Abstract: Objective　To compare and analyze the clinical characteristics, diagnosis, and treatment of different subtypes of severe influenza in neonates to provide a reference for the diagnosis and treatment of neonatal severe influenza. Methods A cohort of 40 neonates with severe influenza who were hospitalized in the neonatology ward of Children's Hospital Affiliated to Zhengzhou University between January 2019 to December 2023 were selected and divided into two groups based on the virus subtype: influenza A (n=23) and influenza B (n=17). A retrospective analysis was conducted to compare general information, clinical manifestations, auxiliary examinations, complications, and treatment outcomes of neonates with severe influenza A and B infection. Results The number of days of hospitalization was longer in cases of influenza A than that of influenza B. The proportion of neonates with severe influenza A who exhibited fever was higher than that for influenza B, and a higher percentage of those with fever had peak temperatures ranging from 38.1 ℃ to 39 ℃. Gastrointestinal symptoms, including vomiting and diarrhea leading to dehydration, were more evident in severe influenza B cases. The proportion of influenza A cases with abnormal creatine kinase-MB isoenzyme levels (>25 U/L) was higher than that of influenza B, and the differences were statistically significant (P<0.05). There were no significant differences between the two types of influenza in other clinical manifestations, the incidence of pneumonia/respiratory failure complications, peripheral blood leukocyte count and classifications, the proportion of abnormal aspartate aminotransferase (AST) (>40 U/L), alanine aminotransferase (ALT) (>40 U/L), and creatine kinase (CK) (>200 U/L), and lactate dehydrogenase (LDH) values (all P>0.05). In terms of treatment, neonates treated with Oseltamivir within 48 hours of onset mainly suffered from influenza A. Among those treated with Oseltamivir, the proportion of influenza A cases whose body temperature returned to normal within 24 hours was relatively higher, whereas, for those whose temperature returned to normal within 24-72 hours, the proportion was relatively higher in influenza B cases. These differences were statistically significant (all P<0.05). Conclusions Severe neonatal influenza usually occurs in winter and spring. After severe infection, fever is more obvious in neonates with influenza A, which is more likely to cause myocardial cell damage. Neonates with influenza A can be treated with Oseltamivir earlier and return to normal body temperature faster than those with influenza B after Oseltamivir treatment. Gastrointestinal symptoms are more common in neonates with severe influenza B.

Mycoplasma pneumoniae pneumonia is an important component of community-acquired pneumonia, which can cause severe extrapulmonary complications of digestive, cardiovascular, blood, urinary and other systems.Accurate and effective biomarkers are significant for the diagnosis and treatment of Mycoplasma pneumoniae pneumonia.Recent studies have shown that new biomarkers such as IL-35, IL-17, neutrophil to lymphocyte ratio(NLR) and S100 protein are involved in the development of Mycoplasma pneumoniae pneumonia.In order to provide reference for the clinical diagnosis and treatment of Mycoplasma pneumoniae pneumonia, this paper reviews the progress of new biomarkers in Mycoplasma pneumoniae pneumonia.

