Background Atmospheric fine particulate matter (PM_2.5) can disrupt the metabolic homeostasis of the liver and accelerate the progression of liver diseases, but there are few studies on the effects of sub-chronic PM_2.5 exposure on the liver metabolome. Objectives To investigate the effects of sub-chronic exposure to concentrated PM_2.5 on hepatic metabolomics in mice by liquid chromatography-mass spectrometry (LC-MS), and to identify potentially affected metabolites and metabolic pathways. Methods Twelve male C57BL/6J (6 weeks old) mice were randomly divided into two groups: a concentrated PM_2.5 exposure group and a clean air exposure group. The mice were exposed to concentrated PM_2.5 using the "Shanghai Meteorological and Environmental Animal Exposure System" at Fudan University. The exposure duration was 8 h per day, 6 d per week, for a total of 8 weeks. The mice's liver tissues were collected 24 h after the completion of exposure. LC-MS was performed to assess changes in the hepatic metabolome. Orthogonal partial least squares discriminant analysis and t-test were employed to identify differentially regulated metabolites between the two groups under the conditions of variable important in projection (VIP)≥1.0 and P<0.05. Metabolic pathway enrichment analysis was performed using MetaboAnalyst 5.0 software and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Results A total of 297 differentially regulated metabolites were identified between the concentrated PM_2.5 exposure group and the clean air group. Among these metabolites, 142 were upregulated and 155 were downregulated. A total of 38 metabolic pathways were altered, with 7 pathways showing significant perturbation (P<0.05). These pathways involved amino acid metabolism, glucose metabolism, nucleotide metabolism, as well as cofactor and vitamin metabolism. The 7 significant metabolic pathways were pantothenic acid and coenzyme A biosynthesis; purine metabolism; amino sugar and nucleotide sugar metabolism; arginine biosynthesis; alanine, aspartate and glutamate metabolism; aminoacyl-tRNA biosynthesis; and fructose and mannose metabolism. Conclusion The results from metabolomics analysis suggest that sub-chronic exposure to PM_2.5 may disrupt hepatic energy metabolism and induce oxidative stress damage. Aspartic acid, succinic acid, ornithine, fumaric acid, as well as purine and xanthine derivatives, were identified as potential early biomarkers of hepatic response to sub-chronic PM_2.5 exposure.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

OBJECTIVE To study the intervention effect of Hippophae rhamnoides oil on glucocorticoid resistance in superantigen-induced atopic dermatitis （AD） mice，and to explore the mechanism of action. METHODS Fifty mice were randomly divided into 5 groups，i.e. normal control group （group A），model group （group B），dexamethasone intervention group （positive control，group C），H. rhamnoides oil intervention group （group D），dexamethasone+H. rhamnoides oil intervention group （group E），with 10 mice in each group. Except for group A，other groups were given 2，4-dinitrochlorobenzene+staphylococcal enterotoxin B to induce the AD mice model. Starting from the 7th day of the experiment，groups C，D and E were given dexamethasone （1.5 mg/kg） and/or H. rhamnoides oil （10 mL/kg） intragastrically，once a day，for 28 consecutive days. After the last medication，the pathomorphological changes of ear tissue were observed by 节作用。E-mail：57667478@qq.com HE staining； the serum levels of immunoglobulin E （IgE） and interleukin 4 （IL-4） were detected by enzyme-linked immunosorbent assay. Positive cell count of glucocorticoid receptor α （GRα） and GRβ in the ear tissue of mice was detected by tyramide signal amplification. The expressions of GRα protein，GRβ protein，and protein kinase B （AKT）/ribosomal protein S6 kinase 1，S6K1 （S6K1） signaling pathway-related proteins were determined by Western blot assay. RESULTS Compared with group B，the skin inflammation in the left ear of the mice was significantly reduced in groups C，D and E，the serum levels of IgE and IL-4 were decreased significantly in groups D and E （P＜ 0.05），while the number of GRα positive cells and GRα protein expression were increased significantly （P＜0.05）； the protein levels of G protein inhibitory subunit 1 （Gαi1），Gαi3，phosphorylated S6K1 （p-S6K1） and phosphorylated AKT （p-AKT） were decreased significantly （P＜0.05）； the number of GRβ positive cells and protein expression of GRβ was decreased significantly in group E（P＜0.05）. Compared with group C，the skin inflammation in the left ear of the mice was almost clear away in group E，the serum levels of IgE and IL-4 were decreased significantly （P＜0.05）； the number of GRα positive cells and GRα protein expression were increased significantly in groups D and E （P＜0.05）； the protein levels of GRβ，Gαi1，p-S6K1 and p-AKT were all decreased significantly in groups D and E（P＜0.05）； and protein level of Gαi3 was decreased significantly in group E （P＜0.05）. CONCLUSIONS H. rhamnoides oil has an intervention effect on superantigen-induced glucocorticoid resistance of AD mice，which may be exerted by inhibition of the Gαi1/3-induced AKT/S6K1 signaling pathway.

