Sepsis is one of the common severe diseases caused by the dysregulated host response to infection， which seriously threatens the life and health of human beings all over the world. The incidence and mortality of the disease are extremely high， and it has always been an urgent problem to be solved in the field of acute and critical diseases. At present， anti-infection， fluid resuscitation， mechanical ventilation and other programs are most used in clinic to treat sepsis， but their poor prognosis and high cost and other issues remain to be resolved. Therefore， it is necessary to explore a new， efficient， safe and inexpensive drug and treatment model at this stage. The treatment of traditional Chinese medicine （TCM） is based on syndrome differentiation and holistic concept. It can effectively regulate the progression of sepsis， maintain the homeostasis of the body， and has fewer adverse reactions. It has achieved good clinical results. In recent years， a large number of studies have shown that TCM can reduce the inflammatory response by regulating the Toll-like receptor 4（TLR4） signaling pathway， thereby reducing the severity and mortality of sepsis patients. However， there is still a lack of systematic exposition of TCM regulating TLR4 signaling pathway in the treatment of sepsis. Therefore， this article summarizes the relationship between TLR4 signaling pathway and sepsis and the mechanism of TCM in the disease by searching and consulting relevant literature in recent years. It is found that some Chinese medicine monomers and active ingredients， Chinese medicine compounds and Chinese medicine preparations can effectively reduce systemic inflammatory response， repair organ damage and improve the prognosis of sepsis by inhibiting the activation of TLR4 signaling pathway. However， due to various limitations， some studies have directly focused on the differential expression and function of TLR4， ignoring the downstream molecular expression and phenotypic effects of TLR4. The alternative mechanism， relationship and specific molecular mechanism of the pathway are still unclear. There are problems such as unclear pharmacokinetics and unclear mechanism in the pro- and anti-inflammatory balance， which need to be further studied and explored in order to provide new ideas for the potential treatment and drug development for sepsis.

Objective:To analyze the clinical features and genetic basis for a child featuring elevated creatine kinase (CK).Methods:Next-generation sequencing (muscular dystrophy-related gene panel) was carried out for the proband. Candidate variants were verified by Sanger sequencing of the child and his parents.Results:The child was found to harbor compound heterozygous variants of the FKTN gene, including a missense c. 536G>C (p.R179T) variant from his father and a non-frameshift c. 1299_1301delGTG (p.W434del) variant from his mother. Both variants were predicted to be pathogenic. Conclusion:The compound heterozygous variants of the FKTN gene probably underlay the disease in this child. Above finding has expanded the mutation spectrum of congenital muscular dystrophy.

