Background It is a research hotspot to study the changes of metabolites and metabolic pathways in the process of coal worker's pneumoconiosis (CWP) by metabonomics and to explore its pathogenesis. Objective To study the change of metabolites in bronchoalveolar lavage fluid (BALF) of patients with CWP and explore the metabolic regulation mechanism of the disease. Methods Patients with CWP who met the national diagnostic criteria according to Diagnosis of occupational pneumoconiosis (GBZ 70-2015) and underwent massive whole lung lavage were selected as the case group, and patients with tracheostenosis who underwent bronchoscopy were selected as the control group. BALF samples were collected from the cases and the controls. After filtering out large particles and mucus, the supernatant was stored in a −80 ℃ refrigerator. The samples were detected and analyzed by liquid chromatography-mass spectrometry after adding extraction solution, cold bath ultrasonication, and high-speed centrifugation, and the metabolic profiles and related data of CWP patients were obtained. The differential metabolites related to the occurrence and development of CWP were screened by multiple statistical analysis; furthermore, we searched the Kyoto Encyclopedia of Genes and Genomes (KEGG) database for potential metabolic pathways involved in the progression. Results There was no significant difference in the general conditions of the subjects, such as weight, height, age, and length of service among the stage I group, the stage II group, the stage III group, and the control group (P˃0.05). When comparing the CWP stage I group with the control group, 48 differential metabolites were screened out, among which 14 were up-regulated and 34 were down-regulated. A total of 66 differential metabolites were screened out between the patients with CWP stage II and the controls, 14 up-regulated and 52 down-regulated differential metabolites. Compared with the control group, 63 differential metabolites were screened out in the patients with CWP stage III, including 11 up-regulated and 52 down-regulated differential metabolites. There were 36 differential metabolites that may be related to the occurrence of CWP, among which 11 differential metabolites were up-regulated, and 25 were down-regulated. Four significant differential metabolic pathways were identified through KEGG database query: linoleic acid metabolic pathway, alanine metabolic pathway, sphingolipid metabolic pathway, and glycerophospholipid metabolic pathway. Conclusion The metabolomic study of BALF show that there are 36 different metabolites in the occurrence and development of CWP, mainly associating with linoleic acid metabolism, alanine metabolism, sphingolipid metabolism, and glycerophospholipid metabolism pathways.

Objective:To evaluate the efficacy and safety of Xiao′er Huangjin Zhike Granules in the treatment of cough caused by acute bronchitis in children, which is defined in TCM terms as a syndrome of phlegm-heat obstructing the lung.Methods:This was a block-randomized, double-blind, placebo-controlled, multicenter clinical trial.From January 2022 to September 2023, 359 children aged 3 to 7 years old diagnosed as acute bronchitis (lung-obstructing phlegm-heat syndrome) were enrolled from 21 participating hospitals and randomly assigned to the experimental group and placebo group in a 3︰1 ratio, and respectively treated with Xiao′er Huangjin Zhike Granules and its matching placebo.Cough resolution/general resolution rate after 7 days of treatment was used as the primary efficacy outcome for both groups.Results:(1)On the seventh day of treatment, the rate of cough disappearance/basically disappearance in the experimental group and placebo group were 73.95% and 57.61% retrospectively, which had statistically significance ( P=0.001).(2)After 7 days of treatment, the median duration of cough disappearance/basic disappearance were 5 days and 6 days in the two groups , with a statistically significant difference ( P=0.006).The area under the curve of cough symptom severity time was 7.20 ± 3.79 in the experimental group and 8.20±4.42 in the placebo group.The difference between the two groups was statistically significant ( P=0.039).(3) After 7 days of treatment, the difference between TCM syndrome score and baseline was -16.0 (-20.0, -15.0) points in the experimental group and -15.0 (-18.0, -12.0) points in the placebo group, with significant difference between the two groups ( P=0.004).In the experimental group, the clinical control rate, the markedly effective rate, the effective rate and the ineffective rate were 49.04%, 28.35%, 16.48% and 6.13% severally; and in the placebo group, the clinical control rate, the markedly effective rate, the effective rate and the ineffective rate were 38.04%, 26.09%, 29.35%, and 6.52% separately, which had statistically significant ( P=0.014).(4) There was no significant difference in the incidence of adverse events or adverse reactions during the trial between both groups.Moreover, while adverse reactions in the form of vomiting and diarrhea were occasionally reported, no serious drug-related adverse event or adverse reaction was reported.(5)The tested drug provided good treatment compliance, showing no statistically significant difference from the placebo in terms of compliance rate. Conclusions:Based on the above findings, it can be concluded that Xiao′er Huangjin Zhike Granules provides good safety, efficacy, and treatment compliance in the treatment of cough caused by acute bronchitis, and lung-obstructing phlegm-heat syndrome, in children.

