Objective:To observe and verify the changes of transcriptome in hyperoxia-induced acute lung injury (HALI), and to further clarify the changes of pathways in HALI.Methods:Twelve healthy male C57BL/6J mice were randomly divided into normoxia group and HALI group according to the random number table, with 6 mice in each group. The mice in the normoxia group were fed normally in the room, and the mice in the HALI group was exposed to 95% oxygen to reproduce the HALI animal model. After 72 hours of hyperoxia exposure, the lung tissues were taken for transcriptome sequencing, and then Kyoto Encyclopedia of Genes and Genomes database (KEGG) pathway enrichment analysis was performed. The pathological changes of lung tissue were observed under light microscope after hematoxylin-eosin (HE) staining. Real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were used to verify the key molecules in the signal pathways closely related to HALI identified by transcriptomics analysis.Results:Transcriptomic analysis showed that hyperoxia induced 537 differentially expressed genes in lung tissue of mice as compared with the normoxia group including 239 up-regulated genes and 298 down-regulated genes. Further KEGG pathway enrichment analysis identified 20 most significantly enriched pathway entries, and the top three pathways were ferroptosis signaling pathway, p53 signaling pathway and glutathione (GSH) metabolism signaling pathway. The related genes in the ferroptosis signaling pathway included the up-regulated gene heme oxygenase-1 (HO-1) and the down-regulated gene solute carrier family 7 member 11 (SLC7A11). The related genes in the p53 signaling pathway included the up-regulated gene tumor suppressor gene p53 and the down-regulated gene murine double minute 2 (MDM2). The related gene in the GSH metabolic signaling pathway was up-regulated gene glutaredoxin 1 (Grx1). The light microscope showed that the pulmonary alveolar structure of the normoxia group was normal. In the HALI group, the pulmonary alveolar septum widened and thickened, and the alveolar cavity shrank or disappeared. RT-RCR and Western blotting confirmed that compared with the normoxia group, the mRNA and protein expressions of HO-1 and p53 in lung tissue of the HALI group were significantly increased [HO-1 mRNA (2 -ΔΔCt): 2.16±0.17 vs. 1.00±0.00, HO-1 protein (HO-1/β-actin): 1.05±0.01 vs. 0.79±0.01, p53 mRNA (2 -ΔΔCt): 2.52±0.13 vs. 1.00±0.00, p53 protein (p53/β-actin): 1.12±0.02 vs. 0.58±0.03, all P < 0.05], and the mRNA and protein expressions of Grx1, MDM2, SLC7A11 were significantly decreased [Grx1 mRNA (2 -ΔΔCt): 0.53±0.05 vs. 1.00±0.00, Grx1 protein (Grx1/β-actin): 0.54±0.03 vs. 0.93±0.01, MDM2 mRNA (2 -ΔΔCt): 0.48±0.03 vs. 1.00±0.00, MDM2 protein (MDM2/β-actin): 0.57±0.02 vs. 1.05±0.01, SLC7A11 mRNA (2 -ΔΔCt): 0.50±0.06 vs. 1.00±0.00, SLC7A11 protein (SLC7A11/β-actin): 0.72±0.03 vs. 0.98±0.01, all P < 0.05]. Conclusions:HALI is closely related to ferroptosis, p53 and GSH metabolism signaling pathways. Targeting the key targets in ferroptosis, p53 and GSH metabolism signaling pathways may be an important strategy for the prevention and treatment of HALI.

