Objective:To analyze the clinical features and inflammatory factors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in children,and to explore the early prediction methods of RMPP.Methods:Children with Mycoplasma pneumoniae who were hospitalized in the Respiratory Department of Qingdao Women and Children's Hospital from January 2022 to December 2023 and underwent electronic bronchoscopic lavage were selected as the study objects.They were divided into RMPP group and GMPP group according to the severity of illness.Clinical features and inflammatory factors between the two groups were compared,and the risk factors of RMPP were analyzed by multivariate Logistic regression model.Receiver operating characteristic (ROC) curve was plotted to evaluate the predictive values.Results:A total of 232 children were included,including 114 cases in RMPP group and 118 cases in GMPP group.Compared with GMPP group,children in RMPP group were younger,had longer fever time and hospitalization time,and had higher levels of blood C-reactive protein,D-dimer,and lactate dehydrogenase(LDH),as well as higher proportion of pleural effusion observed in imaging.The cytokine levels of interferon(IFN)-α,IFN-γ,interleukin(IL)-2,IL-5,IL-6,IL-1β,IL-10 and IL-17 in bronchoalveolar lavage fluid (BALF) were higher in RMPP group.The differences were statistically significant (all P<0.05).Multivariate Logistic analysis showed that longer hospitalization time and fever time，increased levels of D-dimer and LDH in plasma,increased IL-5,IL-6,IL-17,IL-1β and IFN-α in BALF were independent risk factors for RMPP (all P<0.05).The area under ROC curve of hospitalization time,fever time,D-dimer,LDH,IL-5,IL-6,IL-17 and IL-1β were 0.669,0.857,0.606,0.811,0.686,0.890,0.647 and 0.691，respectively(all P<0.05).Among these,the diagnostic value of fever time,LDH and IL-6 was higher.The optimum critical value of fever time was 6.5 days,with a sensitivity of 97.40% and a specificity of 64.90%.The optimum critical value of LDH was 420.77U/L,with a sensitivity of 64.90% and a specificity of 89.50%.The optimal critical value of IL-6 was 293.04pg/mL,with a sensitivity of 91.2% and a specificity of 82.5%. Conclusion:Children with RMPP have long fever time and high inflammatory index.When children with Mycoplasma pneumoniae pneumonia have fever time >6.5 days,blood LDH>420.77 U/L and IL-6>293.04 pg/mL in BALF,it is helpful to identify RMPP at an early stage.

Objective:To analyze the clinical features and inflammatory factors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in children,and to explore the early prediction methods of RMPP.Methods:Children with Mycoplasma pneumoniae who were hospitalized in the Respiratory Department of Qingdao Women and Children's Hospital from January 2022 to December 2023 and underwent electronic bronchoscopic lavage were selected as the study objects.They were divided into RMPP group and GMPP group according to the severity of illness.Clinical features and inflammatory factors between the two groups were compared,and the risk factors of RMPP were analyzed by multivariate Logistic regression model.Receiver operating characteristic (ROC) curve was plotted to evaluate the predictive values.Results:A total of 232 children were included,including 114 cases in RMPP group and 118 cases in GMPP group.Compared with GMPP group,children in RMPP group were younger,had longer fever time and hospitalization time,and had higher levels of blood C-reactive protein,D-dimer,and lactate dehydrogenase(LDH),as well as higher proportion of pleural effusion observed in imaging.The cytokine levels of interferon(IFN)-α,IFN-γ,interleukin(IL)-2,IL-5,IL-6,IL-1β,IL-10 and IL-17 in bronchoalveolar lavage fluid (BALF) were higher in RMPP group.The differences were statistically significant (all P<0.05).Multivariate Logistic analysis showed that longer hospitalization time and fever time，increased levels of D-dimer and LDH in plasma,increased IL-5,IL-6,IL-17,IL-1β and IFN-α in BALF were independent risk factors for RMPP (all P<0.05).The area under ROC curve of hospitalization time,fever time,D-dimer,LDH,IL-5,IL-6,IL-17 and IL-1β were 0.669,0.857,0.606,0.811,0.686,0.890,0.647 and 0.691，respectively(all P<0.05).Among these,the diagnostic value of fever time,LDH and IL-6 was higher.The optimum critical value of fever time was 6.5 days,with a sensitivity of 97.40% and a specificity of 64.90%.The optimum critical value of LDH was 420.77U/L,with a sensitivity of 64.90% and a specificity of 89.50%.The optimal critical value of IL-6 was 293.04pg/mL,with a sensitivity of 91.2% and a specificity of 82.5%. Conclusion:Children with RMPP have long fever time and high inflammatory index.When children with Mycoplasma pneumoniae pneumonia have fever time >6.5 days,blood LDH>420.77 U/L and IL-6>293.04 pg/mL in BALF,it is helpful to identify RMPP at an early stage.

