Impaired lipid metabolism in idiopathic pulmonary alveolar proteinosis

<p>Abstract</p> <p>Background</p> <p>It is well known that lipids abnormally accumulate in the alveoli during idiopathic pulmonary alveolar proteinosis (PAP). It is unclear, however, whether lipids also abnormally accumulate in serum. This study investigated the serum lipid panels in idiopathic PAP patients and explored the relationships between serum levels and the severity of idiopathic PAP.</p> <p>Methods and Results</p> <p>Clinical data including the level of serum lipids were evaluated in 33 non-diabetic idiopathic PAP patients and 157 healthy volunteers. Serum levels of triglyceride were higher in PAP patients than in healthy subjects (median: 192.00 mg/dl (<it>P</it>₂₅: 104.36, <it>P</it>₇₅: 219.00) <it>vs </it>119.56 mg/dl (<it>P</it>₂₅: 78.81, <it>P</it>₇₅: 193.03), <it>P </it>< 0.05), while high-density lipoprotein cholesterol (HDL-C) levels were lower in patients than in the control group (42.50 ± 10.30 <it>vs </it>51.34 ± 12.06 mg/dl, <it>P </it>< 0.01). Forced expiratory volume in one second and forced vital capacity in hypertriglyceridemia patients were lower than those in patients with normal triglyceride. Serum LDL-C and HDL-C ratio correlated negatively with PaO₂(r = -0.403, <it>P </it>< 0.05) and positively with lactate dehydrogenase (r = 0.381, <it>P </it>< 0.05).</p> <p>Conclusions</p> <p>PAP associates with high triglyceride and low HDL levels in the serum, and these lipids provide potential intervention strategy for treatment.</p

IDH1突变体通过抑制JNK的激活减少生长因子缺失诱导的细胞凋亡

文章简介抵抗凋亡和能在血清营养因子缺乏的情况下生长是肿瘤细胞的两个主要特征。JNK的激活是血清饥饿诱导的细胞凋亡所必须的因素。目前研究表明IDH1突变体产生的致癌代谢物2-羟基戊二酸(2-HG)是突变的导致肿瘤形成的主要原因。然而目前尚不清楚2-HG是否能抑制JNK的激活,进而使细胞抵抗血清饥饿诱导的凋亡。课题组以IDH1 R132Q的基因敲入MEF为研究对象

One-Pot Visual Detection of African Swine Fever Virus Using CRISPR-Cas12a

African swine fever virus (ASFV) is a leading cause of worldwide agricultural loss. ASFV is a highly contagious and lethal disease for both domestic and wild pigs, which has brought enormous economic losses to a number of countries. Conventional methods, such as general polymerase chain reaction and isothermal amplification, are time-consuming, instrument-dependent, and unsatisfactorily accurate. Therefore, rapid, sensitive, and field-deployable detection of ASFV is important for disease surveillance and control. Herein, we created a one-pot visual detection system for ASFV with CRISPR/Cas12a technology combined with LAMP or RPA. A mineral oil sealing strategy was adopted to mitigate sample cross-contamination between parallel vials during high-throughput testing. Furthermore, the blue fluorescence signal produced by ssDNA reporter could be observed by the naked eye without any dedicated instrument. For CRISPR-RPA system, detection could be completed within 40 min with advantageous sensitivity. While CRISPR-LAMP system could complete it within 60 min with a high sensitivity of 5.8 × 102 copies/μl. Furthermore, we verified such detection platforms display no cross-reactivity with other porcine DNA or RNA viruses. Both CRISPR-RPA and CRISPR-LAMP systems permit highly rapid, sensitive, specific, and low-cost Cas12a-mediated visual diagnostic of ASFV for point-of-care testing (POCT) applications

