Polymorphic tandem DNA repeats activate the human telomerase reverse transcriptase gene.

Multiple independent sequence variants of the hTERT locus have been associated with telomere length and cancer risks in genome-wide association studies. Here, we identified an intronic variable number tandem repeat, VNTR2-1, as an enhancer-like element, which activated hTERT transcription in a cell in a chromatin-dependent manner. VNTR2-1, consisting of 42-bp repeats with an array of enhancer boxes, cooperated with the proximal promoter in the regulation of hTERT transcription by basic helix-loop-helix transcription factors and maintained hTERT expression during embryonic stem-cell differentiation. Genomic deletion of VNTR2-1 in MelJuSo melanoma cells markedly reduced hTERT transcription, leading to telomere shortening, cellular senescence, and impairment of xenograft tumor growth. Interestingly, VNTR2-1 lengths varied widely in human populations; hTERT alleles with shorter VNTR2-1 were underrepresented in African American centenarians, indicating its role in human aging. Therefore, this polymorphic element is likely a missing link in the telomerase regulatory network and a molecular basis for genetic diversities of telomere homeostasis and age-related disease susceptibilities.

First Report of Leaf Spot on Cucumis melo L. Caused by Arcopilus aureus in China.

Cucumis melo L. is an important fruit with widespread consumption and commercial value. However, an undescribed disease affecting Hami melon (Cucumis melo L. var. Luhoutian) plants has consistently emerged in the Qihe region of Dezhou, Shandong Province of China since 2021. The disease can occur in both seedling and mature stages of Hami melon plants, and in severely diseased areas, the incidence rate was seen as 40 to 80%. During the seedling stage, the initial symptom is the appearance of water-soaked spots on the leaves. As the disease progresses, the leaves develop necrotic spots, and severely affected plants may exhibit stem rot and decay. In the mature stage, the disease primarily affects the leaves, causing necrotic spots and chlorosis. Under conditions of high humidity, black mold can be observed in the affected areas. Small pieces of symptomatic leaves from six different infected plants were collected and surface-sterilized with 5% NaClO for 3 min and 75% alcohol for 30 s for pathogen isolation (Wang et al., 2020). After rinsing with sterile water and blotted on sterile filter paper, the tissues were established on potato dextrose agar (PDA) media and incubated at 28℃ for 3-4 days. Pure isolates showed up at PDA were obtained through single-spore isolation. Colonies of all 16 isolates obtained by single-spore isolation had similar morphological characteristics on the PDA medium, the mycelium of the isolate appears dense and yellowish-brown on the PDA medium, and also secretes a brownish-red pigment on PDA. Under the opticalmicroscope, the perithecia from PDA media are subglobose spherical in shape, 80-100 µm in diameter, brownish by reflected light, wholly and densely hairy. Terminal hairs are very dense, greyish by reflected light, olive brown to reddish brown by transmitted light, thick-walled, arcuate, circinate, or spirally coiled at the apex. The ascospores within the perithecia are elliptical or droplet-shaped, initially colorless hyaline but later becoming subhyaline slightly gray, with dimensions of 7-9 µm × 4-5 µm. The morphological characteristics of the isolates were consistent with the description of Arcopilus aureus (Wang et.al. 2016). The internal transcribed spacer (ITS) region and ß-tubulin genes of three randomly selected isolates were PCR amplified and sequenced using primers ITS4/ITS5 and Bt2a/Bt2b. The sequences of ITS and ß-tubulin genes were submitted to NCBI with GenBank Accession No. OR539527 and OR640972, respectively. Based on morphological features and phylogenetic analysis, we concluded that the isolates belonged to A. aureus. Pathogenicity tests were conducted by placing agar plugs-containing fungal mycelia and agar blocks (control) on leaves of Hami melon seedlings (n=12) grown at 28°C with 60% humidity in a greenhouse, the assay was repeated three times. Symptoms appeared on the pathogen-inoculated leaves seven days after inoculation, whereas the control treatment remained symptomless. The pathogens were reisolated from diseased leaves and identified as A. aureus based on morphological, and molecular phylogenetic analysis, while Koch'sostulate was used to confirm its life mode. To the best of our knowledge, this is the first report of leaf spot caused by A. aureus on Cucumis melo L. in China.