Objective:To investigate the effects of naturally occurring mild hypothermia and artificial mild hypothermia on the expression of high mobility group box 1(HMGB1) in lung tissues of septic mice.Methods:One hundred and twenty BALB/C mice (SPF level) were randomly numbered.Twelve mice with integer multiples of 10 were used as the normal control (NC) group, and the remaining 108 mice were chosen as the septic group.The septic mouse model was established by intra abdominal injection of lipopolysaccharide (LPS) 10 mg/kg.The NC group was given the same dose of normal saline.Anal temperature of the septic mice were measured 1 hour after the model was established successfully, and then were divided into naturally occurring mild hypothermia group and non-mild hypothermia group according to T≤36℃ and T>36℃.In the naturally occurring mild hypothermia group, the mice with T<34℃ were eliminated, and the remaining septic mice were randomly divided into the naturally occurring mild hypothermia(NOMH) observation group and the keep normothermia (KN) group.NOMH group was not given preheating intervention, while KN group was placed in an incubator to maintain the anal temperature between 36.0℃ and 37.5℃.Septic mice in the non-mild hypothermia group were randomly divided into the nonhypothermia (NH) observation group and the artificial mild hypothermia (ATMH) group.The NH group was not treated with hypothermia, while the ATMH group was treated with physical hypothermia, so that the anal temperature of the mice were maintained at 34℃-36℃.Four mice in each group were randomly selected at 6 and 12 hours after modeling, and the concentrations of tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) and HMGB1 in serum were detected by enzyme-linked immunosorbent assay(ELISA). At 12 hours, the survival rate of each group of mice was observed.Then 4 mice of each group were sacrificed and lung tissues were taken.The pathological changes of lung tissues were observed by hematoxylin-eosin (HE) staining, and the expression of HMGB1 in lung tissues was observed by immunohistochemical staining.Real time fluorescence quantitative PCR and Western blot were used to detect the relative expression of HMGB1 at mRNA and protein levels.Results:(1)Twelve hours after modeling, the survival number of NOMH group, ATMH group, KN group and NH group were 36(40), 6(11), 27(40), 4(11), respectively, and there were differences between the four groups (χ 2=32.286, P=0.002). Compared with the other three groups of septic mice, the survival rate was highest in the NOMH group (compared with ATMH group: χ 2=5.222, P=0.022; compared with the KN group: χ 2=6.050, P=0.013; and the NH group: χ 2=11.672, P=0.001), but the differences between the other two groups were not statistically significant (all P>0.05). (2)Compared with the NC group, the concentrations of serum TNF-α, IL-6 and HMGB1 of septic mice in each group were significantly increased at 6 h and 12 h (all P<0.05). Compared with NOMH group, the concentrations of TNF-α, IL-6 and HMGB1 in ATMH group, KN group and NH group were significantly increased at 6 h and 12 h(all P<0.05), and the concentrations of TNF-α, IL-6 and HMGB1 in NH group were the highest at all time points (all P<0.05). The concentrations of TNF-α at 12 h decreased compared with 6 h (all P<0.05), while the concentrations of IL-6 and HMGB1 at 12 h increased compared with 6 h (all P<0.05). (3)HE staining showed that the lung tissue damage were minimal in NOMH group, followed by ATMH group.(4)Immunohistochemical staining showed that the expression of HMGB1 protein was in order of NOMH group, ATMH group, KN group and NH group; (5)The relative expressions of HMGB1 protein in lung tissues of septic mice in NOMH group, ATMH group, KN group, and NH group was 0.280±0.013, 0.320±0.016, 0.340±0.018, and 0.380±0.014, respectively, and the relative expression level of HMGB1 mRNA was 4.86±0.22, 6.02±0.18, 6.26±0.20, and 7.98±0.28, respectively, compared with NC group (HMGB1 protein content was 0.240±0.013, and the relative expression level of HMGB1 mRNA was 2.21±0.12) significantly increased (all P<0.05). Cmpared with NOMH group, the relative expression levels of HMGB1 protein and HMGB1 mRNA in the lung tissues of the ATMH group, KN group and NH group were significantly increased(all P<0.05), with the highest expression level in the NH group(all P<0.05). Conclusion:Mild hypothermia may reduce lung tissue damage by down-regulating the expression of HMGB1 in lung tissues of septic mice, and the improvement of spontaneous mild hypothermia was more significant.

Objective:To investigate the diagnosis and treatment of congenital leukemia and the main factors affecting its prognosis.Methods:Clinical data of children with congenital leukemia admitted to Zhengzhou Children′s Hospital from July 2007 to December 2017 were retrospectively collected.Their clinical characteristics, chemotherapy and factors affecting their long-term survival were analyzed.Results:A total of 23 cases of congenital leukemia were collected, who mostly complained of " increased white blood cells, skin nodules and skin hemorrhage" . Among them, 10 cases abandoned the treatment, who all died according to the follow-up results.Among the 13 treated cases, 7 cases were male, and 6 were female.One of the 13 cases was a twin.Eight cases were acute myeloid leukemia, and 5 cases were acute lymphoblastic leukemia.One case did not perform the fusion gene test. MLL gene was positive in 2 cases and negative in 10 cases.No other fusion genes were detected.Karyotype analysis showed that 1 case was 21-trisomy and 12 cases had a normal karyotype.All 13 patients received symptomatic and/or reduced chemotherapy.The median follow-up time was 4 years and 11 months.Six cases recovered and 7 cases died during the follow-up.One case was diagnosed with acute lymphoblastic leukemia on the 6 th day after the birth in another hospital.He was not treated timely and came to Zhengzhou Children′s Hospital with general contract blocks at the age of 32 days.After checking, he was diagnosed with center leukemia and testicular leukemia.He developed a severe infection in the lung and brain after strong chemotherapy, and died even after the remote consultation with Lurie Children′s Hospital of Chicago.The other 6 cases died of severe infection and multiple organ injuries after chemotherapy, and no one died of leukemia relapse. Conclusion:Reduction chemotherapy may be an important treatment to children with congenital leukemia.

