Objective To study the expression of Toll-like receptor 4(TLR4) in peripheral blood mononuclear cell (PBMCs) and serum interleukin-6(IL-6) in wheezing children under 5 years of age.Methods A total of 224 wheezing children under 5 years of age were divided into API(asthma predictive index)-positive (n=116) and API-negative groups (n=108).Serum level of IL-6 and TLR4 expression on CD14+ monocytes were measured after wheezing was stable for one month.TLR4 expression on CD14+ monoeytes was quantified via flow-cytometry.Serum level of IL-6 was detected by ELISA.Results Serum level of IL-6 and TLR4 expression on CD14+ monocytes of API-positive group were higher than API-negative group [LR4(％):34.9±10.0 vs.30.2± 8.8;IL-6(ng/L):46.4±15.1 vs.40.5±13.6].There was a significant positive correlation between the expression of TLR4 and the content of serum IL-6 in two groups of wheezing children(P＜0.05).Conclusion TLR4 may play a role in the pathogenesis of asthma through promoting the expression of IL-6.TLR4 may be a index to predicting asthma in wheezing children.

Objective To investigate the expression of Toll-like receptor 4 ( TLR4 ) and nuclear factor-κB ( NF-κB) in patients with critically severe hand, foot and mouth disease ( HFMD) and to evaluate the effects of esmolol intervention on those patients.Methods Fifty-two hospitalized children with critically severe HFMD in the Intensive Care Unit of Xuzhou Children′s Hospital were enrolled in the study from May 2014 to May 2015 and randomly divided into two groups, represented as group A and group B.Children in the group A were given routine treatment, while those in the group B were treated with esmolol in addition to the routine therapy.Thirty children with common HFMD were selected as disease control, and thirty healthy children were set up as normal control.Differences in the expression of TLR4, NF-κB, TNF-αand IL-6 among all children were comparatively analyzed.The levels of TLR4, NF-κB, TNF-αand IL-6 in children from groups A and B were detected after 24 hours, 72 hours and five days of treatment and the differences betweenthetwogroupswereanalyzed.Results (1)Comparedwiththechildrenfromdiseasecontroland normal control groups, those with critically severe HFMD showed significantly increased expression of TLR4, NF-κB, TNF-αand IL-6 (P<0.01).(2)No significant differences in the expression of TLR4, NF-κB, TNF-αand IL-6 were found between the two subgroups of children with critically severe HFMD before treat-ment (all P>0.05).The expression of TLR4, NF-κB, TNF-αand IL-6 in children from both subgroups were significantly decreased after receiving corresponding treatments for 24 hours, 72 hours and five days (all P<0.05).Compared with the children form group A, those from group B showed significantly decreased expression of NF-κB, TNF-αand IL-6 after 24 and 72 hours of corresponding treatments (all P<0.05).No significant difference in the expression of TLR4 was observed between the two subgroups after 24 and 72 hours of corresponding treatments (P>0.05).No significant differences in those observed indicators were found between the two subgroups after five days of treatments (all P>0.05).Conclusion The TLR4/NF-κB/proinflammatory factor pathway might play an important role in the development of critically severe HFMD.Treatment with esmolol could inhibit the expression of NF-κB, reduce the secretion of inflammatory factors and alleviate the inflammatory reaction during critically severe HFMD.