The extraordinary advantages associated with mRNA vaccines, including their high efficiency, relatively low severity of side effects, and ease of manufacture, have enabled them to be a promising immunotherapy approach against various infectious diseases and cancers. Nevertheless, most mRNA delivery carriers have many disadvantages, such as high toxicity, poor biocompatibility, and low efficiency in vivo, which have hindered the widespread use of mRNA vaccines. To further characterize and solve these problems and develop a new type of safe and efficient mRNA delivery carrier, a negatively charged SA@DOTAP-mRNA nanovaccine was prepared in this study by coating DOTAP-mRNA with the natural anionic polymer sodium alginate (SA). Intriguingly, the transfection efficiency of SA@DOTAP-mRNA was significantly higher than that of DOTAP-mRNA, which was not due to the increase in cellular uptake but was associated with changes in the endocytosis pathway and the strong lysosome escape ability of SA@DOTAP-mRNA. In addition, we found that SA significantly increased the expression of LUC-mRNA in mice and achieved certain spleen targeting. Finally, we confirmed that SA@DOTAP-mRNA had a stronger antigen-presenting ability in E. G7-OVA tumor-bearing mice, dramatically inducing the proliferation of OVA-specific CLTs and ameliorating the antitumor effect. Therefore, we firmly believe that the coating strategy applied to cationic liposome/mRNA complexes is of potential research value in the field of mRNA delivery and has promising clinical application prospects.

Objective: To analyze the short-time efficacy of empagliflozin in the treatment of glycogen storage disease type Ⅰb (GSD Ⅰb). Methods: In this prospective open-label single-arm study, the data of 4 patients were collected from the pediatric department in Peking Union Medical College Hospital from December 2020 to December 2022. All of them were diagnosed by gene sequencing and had neutropenia. These patients received empagliflozin treatment. Their clinical symptoms such as height and weight increase, abdominal pain, diarrhea, oral ulcer, infection times, and drug applications were recorded at 2 weeks, 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, and 15 months after treatment to assess the therapeutic effect. The liquid chromatography-tandem mass spectrometry method was used to monitor the changes in 1, 5-anhydroglucitol (1, 5AG) concentration in plasma. At the same time, adverse reactions such as hypoglycemia and urinary tract infection were closely followed up and monitored. Results: The 4 patients with GSD Ⅰb were 15, 14, 4 and 14 years old, respectively at the beginning of empagliflozin treatment, and were followed up for 15, 15, 12 and 6 months, respectively. Maintenance dose range of empagliflozin was 0.24-0.39 mg/(kg·d). The frequency of diarrhea and abdominal pain decreased in cases 2, 3, and 4 at 1, 2 and 3 months of treatment, respectively. Their height and weight increased at different degrees.The absolute count of neutrophils increased from 0.84×10⁹, 0.50×10⁹, 0.48×10⁹, 0.48×10⁹/L to 1.48×10⁹, 3.04×10⁹, 1.10×10⁹, 0.73×10⁹/L, respectively. Granulocyte colony-stimulating factor was gradually reduced in 1 patients and stopped in 3 patient. Plasma 1, 5 AG levels in 2 children were significantly decreased after administration of empagliflozin (from 46.3 mg/L to 9.6 mg/L in case 2, and from 56.1 mg/L to 15.0 mg/L in case 3). All 4 patients had no adverse reactions such as hypoglycemia, abnormal liver or kidney function, or urinary system infection. Conclusion: In short-term observation, empagliflozin can improve the symptoms of GSD Ⅰb oral ulcers, abdominal pain, diarrhea, and recurrent infection, also can alleviate neutropenia and decrease 1, 5AG concentration in plasma, with favorable safety.
Humans ; Child ; Child, Preschool ; Adolescent ; Prospective Studies ; Glycogen Storage Disease Type I/drug therapy* ; Neutropenia ; Abdominal Pain ; Diarrhea/drug therapy* ; Hypoglycemia

