Objective:To explore the clinical characteristics of children with septic shock and analyze the drug resistance of blood culture positive bacteria.Methods:The clinical data,positive blood culture strains and drug sensitivity results of 127 children with septic shock admitted to the Department of Intensive Care Medicine of Hunan Children's Hospital from September 2015 to August 2021 were retrospectively analyzed.Results:A total of 134 strains of bacteria or fungi were isolated from the blood culture samples of 127 children with septic shock,and gram-negative strains were the main ones,accounting for 67.16% (90/134).Haemophilus influenzae and Escherichia coli were the main gram-negative bacteria,accounting for 38.81% (52/134) and 20.15% (27/134)，respectively,while Streptococcus pneumoniae was the main gram-positive bacteria,accounting for 8.21% (11/134),and Candida albicans was the main fungus,accounting for 10.45% (14/134).The number of white blood cells,the levels of serum C-reactive protein,procalcitonin,venous blood sugar and arterial blood lactic acid in patients were all significantly higher than normal values,and the white blood cells count and neutrophil percentage in gram-positive bacterial infections were significantly higher than those with gram-negative bacterial infections and fungal infections( P<0.05).Procalcitonin increased most obviously when infected by gram-negative bacteria,and the difference was statistically significant ( P<0.05).Gram-positive strains were sensitive to vancomycin,teicoplanin,and linezolid,but only 50% of Streptococcus pneumoniae were sensitive to penicillin.Gram-negative strains had relatively high drug resistance,among which Klebsiella pneumoniae were only highly resistant to imipenem,cilastatin and levofloxacin,reaching 50%.Haemophilus influenzae was resistant to cephalosporins and β-amides enzyme antibiotic,and the drug sensitivity rate of lactamase antibiotics was high,with a resistance rate of 50% only to ampicillin,cefuroxime,amikacin,and compound sulfamethoxazole.There were not many fungal strains,and most antifungal drugs were effective against blood culture-positive fungi. Conclusion:The main pathogens of infection in children with septic shock are gram-negative bacteria,and have high resistance to general antibiotics.We should pay attention to their drug resistance when using antibiotics empirically.

Objective:To investigate the clinical features of pertussis in children and analyze the risk factors of severe pertussis.Methods:The clinical data of 248 children with pertussis hospitalized in Hunan Children′s Hospital from March 2018 to March 2022 were analyzed retrospectively.According to the age at admission, the patients were divided into two groups: ≤3 months and > 3 months.According to the patient′s condition, they were classified into ordinary group and severe group.According to the pathogens detected, the children were divided into single infection group and mixed infection group.The independent sample t-test, chi- square test were used to analyze the clinical indexes of the infants in above groups. Results:(1)Of 248 hospitalized children with pertussis, 204 cases (82.2%) were less than 1 year old, 92 cases (37.0%) had contact with a coughing family member before, and 169 cases (68.1%) were unvaccinated.Among 248 children, 193 cases (77.8%) had an elevated white blood cell count, and 145 cases (58.4%) had mixed infections.The most common pathogen was respiratory syncytial virus [29/248(11.6%)]. About 173 cases (69.7%) had concurrent pneumonia, and 35 cases (14.1%) had pulmonary consolidation.