Objective:To investigate the clinical significance of serum resistin in juvenile idiopathic arthritis(JIA) patients.Methods:A prospective observational study was performed and 32 cases of patients with systemic onset JIA(SOJIA)(SOJIA group) in children admitted to the nephrorheumatology and outpatient were enrolled at Children′s Hospital of Shanghai between October 2013 and September 2015, 52 cases of other types(N-SOJIA group), and 33 cases of other rheumatic diseases(other rheumatic diseases group), 30 cases of children undergoing health checkups in the child health outpatient clinic(healthy control group)were involved as well.Serum resistin levels were measured by enzyme-linked immunosorbent assay(ELISA), and comprehensive analysis was carried out with clinical data and related laboratory findings.The basic data of gender, age and body mass index(BMI) of each group were collected, and the duration of disease in children in JIA group, rheumatoid factor, antinuclear antibody, white blood cell, hemoglobin, platelet, C reacting protein(CRP), erythrocyte sedimentation rate(ESR), clinical manifestations and current drug use were collected.Using the receiver operating characteristic(ROC)curve analysis of sensitivity and specificity resistin levels in diagnostic systemic juvenile idiopathic arthritis.Results:There was no statistically significant difference in the age, gender and BMI of children in SOJIA group, N-SOJIA group, other rheumatism group and healthy control group.Children in the SOJIA group and the N-SOJIA group had arthritis in clinical manifestations.Fever and rash were more common in the SOJIA group, and the difference was statistically significant ( P<0.01). Laboratory results showed that the sedimentation rates of white blood cells, CRP, and red blood cells were in the SOJIA group was significantly elevated.The antinuclear antibody was mainly found in the N-SOJIA group with a higher positive rate ( P<0.05). The mean serum resistin in the SOJIA group [(17.98±13.78) mg/L] was higher compared to the healthy control group [(1.84±1.66) mg/L], other rheumatic diseases group [(8.00±6.28) mg/L]and the N-SOJIA group [(9.86±6.11) mg/L], the differences were statistically significant ( F=21.625, P<0.01). Resistin was positively correlated with white blood cells and CRP( r=0.532, 0.351, all P<0.05), and had no correlation with BMI, hemoglobin, platelets, and ESR( r=0.059, -0.176, 0.152, 0.203, all P>0.05). Based on serum resistin≥5.55 mg/L as the positive threshold value, the area under ROC curve was 0.802, and the sensitivity and specificity in diagnosis of SOJIA was 96.9% and 49.6%, respectively. Conclusions:Serum resistin is increased in patients with JIA, especially in SOJIA increased significantly; Serum resistin can be used for the diagnosis of SOJIA, and ≥5.55 mg/L can be a suitable cut-off level.