Objective To understand the distribution and changes in antimicrobial resistance of clinically isolated Pseudomonas aeruginosa(P.aeruginosa)in the member hospitals of Hunan Provincial Antimicrobial Resistance Surveillance System from 2012 to 2021.Methods Antimicrobial susceptibility testing by disk diffusion or automa-ted instrument was performed on clinical isolates.Testing results were determined according to the standards of 2022 edition from American Clinical Laboratory Standards Institute(CLSI).Statistical analysis was performed by WHONET 5.6 software.Data were analyzed by trend test(Cochran-armitage)and Chi-square test with SPSS.Results A total of 176 441 strains of P.aeruginosa were surveilled by Hunan Provincial Antimicrobial Resistance Surveillance System from 2012 to 2021.99.4％of the strains were isolated from hospitalized patients,and about 70％of the strains were isolated from respiratory specimens.8.4％of P.aeruginosa were from children(0-17 years old),91.6％were from adults.Antimicrobial susceptibility testing results showed that P.aeruginosa was most sensitive to polymyxin B over 10 years,with a resis-tance rate of less than 6％.Resistance rates to piperacil-lin,piperacillin/tazobactam,ceftazidime,cefepime,aztreonam,imipenem,amikacin,gentamicin,tobramycin,cip-rofloxacin,levofloxacin,and polymyxin B all showed downward trends.A total of 29 920 carbapenem-resistant P.aeruginosa(CRPA)strains were detected.The average isolation rate of CRPA in this province was 18.0％over 10 years.CRPA detection rate from adult was 18.5％,higher than that from children(12.3％),and both showing downward trends.Conclusion The resistance rate of clinically isolated P.aeruginosa in Hunan Province to most commonly used antimicrobial agents is decreasing.

Objective: To investigate the application value of computed tomography (CT) examination of lymph node short diameter in evaluating cardia-left gastric lymph node metastasis in thoracic esophageal squamous cell carcinoma (ESCC). Methods: A total of 477 patients with primary thoracic ESCC who underwent surgical treatment in the Affiliated Cancer Hospital of Zhengzhou University from January 2013 to December 2017 were collected. All of them underwent McKeown esophagectomy plus complete two-field or three-field lymph node dissection. Picture archiving and communication system were used to measure the largest cardia-left gastric lymph node short diameter in preoperative CT images. The postoperative pathological diagnosis results of cardia-left gastric lymph node were used as the gold standard. Receiver operating characteristic (ROC) curve was used to evaluate the efficacy of CT lymph node short diameter in detecting the metastasis of cardia-left gastric lymph node in thoracic ESCC, and determine the optimal cut-off value. Results: The median short diameter of the largest cardia-left gastric lymph node was 4.1 mm in 477 patients, and the largest cardia-left gastric lymph node short diameter was less than 3 mm in 155 cases (32.5%). Sixty-eight patients had cardia-left gastric lymph node metastases, of which 38 had paracardial node metastases and 41 had left gastric node metastases. The lymph node ratios of paracardial node and left gastric node were 4.0% (60/1 511) and 3.3% (62/1 887), respectively. ROC curve analysis showed that the area under the curve of CT lymph node short diameter for evaluating cardia-left gastric lymph node metastasis was 0.941 (95% CI: 0.904-0.977; P<0.05). The optimal cut-off value of CT examination of the cardia-left gastric lymph node short diameter was 6 mm, and the corresponding sensitivity, specificity and accuracy were 85.3%, 91.7%, and 90.8%, respectively. Conclusion: CT examination of lymph node short diameter can be a good evaluation of cardia-left gastric lymph node metastasis in thoracic ESCC, and the optimal cut-off value is 6 mm.
Humans ; Esophageal Squamous Cell Carcinoma/pathology* ; Cardia/surgery* ; Esophageal Neoplasms/pathology* ; Lymphatic Metastasis/pathology* ; Lymph Nodes/pathology* ; Lymph Node Excision ; Tomography, X-Ray Computed/methods* ; Esophagectomy/methods* ; Retrospective Studies

