Homozygous mutation in DNAAF4 causes primary ciliary dyskinesia in a Chinese family

Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disorder that affects the structure and function of motile cilia, leading to classic clinical phenotypes, such as situs inversus, chronic sinusitis, bronchiectasis, repeated pneumonia and infertility. In this study, we diagnosed a female patient with PCD who was born in a consanguineous family through classic clinical manifestations, transmission electron microscopy and immunofluorescence staining. A novel DNAAF4 variant NM_130810: c.1118G>A (p. G373E) was filtered through Whole-exome sequencing. Subsequently, we explored the effect of the mutation on DNAAF4 protein from three aspects: protein expression, stability and interaction with downstream DNAAF2 protein through a series of experiments, such as transfection of plasmids and Co-immunoprecipitation. Finally, we confirmed that the mutation of DNAAF4 lead to PCD by reducing the stability of DNAAF4 protein, but the expression and function of DNAAF4 protein were not affected

CoNIC Challenge: Pushing the Frontiers of Nuclear Detection, Segmentation, Classification and Counting

Nuclear detection, segmentation and morphometric profiling are essential in helping us further understand the relationship between histology and patient outcome. To drive innovation in this area, we setup a community-wide challenge using the largest available dataset of its kind to assess nuclear segmentation and cellular composition. Our challenge, named CoNIC, stimulated the development of reproducible algorithms for cellular recognition with real-time result inspection on public leaderboards. We conducted an extensive post-challenge analysis based on the top-performing models using 1,658 whole-slide images of colon tissue. With around 700 million detected nuclei per model, associated features were used for dysplasia grading and survival analysis, where we demonstrated that the challenge's improvement over the previous state-of-the-art led to significant boosts in downstream performance. Our findings also suggest that eosinophils and neutrophils play an important role in the tumour microevironment. We release challenge models and WSI-level results to foster the development of further methods for biomarker discovery

The associations of serum serotonin with bone traits are age- and gender-specific.

Serotonin plays a potential role in bone metabolism, but the nature and extent of this relationship is unclear and human studies directly addressing the skeletal effect of circulating serotonin are rare.The study aimed to investigate the associations between serum serotonin and bone traits at multiple skeletal sites in women and men.Subjects were part of the CALEX-family study and comprised 235 young women, 121 premenopausal women, 124 postmenopausal women, and 168 men. Body composition was assessed using DXA, as was areal bone mineral density (aBMD) of spine, femur and whole body. In addition, pQCT was used to determine bone properties at tibial midshaft and distal radius. Fasting serum serotonin concentration was assessed using a competitive enzyme-linked immunosorbent assay.Serum serotonin declined with advancing age both in females and males (all p<0.01). Serotonin was negatively correlated with weight, BMI, lean and fat mass in women (r = -0.22 to -0.39, all p<0.001), but positively with height and lean mass in men (all p<0.01). In the premenopausal women, serotonin was negatively correlated with lumbar spine aBMD (r = -0.23, p<0.05) but the statistical significance disappeared after adjustment for weight. Conversely, in postmenopausal women, serotonin was positively correlated with whole body and femur aBMD, as well as with distal radius bone mineral content and volumetric BMD (r = 0.20 to 0.30, all p<0.05), and these associations remained significant after adjustment for weight. In men, no significant associations were found between serotonin and bone traits.Serum serotonin is positively associated with bone traits in postmenopausal women, but not in premenopausal women or men. This partially supports the idea of circulating serotonin playing a role in the regulation of bone metabolism, but also indicates the importance of gender and age specific factors

Perioperative Dexmedetomidine Fails to Improve Postoperative Analgesic Consumption and Postoperative Recovery in Patients Undergoing Lateral Thoracotomy for Thoracic Esophageal Cancer: A Randomized, Double-Blind, Placebo-Controlled Trial

Objectives. Dexmedetomidine is widely used as an adjunct to general anesthesia. In this study, we evaluated the effects of perioperative dexmedetomidine infusion on postoperative analgesia in patients undergoing lateral thoracotomy for thoracic esophageal cancer. Methods. A total of 62 patients undergoing lateral thoracotomy for thoracic esophageal cancer were randomized to receive adjuvant therapy with either dexmedetomidine (0.5 μg/kg intravenous bolus injection for 10 min before induction of anesthesia, followed by continuous infusion of 0.2–0.4 μg/kg/h until the end of surgery, and 0.06 μg/kg/h for 5 days after surgery) or equal volumes of saline. Acute postoperative pain was treated with patient-controlled intravenous sufentanil and flurbiprofen axetil. The primary outcomes of this study were the numbers of analgesic requirements in the first postoperative 72 h. Results. Perioperative dexmedetomidine did not decrease the numbers of analgesic requirements in the first postoperative 72 h (dexmedetomidine group: 12.14 ± 4.76, saline group: 10.89 ± 5.66; p=0.367). Likewise, the groups did not differ with respect to total postoperative analgesic requirements, postoperative pain, perioperative inflammation, blood cell count, incidence of adverse events, surgical recovery (assessed at postoperative days 2 and 5 using the surgical recovery scale), length of hospital stay, hospital cost, incidence of chronic pain, or quality of life. Notably, dexmedetomidine had beneficial effects on decreasing intraoperative opioid consumption and improving postoperative sleep quality. Discussion. Perioperative dexmedetomidine has limited analgesic benefits in lateral thoracotomy for esophageal cancer when added to an opioid-based multimodal anesthetic regimen but can reduce opioid consumption