Objective To investigate the relationship between platelet/hemoglobin ratio(PHR)and the severity of diabetic foot ulcer(DFU)and its predictive value for DFU progression.Methods A retrospective study was performed in 345 DFU patients treated in Department of Endocrinology,the First Affiliated Hospital of Army Medical University from March 2018 to March 2023.Their general demographic information was obtained,and the results of laboratory tests,including hemoglobin Alc(HbA1c),fasting plasma glucose(FPG),biochemical and related blood routine indicators were collected.According to Wanger grading,the patients were assigned into mild(n=145)and severe ulcer groups(n=200).The demographic data and clinical parameters were compared between the 2 groups.Multivariate logistic regression model was applied to identify the independent predictors for severe ulcer in DFU,and receiver operating characteristic(ROC)curve was plotted to evaluate the predictive performance of PHR for DFU progression.Results The severe ulcer group presented remarkable increases in male proportion,HbA1c and FPG levels,platelet(PLT)count and PHR when compared with the mild ulcer group(P＜0.05).Multivariate logistic regression analysis revealed that PHR and male were independent risk factors,while,HDL-C was a protective factor for progression to severe ulcer in DFU patients(P＜0.05).ROC curve analysis showed that the area under the curve of PHR for predicting severe ulcer was 0.701(95％CI:0.646～0.756).Conclusion PHR is strongly associated with the severity of DFU,and shows certain predictive value for the progression to severe ulcer in DFU patients.

To analyze the positivity rate and titer of antinuclear antibody (ANA), as well as nuclear pattern and target antigen of ANA in healthy pregnant women during early pregnancy in Qingdao area. A prospective cohort study design was used to include a total of 9 528 healthy pregnant women registered at the Women and Children′s Hospital Affiliated to Qingdao University from March 2023 to June 2024.Indirect immunofluorescence assay (IIF) was used to detect ANA, its titer and cell staining pattern. Fifteen specific antibodies were tested using the magnetic bar code immunofluorescent luminescence method. Logistic regression model was used to analyze the risk factors of pregnancy with autoimmune disease(AID). The results showed that among 9 528 pregnant women in early pregnancy, 1 346 cases (14.1%) were positive of ANA, including 1 011 cases with a titer of 1∶100 (10.6%), 236 cases (2.5%) with a titer of 1∶320, and 99 cases (1.0%) were detected at a titer >1∶320. Among the 1 346 ANA-positive pregnant women, nuclear granular type accounted for the highest proportion (483 cases, 35.9%), followed by speckled type (347 cases, 25.8%) and cytoplasmic type (176 cases, 13.1%).Then, pregnant women with ANA titers ≥1∶100 were detected 15 specific antibodies.Anti-SSA was tested in 121 cases accounted for the majority, followed by 110 cases with anti-Ro-52, 56 cases with anti-SSB, 51 cases with anti-mitochondrial M2 subtype antibodies and 37 cases with anti-centromere B. In conclusion,in healthy pregnant women in Qingdao area, ANA positivity rate was 14.1%, and the titer of ANA was mainly at 1∶100.The predominant nuclear patterns were nuclear granular and speckled types.The specific autoantibodies were mainly anti-SSA antibodies and anti-Ro-52 antibodies.The detection of ANA and specific autoantibodies is of great significance for early prediction, diagnosis, and intervention of autoimmune diseases during pregnancy.