Objective:To assess the clinical effectiveness and safety of Omalizumab for treating pediatric allergic asthma in real world in China.Methods:The clinical data of children aged 6 to 11 years with allergic asthma who received Omalizumab treatment in 17 hospitals in China between July 6, 2018 and September 30, 2020 were retrospectively analyzed.Such information as the demographic characteristics, allergic history, family history, total immunoglobulin E (IgE) levels, specific IgE levels, skin prick test, exhaled nitric oxide (FeNO) levels, eosinophil (EOS) counts, and comorbidities at baseline were collected.Descriptive analysis of the Omalizumab treatment mode was made, and the difference in the first dose, injection frequency and course of treatment between the Omalizumab treatment mode and the mode recommended in the instruction was investigated.Global Evaluation of Treatment Effectiveness (GETE) analysis was made after Omalizumab treatment.The moderate-to-severe asthma exacerbation rate, inhaled corticosteroid (ICS) dose, lung functions were compared before and after Omalizumab treatment.Changes in the Childhood Asthma Control Test (C-ACT) and Pediatric Asthma Quality of Life Questionnaire (PAQLQ) results from baseline to 4, 8, 12, 16, 24, and 52 weeks after Omalizumab treatment were studied.The commodity improvement was assessed.The adverse event (AE) and serious adverse event (SAE) were analyzed for the evaluation of Omalizumab treatment safety.The difference in the annual rate of moderate-to-severe asthma exacerbation and ICS reduction was investigated by using t test.The significance level was set to 0.05.Other parameters were all subject to descriptive analysis.A total of 200 allergic asthma patients were enrolled, including 75.5% ( n=151) males and 24.5% ( n=49) females.The patients aged (8.20±1.81) years. Results:The median total IgE level of the 200 patients was 513.5 (24.4-11 600.0) IU/mL.Their median treatment time with Omalizumab was 112 (1-666) days.Their first dose of Omalizumab was 300 (150-600) mg.Of the 200 cases, 114 cases (57.0%) followed the first Omalizumab dosage recommended in the instruction.After 4-6 months of Omalizumab treatment, 88.5% of the patients enrolled ( n=117) responded to Omalizumab.After 4 weeks of treatment with Omalizumab, asthma was well-controlled, with an increased C-ACT score [from (22.70±3.70) points to (18.90±3.74) points at baseline]. Four-six months after Omalizumab administration, the annual rate of moderate-to-severe asthma exacerbation had a reduction of (2.00±5.68) per patient year( t=4.702 5, P<0.001), the median ICS daily dose was lowered [0 (0-240) μg vs. 160 (50-4 000) μg at baseline] ( P<0.001), the PAQLQ score was improved [(154.90±8.57) points vs. (122.80±27.15) points at baseline], and the forced expiratory volume in one second % predicted (FEV 1%pred) was increased [(92.80±10.50)% vs. (89.70±18.17)% at baseline]. In patients with available evaluations for comorbidities, including allergic rhinitis, atopic dermatitis or eczema, urticaria, allergic conjunctivitis and sinusitis, 92.8%-100.0% showed improved symptoms.A total of 124 AE were reported in 58 (29.0%) of the 200 patients, and the annual incidence was 0(0-15.1) per patient year.In 53 patients who suffered AE, 44 patients (83.0%) and 9 patients (17.0%) reported mild and moderate AE, respectively.No severe AE were observed in patients.The annual incidence of SAE was 0(0-1.9) per patient year.Most common drug-related AE were abdominal pain (2 patients, 1.0%) and fever (2 patients, 1.0%). No patient withdrew Omalizumab due to AE. Conclusions:Omalizumab shows good effectiveness and safety for the treatment of asthma in children.It can reduce the moderate-to-severe asthma exacerbation rate, reduce the ICS dose, improve asthma control levels, and improve lung functions and quality of life of patients.