(2)Compared with the group > 3 months of age, more patients in the group ≤3 months of age had contact with a coughing family member before, and suffered from cyanosis, dyspnea, respiratory failure, heart failure and pertussis encephalopathy ( χ2=4.612, 20.810, 7.882, 16.617, 13.740, 7.846, all P<0.05). The proportions of patients in the group ≤3 months of age required intensive care unit(ICU) hospitalization and mechanical ventilation were higher than those in the group > 3 months of age ( χ2=14.810, 21.436, all P<0.05). The mortality of the group ≤3 months of age was higher than that of the group >3 months of age ( χ2=12.016, P<0.05). Children ≤3 months of age had a higher WBC level [(27.83±27.70)×10 9/L vs.(23.34±15.28)×10 9/L, t=22.244, P<0.001], longer duration of spasmodic cough [(16.56±9.33) d vs.(15.06±6.16) d, t=10.145, P=0.002] and longer hospitalization time [(11.47±10.48) d vs.(9.48±4.80) d, t=20.050, P<0.001] than those >3 months of age.(3)Compared with the ordinary group, a higher proportion of children in the severe pertussis group were under 3 months old, and had not been vaccinated against pertussis vaccine ( χ2=14.803, 4.475, all P<0.05). The ratio of patients with dyspnea, an lymphocyte count/neutral cell(LC/NC) ratio <1, mixed infections, lung consolidation and pleural effusion in the severe pertussis group was higher than that in the ordinary group ( χ2=116.940, 43.625, 13.253, 106.370, 11.874, all P<0.05). The patients in the severe pertussis group had a higher WBC [(61.66±29.63)×10 9/L vs.(18.83±10.00)×10 9/L, t=112.580, P<0.001] and a lower LC (0.494±0.186 vs.0.676±0.132, t=13.752, P<0.001) than those in the ordinary group.(4)Compared with the single infection group, the proportions of children with fever, dyspnea, fine moist lung rales, an LC/NC ratio <1, and lung consolidation were higher in the mixed infection group ( χ2=8.909, 6.804, 7.563, 8.420, 12.458, all P<0.05). More children in the mixed infection group required ICU hospitalization and mechanical ventilation than those in the single infection group ( χ2=11.677, 7.397, all P<0.05). The mixed infection group had higher respiratory failure and death rates than the single infection group ( χ2=7.980, 4.267, all P<0.05). Compared with the single infection group, the mixed infection group had a higher WBC level [(27.73±24.13)×10 9/L vs.(21.25±14.65)×10 9/L, t=13.318, P<0.001], longer hospitalization time [(11.593±9.010) d vs.(8.339±4.047) d, t=17.283, P<0.001], and a smaller LC ratio (0.626±0.165 vs.0.684±0.132, t=7.997, P=0.005). (5) Logistic regression analysis showed that age ≤3 months, peak WBC and dyspnea were risk factors of severe pertussis. Conclusions:Hospitalized pertussis children are prone to pneumonia and pulmonary consolidation.Patients aged ≤3 months with a large WBC and dyspnea easily develop into severe pertussis.Monitoring blood routine is helpful for judging the severity of the disease.Mixed infections increase the incidence of complications and can impair the treatment effect.

Objective:To investigate the predictive value of sputum heparin binding protein(HBP) in sepsis related acute respiratory distress syndrome(ARDS).Methods:This study was a prospective case-control study.A total of 134 children with sepsis who were admitted in PICU at Hunan Children′s Hospital from January 2020 to November 2021 were included, including 63 children who had completed fiberoptic bronchoscopy.The 63 children were divided into sepsis without ARDS group, sepsis with mild ARDS group, and sepsis with moderate to severe ARDS group according to the presence and severity of ARDS.Sputum was collected and HBP was detected in all children with sepsis when they were admitted to the hospital.The alveolar lavage fluid within 72 hours of admission was reserved for HBP.The levels of interleukin (IL)-6 and tumor necrosis factor (TNF)- α were detected, and the blood biochemistry, pulmonary imaging, pediatric critical case score and other data within 72 hours were collected.Results:(1) Among 63 children with fiberoptic