Opportunistic lung cancer screening with low-dose computed tomography in National Cancer Center of China: The first 14 years' experience.

BACKGROUND: In China, over 50% of lung cancer cases occur in nonsmokers. Thus, identifying high-risk individuals for targeted lung cancer screening is crucial. Beyond age and smoking, determining other risk factors for lung cancer in the Asian population has become a focal point of research. Using 30,000 participants in the prospectively enrolled cohort at China's National Cancer Center (NCC) over the past 14 years, we categorized participants by risk, with an emphasis on nonsmoking females. MATERIALS AND METHODS: Between November 2005 and December 2019, 31,431 individuals voluntarily underwent low-dose computed tomography (LDCT) scans for lung cancer screening at the NCC. We recorded details like smoking history, exposure to hazards, and family history of malignant tumors. Using the 2019 NCCN criteria, participants were categorized into high-, moderate-, and low-risk groups. Additionally, we separated non-high-risk groups into female never smokers (aged over 40) exposed to second-hand smoke (SHS) and others. Any positive results from initial scans were monitored per the I-ELCAP protocol (2006), and suspected malignancies were addressed through collaborative decisions between patients and physicians. We analyzed and compared the detection rates of positive results, confirmed lung cancers, and cancer stages across risk, age, and gender groups. RESULTS: Out of 31,431 participants (55.9% male, 44.1% female), 3695 (11.8%) showed positive baseline LDCT scans with 197 (0.6%; 106 females, 91 males) confirmed as lung cancer cases pathologically. Malignancy rate by age was 0.1% among those aged under 40 years, 0.4% among those aged 40-49 years, 0.8% among those aged 50-59 years, and 1.2% among those aged 60 years and older. From the 25,763 participants (56.9% male, 43.1% female) who completed questionnaires, 1877 (7.3%) were categorized as high risk, 6500 (25.2%) as moderate risk, and 17,386 (67.5%) as low risk. Of the 23,886 in the non-high-risk category, 8041 (33.7%) were females over 40 years old exposed to SHS. The high-risk group showed the highest lung cancer detection rate at 1.4%. However, females exposed to SHS had a notably higher detection rate than the rest of the non-high-risk group (1.1% vs. 0.5%; p < 0.0001). In this cohort, 84.8% of the detected lung cancers were at an early stage. CONCLUSIONS: In our study, using LDCT for lung cancer screening proved significant for high-risk individuals. For non-high-risk populations, LDCT screening could be considered for nonsmoking women with exposure to SHS.

Acupoint thread-embedding for children with tic disorders of spleen deficiency and liver hyperactivity and its effect on serum level of NSE. / ç©´ä½åŸ‹çº¿æ²»ç–—å„¿ç«¥è„¾è™šè‚æ—ºåž‹æŠ½åŠ¨éšœç¢çš„ä¸´åºŠç–—æ•ˆåŠå¯¹è¡€æ¸ NSE水平的影响.

OBJECTIVES: To observe the clinical efficacy of acupoint thread-embedding for children with tic disorders of spleen deficiency and liver hyperactivity and its effect on serum level of neuron-specific enolase (NSE). METHODS: A total of 68 children with tic disorders of spleen deficiency and liver hyperactivity were randomized into an observation group (34 cases, 1 case dropped out) and a control group (34 cases, 3 cases dropped out, 1 case was eliminated). In the observation group, acupoint thread-embedding was applied at Baihui (GV 20) and bilateral Hegu (LI 4), Taichong (LR 3), Pishu (BL 20), Ganshu (BL 18), Quchi (LI 11), Zusanli (ST 36),etc., once every 4 weeks. In the control group, tiapride hydrochloride tablet was given orally, twice a day. Both groups were treated for 12 weeks. Before and after treatment, the Yale global tic severity scale (YGTSS) score and serum level of NSE were observed in the two groups, and the clinical efficacy was evaluated. RESULTS: After treatment, except for vocal tic score of YGTSS in the control group, the each-item scores and total scores of YGTSS and serum levels of NSE in the two groups were decreased compared with those before treatment (P<0.05); the each-item scores and total score of YGTSS and serum level of NSE in the observation group were lower than those in the control group (P<0.05). The total effective rate in the observation group was 87.9% (29/33), which was higher than 76.7% (23/30) in the control group (P<0.05). CONCLUSIONS: Acupoint thread-embedding has a good effect in the treatment of children with tic disorders of spleen deficiency and liver hyperactivity, could reduce the YGTSS score and serum level of NSE.

Ovarian Metastasis From Diffuse Epithelioid Malignant Mesothelioma Revealed by 18 F-FDG PET/CT.