Objective: To analyze the occurrence and risk factors of various occupational hazard incidents in China's power grid enterprises. Methods: A total of 4 191 workers from eight power grid enterprises in Jilin Province, Shandong Province, and Chongqing City were selected using a convenience sampling method. Their exposure in workplace and the occurrence of various occupational hazard incidents from 2018 to 2020 were investigated. Results: Among the participants, 71.7% were engaged in outdoor operations. The incidence rates of occupational hazard emergency, ranking from high to low, were electric ophthalmia, acute mountain sickness, heatstroke, electro-flash dermatitis, sunburn, cold injury, solar ophthalmia, and gas poisoning in confined space, with the rate of 42.3%, 42.3%, 38.1%, 24.3%, 17.4%, 16.5%, 10.0%, and 1.3%, respectively (P<0.01). The results of multivariate logistic regression analysis showed that workers in Jilin Province had a higher risk of cold injury compared to those in Shandong Province and Chongqing City (all P<0.01). Workers in Chongqing City had a higher risk of solar ophthalmia than those in Jilin Province (P<0.01). Workers in inspection and maintenance positions had a higher risk of heatstroke and sunburn compared to those in substation positions (all P<0.05). Power grid workers with protective systems in enterprises had a lower risk of sunburn and solar ophthalmia compared to those without protective systems (all P<0.01). The risks of sunburn and solar ophthalmia among power grid workers increased with age and daily outdoor working time (all P<0.05). Taking protective measures was a protective factor against heatstroke and cold injury (all P<0.01). Conclusion: Power grid workers face the risk of various occupational hazard incidents. Relevant organizations should conduct targeted preventive measures based on regional and worker characteristics, and ensure the implementation of protective systems in different work environments.

Objective:To evaluate the real-world short-term effectiveness of ixekizumab in the treatment of psoriasis, and to investigate factors influencing the effectiveness.Methods:Baseline data and short-term effectiveness evaluation results were retrospectively collected from patients with psoriasis, who received ixekizumab treatment in Department of Dermatology, Xiangya Hospital from November 2019 to September 2021. A descriptive analysis was performed on the baseline characteristics of patients, continuous data were described as median (lower quartile, upper quartile), and categorical data were described as percentages. Comparisons of disease severity scores before and after the treatment with ixekizumab were performed using Wilcoxon signed-rank test or paired McNemar test. Multivariable logistic regression analysis was conducted to explore factors influencing the effectiveness of 4-week ixekizumab treatment.Results:A total of 118 patients with psoriasis were included, including 94 males and 24 females, and their age [ M ( Q1, Q3) ] was 43.4 (32.5, 53.0) years; plaque psoriasis (99 cases, 83.9%) and severe psoriasis (72 cases, 68.6%) predominated among the 118 patients, and skin lesions were mainly located on the scalp (59/116, 50.9%). Among the 49 patients who had received 2-week ixekizumab treatment, 27 (55.1%) achieved a 50% improvement in the psoriasis area and severity index (PASI) score (PASI50) ; after 4-week treatment, 44 (89.8%), 30 (61.2%), 13 (26.5%) and 10 (20.4%) patients achieved PASI50/75/90/100 respectively, and their PASI scores (2.1 [1.1, 7.1]), involved body surface area (3.9% [0.5%, 14.5%]), dermatology life quality index scores (1.0 [0.0, 2.0]) and physician global assessment (PGA) scores (1.0 [1.0, 3.0]) were significantly lower than the corresponding scores at baseline (12.4 [8.8, 23.2], 22.0% [11.3%, 43.4%], 6.0 [3.0, 11.0], 4.0 [3.0, 5.0], respectively; all P < 0.001]. Multivariable logistic regression analysis showed that the baseline body mass index was significantly associated with the PASI75 response rate ( OR = 0.814, 95% CI: 0.659 - 0.958, P = 0.029) and the proportion of patients with PGA0/1 ( OR = 0.743, 95% CI: 0.562 - 0.917, P = 0.017) after 4-week ixekizumab treatment, and the baseline BSA score was significantly associated with the proportion of patients with PGA0/1 after 4-week ixekizumab treatment ( OR = 0.924, 95% CI: 0.870 - 0.968, P = 0.003) . Conclusion:The 4-week ixekizumab treatment significantly decreased the severity of psoriasis, and may be more effective in patients with lower disease severity and lower body mass index at baseline.