Detection Transformer with Multi-Scale Fusion Attention Mechanism for Aero-Engine Turbine Blade Cast Defect Detection Considering Comprehensive Features.

Casting defects in turbine blades can significantly reduce an aero-engine's service life and cause secondary damage to the blades when exposed to harsh environments. Therefore, casting defect detection plays a crucial role in enhancing aircraft performance. Existing defect detection methods face challenges in effectively detecting multi-scale defects and handling imbalanced datasets, leading to unsatisfactory defect detection results. In this work, a novel blade defect detection method is proposed. This method is based on a detection transformer with a multi-scale fusion attention mechanism, considering comprehensive features. Firstly, a novel joint data augmentation (JDA) method is constructed to alleviate the imbalanced dataset issue by effectively increasing the number of sample data. Then, an attention-based channel-adaptive weighting (ACAW) feature enhancement module is established to fully apply complementary information among different feature channels, and further refine feature representations. Consequently, a multi-scale feature fusion (MFF) module is proposed to integrate high-dimensional semantic information and low-level representation features, enhancing multi-scale defect detection precision. Moreover, R-Focal loss is developed in an MFF attention-based DEtection TRansformer (DETR) to further solve the issue of imbalanced datasets and accelerate model convergence using the random hyper-parameters search strategy. An aero-engine turbine blade defect X-ray (ATBDX) image dataset is applied to validate the proposed method. The comparative results demonstrate that this proposed method can effectively integrate multi-scale image features and enhance multi-scale defect detection precision.

Hemiplegia due to hypoglycaemia followed by haemicorea after correction of glycaemic values.

A 69-year-old man suffered from hemiplegia of the left limb due to hypoglycaemia. After 3 h of oral supplementation with sugar water, the patient recovered from hemiplegia but then presented symptoms of haemichorea. To our knowledge, a case of abnormal glucose metabolism complicated with two types of motor disturbance has not been reported previously.

A DMD case caused by X chromosome rearrangement.

Duchenne/Becker muscular dystrophy (DMD/BMD) is one of the most common progressive muscular dystrophy diseases with X-linked recessive inheritance. It is mainly caused by the deletion, duplication and point mutation of DMD gene. In rare cases, it is also caused by the destruction of DMD gene by chromosomal structural rearrangement. Here, we report a case of Duchenne/Becker Muscular dystrophy (DMD/BMD) with typical symptoms but unknown genetic defects after MLPA and next generation sequencing tests in other hospitals. Interestingly, we find a pericentric inversion of X chromosome (Chr.X: g. [31939463-31939465del; 31939466-131765063 inv; 131765064-131765067del]) in this patient. We then use the karyotyping, FISH, long-read sequencing and Sanger sequencing technologies to characterize the chromosome rearrangement. We find that this chromosomal aberration disrupt both the DMD gene and the HS6ST2 gene. The patient present with typical DMD symptoms such as muscle weakness, but no obvious symptoms of Paganini-Miozzo syndrome. Our results suggest that the destruction of DMD gene by structural rearrangement is also one of the important causes of DMD. Therefore, we suggest to provide further genetic testing for those DMD patients with unknown genetic defects through routine genetic testing. Cost-effective karyotyping and FISH should be considered firstly to identify chromosome rearrangements. Long-read sequencing followed by Sanger sequencing could be useful to locate the precise breakpoints. The genetic diagnosis of this case made it possible for reproductive intervention in the patient's family.

C1632 suppresses the migration and proliferation of non-small-cell lung cancer cells involving LIN28 and FGFR1 pathway.

Chemoresistance and migration represent major obstacles in the therapy of non-small-cell lung cancer (NSCLC), which accounts for approximately 85% of lung cancer patients in clinic. In the present study, we report that the compound C1632 is preferentially distributed in the lung after oral administration in vivo with high bioavailability and limited inhibitory effects on CYP450 isoenzymes. We found that C1632 could simultaneously inhibit the expression of LIN28 and block FGFR1 signalling transduction in NSCLC A549 and A549R cells, resulting in significant decreases in the phosphorylation of focal adhesion kinase and the expression of matrix metalloproteinase-9. Consequently, C1632 effectively inhibited the migration and invasion of A549 and A549R cells. Meanwhile, C1632 significantly suppressed the cell viability and the colony formation of A549 and A549R cells by inhibiting DNA replication and inducing G0/G1 cell cycle arrest. Interestingly, compared with A549 cells, C1632 possesses the same or even better anti-migration and anti-proliferation effects on A549R cells, regardless of drug resistance. In addition, C1632 also displayed the capacity to inhibit the growth of A549R xenograft tumours in mice. Altogether, these findings reveal the potential of C1632 as a promising anti-NSCLC agent, especially for chemotherapy-resistant NSCLC treatment.

