Immune checkpoint inhibitors as first-line therapy for non-small cell lung cancer: A systematic evaluation and meta-analysis.

Recently, immune checkpoint inhibitors (ICIs) present promising application prospects in treating non-small cell lung cancer (NSCLC). This study aimed to investigate optimal treatment strategy by comparing the first-line treatment strategies with ICIs in NSCLC. We retrieved relevant studies on first-line therapy of NSCLC with ICIs. Primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary outcomes were treatment-related serious adverse events (tr-SAEs) with grade 3 or higher and objective response rate (ORR). We also conducted a Bayesian network meta-analysis. We included 14 studies involving 7,823 patients and compared seven different interventions. In PD-L1 nonselective NSCLC, nivolumab+ipilimumab had good PFS and ORR, pembrolizumab significantly prolonged OS, and nivolumab had the fewest adverse events (AEs). For PD-L1-positive patients, nivolumab remarkably prolonged OS. For those with negative PD-L1, nivolumab+ipilimumab also showed an advantage. In addition, nivolumab+ipilimumab significantly prolonged the PFS in both PD-L1-negative and -positive patients. For patients with PD-L1 tumor proportion score (TPS) within 1-49%, atezolizumab+chemotherapy remarkably prolonged PFS and OS. For those with PD-L1 TPS ≥50%, pembrolizumab prolonged OS and atezolizumab+chemotherapy significantly prolonged PFS. Nivolumab combined with ipilimumab showed advantages in OS, PFS and ORR in most patients. Nivolumab+ipilimumab may be the optimal first-line therapy for NSCLC.

Long-term Pegylated GH for Children With GH Deficiency: A Large, Prospective, Real-world Study.

CONTEXT: The evidence of long-term polyethylene glycol recombinant human GH (PEG-rhGH) in pediatric GH deficiency (GHD) is limited. OBJECTIVE: This study aimed to examine the effectiveness and safety of long-term PEG-rhGH in children with GHD in the real world, as well as to examine the effects of dose on patient outcomes. DESIGN: A prospective, observational, posttrial study (NCT03290235). SETTING, PARTICIPANTS AND INTERVENTION: Children with GHD were enrolled from 81 centers in China in 4 individual clinical trials and received weekly 0.2 mg/kg/wk (high-dose) or 0.1 to <0.2 mg/kg/wk (low-dose) PEG-rhGH for 30 months. MAIN OUTCOMES MEASURES: Height SD score (Ht SDS) at 12, 24, and 36 months. RESULTS: A total of 1170 children were enrolled in this posttrial study, with 642 patients in the high-dose subgroup and 528 in the low-dose subgroup. The Ht SDS improved significantly after treatment in the total population (P < 0.0001), with a mean change of 0.53 ± 0.30, 0.89 ± 0.48, 1.35 ± 0.63, 1.63 ± 0.75 at 6 months, 12 months, 24 months, and 36 months, respectively. In addition, the changes in Ht SDS from baseline were significantly improved in the high-dose subgroup compared with the low-dose subgroup at 6, 12, 24, and 36 months after treatment (all P < 0.05). A total of 12 (1.03%) patients developed serious adverse events. There was no serious adverse event related to the treatment, and no AEs leading to treatment discontinuation or death occurred. CONCLUSIONS: PEG-rhGH showed long-term effectiveness and safety in treating children with GHD. Both dose subgroups showed promising outcomes, whereas PEG-rhGH 0.2 mg/kg/wk might show additional benefit.

Role and Mechanism of miR-181a-5p in Mice with Chronic Obstructive Pulmonary Disease by Regulating HMGB1 and the NF-κB Pathway.