Objective:To analyze the clinical characteristics of pulmonary vein stenosis (PVS) in children, and to explore its treatment and prognostic factors.Methods:The clinical data of 19 children with PVS treated in Beijing Children′s Hospital, Capital Medical University from October 2016 to March 2022 were analyzed retrospectively.There were 16 males and 3 females.The median age at diagnosis was (2.81±1.95) years.A descriptive analysis of clinical characteristics of children was made.Results:Of the 19 children, 14 cases (73.7%) had primary PVS and 5 cases (26.3%) had secondary PVS after surgery of anomalous pulmonary venous connection (APVC). Thirteen children (68.4%) had hemoptysis.In the hemoptysis children, 5 cases had life-threatening massive hemoptysis, and 11 cases (57.9%) had a history of recurrent respiratory tract infection or pneumonia.Other manifestations of hemoptysis included failure to thrive (6 cases), cyanosis (5 cases), and dyspnea (3 cases). Complications were pulmonary hypertension (6 cases) and right heart failure (3 cases). There were 16 cases (84.2%) of unilateral PVS and 3 cases of bilateral PVS.Interlobular septal thickening, grid shadow and ground glass opacities were found on CT of all PVS cases.Ten cases underwent surgery, and 2 cases of them received angioplasty, but restenosis occurred in both of them.Eight children underwent pulmonary lobectomy, and their clinical symptoms were all relieved after operation.Nine patients were treated conservatively, and 3 cases of them died of bilateral PVS secondary to APVC.The remaining 6 alive cases still had intermittent clinical symptoms during follow-up.Conclusions:Hemoptysis and recurrent respiratory tract infection are the main clinical manifestations of PVS in children, and life-threatening massive hemoptysis can occur.Lobectomy is an effective treatment for unilateral PVS.The prognosis of secondary PVS after APVC is poorer and its mortality is higher, compared with primary PVS.

Objective:To investigate the effects of normal iodized salt diet on urinary iodine concentration and iodine uptake rate in patients with differentiated thyroid cancer (DTC) before 131I treatment. Methods:A prospective study was conducted on patients with DTC (59 male patients and 130 female patients, age (43.7±12.2) years) who received 131I treatment for the first time after total thyroidectomy in the First Affiliated Hospital of Zhengzhou University between January 2021 and April 2022. Patients were divided into normal iodized salt diet group and limited iodized salt diet group according to whether iodized salt diet was administered 4 weeks before 131I treatment. The age, gender, urinary iodine concentration, iodine uptake rate and tumor risk stratification of the two groups were compared by independent-sample t test or χ2 test. In addition, according to the concentration of urinary iodine, patients were divided into group a1 (urinary iodine <200 μg/L) and group a2 (urinary iodine ≥200 μg/L). Logistic regression analysis was used to analyze the factors affecting urinary iodine concentration. Results:The urinary iodine concentration of normal iodized salt diet group was not significantly different from that of non-iodized salt diet group ((140.53±76.66) vs (121.74±74.64) μg/L; t=1.67, P=0.489). The iodine uptake rates at 2 h, 4 h and 24 h in the 2 groups were (3.77±1.06)% vs (3.42±0.97)%, (3.33±1.07)% vs (3.21±1.15)%, (2.90±2.60)% vs (3.23±2.94)%, respectively ( t values: 2.33, 0.68, -0.81, all P>0.05). There were no significant differences in age ( t=0.56, P=0.889), gender ( χ2=1.33, P=0.250) and tumor risk stratification ( χ2=0.14, P=0.709) between the two groups. Logistic regression analysis showed that tumor risk stratification was associated with urinary iodine concentration (odds ratio ( OR)=3.914, 95% CI: 1.505-10.176; P=0.005). Conclusion:Normal iodized salt diet may have no effect on urinary iodine concentration and iodine uptake rate of patients with DTC before 131I treatment.