The chloroplast ribosomal protein large subunit 1 interacts with viral polymerase and promotes virus infection.

Chloroplasts play an indispensable role in the arms race between plant viruses and hosts. Chloroplast proteins are often recruited by plant viruses to support viral replication and movement. However, the mechanism by which chloroplast proteins regulate potyvirus infection remains largely unknown. In this study, we observed that Nicotiana benthamiana ribosomal protein large subunit 1 (NbRPL1), a chloroplast ribosomal protein, localized to the chloroplasts via its N-terminal 61 amino acids (transit peptide), and interacted with tobacco vein banding mosaic virus (TVBMV) nuclear inclusion protein b (NIb), an RNA-dependent RNA polymerase. Upon TVBMV infection, NbRPL1 was recruited into the 6K2-induced viral replication complexes in chloroplasts. Silencing of NbRPL1 expression reduced TVBMV replication. NbRPL1 competed with NbBeclin1 to bind NIb, and reduced the NbBeclin1-mediated degradation of NIb. Therefore, our results suggest that NbRPL1 interacts with NIb in the chloroplasts, reduces NbBeclin1-mediated NIb degradation, and enhances TVBMV infection.

Immunophenotype in acute exacerbation of chronic obstructive pulmonary disease: a cross-sectional study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease, and the immune inflammatory response is thought to play an important role in pathogenesis. However, the immunophenotype of patients with COPD is unknown. Herein, we evaluated the immunophenotype of patients with acute exacerbation of COPD (AECOPD). METHODS: A cross-sectional study was conducted in West China Hospital from September 2018 to October 2019. The proportion of CD4 + T lymphocyte subtypes (Th1, Th2, Th17 and Treg) and levels of serum cytokines in the peripheral blood of patients with AECOPD, stable COPD (SCOPD), healthy smokers (HSs)and healthy controls (HCs) were evaluated. RESULTS: A total of 15 HCs, 19 HSs, 42 patients with SCOPD, and 55 patients with AECOPD were included. Compared to patients with SCOPD, Th1 cells, Th17 cells, Treg cell ratio, Th1/Th2 cell ratio, and the levels of C-reactive protein, interleukin (IL)-6, and IL-10 were significantly increased in patients with AECOPD (P < 0.001), while the proportion of Th2 cells was significantly reduced (P < 0.01). The proportion of Th17 cells was positively correlated with COPD Assessment Test score (r = 0.266, P = 0.009), modified Medical Research Council dyspnea score (r = 0.858, P < 0.0001), and Th1 cell ratio (r = 0.403, P < 0.0001) and negatively correlated with forced vital capacity (r = - 0.367, P = 0.009) and proportion of Th2 cells (r = - 0.655, P < 0.0001). CONCLUSIONS: The immunophenotype of patients with AECOPD shows abnormal activation of Th1, Th17, and Treg cells. There is a correlation between the proportion of Th17 cells and the severity of COPD; therefore, this may represent a novel index for the evaluation of COPD severity. TRIAL REGISTRATION: China Clinical Trials Registry, ChiCTR1800018452, registered 19 September 2018, https://www.chictr.org.cn/index.aspx .

ACT001 inhibits pituitary tumor growth by inducing autophagic cell death via MEK4/MAPK pathway.