bronchoscopy, 29 were in sepsis without ARDS group, 18 were in the sepsis with mild ARDS group, and 16 were in the sepsis with moderate to severe ARDS group.There was no significant difference in the pediatric critical case score and the location of primary infection focus among the three groups at admission.The primary infection focus was respiratory system in 36 cases, whose sputum HBP level was (42.1±9.8) ng/mL, and 27 children with other systems infection, whose sputum HBP level was (37.8±10.8) ng/mL, there was no significant difference between two groups ( t=1.65, P=0.104). (2) There were significant differences in sputum HBP, alveolar lavage fluid HBP, IL-6 and TNF-α levels among sepsis with mild ARDS group, sepsis with moderate and severe ARDS group and sepsis without ARDS group ( P<0.05). The sputum HBP of 34 children with sepsis combined with ARDS was positively correlated with alveolar lavage fluid HBP, IL-6, TNF-α levels and lung injury score, and negatively correlated with SpO 2/FiO 2 ( P<0.05). (3)Among the 34 children with sepsis combined with ARDS, the sputum HBP concentration of children with invasive ventilation was significantly higher than that of children with non-invasive ventilation ( P<0.05). The sputum HBP concentration in children with three or more organ damage was significantly higher than that of children with two or less organ damage ( P<0.05). The sputum HBP concentration of dead children was higher than that of surviving children ( P<0.05). (4) The area under curve of sputum HBP for predicting ARDS was 0.772 (95% CI: 0.655~0.889). When the cut-off point value of sputum HBP was 27.9 mU/L, whose sensitivity and specificity were 70.6% and 79.3%, respectively.The area under curve of sputum HBP for predicting moderate and severe ARDS was 0.793 (95% CI: 0.661~0.926). When the cut-off point value of sputum HBP was 51.55 mU/L, whose sensitivity and specificity were 81.3% and 76.6%, respectively. Conclusion:Sputum HBP is elevated in children with sepsis and ARDS, which is related with the severity of the disease.Sputum HBP has a good predictive value for the diagnosis and severity of children with sepsis and ARDS, and can be used as a clinically effective and convenient evaluation index for children with sepsis related ARDS.

Tolerogenic dendritic cells (tolDCs) facilitate the suppression of autoimmune responses by differentiating regulatory T cells (Treg). The dysfunction of immunotolerance results in the development of autoimmune diseases, such as rheumatoid arthritis (RA). As multipotent progenitor cells, mesenchymal stem cells (MSCs), can regulate dendritic cells (DCs) to restore their immunosuppressive function and prevent disease development. However, the underlying mechanisms of MSCs in regulating DCs still need to be better defined. Simultaneously, the delivery system for MSCs also influences their function. Herein, MSCs are encapsulated in alginate hydrogel to improve cell survival and retention in situ, maximizing efficacy in vivo. The three-dimensional co-culture of encapsulated MSCs with DCs demonstrates that MSCs can inhibit the maturation of DCs and the secretion of pro-inflammatory cytokines. In the collagen-induced arthritis (CIA) mice model, alginate hydrogel encapsulated MSCs induce a significantly higher expression of CD39⁺CD73⁺ on MSCs. These enzymes hydrolyze ATP to adenosine and activate A_2A/2B receptors on immature DCs, further promoting the phenotypic transformation of DCs to tolDCs and regulating naïve T cells to Tregs. Therefore, encapsulated MSCs obviously alleviate the inflammatory response and prevent CIA progression. This finding clarifies the mechanism of MSCs-DCs crosstalk in eliciting the immunosuppression effect and provides insights into hydrogel-promoted stem cell therapy for autoimmune diseases.