Objective:To investigate the prognostic value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in patients with extensive-stage small cell lung cancer (ES-SCLC).Methods:From March 2019 to June 2020, 69 patients (55 males, 14 females, age: 38-87 years) with ES-SCLC who underwent pretreatment 18F-FDG PET/CT in First Affiliated Hospital of Zhengzhou University were retrospectively enrolled. The variables including gender, age, smoking, weight loss, liver metastasis, bone metastasis, malignant effusion, SUV max of the primary tumor, whole-body MTV (wbMTV) and whole-body TLG (wbTLG) (including wbMTV 40%, wbTLG 40%, wbMTV 2.5 and wbTLG 2.5) were analyzed. The predictors of overall survival (OS) were analyzed by using Kaplan-Meier method (log-rank test). Results:Of 69 ES-SCLC patients, 43(62%) died and 26(38%) were still alive by the end of follow-up, with a median survival time of 15.0(95% CI: 11.7-18.3) months. Univariate analysis revealed that age ( χ2=4.53, P=0.033), bone metastasis ( χ2=18.05, P<0.001), liver metastasis ( χ2=27.94, P<0.001), wbMTV 2.5 ( χ2=3.98, P=0.046), and wbTLG 2.5( χ2=5.80, P=0.016) were significant predictors of OS. Conclusion:wbMTV 2.5 and wbTLG 2.5 are assosciated with OS and may provide some reference value for predicting the prognosis of ES-SCLC patients.

Objective:To explore the relationship between B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutation and clinical pathological features in patients with differentiated thyroid cancer (DTC), and to evaluate the value of BRAF V600E mutation in predicting the efficacy and follow-up of 131I treatment in DTC patients with different risk stratification. Methods:From January 2018 to June 2022, 893 DTC patients (205 males, 688 females, age (42.3±11.9) years) treated with 131I after total thyroidectomy in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. Patients were divided into BRAF V600E mutation group ( n=729) and wild-type group ( n=164). According to the 2015 American Thyroid Association (ATA) guidelines, patients were divided into low-risk (39 cases), medium-risk (498 cases) and high-risk (356 cases), and the curative effect was divided into excellent response (ER) and non-excellent response (NER). The χ2 test, independent-sample t test and Mann-Whitney U test were used to compare differences between the two groups. Logistic regression analysis was performed to predict the influencing factors of treatment effect in DTC patients with different risk stratification. Results:The differences in age≥45 years, N stage, unilateral or bilateral DTC, multifocus, mode of operation, number and size of metastatic lymph nodes were statistically significant between BRAF V600E mutation group and wild-type group ( χ2 values: 4.45-17.40, t=-4.08, z=-3.08, all P<0.05). In medium- and high-risk stratification, the stimulated thyroglobulin (sTg) levels before and after 131I treatment were slightly higher in the BRAF V600E mutation group, while significantly sharp decreased of sTg and thyroglobulin antibody (TgAb) in wild-type group ( z value: from -9.30 to -2.65, all P<0.05). In medium- and high-risk stratification, 69.0%(60/87) and 64.3%(45/70) of BRAF V600E wild-type patients reached ER after 131I treatment, which were higher than those of mutant patients (57.4%(236/411) and 45.8%(131/286); χ2 values: 3.96, 7.39, P values: 0.046, 0.007). BRAF V600E mutation was the independent predictor affecting the efficacy of 131I treatment in DTC patients with medium- and high-risk stratification (odds ratio ( OR): 0.411 (95% CI: 0.196-0.864), 0.192 (95% CI: 0.096-0.384), P values: 0.019, <0.001). Conclusions:DTC patients with BRAF V600E mutation are related to the high invasiveness, and show poor improvement in biochemical indicators after initial 131I treatment. In addition, BRAF V600E mutation is an important factor in predicting the therapeutic effect of 131I in DTC patients with medium- and high-risk stratification.

Objective:To analyze the clinical characteristics, treatment course and prognosis of children with intermediate-high risk pulmonary embolism.Methods:The clinical data of 48 children with pulmonary embolism treated in Beijing Children′s Hospital, Capital Medical University from January 2017 to December 2021 were analyzed retrospectively.Including 12 intermediate-high risk cases and 36 low-risk cases.The clinical manifestations, laboratory results, treatment and prognosis were compared between groups by the t-test, rank sum test and Chi- square test with the yates continuity correlation or Fisher′ s exact test. Results:There were no significant differences in the sex and age between the intermediate-high risk group and the low-risk group.The proportions of patients with shortness of breath, dyspnea, cyanosis or hypoxemia were higher in the intermediate-high risk group than those of in low-risk group.Twelve children in the low-risk group did not have specific symptoms of pulmonary embolism.There were no significant differences in the D-dimer level, and the distribution of pulmonary embolism between the two groups (all P>0.05). However, the proportion of children with other thromboembolism in the intermediate-high risk group was significantly higher than that of the low-risk group, among which heart thrombosis was the most common (7 cases). There were no significant differences in the underlying diseases and thrombophilia between the two groups (all P>0.05). The treatment of the intermediate-high risk group was more active: 6/12(50.00%) patients in the intermediate-high risk group received reperfusion treatment, including 3 cases of systemic thrombolysis, 1 case of catheter thrombolysis, and 2 cases of thrombectomy.In the low-risk group, only 1 case was treated with systematic thrombolysis.Unfavorable outcomes were reported in 3/48 (6.25%) patients, including 1 death of massive bleeding after catheter-directed thrombolysis in the acute phase, 1 case of recurrent pulmonary embolism after self-decided withdrawal and 1 case of progression of pulmonary embolism that was managed by surgical thrombectomy, all of whom were in the intermediate-high risk group. Conclusions:Shortness of breath, dyspnea, cyanosis or hypoxemia and co-existed venous thromboembolism were more common in intermediate-high risk cases.The treatment regimen of was more aggressive, but the incidence of unfavorable outcomes was higher in intermediate-high risk group; further research is needed to determine the risk factors for intermediate-high risk pulmonary embolism in children.