ACT001, derived from traditional herbal medicine, is a novel compound with effective anticancer activity in clinical trials. However, little is known regarding its role in pituitary adenomas. Here, we demonstrated that ACT001 suppressed cell proliferation and induced cell death of pituitary tumor cells in vitro and in vivo. ACT001 was also effective in suppressing the growth of different subtypes of human pituitary adenomas. The cytotoxic mechanism ACT001 employed was mainly related to autophagic cell death (ACD), indicated by autophagosome formation and LC3-II accumulation. In addition, ACT001-mediated inhibitory effect decreased when either ATG7 was downregulated or cells were cotreated with autophagy inhibitor 3-methyladenine (3-MA). RNA-seq analysis showed that mitogen-activated protein kinase (MAPK) pathway was a putative target of ACT001. Specifically, ACT001 treatment promoted the phosphorylation of JNK and P38 by binding to mitogen-activated protein kinase kinase 4 (MEK4). Our study indicated that ACT001-induced ACD of pituitary tumor cells via activating JNK and P38 phosphorylation by binding with MEK4, and it might be a novel and effective anticancer drug for pituitary adenomas.

A Predicted Stem Loop in Coat Protein-Coding Sequence of Tobacco Vein Banding Mosaic Virus Is Required for Efficient Replication.

Potyviral coat protein (CP) is involved in the replication and movement of potyviruses. However, little information is available on the roles of CP-coding sequence in potyviral infection. Here, we introduced synonymous substitutions to the codon C574G575C576 coding conserved residue arginine at position 192 (R192) of tobacco vein banding mosaic virus (TVBMV) CP. Substitution of the codon C574G575C576 to A574G575A576 or A574G575G576, but not C574G575A576, C574G575T576, or C574G575G576, reduced the replication, cell-to-cell movement, and accumulation of TVBMV in Nicotiana benthamiana plants, suggesting that C574 was critical for replication of TVBMV. Nucleotides 531 to 576 of the TVBMV CP-coding sequence were predicted to form a stem-loop structure, in which four consecutive C-G base pairs (C576-G531, C532-G575, C574-G533, and C534-G573) were located at the stem. Synonymous substitutions of R178-codon C532G533C534 to A532G533A534 and A532G533G534, but not C532G533A534, C532G533T534, or C532G533G534, reduced the replication levels, cell-to-cell, and systemic movement of TVBMV, suggesting that C532 was critical for TVBMV replication. Synonymous substitutions disrupting base pairs C576-G531 and C534-G573 did not affect viral accumulation. After three serial-passage inoculations, the accumulation of spontaneous mutant viruses was restored, and codons A532G533A534, A532G533G534, A574G575A576, or A574G575G576 of mutants were each separately changed to C532G533A534, C532G533G534, C574G575A576, or C574G575G576. Synonymous mutation of R178 and R192 also reduced viral accumulation in N. tabacum plants. Therefore, we concluded that the two consecutive C532-G575 and C574-G533 base pairs played critical roles in TVBMV replication via maintaining the stability of the stem-loop structures formed by nucleotides 531 to 576 of the CP-coding sequence.

[ß-arrestin2 recruitment by ß-adrenergic receptor agonists and antagonists].

A large number of ß-adrenergic receptor (ß-AR) agonists and antagonists are widely used in the treatment of cardiovascular diseases and other diseases. Nonetheless, it remains unclear whether these commonly used ß-AR drugs can activate downstream ß- arrestin-biased signaling pathways. The objective of this study was to investigate ß-arrestin2 recruitment effects of ß-AR agonists and antagonists that were commonly used in clinical practice. We used TANGO (transcriptional activation following arrestin translocation) assay to detect the ß-arrestin2 recruitment by ß-AR ligands in HEK293 cell line (HTLA cells) stably transfected with tetracycline transactivator protein (tTA) dependent luciferase reporter and ß-arrestin2-TEV fusion gene. Upon activation of ß-AR by a ß-AR ligand, ß-arrestin2 was recruited to the C terminus of the receptor, followed by cleavage of the G protein-coupled receptors (GPCRs) fusion protein at the TEV protease-cleavage site. The cleavage resulted in the release of tTA, which, after being transported to the nucleus, activated transcription of the luciferase reporter gene. The results showed that ß-AR non-selective agonists epinephrine, noradrenaline and isoprenaline all promoted ß-arrestin2 recruitment at ß1-AR and ß2-AR. ß1-AR selective agonists dobutamine and denopamine both promoted ß-arrestin2 recruitment at ß1-AR. ß2-AR selective agonists procaterol and salbutamol promoted ß-arrestin2 recruitment at ß2-AR. ß-AR non-selective antagonists alprenolol and pindolol promoted ß-arrestin2 recruitment at ß1-AR. ß1-AR selective antagonists celiprolol and bevantolol showed ß-arrestin2 recruitment at ß1-AR. ß2-AR selective antagonists butoxamine showed ß-arrestin2 recruitment at ß1-AR. These results provide some clues for the potential action of ß-AR drugs, and lay a foundation for the screening of ß-arrestin-biased ß-AR ligands.