Objective:To study the effectiveness and safety of programmed cell death receptor 1(PD-1) monoclonal antibody combined with chemotherapy in the preoperative neoadjuvant treatment of stage ⅢA non-small cell lung cancer(NSCLC).Methods:A total of 65 patients with stage ⅢA NSCLC who underwent preoperative neoadjuvant treatment in our hospital from January 2019 to October 2020 were selected. According to the preoperative neoadjuvant treatment plan, they were divided into control group(31 cases) and observation group(34 cases). Patients in the control group were treated with albumin-bound paclitaxel and cisplatin for injection, and the patients in the observation group were treated with immunotherapy(carrelizumab/sintilizumab) on the basis of the control group, all underwent 2 cycles of preoperative neoadjuvant treatment. Compared the clinical efficacy of imaging, T lymphocyte subsets, drug side effects, surgical resection rate, major pathological remission(MPR), complete pathological remission(pCR) and postoperative complications of the two groups of patients, and analyzed the factors those affected MPR.Results:The clinical efficacy of PR and ORR of imaging in the observation group was better than that of the control group( P<0.05). The positive rate of CD3 + cells, the positive rate of CD4 + cells, the positive rate of CD8 + cells and the ratio of CD4 + /CD8 + cells in the observation group after treatment were higher than those in the control group( P<0.05). The drug toxicity of the observation group was higher than that of the control group in RCCEP/rash, abnormal thyroid function, and abnormal myocardial enzymes( P<0.05). Compared among the observation group(carrelizumab group/sintilizumab group), the toxicity of carrelizumab group was higher than that of sintilizumab group in RCCEP/skin rash, bone marrow suppression and abnormal myocardial enzymes( P<0.05). The MPR and pCR of the observation group were higher than those of the control group( P<0.05). There was no significant difference in surgical resection rate, surgical methods and postoperative complications between the two groups( P>0.05). The results of univariate analysis showed that ECOG score, pathological type, neoadjuvant treatment plan were related to MPR( P<0.05). The results of binary logistic regression analysis showed that ECOG score and neoadjuvant treatment plan were independent risk factors affecting MPR( P<0.05). Conclusion:PD-1 monoclonal antibody combined with chemotherapy can enable patients to obtain better MPR and pCR, and can improve the immune function of patients. But the side effects caused by immunotherapy drugs are worthy of attention, and the side effects are different between different immune drugs.

Objective To investigate the expression and clinical significance of Bcl-2/adenovirus E1B19kDa interacting protein 3 (BNIP3) in serum and cerebrospinal fluid (CSF) of patients with severe hand, foot and mouth disease (HFMD). Methods Ninety children with HFMD were classified into three groups with 30 in each group:critical group (clinical stage 3), severe group (clinical stage 2) and common group (clinical stage 1, excluding encephalitis with CSF and other examinations). Another thirty healthy children were randomly selected as the control group. The levels of BNIP3 in serum and CSF were detected before and after treatment. Moreover, serum neuro-specific enolase ( NSE) and S100B protein were also measured to analyze their correlation with BNIP3. Receiver operating characteristic ( ROC) curve was used to evaluate the prediction efficiency of BNIP3 for the severity of HFMD. Results The levels of serum BNIP3, S100B protein and NSE in the critical group were higher than those in the other three groups ( P<0. 01). CSF BNIP3 level in the critical group were significantly higher than that in the common and severe groups (P<0. 01). Serum BNIP3, S100B protein and NSE were significantly higher in the severe group than in common and control groups (P<0. 01). CSF BNIP3 was significantly increased in the severe group as compared with that in the common group (P<0. 01). After treatment, the levels of BNIP3, S100B protein and NSE in serum and BNIP3 in CSF were decreased in both critical and severe groups (P<0. 01). The lev-els of BNIP3 in serum and CSF were positively correlated with the level of S100B protein and NSE ( P<0. 01). Serum BNIP3 had the highest Youden value at the cut-off value of 3. 015μg/L, with a sensitivity of 83. 33％ and a specificity of 90. 00％, in the prediction of severe HFMD. CSF BNIP3 had the highest Youden value at the cut-off value of 1. 735 μg/L, with a sensitivity of 73. 33％ and a specificity of 93.33％, in the prediction of severe HFMD. Conclusions BNIP3 is involved in the pathological process of brain injury in children with severe HFMD. Detection of BNIP3 helps evaluate the severity and prognosis of HFMD.