Objective To explore the clinical feature, treatment and prognosis of hepatitis associated aplastic anemia (HAAA) in children. Method The clinical data of 5 children with HAAA were retrospectively analyzed. Results There were 5 patients (4 males and 1 female) with median age of 10 years (7~13 years ). The detection of hepatitis A, B, C, and E were all negative in these 5 children during their acute hepatitis period. In 2 children, parvovirus B19 antibody and EB virus were negative and the proportion of CD4+T cells and the ratio of CD4+/CD8+ were decreased, and the proportion of CD8+T cells was increased by T-lymphocyte subsets analysis. Three children were treated with anti-thymocyte globulin combined with cyclosporine, 2 of whom achieved complete remission and 1 died of pulmonary fungal infection. One child was treated with cyclosporine only and achieved partial remission. One child lost follow-up after giving up treatment. Conclusion HAAA in children can be caused by viral seronegative hepatitis, and usually has T lymphocyte immune disorders. Immunosuppressive therapy is effective. .

Objective To study the prognosis of hepatoblastoma (HB) in children.Methods Retrospective analysis on the clinical data and follow-up of children with HB admitted from September 2010 to February 2015 and sum up the clinical outcome and prognosis.Results Thirty-six children with HB (23 males and 13 females) were enrolled. The median age on diagnosiswas 20 months. Allthe36 patients received follow-up, the median follow-up time was 37 months (7~71 months).(1) Of the 36 patients, 8 died. The prognosis of patients with stageⅠorⅡwas signiflcantly better than those with stage Ⅲ or Ⅳ(P<0.05). The prognosis of patients with fetal type was signiflcantly better than those with other subtypes (P<0.05). (2) Serum AFP level of 35 newly diagnosed cases increased, AFP level of survivors returned to normal after treatment. Of the 8 died patients, 3 patients had AFP elevated when relapsed, 5 cases had a persistently high AFP level after adjuvant chemotherapy. The levels of LDH, CRP, and AST at diagnosis had signiflcant influence on the prognosis (P<0.05).Conclusions Serum AFP can be a monitoring indicator for recurrence and prognosis of hepatoblastoma. POG / CCG staging, pathology classiflcation are key points when assessing the prognosis of hepatoblastoma. The prognosis of patients with high levels of LDH, CRP, and AST might be worse.

Objective To investigate the role of regulatory B cells (Breg)in children with newly diagnosed immune thrombocytopenia (ITP).Methods A total of 35 newly diagnosed ITP children admitted to the Pediatric De-partment,the First Affiliated Hospital of Zhengzhou University from January to December 201 4 were recruited in this study,and another 20 gender -and age -matched healthy children from the Department of Medical Examination Center of the same Hospital were recruited as controls during the same period.Peripheral blood samples (3 mL from each chil-dren)were collected from all the newly diagnosed ITP children and the normal controls.Breg cells were tested by Flow Cytometry,and the expression levels of interleukin -1 0 (IL -1 0)and transforming growth factor -β1 (TGF -β1 ) mRNA were measured by real time fluorescence quantitative polymerase chain reaction.Meanwhile,the correlation be-tween Breg cells and the expression levels of IL -1 0,TGF -β1 mRNA were analyzed by Pearson correlation.Results The percentages of Breg cells in the peripheral blood of the newly diagnosed ITP children [(2.37 ±0.67)%]were sig-nificantly lower than those of the normal controls [(4.92 ±1 .32)%],and there was a significant difference (t =-7.47,P =0.000);the expression levels of IL -1 0 mRNA in the newly diagnosed ITP children(0.202 ±0.059) were significantly decreased compared with those of the normal controls(0.41 5 ±0.21 2),and there was a significant difference(t =-5.1 75,P =0.000);while the expression levels of TGF -β1 mRNA in the newly diagnosed ITP chil-dren(1 .587 ±0.823)were significantly increased than those in the normal controls(0.61 9 ±0.322),and there was a significant difference(t =4.081 ,P =0.001 ).There was a significant positive correlation between Breg cells and the ex-pression levels of IL -1 0 mRNA(rs =0.828,P <0.05),but no correlation between Breg cells and expression level of TGF -β1 mRNA was found (rs =0.527,P =0.1 1 7).Conclusions The decrease expressions of Breg cells can be found in the newly diagnosed ITP children,and the abnormal expression of Breg cells may play a key role in the immu-nological pathogenesis of the newly diagnosed ITP children.