Objective:To evaluate the effects of split-filter dual-energy CT (SF-DECT) in improving image quality at low doses in the process of abdominal examinations for children.Methods:A preliminary study was conducted using child phantoms. Furthermore, 20 children aged 4-6 years were recruited prospectively for clinical validation from June 2020 to December 2020. Conventional single-energy CT (SECT) and SF-DECT were employed to scan the abdominal areas of the phantoms and children. Then, the CT values, image noise, contrast to noise ratios (CNRs), and image subjective scores of SF-DECT and SECT were compared under various doses (1, 2, 3, and 4 mGy).Results:For the phantoms under doses of 3 and 4 mGy, SF-DECT decreased the image noise by 18.9% and 23.6%, respectively, and increased the liver and kidney CNRs (CNR liv and CNR kid) by 12.8% and 31.9% at most, respectively, compared to SECT ( Z = 3.00, 5.17, P < 0.001). For children, SF-DECT decreased image noise ( Z = 4.64, P < 0.001) and increased CNR liv and CNR kid ( Z = 3.78, 3.39, P < 0.001). For both the phantoms and the children, the subjective scores of images scanned using the SF-DECT were higher than those scanned using the SECT ( Z = 1.96-3.80, P < 0.05). Conclusions:Compared with SECT, SF-DECT can improve the quality of children′s abdominal images. This technique has a certain prospect of optimizing abdominal CT for children. However, it is necessary to conduct in-depth clinical research to verify the result.

Despite being a common therapy for hepatocellular carcinoma (HCC), insufficient thermal ablation can leave behind tumor residues that can cause recurrence. This is believed to augment M2 inflammatory macrophages that usually play a pro-tumorigenic role. To address this problem, we designed d-mannose-chelated iron oxide nanoparticles (man-IONPs) to polarize M2-like macrophages into the antitumor M1 phenotype. In vitro and in vivo experiments demonstrated that man-IONPs specifically targeted M2-like macrophages and accumulated in peri-ablation zones after macrophage infiltration was augmented under insufficient microwave ablation (MWA). The nanoparticles simultaneously induced polarization of pro-tumorigenic M2 macrophages into antitumor M1 phenotypes, enabling the transformation of the immunosuppressive microenvironment into an immunoactivating one. Post-MWA macrophage polarization exerted robust inhibitory effects on HCC progression in a well-established orthotopic liver cancer mouse model. Thus, combining thermal ablation with man-IONPs can salvage residual tumors after insufficient MWA. These results have strong potential for clinical translation.

Objective: We investigated changes in the intestinal flora of children with Mycoplasma pneumoniae pneumonia (MPP). Methods: Between September 2019 and November 2019, stool samples from 14 children with MPP from The Fourth Hospital of Baotou city, Inner Mongolia Autonomous Region, were collected and divided into general treatment (AF) and probiotic (AFY) groups, according to the treatment of "combined Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus cereus tablets live". High-throughput 16S rDNA sequencing was used to identify intestinal flora. Results: Intestinal flora abundance and diversity in children with MPP were decreased. Both Shannon and Simpson indices were lower in the AF group when compared with healthy controls ( P < 0.05). When compared with healthy controls, the proportion of Enterorhabdus was lower in the AF group, while the proportion of Lachnoclostridium was higher ( P < 0.05). The proportion of Bifidobacteria and Akkermansia was lower in the AFY group but Enterococcus, Lachnoclostridium, Roseburia, and Erysipelatoclostridium proportions were higher. The proportion of Escherichia coli- Shigella in the AFY group after treatment was decreased ( P < 0.05). Conclusions The intestinal flora of children with MPP is disturbed, manifested as decreased abundance and diversity, and decreased Bifidobacteria. Our probiotic mixture partly improved intestinal flora disorders.
Child ; DNA, Ribosomal ; Escherichia coli ; Gastrointestinal Microbiome ; Humans ; Mycoplasma pneumoniae ; Pneumonia, Mycoplasma ; Technology