Objective:To compare the effect of extracorporeal membrane oxygenation(ECMO)on pulmonary transplantation(LTx)in patients with idiopathic pulmonary fibrosis(IPF)complicated with pulmonary hypertension(PH).Methods:From January 2017 to December 2020, clinical data were retrospectively reviewed for 112 IPF patients complicated with PH undergoing LTx assisted by venous ECMO(VV-ECMO group, n=68)or venous arterial ECMO(VA-ECMO group, n=44). Gender, age, mechanical ventilation time, oxygenation index, cold ischemic time, preoperative gender, age, smoking history, PO 2, PCO 2, PH degree, NYHA cardiac function grade, right cardiac function, ejection fraction(EF)and complications(hypertension & diabetes)of two groups were compared. Intraoperative approach, operative duration, ECMO transfer time, blood loss, blood transfusion, urine volume, postoperative blood transfusion, mechanical ventilation time, ICU stay time, re-thoracotomy, pulmonary infection, primary graft dysfunction(PGD)and renal insufficiency were recorded. And the effects of two different diversion modes on early postoperative complications and short-term outcomes of LTx were further analyzed by multiple factors. Cox proportional risk model was employed for comparing VV-ECMO and VA-ECMO flow patterns with factors related to recipient survival after transplantation. Results:The preoperative PO 2 of 58.3(51.3, 72.0)mmHg was significantly lower in VV-ECMO bypass group than that of 73.2(63.3, 96.8)mmHg in VA-ECMO group and the difference was statistically significant( P<0.006). Compared with VV-ECMO group, 24(54.5%), 15(34.1%)and 22(50.0%)had NYHA class Ⅲ, severe PH and preoperative right heart enlargement in VA-ECMO group respectively and the differences were statistically significant compared with 17(25.0%), 6(8.8%)and 16(23.5%)in VV-ECMO group( P<0.05 for all). No significant inter-group differences existed in postoperative PGD, postoperative mechanical ventilation time(≥3 d), pulmonary infection, postoperative thoracotomy ratio, postoperative renal insufficiency, ICU stay, hospital stay and other aspects( P>0.05). And 6-month postoperative survival rates of VV-ECMO and VA-ECMO groups were 80.9% and 61.4%, respectively and no significant inter-group difference existed in short-term survival rate(6 months)after adjustment by multivariate Cox regression model( P>0.05). Multivariate statistics indicated that the risk of delayed postoperative withdrawal was 14.452-fold higher in VV-ECMO group than in VA-ECMO group and the inter-group difference was statistically significant(95% CI: 2.448-85.323, P=0.03). Conclusions:No differences exist in postoperative complications or short-term survival rate between IPF recipients with mild PH on VV-ECMO mode and IPF recipients with severe PH on VA-ECMO mode. VV-ECMO flow reversal can delay the transplant back-off time.

Objective:To explore the clinical significance of serum Chromogranin A (CGA) level in predicting the prognosis of children with severe hand, foot, and mouth disease (HFMD) and complicating neurogenic pulmonary edema (NPE).Methods:A total of 162 patients with HFMD admitted in our hospital from January 2017 to December 2019 were enrolled in the study; and 40 age-matched healthy children were selected as controls. According to the disease severity and complication the patients were divided into three groups: mild group ( n=88), severe without NPE group ( n=46) and severe with NPE group ( n=28). In 72 severe HFMD patients 16 cases died (fatal group) and 56 cases survived (survival group) within 28 days of hospitalization. The serum CGA, LAC, GLU, WBC, PCT, IL-6, cTnT were measured in all subjects. SPSS 23.0 software was used for data analysis, and the receiver operating characteristic (ROC) curve was used to evaluate the various indicators for predicting the prognosis of severe HFMD combined with NPE. Results:The serum CGA, GLU, LAC, IL-6 and cTnT levels in severe HFMD group with NPE significantly higher than those in the other three group ( H=61.554, 79.031, 86.994, 36.477, 75.021, all P<0.05 ). The serum CGA, LAC, GLU and IL-6 levels in the fatal group were significantly higher than those in survival group ( Z=-6.094, -4.621, -4.283, -5.504, all P<0.05). There was no significant difference in the levels of WBC, PCT and cTnT between the survival group and the fatal group ( P>0.05). The area under the receiver operating curve (AUC) of serum CGA was 0.890 (95% CI: 0.833-0.947) for predicting the prognosis of patients and the best cut-off value was 120.59 μg/L. Conclusion:The detection of serum CGA levels may be beneficial for the early diagnosis of severe HFMD with NPE, and can be used as one of the predictors of death from severe HFMD.