Objective: To investigate the application value of computed tomography (CT) examination of lymph node short diameter in evaluating cardia-left gastric lymph node metastasis in thoracic esophageal squamous cell carcinoma (ESCC). Methods: A total of 477 patients with primary thoracic ESCC who underwent surgical treatment in the Affiliated Cancer Hospital of Zhengzhou University from January 2013 to December 2017 were collected. All of them underwent McKeown esophagectomy plus complete two-field or three-field lymph node dissection. Picture archiving and communication system were used to measure the largest cardia-left gastric lymph node short diameter in preoperative CT images. The postoperative pathological diagnosis results of cardia-left gastric lymph node were used as the gold standard. Receiver operating characteristic (ROC) curve was used to evaluate the efficacy of CT lymph node short diameter in detecting the metastasis of cardia-left gastric lymph node in thoracic ESCC, and determine the optimal cut-off value. Results: The median short diameter of the largest cardia-left gastric lymph node was 4.1 mm in 477 patients, and the largest cardia-left gastric lymph node short diameter was less than 3 mm in 155 cases (32.5%). Sixty-eight patients had cardia-left gastric lymph node metastases, of which 38 had paracardial node metastases and 41 had left gastric node metastases. The lymph node ratios of paracardial node and left gastric node were 4.0% (60/1 511) and 3.3% (62/1 887), respectively. ROC curve analysis showed that the area under the curve of CT lymph node short diameter for evaluating cardia-left gastric lymph node metastasis was 0.941 (95% CI: 0.904-0.977; P<0.05). The optimal cut-off value of CT examination of the cardia-left gastric lymph node short diameter was 6 mm, and the corresponding sensitivity, specificity and accuracy were 85.3%, 91.7%, and 90.8%, respectively. Conclusion: CT examination of lymph node short diameter can be a good evaluation of cardia-left gastric lymph node metastasis in thoracic ESCC, and the optimal cut-off value is 6 mm.
Humans ; Esophageal Squamous Cell Carcinoma/pathology* ; Cardia/surgery* ; Esophageal Neoplasms/pathology* ; Lymphatic Metastasis/pathology* ; Lymph Nodes/pathology* ; Lymph Node Excision ; Tomography, X-Ray Computed/methods* ; Esophagectomy/methods* ; Retrospective Studies

Objective: To analyze the blood pressure measurement of Chinese adult residents in 2018 and provide a scientific basis for early detection and intervention of hypertension. Methods: In 2018, China Chronic Disease and Risk Factor Surveillance were conducted in 298 counties (districts) of 31 provinces (autonomous regions, municipalities) across the country, using a multi-stage stratified cluster random sampling method to survey permanent residents aged 18 years and above. We selected 184 509 people and carried out a face-to-face questionnaire survey and body measurement method to collect demographic data, major chronic diseases, and blood pressure measurement information of the survey subjects. Blood glucose and blood lipid-related indicators were obtained by laboratory testing. There were 170 551 adult residents included in the study after excluding abnormal and missing data for key variables. After complex weighting, blood pressure detection rates and detection times in people with different blood pressure levels and other diseases were analyzed. SAS 9.4 software was used to perform the χ²-test and trend test. Results: Among adult residents in China, the proportions of those with normal blood pressure, commonly recognized 'high' blood pressure, and newly detected hypertension who had their blood pressure tested within three months were 44.4%, 50.4%, and 52.6%, respectively. The proportions all appeared higher in women than in men (all P<0.05), in urban than in rural areas (all P<0.05), and showed an increasing trend with age (all P<0.001); The proportion of these three populations who had never had their blood pressure measured was 27.6%, 24.2%, and 23.5% respectively. The proportion of people with diagnosed hypertension who had their blood pressure tested within seven days was 44.0%, 51.4% in urban areas, higher than 37.7% in rural areas (P<0.001), and the proportion of people who had their blood pressure tested increased with education, per capita annual income and BMI (all P<0.001). Conclusions: The behavior of regular self-monitoring of blood pressure among adult residents in China still needs to be improved, especially among men and rural areas. Relevant health promotion and education should be strengthened. More targeted policies and measures should be developed to improve blood pressure measurement behavior in people with normal high blood pressure and other high-risk groups to control elevated blood pressure effectively.
Adult ; Asian People ; Blood Pressure ; Blood Pressure Determination ; China/epidemiology* ; Female ; Humans ; Hypertension/epidemiology* ; Male ; Rural Population