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease. This study explored the mechanism of miR-181a-5p in the inflammatory response in COPD mice. COPD mouse models were established by cigarette smoke (CS) exposure following pretreatment with recombinant adeno-associated virus (rAAv)-miR-181a-5p, si-HMGB1 (high mobility group box 1), and NF-κB pathway inhibitor PDTC, respectively. Pathological changes of lung tissues were determined by HE staining. Bronchoalveolar lavage fluid was collected to count total cells, neutrophils, and lymphocytes using a Countess II automatic cell counter. Expressions of neutrophil elastase (NE) and inflammatory factors (TNF-α, IL-6, IL-8, and IFN-γ) were detected by ELISA. Binding relationship between miR-181a-5p and HMGB1 was predicted on starBase and validated by dual-luciferase assay. miR-181a-5p expression was detected by RT-qPCR, and expressions of HMGB1, IκBα, and p-IκBα were detected by western blot. The expression level of miR-181a-5p was lower in lung tissues. miR-181a-5p overexpression alleviated inflammatory response and pathological changes of lung tissues in COPD mice, with decreased pulmonary inflammation scores, total cells, neutrophils, and lymphocytes and expressions of NE and inflammatory factors. HMGB1 expression level was increased in COPD mice. miR-181a-5p targeted HMGB1. si-HMGB1 relieved inflammatory responses in COPD mice. NF-κB was activated in COPD mice, evidenced by degraded IκBα and increased p-IκBα levels. si-HMGB1 significantly restrained the activation of NF-κB pathway. Briefly, miR-181a-5p targets HMGB1 to inhibit the NF-κB pathway, thus alleviating the inflammatory response in COPD mice.

CCLOWW: A grade-level Chinese children's lexicon of written words.

In this article, we present the Chinese Children's Lexicon of Written Words (CCLOWW), the first grade-level database that provides frequency statistics of simplified Chinese characters and words for children. The database computes from a corpus of 34,671,424 character tokens and 22,427,010 word tokens (including single- and multicharacter words), extracted from 2131 books. It contains 6746 different character types and 153,079 different word types. CCLOWW provides several frequency indices of simplified Chinese for three grade levels (grade 2 and below, grades 3-4, grades 5-6) to profile children's experience with written Chinese in and outside of school. We describe in this article the distributions of frequency and contextual diversity of the characters and words, as well as word length and syntactic categories of the words in the corpus and the subcorpora. We also report results of correlation analyses with other written corpora and of several naming and lexicon decision experiments. The findings suggest that CCLOWW frequency measures correlate well with other corpora. Importantly, they could reliably predict children's and adults' naming and lexical decision performances. They could also explain variance in adults' visual word recognition, in addition to frequency measures computed in an adult corpus, indicating that early print exposure might influence readers' lexical processing later on beyond an age of acquisition effect. CCLOWW will help researchers in language processing and development as well as educators with selecting language materials appropriate for children's developmental stages. The database is freely available online at https://www.learn2read.cn/database/ .

Short-term efficacy and safety of a lower dose of polyethylene glycol recombinant human growth hormone in children with growth hormone deficiency: A randomized, dose-comparison study.

Objective: Polyethylene glycol recombinant human growth hormone (PEG-rhGH, Jintrolong®) is the first long-acting rhGH preparation that is approved to treat children with growth hormone deficiency (GHD) in China. Clinical experience with dose selections of PEG-rhGH is scarce. The present study compared the efficacy and safety of a lower dose to increase dosing regimens of PEG-rhGH treatment. Methods: A multicenter, randomized, open-label, dose-comparison clinical study was conducted to compare the improvements in the height standard deviation score (Ht SDS), height velocity (HV), insulin-like growth factor-1 (IGF-1) SDS, and safety profiles of children with GHD who are treated with 0.2 mg/kg/week of PEG-rhGH dose or 0.14 mg/kg/week for 26 weeks. Results: Ht SDS, HV, and IGF-1 SDS increased significantly after PEG-rhGH treatment in the two dose groups (p < 0.05). The improvements of Ht SDS, HV, and IGF-1 SDS were more significant in the high-dose group than in the low-dose group (p < 0.05). Ht SDS improvement in low-dose group was not non-inferiority to that in the high-dose group (p = 0.2987). The incidences of adverse events were comparable between the two groups. Conclusion: The improvements of Ht SDS, HV, and IGF-1 SDS were more significant in the high-dose group than in the low-dose group (p < 0.05). PEG-rhGH at the dose of 0.14 mg/kg/week was effective and safe for children with GHD. Clinical Trial Registration: clinicaltrials.gov, identifier NCT02908958.