Background As a complex organic pollutant, polycyclic aromatic hydrocarbons (PAHs) exposure shares the common exposure characteristics of multiple hydroxyl metabolites. Most studies have analyzed independent effect of each PAHs metabolite and have adjusted for the potential confounding effects induced by other metabolites concomitantly, without considering possible interactions among them. Proper statistical methods are needed to study their toxic effects. Objective To explore the applicability of logistic regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) in evaluating the correlation between mixed exposures to exogenous chemicals and health outcomes, compare the advantages and limitations of the three models, and propose analytical strategies for evaluating the health effects of mixed chemical exposure for application in the analysis of the association between PAHs exposure and cognition. Methods Urine samples were collected of workers from a coke oven plant and a water treatment plant in Shanxi Province, who participated in their routine employee healthexamination. Mono-hydroxylated PAHs were detected by high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS), cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). A cut-off value of MoCA less than 26 was considered mild cognitive impairment (MCI). According to a predetermined inclusion and exclusion criteria, 1 051 cases were included in the final data analysis. Logistic regression, WQS regression, and BKMR were used to analyze the relationship between PAHs metabolites and MCI. Results The prevalence rate of reporting MCI among the 1 051 workers was 21.7% (228/1 051). The concentration of 2-hydroxynathalene (2-OHNAP) was the highest among the 11 PAHs metabolites with a median concentration of 0.30 μg·L⁻¹, followed by 9-hydroxyphenanthrene (9-OHPHE) (0.26 μg·L⁻¹). There were significant differences between the two groups in 2-OHNAP, 1-hydroxynaphthalene (1-OHNAP), 2-hydroxyfluorene (2-OHFLU), 9-OHPHE, 1-hydroxyphenanthrene (1-OHPHE), and 1-hydroxypyrene (1-OHPYR) (all Ps<0.05). In the logistic regression, 2-OHNAP and 2-OHPHE were associated with MCI, and the OR (95%CI) for reporting MCI was 1.28 (1.01-1.67) and 1.27 (1.00-1.72) for each 10-fold increase in 2-OHNAP and 2-OHPHE concentrations, respectively. In the WQS regression analysis, the WQS index was positively correlated with the prevalence rate of reporting MCI (OR=1.37, 95%CI: 1.10-1.72). In the BKMR analysis, compared with the median exposure levels of all chemicals, the overall effect was statistically significant when all PAHs metabolites concentrations were at or above their 30th percentile; when all exposures were at the 75th percentile, the risk of reporting MCI increased by 6%. Conclusion Based on the results of these three models, 2-OHNAP and 2-OHPHE are the most important factors related to cognitive. It is recommended to use a combination of traditional logistic regression and either WQS or BKMR to study the association between PAHs and MCI.

Objective:To evaluate the value and identify the prognosic factors of postoperative radiotherapy (PORT) in completely resected stage Ⅲ(pN 2) lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) wild-type who received adjuvant chemotherapy. Methods:Clinical data of 172 patients with stage Ⅲ(pN 2) EGFR wild-type lung adenocarcinoma who underwent radical resection and adjuvant chemotherapy from 2009 to 2016 were retrospectively analyzed. All patients received platinum-based adjuvant chemotherapy combining two drugs for>4 cycles, and divided into the PORT group and the non-PORT group. The survival rate was calculated by Kaplan- Meier method and log-rank test, and multivariate prognostic analysis was performed by Cox’s regression model. Results:Among 172 patients, the median overall survival (OS), 3-year and 5-year OS rates were 40 months, 55.9% and 28.3%, respectively. The median disease-free survival (DFS), 3-year and 5-year DFS rates were 17 months, 24.5% and 13.0%, respectively. DFS was significantly improved in the PORT group (29 months vs. 13 months, P=0.001), whereas OS did not significantly differ between two groups (51 months vs. 38 months, P=0.151). In subgroup analysis, DFS of patients with multistation N 2 or the number of N 2 metastases of≥3 or skip N 2 in the PORT group was significantly longer ( P<0.05), whereas PORT exerted no significant effect on OS ( P>0.05). Conclusions:For patients with completely resected stage Ⅲ(N 2) EGFR wild-type lung adenocarcinoma receiving adjuvant chemotherapy, PORT might increase DFS and have a trend toward longer OS. However, these findings remain to be validated by large sample size investigations.