A case with mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency(HMGCSD)was related and foreign and domestic reported cases were reviewed.The female proband was 7 months and 16 days old, and admitted to the hospital due to acute onset of " fever for 4 days, wheezing for 3 hours, dyspnea and moaning for 2 hours" . She was mainly manifested as encephalopathy, hepatomegaly, liver function damage, low ketone hypoglycemia, and hyperlipidemia.She died of respiratory and circulatory failure on the third day of hospitalization.Two compound he-terozygous variants in HMGCS2 gene were found by total exome sequencing, namely, c.1061+ 1 G> C and c. 476 G> T. HMGCSD could be diagnosed by gene detection in combination with clinical features of the patient. Thirteen literatures related to HMGCSD were collected, including 26 patients in total, with the age of onset ranging from 3 months to 6 years. The main cause of the disease was insufficient intake, mainly manifested as hypoglycemia accompanied by low ketone, hepatomegaly, liver damage, etc. A high level of urinary 4- hydroxy-6- methyl-2- pyrone might be a strong indicator of HMGCSD. Three died during the acute attack. Up to now, there were 32 mutations in HMGCS2 reported in 26 patients, and the main type was missense mutation. In this article, the second case of HMGCSD in China was identified, and 2 novel variants of HMGCS2 were found, which extended the clinical phenotype and mutation spectrum of HMGCSD.

Objective To explore the protective effect of magnesium sulfate on the nerve injury in severe hand, foot and mouth disease ( HFMD) caused by enterovirus A71 ( EV-A71) and to investigate its clinical and prognostic effects.Methods A total of 240 cases of severe HFMD with EV-A71 infection and nerve injury were enrolled.According to the random number table method, the patients were randomly divided into conventional treatment group (control group) and magnesium sulfate treatment group ( treatment group), with 120 cases in each group.The control group was given the routine treatment, and the treatment group was given the magnesium sulfate adjuvant treatment on the basis of routine treatment.The neurological symptoms and signs, clinical efficacy and prognosis were observed before and after treatment in the two groups.The blood and cerebrospinal fluid neuron-specific enolase ( NSE), S100-βprotein and neuropeptide Y ( NPY) were analyzed before and after treatment.The amplitude integrated electroencephalogram (aEEG) was used to monitor the abnormal recovery of EEG.The t-test was applied to analyze quantitative data, and the chi-square test was used for qualitative data comparison.Results Among children with severe HFMD, there were 83 cured cases, 29 improved cases and 8 ineffective cases in control group, with the total effective rate of 93.3%; while in the treatment group, 101 cases were cured, 18 cases were improved and 1 case was ineffective, the total effective rate was 99.2%.The therapeutic effects (Z＝2.918, P＝0.004) and the total effective rate ( χ2 ＝4.156, P＝0.041) were statistically significantly different between the two groups.Three days after treatment, the average levels of serum NSE, S100-βprotein and NPY in magnesium sulfate treatment group were significantly lower than those in control group (t＝-7.239,-10.020 and -11.053, respectively, all P＜0.01).Five days after treatment, the average levels of cerebrospinal fluid NSE, S100-β protein and NPY in magnesium sulfate treatment group were significantly lower than those in control group ( t＝-6.546,-13.308 and -10.258, respectively , all P＜0.01).After treatment, the neurological function score in treatment group was significantly lower than that in control group and that before treatment , and the differences were statistically significant ( t ＝-9.473 and 12.162, respectively, both P ＜0.01 ).The recovery time of the main symptoms and signs in treatment group was ( 2.33 ±0.76 ) d, which was significantly shorter than that of control group ([3.21 ±0.82] d), the difference was statistically significant (t＝-12.52, P＜0.05).The average length of hospital stay in treatment group was (5.79 ±1.42) d, which was shorter than that in control group ([ 6.71 ±1.46 ] d ), and the difference was statistically significant ( t＝-4.932, P＜0.05).Of the 240 children with severe HFMD, 194 (80.8%) patients had abnormal aEEG.Before treatment, the aEEG abnormal rates in control group and the magnesium sulfate treatment group were 79.2%(95 cases) and 82.5%(99 cases), respectively, there was no significant difference ( χ2 ＝0.430, P＞0.05); while after treatment for 3 days, 76 cases in treatment group returned to normal, and the recovery rate of aEEG was 76.8%, which was higher than that in control group (52.6%). The difference was statistically significant ( χ2 ＝12.406, P ＜0.05 ).Conclusions Magnesium sulfate adjuvant therapy can reduce the abnormal levels of NSE, S100-βand NPY in blood and cerebrospinal fluid, relieve clinical symptoms, shorten the course of disease and average length of hospital stay, improve the neurological function score, and promote the recovery of abnormal aEEG.Thus, it has neuroprotective effect on severe HFMD with nervous system lesion.