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

Objective:To investigate the knowledge, attitudes, and practices (KAP) of pulse oximetry among pediatric healthcare providers in China and analyze the factor influencing the KAP.Methods:A self-developed questionnaire was used for an online research on the KAP of 11 849 pediatric healthcare providers from 31 provinces, autonomous regions, and municipalities of China from March 11 to 14, 2022.The factors influencing the KAP of pulse oximetry among pediatric healthcare providers were examined by Logistic regression. Results:The scores of KAP, of pulse oximetry were 5.57±0.96, 11.24±1.25 and 11.19±4.54, respectively.The corresponding scoring rates were 69.61%, 74.95%, and 55.99%, respectively. Logistic regression results showed that the gender and working years of pediatric healthcare providers, the region they were located, and whether their medical institution was equipped with pulse oximeters were the main factors affecting the knowledge score (all P<0.05). Main factors influencing the attitude score of pediatric healthcare providers included their knowledge score, gender, educational background, working years, region, medical institution level, and whether the medical institution was equipped with pulse oximeters (all P<0.05). For the practice score, the main influencing factors were the knowledge score, gender, age, and whether the medi-cal institution was equipped with pulse oximeters (all P<0.05). Conclusions:Chinese pediatric healthcare providers need to further improve their knowledge about and attitudes towards pulse oximetry.Pulse oximeters are evidently under-used.It is urgent to formulate policies or guidelines, strengthen education and training, improve knowledge and attitudes, equip more institutions with pulse oximeters, and popularize their application in medical institutions.

OBJECTIVE: To analyze the clinical features of acute myeloid leukemia (AML)/high-risk myelodysplastic syndrome (MDS) patients aged over 60 years old. METHODS: The clinical data of 61 elderly newly diagnosed patients with AML and high-risk MDS who submitted to the Department of Hematology/Oncology of the First Affiliated Hospital of Tsinghua University from January 2009 to April 16, 2021 were retrospectively analyzed. These patients were divided into chemotherapy group (45 cases) and supportive treatment group (16 cases). The overall survival (OS) was analyzed by Kaplan-Meier method, and the prognostic factors of survival were analyzed by multivariate Cox regression. RESULTS: After 2 cycles of induction chemotherapy, the complete remission (CR) rate was 37.8% (17/45), and overall response rate was 62.2% (28/45) in the chemotherapy group. The median OS in the chemotherapy group and supportive treatment group was 11.3 (0.07-43) and 1.6 (0.33-7.72) months, respectively (P<0.001). The median OS in patients who reached CR or did not reach after 1 cycle of induction chemotherapy was 19.8 (10-30.63) and 8.17 (0.07-43) months, respectively (P<0.05), while after 2 cycles was 22.7 (4.2-43) and 7.26 (0.07-26) months, respectively (P<0.001). Univariate analysis showed that age > 80 years old, CCI score > 2, PS score > 2 and supportive treatment were the adverse prognostic factors for OS. Further multivariate analysis suggested that chemotherapy was the only independent prognostic factor for OS (HR=0.140, 95%CI: 0.048-0.409, P<0.001). In the chemotherapy group, univariate analysis showed that CCI score > 2 and failure to reach CR after induction chemotherapy were poor prognostic factors. Multivariate analysis showed that CCI score > 2 (HR=0.139, 95%CI: 0.050-0.384, P<0.001) and failure to achieve CR after induction chemotherapy (HR=0.103, 95%CI: 0.041-0.259, P<0.001) were the adverse prognostic factors for OS. The patients were tolerant to side-effect of chemotherapy. CONCLUSION Appropriate chemotherapy can prolong the survival of elderly patients with AML and high-risk MDS.
Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Humans ; Induction Chemotherapy ; Leukemia, Myeloid, Acute/drug therapy* ; Middle Aged ; Prognosis ; Remission Induction ; Retrospective Studies