Objective: To investigate the efficacy of alternative donor (AD) in the treatment of aplastic anemia (AA) in children. Methods: The clinical data of AA children who received AD HSCT in our center from Apr. 2010 to Dec. 2016 were retrospectively analyzed. The overall survival (OS) rate, implant success rate, incidence of acute and chronic graft-versus-host disease (GVHD) were statistically analyzed. Results: A total of 109 children with acquired AA, including 64 severe AA (SAA) , 32 very severe AA (VSAA) and 13 transfusion dependent non-severe AA (NSAA) , were recruited in this retrospective AD HSCT study, the median age was 6 (0.8-18) years old. Of them, 44 patients with 10/10 matched unrelated donor (MUD) , 44 patients with mismatched unrelated donor (MMUD) and 21 patients with mismatched related donor (MMRD) . All patients did not receive ATG before HSCT and the active infection was excluded. Except 3 patients suffered from a second graft failure (2 of them rescued by second HSCT) , 106/109 (97.2%) were engrafted with neutrophil and platelet recovery occurring at a median of 13 days (range, 9-19) and 16 days (range, 10-81) post-transplant. Until day 100 post transplantation, the incidence was 74.3% (81/109) for acute GVHD (aGVHD) and 39.4% (43/109) for grade Ⅱ-Ⅳ aGVHD, 30.7% (31/101) and 9.9% (10/101) for overall chronic GVHD (cGVHD) and moderate cGVHD, respectively, and nobody developed an extend cGVHD. After median follow up of 39 (0.7-103) months for all patients, 13 of 109 patients died. The estimated 5-year overall survival (OS) of the entire cohort was 88.1% (95%CI 81.1%-91.4%) with no difference among the MUD, MMUD and MMRD cohort (93.2%, 84.1% and 85.7%, respectively, P=0.361) . Conclusion These excellent outcomes suggest that unmanipulated AD PBSC is a good HSCT source for children with SAA. It’s reasonable to consider AD HSCT as first line therapy for SAA children without matched sibling donor. Better strategies are required to prevent GVHD.

Objective:To retrieve, evaluate and summarize the evidence of perioperative delirium prevention and care in elderly patients with fractures, and provide a basis for standardized prevention, care and management in clinical practice.Methods:The evidence was systematically retrieved from the Guidelines International Network, National Guidelines Library, Institute for Healthcare Optimization, UpToDate, BMJ Best Practice, Joanna Briggs Institute Center for Evidence Based Health Care, Cochrane Library, Yimaitong, CINAHL, Embase, BMJ, PubMed, CNKI , Wanfang, and China Biology Medicine disc (CBMdisc) , including guidelines, evidence summary, systematic reviews, best practice information, and randomized controlled trials (RCT) published up to December 1, 2019.Results:Finally, 15 articles were included, including 2 clinical decision-making, 5 guidelines, 5 systematic reviews, 2 summaries of evidence, and 1 RCT. The best evidence included 11 aspects such as delirium risk factor assessment, assessment tools, assessment timing, and qualifications of assessors, with a total of 25 pieces of evidence.Conclusions:Perioperative delirium in elderly patients with fractures has not yet gained the full attention from healthcare professionals. Medical institutions should establish standardized procedures for the evaluation, prevention, and care of elderly patients with fractures based on evidence-based evidence transformation, improve the health education system for medical staff and patients, formulate corresponding norms, improve the level of delirium care, and improve patients' outcomes.

