Rare tumors: a blue ocean of investigation / 医学前沿

Advances in novel drugs, therapies, and genetic techniques have revolutionized the diagnosis and treatment of cancers, substantially improving cancer patients' prognosis. Although rare tumors account for a non-negligible number, the practice of precision medicine and development of novel therapies are largely hampered by many obstacles. Their low incidence and drastic regional disparities result in the difficulty of informative evidence-based diagnosis and subtyping. Sample exhaustion due to difficulty in diagnosis also leads to a lack of recommended therapeutic strategies in clinical guidelines, insufficient biomarkers for prognosis/efficacy, and inability to identify potential novel therapies in clinical trials. Herein, by reviewing the epidemiological data of Chinese solid tumors and publications defining rare tumors in other areas, we proposed a definition of rare tumor in China, including 515 tumor types with incidences of less than 2.5/100 000 per year. We also summarized the current diagnosis process, treatment recommendations, and global developmental progress of targeted drugs and immunotherapy agents on the status quo. Lastly, we pinpointed the current recommendation chance for patients with rare tumors to be involved in a clinical trial by NCCN. With this informative report, we aimed to raise awareness on the importance of rare tumor investigations and guarantee a bright future for rare tumor patients.

Efficacy of Omalizumab in the treatment of moderate-to-severe allergic asthma with allergic comorbidities in children / 中华实用儿科临床杂志

Objective:To investigate the clinical efficacy of Omalizumab in the treatment of moderate-to-severe allergic asthma with allergic comorbidities in children.Methods:The clinical data of 50 children with moderate-to-severe allergic asthma and allergic comorbidities, who were treated with Omalizumab and completed 12-month follow-up in the Department of Pediatrics of Peking University First Hospital from July 2018 to March 2022, were retrospectively analyzed.A comparison was performed on the scale scores of childhood allergic asthma and allergic comorbidities including allergic rhinitis (AR) and chronic spontaneous urticaria (CSU), pulmonary function test indices and fractional exhaled nitric oxide (FeNO) concentration before and after treating with Omalizumab.The data were compared by ANOVA, paired t-test, chi- square test and rank sum test. Results:(1)Improvement of clinical symptoms: after 12 months of Omalizumab treatment, the childhood asthma control test score of 42 children aged ≤11 years increased from (20.98±5.03) points to (26.95±0.22) points ( F=18.189, P<0.001). The asthma control questionnaire 7 score of 50 children decreased from (0.89±0.11) points to (0.10±0.02) points ( F=5.662, P=0.006). The score of visual analogue scale of 47 children with AR decreased from (11.00±1.65) points to (0.2±0.14) points ( F=14.901, P<0.001), and the urticaria control test score of 13 children with CSU decreased from (4.82±0.88) points to (1.87±0.61) points ( F=4.329, P=0.018). (2)Improvement of quality of life: compared with those before treatment, the pediatric asthma quality of life questionnaire score in 50 children increased from (124.50±32.13) points to (159.40±6.21) points ( F=12.052, P<0.001), and global evaluation of asthma treatment effectiveness decreased from (2.23±0.70) points to (1.07±0.26) points ( F=68.865, P<0.001) after Omalizumab treatment for 12 months.(3)Improvement of pulmonary function results: after 12 months of Omalizumab treatment, the number of children with forced expiratory volume in one second/forced vital capacity< 80% decreased from 13 cases (26%) to 1 case (2%), and the values increased from (91.39±12.88)% to (96.96±8.54)%( χ2=11.960; t=2.486, all P<0.05). The peak expiratory flow of predicted value increased from (86.73±16.05)% to (94.01±13.11)% ( t=2.445, P<0.05). The number of children with two indicators among the forced expiratory flow at 50% of forced vital capacity exhaled, forced expiratory flow at 75% of forced vital capacity exhaled and maximal mid-expiratory flow lower than 65% decreased from 31 cases (62%) to 7 cases (14%) ( χ2=24.450, P<0.001). There was no significant difference in FeNO concentration before and after treatment ( P>0.05). Safety of Omalizumab: no obvious adverse reactions were found during treatment and follow-up. Conclusions:Omalizumab can significantly improve the clinical symptoms, small airway function and quality of life of children with allergic asthma and concomitant AR or CSU.It is a potential targeted drug for treating a variety of allergic diseases in children.

Case series study on efficacy and safety of Omalizumab in the treatment of moderate-to-severe allergic asthma in children / 中华实用儿科临床杂志