Residues R192 and K225 in RNA-Binding Pocket of Tobacco Vein Banding Mosaic Virus CP Control Virus Cell-to-Cell Movement and Replication.

Potyviruses move to neighboring cells in the form of virus particles or a coat protein (CP)-containing ribonucleoprotein complex. However, the precise roles of RNA-binding residues in potyviral CP in viral cell-to-cell movement remain to be elucidated. In this study, we predicted the three-dimensional model of tobacco vein banding mosaic virus (TVBMV)-encoded CP and found nine residues presumably located in the CP RNA-binding pocket. Substitutions of the two basic residues at positions 192 and 225 (R192 and K225) with either alanine, cysteine, or glutamic acid abolished TVBMV cell-to-cell and systemic movement in Nicotiana benthamiana plants. These substitutions also reduced the replication of the mutant viruses. Results from the electrophoretic mobility shift assay showed that the RNA-binding activity of mutant CPs derived from R192 or K225 substitutions was significantly lower than that of wild-type CP. Analysis of purified virus particles showed that mutant viruses with R192 or K225 substitutions formed RNA-free virus-like particles. Mutations of R192 and K225 did not change the CP plasmodesmata localization. The wild-type TVBMV CP could rescue the deficient cell-to-cell movement of mutant viruses. Moreover, deletion of any of the other seven residues also abolished TVBMV cell-to-cell movement and reduced the CP RNA-binding activity. The corresponding nine residues in watermelon mosaic virus CP were also found to play essential roles in virus cell-to-cell movement. In conclusion, residues R192 and K225 in the CP RNA-binding pocket are critical for viral RNA binding and affect both virus replication and cell-to-cell movement.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Alterations of gut microbiota in gestational diabetes patients during the second trimester of pregnancy in the Shanghai Han population.

BACKGROUND: The causes of gestational diabetes mellitus (GDM) are still unclear. Recent studies have found that the imbalance of the gut microbiome could lead to disorders of human metabolism and immune system, resulting in GDM. This study aims to reveal the different gut compositions between GDM and normoglycemic pregnant women and find the relationship between gut microbiota and GDM. METHODS: Fecal microbiota profiles from women with GDM (n = 21) and normoglycemic women (n = 32) were assessed by 16S rRNA gene sequencing. Fasting metabolic hormone concentrations were measured using multiplex ELISA. RESULTS: Metabolic hormone levels, microbiome profiles, and inferred functional characteristics differed between women with GDM and healthy women. Additionally, four phyla and seven genera levels have different correlations with plasma glucose and insulin levels. Corynebacteriales (order), Nocardiaceae (family), Desulfovibrionaceae (family), Rhodococcus (genus), and Bacteroidetes (phylum) may be the taxonomic biomarkers of GDM. Microbial gene functions related to amino sugar and nucleotide sugar metabolism were found to be enriched in patients with GDM. CONCLUSION: Our study indicated that dysbiosis of the gut microbiome exists in patients with GDM in the second trimester of pregnancy, and gut microbiota might be a potential diagnostic biomarker for the diagnosis, prevention, and treatment of GDM.

The amino acid variants in HLA II molecules explain the major association with adult-onset Still's disease in the Han Chinese population.