Objective The study was to investigate the activation of tumor necrosis factor α (TNF-α) mRNA transcription and protein expression in peripheral blood and activation of signal path PI3K/AKT in patients with chronic heart failure. Methods From February 2015 to April 2018, 244 patients with heart failure in the cardiovascular department of our hospital were selected as heart failure group, while 244 healthy cases were enrolled as the control group at the same time. The peripheral blood samples of two groups were collected. We detected the transcription and protein expression of TNF-α mRNA and the activation of PI3K, AKT in peripheral blood. The left ventricular ejection fraction (LVEF) were measured in two groups. The correlations between influencing factors and LVEF were analyzed. Results The levels of PI3K, AKT in the heart failure group were higher than those in the control group. The differences were statistically significant respectively (P < 0.05). The mRNA relative content and protein content of TNF-α in peripheral blood mononuclear cells of heart failure group were higher compared with those of control group (P < 0.05). The LVEF of heart failure group was significantly lower than that of the control group (34.50 ± 6.33) ％ versus (55.60 ± 2.49) ％, P < 0.001). Among 244 patients with heart failure, Spearman correlation analysis showed that there were significant positive correlations between TNF-a mRNA and protein expression levels and the levels of PI3K, AKT respectively (P < 0.05). Multiple factors unconditional Logistic regression analysis showed that the TNF-α mRNA, protein expression and PI3K, AKT levels in peripheral blood were independent risk factors for LVEF (P < 0.05). Conclusion The expression levels of PI3K, AKT and TNF-α are all significantly increased in chronic heart failure patients, which could participate in the occurrence and development of heart failure.

Objective To observe the dynamic changes of plasma mitochondrial DNA (mtDNA) in children with sepsis in order to explore the clinical value of it in evaluation of these cases. Methods A total of 37 sepsis children admitted from June 2016 to January 2017 in the intensive care unit of Hunan Children's Hospital were enrolled for this prospectively study. And another 27 healthy children with similar age and gender were randomly selected as the control group. The venous blood samples were taken on the 1st, 3rd and 7th day after admission. Fluorescence quantitative PCR was used to detect the plasma mtDNA level. Meanwhile, the laboratory examinations such as detections of CRP and PCT were carried out. The diagnosis of sepsis and septic shock was based on Sepsis Criteria 3. Patients with genetic metabolic disease, liver and kidney disease, end-stage of tumors were excluded. Data of two groups were analyzed with Mann-Whitney U test. The sensitivity and specifi city were assessed by receiver operating curve (ROC). Results The plasma mtDNA level in the sepsis group 3 384.4(1 368.5, 6 857.5) pg/mL was higher than that in the healthy control group 1 904.8(1 267.9, 2 395.5) pg/mL with statistical signifi cance (P<0.05). The levels of plasma mtDNA in the sepsis multi-organ dysfunction group were higher than those in the single organ disorder group at day 1,3,7, with statistically signifi cant in three intervals (P <0.05). The level of plasma mtDNA in sepsis group were signifi cantly higher than those in non-shock group at day 1,3,7, with statistical difference (P <0.05). The plasma mtDNA levels in the non-survival group were higher than those in survival group 13 515.1(4 832.7,152 348.5)vs.2 780.0(1 226.8,5 261.2)on day 1;5 842.4(3 402.8,101 937.5)vs.1 450.5(710.6,2 481.6)on day 3 with statistical difference(P<0.05).there was no significant difference in mtDNA on day 7 was 1 045.1 vs.741.8(334.0,1 254.6)between survival group and non-survival group (P >0.05). In respect of diagnostic effi cacy of plasma mtDNA, PCT and CRP in predicting sepsis MODS, the largest area under the ROC curve of plasma mtDNA was 0.848 occurring on the 1st day, when the critical value was 2 176.2 pg/mL, the sensitivity and specifi city was 89% and 72%, respectively, and the difference was statistically signifi cant(P<0.01). When the critical value of CRP was 71.3 mg/L, the sensitivity and specifi city was 58% and 67% respectively. When the critical value of PCT was 7.24 ng/L, the sensitivity and specifi city were 84% and 61%, respectively. The plasma mtDNA peaked on day 1 followed by a downward changes. Conclusions The elevated level of plasma mtDNA in sepsis children was associated with organ dysfunction, indicating that it can be used as one of biomarkers for the diagnosis of sepsis MODS in children. The level of plasma mtDNA in children with sepsis was significantly high on the first and third day after admission, which was positively correlated with the severity of sepsis and it has certain value in assessment of the disease.