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Focal epilepsy accounts for 60% of all forms of epilepsy, but the pathogenic mechanism is not well understood. In this study, three novel mutations in NPRL3(nitrogen permease regulator-like 3), c.937_945del, c.1514dupC and 6,706-bp genomic DNA (gDNA) deletion, were identified in three families with focal epilepsy by linkage analysis, whole exome sequencing (WES) and Sanger sequencing. NPRL3 protein is a component of the GATOR1 complex, a major inhibitor of mTOR signaling. These mutations led to truncation of the NPRL3 protein and hampered the binding between NPRL3 and DEPDC5, which is another component of the GATOR1 complex. Consequently, the mutant proteins enhanced mTOR signaling in cultured cells, possibly due to impaired inhibition of mTORC1 by GATOR1. Knockdown of nprl3in Drosophilaresulted in epilepsy-like behavior and abnormal synaptic development. Taken together, these findings expand the genotypic spectrum of NPRL3-associated focal epilepsy and provide further insight into how NPRL3mutations lead to epilepsy.

A resorufin-based isoform-specific fluorescent probe (CHPO) has been designed and developed for highly selective and sensitive sensing cytochrome P450 1A1 (CYP1A1) activities in complex biological systems. CHPO has been successfully used for high-throughput screening of CYP1A1 inhibitors and sensing CYP1A1 activities in living systems, which strongly facilitate the investigations on the biological functions of CYP1A1 in complex biological systems.

In this study, the pectin of waste seed melon peel in Xinjiang was used as raw material to prepare seed melon pectin oligosaccharide (Sm-POS). The separation and purification of Sm-POS were carried out by HPD-750 macroporous resin chromatography column and gel chromatography to further study the molecular structure of its active component with antibacterial effect by FT-IR, NMR, and LC/MS.

This paper reports the use of chromatographic profiles of breath volatiles to determine disease markers in lung cancer patients and healthy volunteers. The volatile fraction was isolated by headspace solid-phase microextraction (HS-SPME) and analyzed by flow-modulated comprehensive two-dimensional gas chromatography and flame ionization (GC × GC-FID). Following the experiments, collected data were transformed, and partial least-squares discriminant analysis (PLS-DA) as well as Mann–Whitney Test were carried out to model the data and discover breath metabolites with a significant concentration difference between patients and healthy subjects. Using the abovementioned method, lung cancer patients and healthy controls could be correctly distinguished based on metabolic VOCs abnormality in human breath. Five potential target compounds including acetone, isoprene, methanol, pentane and propanol were identified. Lung cancer patients show higher concentrations of propanol (7415.3 ng L−1), acetone (1811.6 ng L−1) and methanol (225 ng L−1) compared with those of healthy volunteers (1975.3 ng L−1, 579.9 ng L−1, 76.8 ng L−1, respectively). In addition, there is no significant relationship between breath VOCs and gender or body mass index (BMI). This approach will facilitate the comparison of complex breath VOC profiles and diseases. These findings may offer valuable and reliable information for the early diagnosis and prognosis of lung cancer.

Objective. This epidemiological investigation aimed at determining the current situation regarding the diagnosis and treatment of chronic obstructive pulmonary disease (COPD), especially missed diagnosis and missed treatment, in a group of individuals residing in an island area of Ningbo. Methods. Adults ≥60 years of age were selected from an island area of Ningbo. All participants completed a COPD-Screening Questionnaire and underwent a post-bronchodilator pulmonary function test. COPD-positive individuals then completed a questionnaire surveying the status of diagnosis and treatment of COPD and the reasons for missed diagnosis and treatment. The data were collated and analyzed using SPSS version 22.0 (IBM Corporation, Armonk, NY, USA). Findings. (1) A total of 1526 individuals were screened, of whom 1371 (89.8%) were eventually included in data analysis. From these, 254 were diagnosed with spirometry-defined COPD, corresponding to an overall prevalence of 18.5%. Prevalence was higher in men (28.9%) than in women (8.3%) among the sample. (2) According to chi-squared test results, risk factors for COPD included sex, age, smoking history (pack-years), cough, and dyspnea. Body mass index, family history of respiratory diseases, and exposure to biomass smoke from cooking were not risk factors for COPD. (3) Multivariate logistic regression analysis revealed that age and smoking were independent risk factors for COPD. (4) Receiver operating curve analysis revealed that, at a cutoff of 19.5, the highest sum of sensitivity and specificity was 69.7% and 75.5%, respectively. The COPD-Screening Questionnaire could be used as a preselection method to screen for COPD in primary care settings. (5) Of 254 individuals diagnosed with COPD, only 10 had a history of COPD and only 35 had a previous diagnosis of pneumonia or bronchitis. These data revealed that the rate of missed diagnosis of COPD in the Ningbo island area was 96.1%. Conclusion. The prevalence of COPD among elderly individuals in the Ningbo island area was significantly higher than in other parts of China. Moreover, the rate of missed diagnosis of COPD in the Ningbo island area was extremely high. Smoking and age were independent factors for the occurrence of COPD.

Background. We evaluated the utility of galactomannan (GM) in bronchoalveolar lavage fluid (BALF) for the diagnosis of invasive pulmonary aspergillosis (IPA) in nonneutropenic patients. Methods. A total of 183 patients were included in the final analysis. Bronchoscopies and the detection of GM in BALF were all performed on them. Results. Ten cases of IPA were diagnosed. ROC data demonstrated that, for diagnosing IPA, an optimal cutoff value for GM in BALF of 0.76 yielded a sensitivity of 100.0% and a specificity of 76.2%. Symptoms and radiological findings had no significant difference between proven or probable IPA group and non-IPA group. In our case-control analysis, although nine patients with false-positive results received treatment with Piperacillin/tazobactam, there was no significant difference between case and control group. Conclusions. BALF GM detection is a valuable adjunctive diagnostic tool. Our retrospective study suggests that the optimal value of GM detection in BALF is 0.76 in nonneutropenic patients.