Adult-onset Still's disease (AOSD) is a rare autoinflammatory disease with systemic involvement, and its pathophysiology remains unclear. Genome-wide association studies (GWAS) in the Chinese population have revealed an association between AOSD and the major histocompatibility complex (MHC) locus; however, causal variants in the MHC remain undetermined. In the present study, we identified independent amino-acid polymorphisms in human leukocyte antigen (HLA) molecules that are associated with Han Chinese patients with AOSD by fine-mapping the MHC locus. Through conditional analyses, we identified position 34 in HLA-DQα1 (p = 1.44 × 10-14) and Asn in HLA-DRß1 position 37 (p = 5.12 × 10-11) as the major determinants for AOSD. Moreover, we identified the associations for three main HLA class II alleles: HLA-DQB1*06:02 (OR = 2.70, p = 3.02 × 10-14), HLA-DRB1*15:01 (OR = 2.44, p = 3.66 × 10-13), and HLA-DQA1*01:02 (OR = 1.97, p = 1.09 × 10-9). This study reveals the relationship between functional variations in the class II HLA region and AOSD, implicating the MHC locus in the pathogenesis of AOSD.

Crispr/Cas9-mediated cleavages facilitate homologous recombination during genetic engineering of a large chromosomal region.

Homologous recombination over large genomic regions is difficult to achieve due to low efficiencies. Here, we report the successful engineering of a humanized mTert allele, hmTert, in the mouse genome by replacing an 18.1-kb genomic region around the mTert gene with a recombinant fragment of over 45.5 kb, using homologous recombination facilitated by the Crispr/Cas9 technology, in mouse embryonic stem cells (mESCs). In our experiments, with DNA double-strand breaks (DSBs) generated by Crispr/Cas9 system, the homologous recombination efficiency was up to 11% and 16% in two mESC lines TC1 and v6.5, respectively. Overall, we obtained a total of 27 mESC clones with heterozygous hmTert/mTert alleles and three clones with homozygous hmTert alleles. DSBs induced by Crispr/Cas9 cleavages also caused high rates of genomic DNA deletions and mutations at single-guide RNA target sites. Our results indicated that the Crispr/Cas9 system significantly increased the efficiency of homologous recombination-mediated gene editing over a large genomic region in mammalian cells, and also caused frequent mutations at unedited target sites. Overall, this strategy provides an efficient and feasible way for manipulating large chromosomal regions.

Multislice spiral CT images combined with CEA and lymphocyte-to-neutrophil ratio predict recurrence and post-operative metastasis of rectal cancer.

To explore the early predictors of post-operative recurrence and metastasis of rectal cancer, analyse the associated risk, and construct a model. Retrospective collection. Four hundred patients with rectal cancer underwent surgical resection and pathological diagnosis from September 2013 to September 2014. During the post-operative period, the patients were tested by imaging examination, serum tumour markers, and routine blood follow-up for at least 3 years. Preoperative CT examination of tumour size, lymphocyte-to-neutrophil ratio, and CEA were significant biomarkers for predicting recurrence and/or metastasis of post-operative rectal cancer. The stratified threshold of the lesion size cut-off point in CT images of patients with rectal cancer was 18.75 cm3, the cut-off point value of the lymphocyte-to-neutrophil ratio was 0.33, and the CEA cut-off point value was 16.97 ng/ml. We used the cut-off point to perform stratified survival analysis to obtain two K-M curves and conduct a log-rank test. The Cox multivariate risk regression results were as follows: preoperative CT images of lesion size, lymphocyte-to-neutrophil ratio, and CEA. The AUC of the normogram model for the prediction of post-operative recurrence and metastasis of rectal cancer is 0.939. Preoperative CT examination of tumour size can predict post-operative recurrence and metastasis of rectal cancer and can be used to analyse its risk. The lymphocyte-to-neutrophil ratio and CEA can also predict post-operative tumour recurrence and metastasis risk.

Efficacy and safety of dupilumab for the treatment of uncontrolled asthma: a meta-analysis of randomized clinical trials.