Objective:To explore the clinical efficacy and safety of the new targeted anti-immunoglobulin E (IgE) drug Omalizumab in the treatment of children with moderate and severe allergic bronchial asthma in China.Methods:The clinical data of children with moderate and severe allergic asthma who were treated in the Department of Pediatrics of Peking University First Hospital from July 2018 to January 2020 and treated with Omalizumab were retrospectively analyzed.A comparison was performed on the changes of questionnaires, including childhood asthma control test (C-ACT), pediatric asthma quality of life questionnaire (PAQLQ), mini-asthma quality of life questionnaire (Mini-AQLQ) and global evaluation of asthma treatment effectiveness (GETE), pulmonary function test, including forced expiratory volume in the first second (FEV 1), percentage to predicted value (FEV 1% pred) and small airway function, fractional concentration of exhaled nitric oxide (FeNO) and so on, before and after treating with Omalizumab. Results:A total of 15 pediatric patients completed 16 weeks of treatment follow-up.After 16 weeks of Omazumab treatment, the score of C-ACT increased from (16.001.66) scores to (25.38±0.64) scores ( F=11.969, P<0.001), PAQLQ increased from (118.08 ± 23.78) scores to (141.00 ± 11.91) scores ( F=9.289, P=0.001), Mini-AQLQ increased from (78.93±7.43) scores to (97.92±3.12) scores ( F=4.145, P=0.042), and GETE decreased from (2.47±0.27) scores to (1.60±0.19) scores ( t=2.982, P=0.010). The actual value of FEV 1, FEV 1% pred, the maximum expiratory flow percentage of the predicted value (PEF% pred), forced expiratory flow at 25% (MEF 75), forced expiratory flow at 50% (MEF 50) and maximum midexpiratory flow (MMEF 75/25), increased from (1.96±0.12) L to (2.17±0.21) L ( F=0.425, P=0.789), (81.46±2.85)% to (82.64±1.55)% ( F=0.926, P=0.465), (82.05±3.58)% to (91.10±4.67)% ( F=1.909, P=0.128), (60.36±7.43)% to (76.94±4.65)% ( F=2.120, P=0.096), (52.72±3.75)% to (73.80±8.34)% ( F=3.140, P=0.047) and (60.05±8.47)% to (74.86±10.85)% ( F=7.860, P=0.010), respectively.FeNO decreased from 25.0 (14.5, 35.5) μg/L to 20.0 (18.5, 30.0) μg/L ( Z=-0.206, P=0.840). Transient headache was observed in 1 case and evanescent eruption in 2 cases during the treatment, respectively. Conclusions:Omalizumab can significantly improve the clinical manifestations, lung function indicators and quality of life of children with moderate and severe allergic asthma, and has good safety.Thus, it is expected to play an important role in the treatment of children with moderate-to-severe allergic asthma.

Advances in inflammasome and pulmonary disease and its intervention / 中华实用儿科临床杂志

Nucleotide-binding oligomerization domain like receptors (NLRs) can recognize conserved sequences of microorganisms and initiate inflammation,nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) is one of the most representative members of the NLRs family.Activated by a variety of endogenous or exogenous dangerous signals,NLRP3 combines with apoptosis-associated speck-like protein (ASC) and caspase-1 to form inflammasome.And then it acts on downstream inflammatory factors such as interleukin-1β (IL-1β) and interleukin-18 (IL-18) to promote their maturation and secretion.At the same time,it can interact with gasdermin D(GSDMD) and eventually lead to pyroptosis.It was found that,NLRP3 was closely related to the occurrence and development of pulmonary diseases.Finding inhibitors of key proteins in NLRP3 inflammasome pathway may provide a new way to treat related diseases.This article reviews the composition of NLRP3 inflammasome,the relationship between NLRP3 inflammasome and the occurrence of pulmonary diseases,and the advances in intervention research.

Advances in inflammasome and pulmonary disease and its intervention / 中华实用儿科临床杂志

Nucleotide-binding oligomerization domain like receptors (NLRs) can recognize conserved sequences of microorganisms and initiate inflammation, nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) is one of the most representative members of the NLRs family.Activated by a variety of endogenous or exogenous dangerous signals, NLRP3 combines with apoptosis-associated speck-like protein(ASC) and caspase-1 to form inflammasome.And then it acts on downstream inflammatory factors such as inter-leukin-1β (IL-1β) and interleukin-18 (IL-18) to promote their maturation and secretion.At the same time, it can interact with gasdermin D(GSDMD)and eventually lead to pyroptosis.It was found that, NLRP3 was closely related to the occurrence and development of pulmonary diseases.Finding inhibitors of key proteins in NLRP3 inflammasome pathway may provide a new way to treat related diseases.This article reviews the composition of NLRP3 inflammasome, the relationship between NLRP3 inflammasome and the occurrence of pulmonary diseases, and the advances in intervention research.

Long non-coding RNAs show different expression profiles and display competing endogenous RNA potential in placenta accreta spectrum disorders / 南方医科大学学报

OBJECTIVE@#To investigate the expression profile of long non-coding RNAs (lncRNA) and identify potential lncRNA-related competing endogenous RNAs (ceRNA) in placenta accrete spectrum disorders (PAS).@*METHODS@#Five tissue specimens of placental implantation and 5 adjacent normal placental tissues were collected from cesarean section deliveries complicated by PAS in our hospital between December, 2017 and June, 2018. Human microarrays were used to identify the lncRNAs that were differentially expressed in PAS, and 5 of the identified lncRNAs were further validated using qRT-PCR. GO and KEGG pathway analyses were performed to indentify the most significant enrichment functions. A ceRNA network was constructed based on ENST00000511361 (RP5-875H18.4), NR_027457 (LINC00221) and NR_126415 (FOXP4-AS1) to pinpoint the potential lncRNAs-related ceRNA.@*RESULTS@#A total of 329 lncRNAs and 179 mRNAs were identified to have differential expression in PAS. The results of qRT-PCR were consistent with the human microarrays results. Transforming growth factor-β (TGF-β) signaling pathway was the most significantly enriched pathway. The constructed ceRNA network suggested that RP5-875H18.4--miRNA-218--SLIT2 had a potential ceRNA regulatory mechanism in PAS.@*CONCLUSIONS@#The differentially expressed lncRNAs are involved in the occurrence and progression of PAS possibly by regulating the TGF-β signaling pathway. The ceRNA network of RP5-875H18.4--miRNA-218--SLIT2 may play a role in the occurrence of PAS.