix disease.

Layered self-standing diamond films, consisting of an upper layer, buffer layer, and a lower layer, were fabricated by fluctuating the ratio of methane to hydrogen in high power dc arc plasma jet chemical vapor deposition. There were micrometer-sized columnar diamond crystalline grains in both upper layer and lower layer. The size of the columnar diamond crystalline grains was bigger in the upper layer than that in the lower layer. The orientation of the upper layer was (110), while it was (111) for the lower layer. Raman results showed that no sp3 peak shift was found in the upper layer, but it was found and blueshifted in the lower layer. This indicated that the internal stress within the film body could be tailored by this layered structure. The buffer layer with nanometer-sized diamond grains formed by secondary nucleation was necessary in order to form the layered film. Growth rate was over 10μm∕h in layered self-standing diamond film fabrication.

Layered self-standing diamond films, two-, three- and four-layered films, were fabricated by varying the ratio of methane to hydrogen in high-power DC arc plasma jet CVD. Results of scanning electronic microscopy (SEM) and Raman spectra showed that the layered films were constructed by the micro-crystalline grains layer/nano-crystalline grains layer. The residual stress within the films were balanced, and even diminished in the certain layer. The grain size was calculated by X-ray diffraction (XRD). The layer containing nanocrystalline grains due to a plenty of secondary nucleation can weakly inherit the columnar growth feature of the overlaid layer containing micro-crystalline grains. The grain size and growth orientation of the layer containing micro-crystalline grains can be adjusted by introduction of a mid-layer containing nano-crystalline grains. Growth rate was over 10mm/h in layered film fabrication.

Gas phase species were diagnosed by in situ spatially resolved OES in high power DC arc plasma jet CVD system. CH, C2, H were found as main species in this deposition plasma environment. Concentration of species was studied with the variation of deposition parameters such as methane concentration, substrate temperature and gas flow rate. C2 was found to be the most sensitive species to deposition parameters. The electron mean temperature was deduced from Hγ/Hβ, and changed little no matter how the deposition parameters varied. Self-standing diamond films with (111) orientation were grown within the modified species atmosphere where the intensity ratio of CH/C2 was higher than 0.41.

Although related bone marrow transplantation (BMT) is effective for thalassemia, less than 30% of patients have sibling donors. Here, we report unrelated BMT in nine thalassemic children using a high-resolution HLA typing technique to identify donors. HLA mismatches between donors and recipients were 0, 1 and 2 in 2, 5 and 2 cases, respectively. The results showed that white blood cells, platelets and hemoglobin all returned to normal at various time points, and blood transfusion was eliminated from 13 to 62 days after transplantation. Full engraftment was achieved in eight patients while ABO blood types were replaced with that of donors in five of the six ABO mismatched recipients. Acute skin GVHD was found in seven patients and acute liver GVHD in one. One patient with acute intestinal GVHD eventually developed chronic GVHD. One patient died of pulmonary hemorrhage in spite of having a fully functional graft. We conclude that this is the first successful application of unrelated BMT for thalassemia major in Chinese people and that the results will certainly expand donor resources and greatly enhance the survival and quality of life of thalassemic patients.

The Shi Yang Jiang Bridge, located approximately 200 km southwest of Kunming, Yunnan, is a six-span, simply supported, concrete slab on precast girder structure carrying two lanes of traffic. The existing bridge has a high vulnerability of collapsing under moderate to large earthquakes. In 2004, this bridge was selected by the Yunnan Provincial Department of Communications (PDOC) as a pilot project for seismic retrofitting of existing highway bridges. This pilot project is being co-sponsored by the Ministry of Communications (MOC), through a five-year applied research program-Western Provinces Transportation Development Research Program, and by the Canadian International Development Agency (CIDA), carried out under a five-year technical assistance program China Western Roads Development Project. The seismic assessment and retrofit design for the Shi Yang Jiang Bridge are based upon the recently proposed Chinese Specifications of Earthquake Resistance Design for Highway Bridges' (draft version for discussions), and supplemented by the Caltrans Seismic Design Criteria(2). The recommended retrofit strategy includes a number of innovative rehabilitation concepts and techniques. This paper will examine both design and construction challenges of the pilot project together with detailed discussions on (a) effective modelling and analysis of the existing bridge; (b) development of a cost-effective strategy for seismic retrofitting; and (c) advantages of semi-integral abutments for earthquake-resistance design.