To analyze the positivity rate and titer of antinuclear antibody (ANA), as well as nuclear pattern and target antigen of ANA in healthy pregnant women during early pregnancy in Qingdao area. A prospective cohort study design was used to include a total of 9 528 healthy pregnant women registered at the Women and Children′s Hospital Affiliated to Qingdao University from March 2023 to June 2024.Indirect immunofluorescence assay (IIF) was used to detect ANA, its titer and cell staining pattern. Fifteen specific antibodies were tested using the magnetic bar code immunofluorescent luminescence method. Logistic regression model was used to analyze the risk factors of pregnancy with autoimmune disease(AID). The results showed that among 9 528 pregnant women in early pregnancy, 1 346 cases (14.1%) were positive of ANA, including 1 011 cases with a titer of 1∶100 (10.6%), 236 cases (2.5%) with a titer of 1∶320, and 99 cases (1.0%) were detected at a titer >1∶320. Among the 1 346 ANA-positive pregnant women, nuclear granular type accounted for the highest proportion (483 cases, 35.9%), followed by speckled type (347 cases, 25.8%) and cytoplasmic type (176 cases, 13.1%).Then, pregnant women with ANA titers ≥1∶100 were detected 15 specific antibodies.Anti-SSA was tested in 121 cases accounted for the majority, followed by 110 cases with anti-Ro-52, 56 cases with anti-SSB, 51 cases with anti-mitochondrial M2 subtype antibodies and 37 cases with anti-centromere B. In conclusion,in healthy pregnant women in Qingdao area, ANA positivity rate was 14.1%, and the titer of ANA was mainly at 1∶100.The predominant nuclear patterns were nuclear granular and speckled types.The specific autoantibodies were mainly anti-SSA antibodies and anti-Ro-52 antibodies.The detection of ANA and specific autoantibodies is of great significance for early prediction, diagnosis, and intervention of autoimmune diseases during pregnancy.

OBJECTIVE To systematically review the background of bioequivalence assessment of nasal sprays and nasal aerosols and the guiding considerations for the bioequivalence assessment of these complex drug-device combination products by regulatory authorities in the United States, the European Union(EU) and China. METHODS This article provided detailed explanations on the innovative weight of evidence assessment approach adopted by the US Food and Drug Administration(FDA), and the statistical rationale, methods and considerations for the bioequivalence assessment of nasal sprays and nasal aerosols. Using the calculation methods described in the draft guidance for budesonide inhalation suspension and the draft guidance for fluticasone nasal spray propionate issued by FDA, the statistical parameters of two-sided and one-sided population bioequivalence calculation were realized through R language programming, and pseudo-code for the population bioequivalence (PBE) calculation programs was provided. This article also presented a comprehensive review of published guidelines and summaries review principles of the EU and China for nasal sprays and nasal aerosols equivalence assessment. RESULTS & CONCLUSION Nasal sprays/nasal aerosols is the focus of innovative and generic drug development in recent years. This paper provided valuable considerations references for the research and development, quality control and bioequivalence evaluation of generic preparations of nasal sprays/nasal aerosols.