OBJECTIVETo explore significance of serum soluble CD163(sCD163) and soluble CD25(sCD25) in diagnosis and guiding treatment of children with hemophagocytic lymphohistiocytosis (HLH).

METHODData of 42 cases of children with HLH, 32 cases of non-HLH children with infection presented to First Affiliated Hospital of Zhengzhou University pediatric clinic and ward were collected from December 2013 to December 2014. Twenty-four healthy children were enrolled into a normal control group in the same period.Peripheral venous blood specimens (3 ml) were taken from the children with HLH after fasting before treatment, two weeks after treatment and eight weeks after treatment.Peripheral venous blood specimens (3 ml) were also taken from children of non-HLH infected group and normal control group after fasting at the initial visit. Serum sCD163 and sCD25 levels in the peripheral blood in three groups were determined by ELISA. According to cause of disease, children with HLH were divided into infection-related HLH, tumor-related HLH, primary HLH and others; relationship between serum sCD163 and sCD25 level and cause of disease was analyzed.

RESULTSerum sCD163 of HLH group ((6 094 ± 2 769) µg/L) and serum sCD163 of non-HLH infection group ((2 174 ± 950) µg/L) were significantly higher than that of normal control group ((777 ± 256) µg/L), F=71.396, P<0.05), and the differences among groups were statistically significant (P<0.05); serum sCD25 of HLH group ((41 963 ± 31 821) ng/L) and serum sCD25 of non-HLH infection group ((6 700 ± 4 105) ng/L) were significantly higher than that of normal control group ((2 440 ± 1 870) ng/L, F=37.513, P<0.05).There was no statistically significant difference between the non-HLH infection group with the normal control group (P>0.05), and the difference between the remaining groups was statistically significant (P<0.05). And serum sCD163 and sCD25 level of HLH group had a positive linear correlation, and Pearson correlation coefficient r=0.742 (t=7.000, P<0.05). The difference of serum sCD163 and sCD25 level among the different cause of disease in HLH group was significant (P<0.05).Pairwise comparison showed that serum sCD163 and sCD25 level of tumor-associated HLH group significantly increased as compared with infection-associated HLH group (P<0.05), but the difference was not statistically significant between the other groups (all P>0.05). Serum sCD163 and sCD25 level of HLH group before treatment, 2 weeks and 8 weeks after treatment showed a statistically significant tendency of decrease (P<0.05). Seen from the ROC curve, when sCD163 cut-off point was 2 359.08 µg/L, the diagnostic sensitivity was 83.3%, and specificity was 83.9%.When sCD25 cut-off point was 14 901.024 ng/L, the diagnosis sensitivity was 76.2%, and specificity was 98.2%.

CONCLUSIONSerum sCD163 and sCD25 levels may be used for diagnosis of HLH.Dynamically monitoring of serum sCD163 and sCD25 level can help to determine deterioration of HLH and guide treatment.

Antigens, CD ; blood ; Antigens, Differentiation, Myelomonocytic ; blood ; Case-Control Studies ; Child ; Enzyme-Linked Immunosorbent Assay ; Humans ; Interleukin-2 Receptor alpha Subunit ; blood ; Lymphohistiocytosis, Hemophagocytic ; blood ; diagnosis ; therapy ; ROC Curve ; Receptors, Cell Surface ; blood ; Sensitivity and Specificity

ABSTRACTOBJECTIVE To detect and quantize four properties and five tastes of diaphoretic medicine with electronic nose and electronic tongue.METHODS 17 traditional Chinese medicine and 8 western medicinea total of 25were detected by e-lectronic nose.The similarities and differences of PCA and radar map were analyzed and the bitterness value of some drugs by electronic tonguewhich provided a quantitative basis for determination.RESULTS The PCAradar map and bitterness value of diaphoretic medicine displayed similarities and differences with western medicinewhich accorded with the smell.CONCLU-SION Electronic nose and electronic tongue can be used to detect and quantize four properties and five tastes of Chinese and western medicine.