A retrospective study of the role of hypercapnia in patients with acromegaly

Abstract Background Acromegaly is a multisystemic disease characterized by an excessive release of growth hormone (GH) and insulin-like growth factor-1. Obstructive sleep apnea (OSA) is a common consequence of acromegaly, and hypercapnia is frequently observed in patients with acromegaly, OSA, and obesity. However, the effects of hypercapnia on acromegaly remain unknown. This study was designed to investigate whether there are differences in clinical symptoms, sleep variables, and biochemical remission after surgery for acromegaly in patients with OSA with or without hypercapnia. Methods A retrospective analysis was conducted involving patients with acromegaly and OSA. The pharmacotherapy history for acromegaly before surgery, anthropometric measures, blood gas, sleep monitoring data, and biochemical assays of hypercapnic and eucapnic individuals were collected 1–2 weeks before surgery. Univariate and multivariate logistic regression analyses were performed to determine the risk factors for failed postoperative biochemical remission. Results In this study, 94 patients with OSA and acromegaly were included. Among them, 25 (26.6%) had hypercapnia. The hypercapnic group had higher body mass index (92% vs. 62.3%; p = 0.005) and poorer nocturnal hypoxemia index. No serological differences were found between the two groups. According to the post-surgery GH level, 52 patients (55.3%) reached biochemical remission. Univariate logistic regression analysis revealed that diabetes mellitus (odds ratio [OR], 2.59; 95% confidence interval [CI], 1.02–6.55), instead of hypercapnia (OR, 0.61; 95% CI, 0.24–1.58), was associated with lower remission rates. Patients who received pharmacotherapy for acromegaly before surgery (OR, 0.21; 95% CI, 0.06–0.79) and had higher thyroid-stimulating hormone levels (OR, 0.53; 95% CI, 0.32–0.88) were more likely to have biochemical remission after surgery. Multivariate analysis further showed that only diabetes mellitus (OR, 3.29; 95% CI, 1.15–9.46) and preoperative pharmacotherapy (OR, 0.21; 95% CI, 0.06–0.83) remained significant. Hypercapnia, hormone levels, and sleep indicators had no effect on biochemical remission after surgery. Conclusions Single-center evidence shows that hypercapnia alone may not be a risk factor for lower biochemical remission rates. Correcting hypercapnia does not appear to be required before surgery. More evidence is needed to further support this conclusion

Establishment and application of a survival rate graph model based on biomarkers and imaging indexes after primary hepatocellular carcinoma resection

Abstract Background Primary liver cancer (PLC) is a highly malignant disease. This study developed an effective and convenient tool to evaluate survival times of patients after hepatectomy, which can provide a reference point for clinical decisions. Methods Clinical and laboratory data of 243 patients with PLC after hepatectomy were collected. Univariate cox regression analysis, Lasso regression analysis and multivariate cox regression analysis were used to determine the best prediction index. Multivariate cox regression analysis was used to construct a survival prediction model. A receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were used to verify the model. The patients in this model were divided into was divided into high‐risk and low‐risk groups according to the optimal cut‐off value of the ROC curve for different prognostic years. Kaplan–Meier survival analysis and log‐rank test were used to analyse the survival differences between the two groups. Results Tumour size, portal vein thrombosis, distant metastasis, alpha‐fetoprotein and protein induced by vitamin K absence or antagonist‐II levels were independent risk factors for overall survival (OS) after PLC surgery. The area under the concentration‐time curve for 2‐, 3‐ and 4‐year survival of patients was 0.710, 0.825 and 0.919, respectively, with a good calibration of the Hosmer–Lemeshow test (p > 0.05) and net benefit. The mortality rates in patients with 2, 3 and 4 years of survival were 70.59%, 67.83% and 66.67% for the high‐risk group and 21.84%, 22.50% and 22.67% for the low‐risk group, respectively. The mortality rate of the high‐risk group was significantly higher than that of the low‐risk group (p < 0.05). Conclusion The OS model of prognosis after PLC surgery constructed in this study can be used to predict the 2‐, 3‐ and 4‐year survival prognoses of patients, and patients with different prognosis years can be re‐stratified so that they achieve more accurate and personalised assessment, thereby providing a reference point for clinical decision‐making