Objective:To explore the prognostic effect and safety of neurally adjusted ventilatory assist (NAVA) mode on the patients with severe neurological cerebrovascular disease undergoing mechanical ventilation.Methods:A prospective study was conducted. Fifty-four patients with cerebrovascular disease undergoing mechanical ventilation admitted to the neurosurgery intensive care unit (NSICU) of the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital) from December 2020 to May 2022 were enrolled. They were divided into NAVA group and pressure support ventilation (PSV) group by computer random number generator with 27 patients in each group. The ventilation time of the two groups was ≥72 hours. The general basic data of the two groups were recorded. The time without mechanical ventilation 28 days after enrollment, total length of mechanical ventilation, survival rate of 90 days after enrollment, length of NSICU stay, total length of hospital stay, NSICU mortality, in-hospital mortality, Glasgow outcome score (GOS), complications related to mechanical ventilation, and changes of respiratory mechanics indexes, arterial blood gases, vital signs, and diaphragm function indexes were observed.Results:The time without mechanical ventilation 28 days after enrollment in the NAVA group was significantly longer than that in the PSV group [days: 22 (15, 26) vs. 6 (0, 23), P < 0.05]. However, there were no significant differences in the total length of mechanical ventilation, 90-day survival rate, length of NSICU stay, total length of hospital stay, NSICU mortality, in-hospital mortality, GOS score, and incidence of mechanical ventilator-related complications between the two groups. In terms of respiratory mechanics parameters, the expiratory tidal volume (VTe) on 3 days after mechanical ventilation of patients in the NAVA group was significantly lower than that on 1 day and 2 days, and significantly lower than that in the PSV group [mL: 411.0 (385.2, 492.6) vs. 489.0 (451.8, 529.4), P < 0.01]. Minute ventilation (MV) at 2 days and 3 days in the NAVA group was significantly higher than that at 1 day, and significantly higher than that in the PSV group at 2 days [L/min: 9.8 (8.4, 10.9) vs. 7.8 (6.5, 9.8), P < 0.01], while there was no significant change of MV in the PSV group. At 1 day, peak airway pressure (Ppeak) and mean airway pressure (Pmean) in the NAVA group were significantly lower than those in the PSV group [Ppeak (cmH 2O, 1 cmH 2O≈0.098 kPa): 14.0 (12.2, 17.0) vs. 16.6 (15.0, 17.4), Pmean (cmH 2O): 7.0 (6.2, 7.9) vs. 8.0 (7.0, 8.2), both P < 0.05]. However, there was no significant difference in the Ppeak or Pmean at 2 days and 3 days between the two groups. In terms of arterial blood gas, there was no significant difference in pH value between the two groups, but with the extension of mechanical ventilation time, the pH value at 3 days of the two groups was significantly higher than that at 1 day. Arterial partial pressure of oxygen (PaO 2) at 1 day in the NAVA group was significantly lower than that in the PSV group [mmHg (1 mmHg≈0.133 kPa): 122.01±37.77 vs. 144.10±40.39, P < 0.05], but there was no significant difference in PaO 2 at 2 days and 3 days between the two groups. There was no significant difference in arterial partial pressure of carbon dioxide (PaCO 2) or oxygenation index (PaO 2/FiO 2) between the two groups. In terms of vital signs, the respiratory rate (RR) at 1, 2, and 3 days of the NAVA group was significantly higher than that of the PSV group [times/min: 19.2 (16.0, 25.2) vs. 15.0 (14.4, 17.0) at 1 day, 21.4 (16.4, 26.0) vs. 15.8 (14.0, 18.6) at 2 days, 20.6 (17.0, 23.0) vs. 16.7 (15.0, 19.0) at 3 days, all P < 0.01]. In terms of diaphragm function, end-inspiratory diaphragm thickness (DTei) at 3 days in the NAVA group was significantly higher than that in the PSV group [cm: 0.26 (0.22, 0.29) vs. 0.22 (0.19, 0.26), P < 0.05]. There was no significant difference in end-expiratory diaphragm thickness (DTee) between the two groups. The diaphragm thickening fraction (DTF) at 2 days and 3 days in the NAVA group was significantly higher than that in the PSV group [(35.18±12.09)% vs. (26.88±8.33)% at 2 days, (35.54±13.40)% vs. (24.39±9.16)% at 3 days, both P < 0.05]. Conclusions:NAVA mode can be applied in patients with neuro-severe cerebrovascular disease, which can prolong the time without mechanical ventilation support and make patients obtain better lung protective ventilation. At the same time, it has certain advantages in avoiding ventilator-associated diaphragm dysfunction and improving diaphragm function.