Objective To explore the relationship between organizational innovation atmosphere and nurses′job satisfaction in China. Methods 300 nurses were sampled during January-February 2018 using convenience sampling method, for a questionnaire survey with the general information questionnaire, nurse organizational innovation atmosphere scale and Minnesota satisfaction scale. Results 282 valid questionnaires were recovered out of 300 questionnaires issued, accounting for 94% of valid recovery rate. The score of organizational innovation atmosphere was 81.35 ± 14.51, and that of job satisfaction was 69.85 ± 14.91, proving a correlation between organizational innovation atmosphere and job satisfaction (P<0.01). A hierarchical regression analysis showed that, with demographic data under control, the regression model can explain 52% of the variance in nurses′ job satisfaction.Conclusions Organizational innovation atmosphere and nurses′ job satisfaction of the hospital are both at a higher level. Good organizational innovation atmosphere contributes to higher job satisfaction of nurses.

Objective: To investigate the changes and clinical significance of Caveolin-1, matrix metalloproteinase-9(MMP-9) and interleukin-1β(IL-1β)in cerebrospinal fluid of children with bacterial meningitis or viral encephalitis. Methods: Thirty-six cases of children with bacterial meningitis, 42 cases of children with viral encephalitis, and 20 cases of children with non-nervous system infection were selected from September 2016 to June 2018 at the Third Affiliated Hospital of Zhengzhou University.The levels of Caveolin-1, MMP-9 and IL-1β in cerebrospinal fluid were detected by using enzyme linked immunosorbent assay(ELISA). Results: Cerebrospinal fluid Caveolin-1, MMP-9 , IL-1β levels in the acute phase of bacterial meningitis were(49.06±8.96) ng/L, (134.79±18.88) μg/L, (100.02±14.67) μg/L, respectively, and (29.13±7.25) ng/L, (18.69±7.23) μg/L, (47.57±8.95) μg/L in recovery phase, which were higher than those of the controls[(11.18±2.24) ng/L, (11.53±3.54) μg/L, (39.75±7.08) μg/L)], and the differences were significant (all P<0.05). Cerebrospinal fluid Caveolin-1, MMP-9, IL-1β levels in the acute phase of viral encephalitis were (42.71±10.48) ng/L, (62.78±17.39) μg/L, (57.97±11.28) μg/L, respectively, and (29.13±7.25) ng/L, (18.69±7.23) μg/L, (47.57±8.95) μg/L in recovery phase, which were higher than those of controls, and the differences were significant (all P<0.05). The levels of Caveolin-1, MMP-9 and IL-1β in cerebrospinal fluid of bacterial meningitis group and viral encephalitis group were significantly higher than those of convalescent group (all P<0.05). The levels of Caveolin-1, MMP-9, IL-1β in cerebrospinal fluid of bacterial meningitis group were significantly higher than those in viral encephalitis group (all P<0.05) in the acute phase, and no significant difference was found in the recovery phase(all P>0.05). Cerebrospinal fluid Caveolin-1, MMP-9, IL-1β showed no significant difference among children with different severity of intracranial infection.Correlation analysis showed that there was a positive correlation between Caveolin-1, MMP-9 and IL-1 β levels in cerebrospinal fluid of acute in bacterial meningitis group and viral encephalitis group(Caveolin-1 and MMP-9: R²=0.239, P<0.05; MMP-9 and IL-1β: R²=0.766, P<0.01; Caveolin-1 and IL-1β: R²=0.245, P<0.05). Conclusions Caveolin-1, MMP-9 and IL-1 β involved in the pathogenesis of intracranial infection in children, and the effects of different pathogens on intracranial infection were different.