Efficacy of Nalbuphine with Flurbiprofen on Multimodal Analgesia with Transverse Abdominis Plane Block in Elderly Patients Undergoing Open Gastrointestinal Surgery: A Randomized, Controlled, Double-Blinded Trial

Objective. To assess different doses of nalbuphine with flurbiprofen compared to sufentanil with flurbiprofen in multimodal analgesia efficacy for elderly patients undergoing gastrointestinal surgery with a transverse abdominis plane block (TAPB). Methods. 158 elderly patients scheduling for elective open gastrointestinal surgery under general anesthesia and TAPB were randomly assigned to four groups according to different doses of nalbuphine with flurbiprofen in postoperative intravenous analgesia (PCIA). Postoperative pain intensity, effective pressing numbers of PCIA, and adverse effects were recorded at 6, 12, 24, and 48 hours after surgery. Results. Postoperative pain intensity, effective pressing numbers, and the incidence of postoperative nausea and vomiting (PONV) were similar among the four groups after surgery, while the severity of PONV was decreased in Group L compared with Group S at 6, 12, and 48 h after surgery. No individual experienced pruritus, respiratory depression, or hypotension. Conclusions. Low dose of nalbuphine (15 μg·kg−1·ml−1) combined with flurbiprofen is superior for elderly patients undergoing elective open gastrointestinal surgery with TAPB in terms of the efficient postoperative analgesia and decreased severity of PONV. This trial is registered with NCT02984865

LncRNA SNHG4 promotes the proliferation, migration, invasiveness, and epithelial–mesenchymal transition of lung cancer cells by regulating miR-98-5p

Long noncoding RNA small nucleolar RNA host gene 4 (SNHG4) is usually up-regulated in cancer and regulates the malignant behaviors of cancer cells. However, its role in lung cancer remains elusive. In this study, we silenced the expression of SNHG4 in NCI-H1437 and SK-MES-1, two representative non-small-cell lung cancer cell lines, by transfecting them with siRNA (small interfering RNA) that specifically targets SNHG4. We observed a significantly inhibited cell proliferation in vitro and reduced tumor growth in vivo after SNHG4 silencing. SNHG4 knockdown also led to cell cycle arrest at G1 phase, accompanied with down-regulation of cyclin-dependent kinases CDK4 and CDK6. Migration and invasion of these two cell lines were remarkably inhibited after SNHG4 silencing. Moreover, our study revealed that epithelial-mesenchymal transition (EMT) of lung cancer cells was suppressed by SNHG4 silencing as evidenced by up-regulated E-cadherin and down-regulated SALL4, Twist and vimentin. In addition, we found that SNHG4 silencing induced elevation in miR-98-5p. MiR-98-5p inhibition abrogated the effect of SNHG4 silencing on proliferation and invasion of lung cancer cells. In conclusion, our findings demonstrate that SNHG4 is required by lung cancer cells to maintain malignant phenotype. SNHG4 probably exerts its pro-survival and pro-metastatic effects by sponging anti-tumor miR-98-5p.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Novel g‑C₃N₄/CoO Nanocomposites with Significantly Enhanced Visible-Light Photocatalytic Activity for H₂ Evolution

Novel g-C₃N₄/CoO nanocomposite application for photocatalytic H₂ evolution were designed and fabricated for the first time in this work. The structure and morphology of g-C₃N₄/CoO were investigated by a wide range of characterization methods. The obtained g-C₃N₄/CoO composites exhibited more-efficient utilization of solar energy than pure g-C₃N₄ did, resulting in higher photocatalytic activity for H₂ evolution. The optimum photoactivity in H₂ evolution under visible-light irradiation for g-C₃N₄/CoO composites with a CoO mass content of 0.5 wt % (651.3 μmol h^–1 g^–1) was up to 3 times as high as that of pure g-C₃N₄ (220.16 μmol h^–1 g^–1). The remarkably increased photocatalytic performance of g-C₃N₄/CoO composites was mainly attributed to the synergistic effect of the junction or interface formed between g-C₃N₄ and CoO

Correlations between serum serotonin and bone traits.

<p>Data shown are unadjusted values of Pearson correlation coefficients/weight-adjusted partial correlation coefficients in women, and unadjusted values/height-adjusted values in men. BMI: body mass index; BMC: bone mineral content; aBMD: areal bone mineral density; vBMD: volumetric bone mineral density; CSA: cross-sectional area.</p>a<p>: P<0.05; ^b: P<0.01; ^c: P<0.001.</p><p>Correlations between serum serotonin and bone traits.</p