Objective:To investigate the epidemiological and clinical characteristics of human parainfluenza viruses (HPIVs) infection among hospitalized children with community-acquired pneumonia (CAP) in China, and provide basic data for diagnosis, treatment and prevention of HPIVs infection.Methods:From November 2014 to February 2020, 5 448 hospitalized children with CAP were enrolled in 14 hospitals in 11 provinces and municipalities directly under the Central Government in southern China and northern China. Nasopharyngeal aspirates or throat swabs were collected, and the nucleic acids of 18 types respiratory viruses including HPIV1-4 were screened by suspension array technology. Demographic data and clinical information were collected for statistical analysis.Results:The total detection rate of HPIVs in 5 448 children with CAP was 8.83% (481/5 448), and the detection rate in males was higher than that in females (62.79% vs. 37.21%; χ2=0.000, P=0.992). The detection rate of HPIVs in 1~< 3 years age group was higher than that in other age groups, and the difference was statistically significant ( χ2=61.893, P<0.001). The detection rate of HPIVs in the northern region was higher than that in the southern region (9.02% vs 8.65%), but the difference was not statistically significant ( χ2=0.239, P=0.625). The prevalence of HPIV1-4 in northern and southern China was not completely same. HPIV1 was mainly prevalent in autumn in both northern and southern regions. HPIV2 was prevalent in summer in northern China, and the detection rate was low in southern China. HPIV3 reached its peak in both spring and summer in both northern and southern China, but its duration was longer in southern China than in northern China. HPIV4 is mainly popular in autumn in both southern China and northern China. Among 481 children infected with HPIVs, 58.42% (281/481) were infected with HPIV alone, and the main clinical manifestations were cough (90.75%) and fever (68.68%). Out of the HPIV-positive cases, 42.62% (205/481) were co-infected with another type of HPIV or a different virus, while 11.43% (55/481) had co-infections with two or more different viruses. HPIV3 was the most common type of co-infection with other viruses. HPIV3 infection accounted for the largest proportion (76.80%) in 47 HPIVs-positive children with severe pneumonia. Conclusions:HPIVs is one of the most important pathogens causing CAP in children in China, and children under 3 years of age are the main populations of HPIVs infection. The prevalence characteristics of all types of HPIVs in children in the north and south are not completely same. HPIV3 is the dominant type of HPIV infections and causes more severe diseases.

Objective:A case of cystic fibrosis admitted in the Respiratory Department of Beijing Children′s Hospital, Capital Medical University in June 2018 and underwent lung transplantation later was analyzed retrospectively.A 10-year-old girl had intermittent productive cough for more than 4 years with clubbed-finger.The lung high resolution CT (HRCT) showed bronchiectasis and mucus impaction, and the nasal sinus HRCT showed sinusitis.She had cystic fibrosis transmembrane conductance regulator ( CFTR) gene complex heterozygous mutation and positive sweat test.The immunoglobulin E (IgE) level and eosinophil count increased, and aspergillus fumigatus-specific IgE was positive.She was diagnosed as cystic fibrosis, allergic bronchopulmonary aspergillosis and sinusitis.Anti-infection, glucocorticoid and symptomatic treatment were given.During the following 21 months, the child had repeated respiratory difficulties and respiratory failure.Her lung function declined.Bilateral lung transplantation was performed in March 2020.She had a good recovery at more than 1 year and 3 months postoperatively.