Objective: To observe the neuro-protective effect of Levocarnitine on severe hand, foot and mouth disease (HFMD) after enterovirus 71(EV71) infection, to preliminarily explore the possible mechanism preliminarily. Methods: One hundred and thirty-two children with EV71 infection and HFMD combined with serum S100 protein and neuronspecific enolase (NSE) abnormalities who were admitted to Children′s Hospital Affiliated to Zhengzhou University from March 2015 to July 2016 were enrolled in the study.They were divided into the routine group and the Levocarnitine group by the random number grouping method.The routine group (66 cases, including 32 males and 34 females, median age of 2 years and 3 months) was given symptomatic treatment such as antiviral therapy while the Levo-carnitine group (66 cases, including 36 males and 30 females, median age of 2 years and 5 months) was treated with Levocarnitine for neuroprotection on the basis of routine group.Forty healthy children (23 males and 17 females, median age of 2 years and 6 months) who were examined at the Children′s Hospital Affiliated to Zhengzhou University during the same period were selected as the healthy control group.The levels of S100, NSE, soluble apoptosis-related factors (sFas), soluble apoptosis-related factor ligands (sFasL), malondialdehyde (MDA), superoxide dismutase (SOD) in serum were compared between the healthy control group and children with HFMD.The levels of above-mentioned indexes in cerebrospinal fluid and serum, efficacy-related indicators such as duration of fever, white blood cell count on the 3^rd day of treatment, time to remission of nervous system symptoms, time of disease progression and critical conversion rate were compared between 2 groups of children with HFMD.The correlation between sFas, sFasL, MDA, SOD and S100, NSE was performed Results: (1) The levels of S100 [(0.38±0.16) μg/L vs. (0.06±0.23) μg/L], NSE [(43.70±8.80) μg/L vs. 10.10±3.60) μg/L], sFas [(6.61±1.86) μg/L vs. (3.88±1.22) μg/L], sFasL[(101.40±20.7) μg/L vs. (54.4±13.3) μg/L] and MDA[(11.98±2.54) nmol/L vs. (4.08±1.45) nmol/L] in serum of HFMD group were significantly higher than those of the healthy control group (t=-12.245, -22.895, -8.273, -12.803, -17.960, all P<0.05), while the SOD level [(57.10±10.40) kU/L vs. (70.3±14.4) kU/L] was significantly lower (t=5.457, P<0.05). (2) With the extension of treatment time for HFMD children in the two groups, S100 and NSE in cerebrospinal fluid, S100, NSE, sFas, sFasL and MDA in serum decreased, while SOD level increased.On the 3^rd and 7^th day after treatment, S100 (t₃=3.491, t₇=14.434), NSE (t₃=2.920, t₇=23.490) in cerebrospinal fluid, S100 (t₃=5.277, t₇=3.614), NSE (t₃=4.652, t₇=10.525), sFas (t₃=6.399, t₇=7.514), sFasL (t₃=11.155, t₇=8.804) and MDA (t₃=6.348, t₇=7.499) in serum of Levocarnitine group were significantly lower than those of routine group (all P<0.05), while SOD (t₃=3.162, t₇=-3.529) was significantly higher than that of routine group (P<0.05). (3) The relief time of neurological symptom in levocarnitine group was significantly shorter than that in the routine group [(1.23±0.65) d vs. (1.84±0.47) d], and WBC on the 3^rd day after treatment [(9.14±2.93)×10⁹/L vs. (7.12±2.58)×10⁹/L] and the progression time of the disease [(29.74±7.85) h vs. (17.36±8.73) h] were significantly better than the those in the routine group (t=-6.178, 4.204, 8.567, all P<0.05). The critical conversion rates of Levocarnitine group and the routine group were 7.58% and 18.18%, respectively, and the difference in critical conversion rate was not statistically significant (χ²=2.316, P>0.05). (4)There was a positive correlation between S100 and sFas, sFasL, MDA in children with HFMD (r=0.373, 0.735, 0.334, P<0.05). NSE was positively correlated with sFas and sFasL (r=0.479, 0.601, all P<0.05), while SOD and S100 were negatively correlated with NSE (r=-0.425, -0.460, all P<0.05). Conclusions Levocarnitine has good curative effect on severe HFMD in children infected by enterovirus EV71, which can effectively protect the cranial nerves.The mechanism may be related to scavenging oxygen free radicals and blocking nerve cell apoptosis.