BACKGROUND: Several recent clinical trials have assessed the effects of dupilumab in uncontrolled asthma, but reached no definite conclusion. We therefore conducted this meta-analysis to evaluate the overall efficacy and safety of dupilumab for the treatment of uncontrolled asthma. METHODS: All randomized controlled trials were included. Standard mean differences (SMD) or relative risks (RR) were calculated using Fixed-or random-effects models. RESULTS: Five studies involving 3369 patients were identified. Pooled analysis showed significant improvements in the first-second forced expiratory volume (FEV1) (SMD = 4.29, 95% CI: 2.78-5.81) and Asthma Quality of Life Questionnaire scores (SMD = 4.39, 95% CI: 1.44-7.34). Dupilumab treatments were also associated with significantly decreased 5-item Asthma Control Questionnaire scores (SMD = - 4.95, 95% CI: - 7.30 to - 2.60), AM and PM asthma symptom scores (SMD = - 5.09, 95% CI: - 6.40 to - 3.77; SMD = - 4.92, 95% CI: - 5.98 to - 3.86, respectively), and severe exacerbation risk (RR = 0.73; 95% CI: 0.67-0.79) compared with placebo, with similar incidence of adverse events (RR = 1.0; 95% CI: 0.96-1.04). CONCLUSION: Dupilumab treatment is relatively well-tolerated and could significantly improve FEV1, symptoms, asthma control, and quality of life, and reduced severe exacerbation risk in patients with uncontrolled asthma.

Clinical features and current treatments of adult-onset Still's disease: a multicentre survey of 517 patients in China.

OBJECTIVES: As a rare systemic autoinflammatory disease, adult-onset Still's disease (AOSD) has heterogeneous clinical manifestations, response to treatment and outcome. This study tried to assess the clinical characteristics, laboratory tests, and treatments of Chinese AOSD patients, and make a retrospective analysis. METHODS: We collected from 7 hospitals in China a total of 517 Chinese patients with AOSD who satisfied the Yamaguchi criteria. We retrospectively evaluated their clinical features, laboratory tests, treatments and compared them with published data from different studies. All the data in this study were from medical records and further statistic analyses. RESULTS: We evaluated a total of 517 AOSD patients, 72% female, average age of onset was 37.7; spiking fever, rash and arthralgia occurred in 472 (91.3%), 413 (79.9%), 378 (73.1%) cases, respectively. There were 439/513 (85.6%) cases with leukocytosis and 456/476 (95.8%) cases with raised serum ferritin. The highest frequently used medications and regimens for remission were glucocorticoids (498/517, 96.3%), methotrexate (273/517, 52.8%) and hydroxychloroquine (174/517, 33.7%). 84.4%. 357/423 of AOSD cases were able to achieve initial remission with different regimens, mostly including glucocorticoids, methotrexate or hydroxychloroquine. 47.2% of them (244/517) received 30

Long-term follow-up of self-expandable metallic stents in benign tracheobronchial stenosis: a retrospective study.

BACKGROUND: Self-expandable metallic stents (SEMSs) have enabled a approving management of malignant airway stenosis. However, the long-term efficacy and safety of this treatment in patients with benign airway stricture are unclear. We conducted this study to retrospectively determine the efficacy and long-term outcomes in patients who have undergone SEMS placement for benign tracheobronchial stenosis. METHODS: All patients treated with SEMSs from July 2003 to June 2016 were reviewed for symptomatic response, complications, and long-term outcomes. RESULTS: Total 131 stents were successfully deployed in 116 patients. Ninety-eight patients demonstrated clinical improvement after stent insertion (84.48%; 95% confidence interval [CI]: 77.89-91.07). Compared with uncovered stents, covered stents were associated with more sore throats complaints or chest pain (13.89% versus 28.81%, P = 0.036) and with higher incidences of major and minor granulation tissue formation and with recurrent stenosis (4.17% versus 15.25%, P = 0.029; 11.11% versus 37.29%, P < 0.0001 and 9.72% versus 28.81%, P = 0.005, respectively). Each covered and uncovered stent developing tissue hyperplasia required a median of 2 (range: 1-15) and 1(range: 1-7) fibrobronchoscope with electrocautery therapy, respectively. At follow-up (median: 1276 days; range: 2-4263), 68 patients had complete resolution, 15 remained under interventional treatment, 8 had bronchial occlusions, 7 underwent surgery, 14 were lost to follow-up, and 4 died of stent unrelated causes. CONCLUSION: SEMS placement achieved most clinical improvement among patients in our study, if adequate endotracheal measures were used to address stent-related complications. The use of permanent SEMSs for benign tracheobronchial stenosis was effective and safe for the majority of patients in a long-term follow-up. TRIAL REGISTRATION: The study has been retrospectively registered in the China Clinical Trial Registry on October 21, 2018 (Registry ID: ChiCTR1800019024 ).