The present study focused on the potential mechanism of betulin (BT), a pentacyclic triterpenoid isolated from the bark of white birch (Betula pubescens), against chronic alcohol-induced lipid accumulation and metaflammation. AML-12 and RAW 264.7 cells were administered ethanol (EtOH), lipopolysaccharide (LPS) or BT. Male C57BL/6 mice were fed Lieber-DeCarli liquid diets containing 5% EtOH for 4 weeks, followed by single EtOH gavage on the last day and simultaneous treatment with BT (20 or 50 mg/ kg) by oral gavage once per day. In vitro, MTT showed that 0-25 mM EtOH and 0-25 μM BT had no toxic effect on AML-12 cells. BT could regulate sterolregulatory-element-binding protein 1 (SREBP1), lipin1/2, P2X7 receptor (P2X7r) and NOD-like receptor family, pyrin domains-containing protein 3 (NLRP3) expressions again EtOH-stimulation. Oil Red O staining also indicated that BT significantly reduced lipid accumulation in EtOH-stimulated AML-12 cells. Lipin1/2 deficiency indicated that BT might mediate lipin1/2 to regulate SREBP1 and P2X7r expression and further alleviate lipid accumulation and inflammation. In vivo, BT significantly alleviated histopathological changes, reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and triglyceride (TG) levels, and regulated lipin1/2, SREBP1, peroxisome proliferator activated receptor α/γ (PPARα/γ) and PGC-1α expression compared with the EtOH group. BT reduced the secretion of inflammatory factors and blocked the P2X7rNLRP3 signaling pathway. Collectively, BT attenuated lipid accumulation and metaflammation by regulating the lipin1/2-mediated P2X7r signaling pathway.

OBJECTIVE: To analyze the kinetic characteristics of lymphocyte subsets and myeloid-derived suppressor cell (MDSC) in patients who newly diagnosed intermediate- to high-risk aGVHD and treated with steroids-ruxolitinib as the first line therapy from a single-arm, open clinical trial (NCT04061876). METHODS: We prospectively observed the efficacy of 23 patients having intermediate- to high-risk aGVHD and treated with steroids-ruxolitinib as the first line therapy. The kinetic characteristics of lymphocyte subsets and MDSC were monitored, and then we compared them in steroids-ruxolitinib group (n=23), free-aGVHD group (n=20) and steroids group (n=23). RESULTS: Of the 23 patients, the CR rate was 78.26% (18/23) on day 28 after first-line treatment with steroids-ruxolitinib. On day 28 after treatment, patients had lower level of CD4⁺CD29⁺ T cells (P=0.08) than that of pre-treatment, whereas levels of other lymphocyte subsets in this study were higher than that of pre-treatment; CD4⁺CD29⁺ T cells in CR patients decreased, compared with refractory aGVHD patients. On day 28 of treatment, CD8⁺CD28^- T cells (P=0.03) significantly increased in patients with aGVHD than that in patients without aGVHD, so did CD8⁺CD28^- T / CD8⁺CD28⁺ T cell ratio (P=0.03). Compared with patients without aGVHD, patients with aGVHD had lower level of G-MDSC, especially on day 14 after allo-HSCT (P=0.04). Compared with pre-treatment, M-MDSC was higher in CR patients on day 3 and 7 post-treatment (P₃=0.01, P₇=0.03), e-MDSC was higher on day 28 post-treatment (P=0.01). Moreover, compared with CR patients, M-MDSC was lower in refractory aGVHD patients on day 3 post-treatment (P=0.01) and e-MDSC was lower on day 28 post-treatment (P=0.01). Compared with steroids group, MDSC in steroids-ruxolitinib group was higher, with the most significant difference in M-MDSC (P₃=0.0351; P₇=0.0142; P₁₄=0.0369). CONCLUSION We found that patients newly diagnosed intermediate- to high-risk aGVHD receiving first-line therapy with steroids-ruxolitinib achieved high response rate. Moreover, the novel first-line therapy has a small impact on the immune reconstitution of patients after allo-HSCT. Elevated MDSC might predict a better response in aGVHD patients receiving this novel first-line therapy. M-MDSC responded earlier to steroids-ruxolitinib than e-MDSC, G-MDSC.
Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Kinetics ; Myeloid-Derived Suppressor Cells ; Nitriles ; Pyrazoles ; Pyrimidines ; Retrospective Studies ; Steroids