Objective    To evaluate the efficacy and safety of programmed cell death receptor 1 (PD-1) inhibitor combined with chemotherapy in the preoperative neoadjuvant treatment of stage Ⅲ non-small cell lung cancer (NSCLC). Methods    The clinical data of 68 patients with stage Ⅲ NSCLC who underwent preoperative neoadjuvant treatment in our hospital from June 2019 to October 2020 were analyzed and divided into two groups according to a random number table. There were 34 patients in the control group including 19 males and 15 females with an average age of 59.41±4.77 years. In the observation group, there were 34 patients including 21 males and 13 females with an average age of 61.15±6.24 years. The patients in the control group were treated with albumin-bound paclitaxel and cisplatin for injection, and the patients in the observation group were treated with carrelizumab on the basis of the control group, and both groups received 2 cycles of preoperative neoadjuvant therapy. We compared the clinical efficacy of imaging, T lymphocyte subsets, drug side effects, surgical resection rate, major pathological remission (MPR), complete pathological remission (pCR) and postoperative complications of the two groups of patients, and analyzed the influencing factors for MPR. Results    The objective response rate (ORR) of imaging in the observation group (70.6%) was higher than that in the control group (38.2%, P<0.05). The positive rate of CD3+ cells, the positive rate of CD4+ cells, the positive rate of CD8+ cells and the ratio of CD4+/CD8+ cells in the observation group after treatment were higher than those in the control group (P<0.05). The drug toxicity of the observation group was higher than that of the control group in the reactive cutaneouscapillary endothelial proliferation (RCCEP)/rash, abnormal thyroid function, and abnormal myocardial enzymes (P<0.05). The MPR (66.7%) and pCR (51.9%) of the surgical observation group were higher than those of the surgical control group (MPR: 19.2%, pCR: 7.7%, P<0.05). There was no statistical difference in surgical resection rate and postoperative complications between the two groups (P>0.05). Univariate analysis showed that ECOG score, pathological type, neoadjuvant treatment plan and surgical resection were related to MPR (P<0.05). The results of binary logistic regression analysis showed that Eastern Cooperative Oncology Group (ECOG) score and neoadjuvant treatment plan were independent risk factors for MPR (P<0.05). Conclusion    The clinical efficacy of PD-1 inhibitor combined with chemotherapy in the preoperative neoadjuvant treatment of stage Ⅲ NSCLC patients is definite, and it can significantly improve the patients' MPR, pCR and cellular immune function, but the side effects caused by immunotherapy drugs need to be concerned.

Objective: To investigate the expression and clinical significance of Bcl-2/adenovirus E1B19kDa interacting protein 3 (BNIP3) in serum and cerebrospinal fluid (CSF) of patients with severe hand, foot and mouth disease (HFMD). Methods: Ninety children with HFMD were classified into three groups with 30 in each group: critical group (clinical stage 3), severe group (clinical stage 2) and common group (clinical stage 1, excluding encephalitis with CSF and other examinations). Another thirty healthy children were randomly selected as the control group. The levels of BNIP3 in serum and CSF were detected before and after treatment. Moreover, serum neuro-specific enolase (NSE) and S100B protein were also measured to analyze their correlation with BNIP3. Receiver operating characteristic (ROC) curve was used to evaluate the prediction efficiency of BNIP3 for the severity of HFMD. Results: The levels of serum BNIP3, S100B protein and NSE in the critical group were higher than those in the other three groups (P<0.01). CSF BNIP3 level in the critical group were significantly higher than that in the common and severe groups (P<0.01). Serum BNIP3, S100B protein and NSE were significantly higher in the severe group than in common and control groups (P<0.01). CSF BNIP3 was significantly increased in the severe group as compared with that in the common group (P<0.01). After treatment, the levels of BNIP3, S100B protein and NSE in serum and BNIP3 in CSF were decreased in both critical and severe groups (P<0.01). The levels of BNIP3 in serum and CSF were positively correlated with the level of S100B protein and NSE (P<0.01). Serum BNIP3 had the highest Youden value at the cut-off value of 3.015 μg/L, with a sensitivity of 83.33% and a specificity of 90.00%, in the prediction of severe HFMD. CSF BNIP3 had the highest Youden value at the cut-off value of 1.735 μg/L, with a sensitivity of 73.33% and a specificity of 93.33%, in the prediction of severe HFMD. Conclusions BNIP3 is involved in the pathological process of brain injury in children with severe HFMD. Detection of BNIP3 helps evaluate the severity and prognosis of HFMD.