Objective: To investigate the value of abnormal expression of HLA-DR on peripheral blood monocytes in evaluating the immune function status, clinical prognosis and severity of patients with hand, foot and mouth disease (HFMD). Methods: From June 2017 to October 2018, 100 cases of mild HFMD, 80 cases of severe HFMD, 32 cases of critical HFMD and 40 healthy children (control group) were recruited in this study. The patients were divided into two groups, lower DR group (DR-L, HLA-DR expression<30%) and normal DR group (DR-N, HLA-DR expression>30%) according to the HLA-DR expression on monocytes. Flow cytometry was used to detect the CD14⁺ monocytes expressing HLA-DR and the absolute count of lymphocyte subsets. Immunoturbidimetry was used to detect the levels of IgG, IgM and IgA in plasma samples. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the levels of IFN-γ and IL-10 in plasma samples. Pediatric critical illness score (PCIS) and the pediatric risk of mortality Ⅲ (PRISM Ⅲ) were used to estimate the severity of HFMD. Results: ① There were significant differences in HLA-DR expression on monocytes among children with mild, severe and critical HFMD (F=47.102, P<0.05). Patients with critical HFMD had the lowest HLA-DR expression (P<0.05). ② The numbers of CD14⁺ monocytes, CD3⁺ T cells, CD4⁺ T cells, CD8⁺ T cells, B cells and NK cells in peripheral blood of the DR-L group were significantly lower than those of the DR-N group and the normal group, especially in patients with severe or critical HFMD (P<0.05). ③ There was no significant difference in the level of IgG, IgA or IgM among the DR-L, DR-N and control groups (P>0.05). ④ Compared with the DR-N group, the DR-L group showed decreased IFN-γ level and increased IL-10 level in plasma (P<0.05). The ratio of IFN-γ/IL-10 of the DR-L group was lower than that of the DR-N group and control group (P<0.05). HLA-DR expression was negatively correlated with the concentration of IL-10 in plasma (r=-0.704, P<0.05), and positively correlated with the IFN-γ/IL-10 ratio (r=0.773, P<0.05). ⑤ Compared with the DR-N group, the DR-L group showed lower PCIS and higher PRISM Ⅲ. HLA-DR expression was positively correlated with PCIS (r=0.715, P=0.00) and negatively correlated with PRISM Ⅲ (r=-0.610, P=0.00). ⑥ The incidence of pulmonary edema, pulmonary hemorrhage and cardiopulmonary failure and the mortality of HFMD patients in the DR-L group were significantly higher than those in the DR-N group (P<0.05). Conclusions Patients with severe or critical HFMD had cellular immune dysfunction and abnormal HLA-DR expression on CD14⁺ monocytes. Assessing the expression of HLA-DR on monocytes could be used to evaluate the cellular immunity of patients with severe or critical HFMD. Lower expression of HLA-DR on CD14⁺ monocytes might be associated with severe HFMD and poor prognosis.