Objective:To analyze food intolerance status in children in Qingdao by detecting the serum levels of food-specific IgG (sIgG).Methods:In this cross-sectional study, a total of 4 249 children aged 0 to 14 years (all were permanent residents of Qingdao City) admitted to Women and Children′s Hospital Affiliated to Qingdao University from May 2017 to December 2020 for suspected food intolerance were selected as the study objects with the whole sampling method. According to the age, the objects were divided into 4 groups: 0-<1 year group (440 cases), 1-<3 years group (1 761 cases), 3-<6 years group (1 193 cases), and ≥6 years group (855 cases). Positive condition of serum sIgG antibodies of 14 kinds of food in the children were detected by enzyme-linked immunosorbent assay. Chi-square test was used to compare the positive rate of the antibodies among different foods, gender and age groups.Results:The total positive rate of food sIgG antibody in 4 249 children was 95.32% (4 050/4 249), the highest positive rate was found in eggs (81.50%) and the lowest positive rate was found in pork (1.15%). The positive rates of sIgG antibody in milk (54.98% vs 49.69%, χ2=11.627), crab (5.59% vs 3.71%, χ2=8.049) and shrimp (4.62% vs 2.75%, χ2=9.784) in boys were significantly higher than those in girls, and the positive rates of sIgG antibody in tomato (49.19% vs 45.54%, χ2=5.510), cod (8.53% vs 5.96%, χ2=10.512) and beef (2.58% vs 1.70%, χ2=3.959) in girls were significantly higher than those in boys (all P<0.05). The total positive rate of sIgG antibody in 14 foods was the lowest in 0-<1 year group (89.09%), and it was the highest in 3-<6 years group (96.98%) ( χ2=63.950, P<0.001). The highest positive rate in 0-<1 year group was found in tomato (56.36%), and it was eggs (85.29%, 88.94%, 85.50%) in all the other 3 groups. The positive rates of corn and beef decreased with age ( χ2=44.098, 20.106, P<0.001), while those of cod and mushroom increased with age ( χ2=32.315, 40.338, P<0.001). The positive rate of wheat (57.13%, χ2=42.273), tomato (57.01%, χ2=209.862), soybean (24.99%, χ2=92.580), crab (6.81%, χ2=33.201), shrimp (6.25%, χ2=47.863) were all the highest in 1-<3 years group among the 4 groups (all P<0.001), and the positive rate of chicken was the highest in 3-<6 years group (7.88%, χ2=29.875; P<0.001). Conclusions:Children in Qingdao have a high level of food intolerance, and the highest positive rate is for eggs. Milk, crab and shrimp should be focused on for boys, while tomatoes, cod and beef shoud be paid more attention to for girls. Children of different ages have different kinds of food intolerance, and their diets should be adjusted reasonably according to the characteristics.

Objective:To evaluate the role of miR-188-5p in oxygen-glucose deprivation and restoration (OGD/R) injury to mouse neuroblastoma (N2a) cells and its relationship with small ubiquitin-like modifier-specific proteases 3 (SENP3).Methods:N2a cells were cultured and divided into 5 groups ( n=23 each) using a random number table method: control group (group C), OGD/R group, group NC, transfection of mir-188-5p agonist group (group M) and transfection of mir-188-5p inhibitor group group (group I). Cells in group C were cultured routinely.Cells in group NC, group M and group I were transfected with mir-188-5p negative control miRNA, agonist and inhibitor, respectively.N2a cells were subjected to OGD for 3 h followed by restoration of oxygen-glucose supply to establish the model of OGD/R injury.At 24 h of oxygen-glucose restoration, the cell viability was recorded by the cell counting kit-8 assay, the amount of lactic dehydrogenase (LDH) released was detected, the expression of miR-188-5p and SENP3 mRNA was detected by quantitative real-time polymerase chain reaction, and SENP3 expression was determined by Western blot.The targeting relationship between miR-188-5p and SENP3 mRNA was detected using dual luciferase reporter assay. Results:Compared with group C, the cell viability was significantly decreased, amount of LDH released was increased, and expression of SENP3 and its mRNA was up-regulated in the other 4 groups, miR-188-5p expression was down-regulated in OGD/R and I groups, and miR-188-5p expression was up-regulated in group M ( P<0.05 or 0.01). Compared with group OGD/R, the cell viability was significantly decreased, amount of LDH released was increased, and expression of SENP3 and its mRNA was up-regulated, and miR-188-5p expression was down-regulated in group I, and the cell viability was increased, amount of LDH released was decreased, expression of SENP3 and its mRNA was down-regulated, and miR-188-5p expression was up-regulated in group M ( P<0.05 or 0.01). The dual luciferase reporter assay showed that miR-188-5p could act directly on SENP3. Conclusion:miR-188-5p is involved in OGD/R injury, which is associated with targeted down-regulation of SENP3 expression in N2a cells.

Objective:To explore the patient-ventilator interaction of neurally adjusted ventilatory assist (NAVA) in patients with severe neurological diseases.Methods:A prospective study was conducted. Sixteen severe neurological patients with tracheotomy admitted to neurosurgery intensive care unit (NSICU) of Yijishan Hospital of the First Affiliated Hospital of Wannan Medical College from September 2019 to February 2020 were enrolled. According to the random number table method, they were treated with pressure support ventilation (PSV) mode followed by NAVA mode or NAVA mode followed by PSV mode mechanical ventilation. Each mode was ventilated for 24 hours. The number of auto-triggering, ineffective trigger, double trigger, inspiratory trigger delay, premature cycling, late cycling, and patient-ventilator asynchronous time (inspiratory trigger delay time, premature cycling time, and late cycling time) within 1 minute were recorded every 8 hours for 3 minutes. The average number of asynchronies per minute, asynchrony index (AI), total AI, asynchrony time, arterial blood gas analysis, and coefficient variation (CV%) of respiratory mechanics parameters of each asynchrony type between the two modes were compared.Results:There were significant decrease in the number or AI of auto-triggering, ineffective trigger, inspiratory trigger delay, premature cycling, and late cycling with NAVA mode ventilation compared with PSV mode ventilation [auto-triggering times (times/min): 0.00 (0.00, 0.00) vs. 0.00 (0.00, 0.58), auto-triggering AI: 0.00 (0.00, 0.00) vs. 0.00 (0.00, 0.02), ineffective trigger times (times/min): 0.00 (0.00, 0.33) vs. 1.00 (0.33, 2.17), ineffective trigger AI: 0.00 (0.00, 0.02) vs. 0.05 (0.02, 0.09), inspiratory trigger delay times (times/min): 0.00 (0.00, 0.58) vs. 0.67 (0.33, 1.58), inspiratory trigger delay AI: 0.00 (0.00, 0.02) vs. 0.05 (0.02, 0.09), premature cycling times (times/min): 0.00 (0.00, 0.33) vs. 0.33 (0.08, 1.00), premature cycling AI: 0.00 (0.00, 0.01) vs. 0.02 (0.00, 0.05), late cycling times (times/min): 0.00 (0.00, 0.00) vs. 1.17 (0.00, 4.83), late cycling AI: 0.00 (0.00, 0.00) vs. 0.07 (0.00, 0.25), all P < 0.05]. But there was significant increase in the number or AI of double trigger with NAVA mode ventilation as compared with PSV mode ventilation [times (times/min): 1.00 (0.33, 2.00) vs. 0.00 (0.00, 0.00), AI: 0.04 (0.02, 0.11) vs. 0.00 (0.00, 0.00), both P < 0.05]. Total AI and incidence of total AI > 0.1 showed significant decrease during NAVA mode ventilation as compared with PSV mode ventilation [total AI: 0.08 (0.04, 0.14) vs. 0.22 (0.18, 0.46), incidence of total AI > 0.1: 37.50% (6/16) vs. 93.75% (15/16), both P < 0.01]. There was no significant difference in asynchronous time or arterial blood gas analysis between the two modes. There were significant increases in variances of peak airway pressure (Ppeak) and expiratory tidal volume (VTe) during NAVA mode ventilation as compared with PSV mode ventilation [Ppeak coefficient of variation (CV%): 11.25 (7.12, 15.17)% vs. 0.00 (0.00, 2.82)%, VTe CV%: (8.93±5.53)% vs. (4.71±2.61)%, both P < 0.05]. Conclusions:Compared with PSV mode, NAVA mode can reduce the occurrence of patient-ventilator asynchronous events, reduce the AI and the occurrence of serious patient-ventilator asynchronous events, so as to improve the patient-ventilator interaction. NAVA and PSV modes can achieve the same gas exchange effect. At the same time, NAVA mode has potential advantages in avoiding insufficient or excessive ventilation support, diaphragm protection and prevention of ventilator-induced lung injury.