ABSTRACT: Diffuse epithelioid malignant mesothelioma (MM) with metastasis to the ovary is rare. We reported FDG PET/CT findings in a 39-year-old woman with ovarian metastasis from diffuse epithelioid MM. The ultrasound findings at the external hospital revealed multiple masses in the hepatic hilus. FDG PET/CT examination was recommended to evaluate the nature of the lesions. It showed that 2 hypodense lesions in the perihepatic space had intense activity, and there was an additional FDG lesion in the right ovary, which was later confirmed as diffuse epithelioid MM with ovarian metastasis by pathological examination.

The fibroblast growth factor system in cognitive disorders and dementia.

Cognitive impairment is the core precursor to dementia and other cognitive disorders. Current hypotheses suggest that they share a common pathological basis, such as inflammation, restricted neurogenesis, neuroendocrine disorders, and the destruction of neurovascular units. Fibroblast growth factors (FGFs) are cell growth factors that play essential roles in various pathophysiological processes via paracrine or autocrine pathways. This system consists of FGFs and their receptors (FGFRs), which may hold tremendous potential to become a new biological marker in the diagnosis of dementia and other cognitive disorders, and serve as a potential target for drug development against dementia and cognitive function impairment. Here, we review the available evidence detailing the relevant pathways mediated by multiple FGFs and FGFRs, and recent studies examining their role in the pathogenesis and treatment of cognitive disorders and dementia.

Radiomic-signature changes after early treatment improve the prediction of progression-free survival in patients with advanced anaplastic lymphoma kinase-positive non-small cell lung cancer.

BACKGROUND: The prognosis of lung cancer varies widely, even in cases wherein the tumor stage, genetic mutation, and treatment regimens are the same. Thus, an effective means for risk stratification of patients with lung cancer is needed. PURPOSE: To develop and validate a combined model for predicting progression-free survival and risk stratification in patients with advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) treated with ensartinib. MATERIAL AND METHODS: We analyzed 203 tumor lesions in 114 patients and evaluated average radiomic feature measures from all lesions at baseline and changes in these features after early treatment (Δradiomic features). Combined models were developed by integrating clinical with radiomic features. The prediction performance and clinical value of the proposed models were evaluated using receiver operating characteristic analysis, calibration curve, decision curve analysis (DCA), and Kaplan-Meier survival analysis. RESULTS: Both the baseline and delta combined models achieved predictive efficacy with a high area under the curve. The calibration curve and DCA indicated the high accuracy and clinical usefulness of the combined models for tumor progression prediction. In the Kaplan-Meier analysis, the delta and baseline combined models, Δradiomic signature, and two selected clinical features could distinguish patients with a higher progression risk within 42 weeks. The delta combined model had the best performance. CONCLUSION: The combination of clinical and radiomic features provided a prognostic value for survival and progression in patients with NSCLC receiving ensartinib. Radiomic-signature changes after early treatment could be more valuable than those at baseline alone.

An Assessment of the Predictive Performance of Current Machine Learning-Based Breast Cancer Risk Prediction Models: Systematic Review.

BACKGROUND: Several studies have explored the predictive performance of machine learning-based breast cancer risk prediction models and have shown controversial conclusions. Thus, the performance of the current machine learning-based breast cancer risk prediction models and their benefits and weakness need to be evaluated for the future development of feasible and efficient risk prediction models. OBJECTIVE: The aim of this review was to assess the performance and the clinical feasibility of the currently available machine learning-based breast cancer risk prediction models. METHODS: We searched for papers published until June 9, 2021, on machine learning-based breast cancer risk prediction models in PubMed, Embase, and Web of Science. Studies describing the development or validation models for predicting future breast cancer risk were included. The Prediction Model Risk of Bias Assessment Tool (PROBAST) was used to assess the risk of bias and the clinical applicability of the included studies. The pooled area under the curve (AUC) was calculated using the DerSimonian and Laird random-effects model. RESULTS: A total of 8 studies with 10 data sets were included. Neural network was the most common machine learning method for the development of breast cancer risk prediction models. The pooled AUC of the machine learning-based optimal risk prediction model reported in each study was 0.73 (95% CI 0.66-0.80; approximate 95% prediction interval 0.56-0.96), with a high level of heterogeneity between studies (Q=576.07, I2=98.44%; P<.001). The results of head-to-head comparison of the performance difference between the 2 types of models trained by the same data set showed that machine learning models had a slightly higher advantage than traditional risk factor-based models in predicting future breast cancer risk. The pooled AUC of the neural network-based risk prediction model was higher than that of the nonneural network-based optimal risk prediction model (0.71 vs 0.68, respectively). Subgroup analysis showed that the incorporation of imaging features in risk models resulted in a higher pooled AUC than the nonincorporation of imaging features in risk models (0.73 vs 0.61; Pheterogeneity=.001, respectively). The PROBAST analysis indicated that many machine learning models had high risk of bias and poorly reported calibration analysis. CONCLUSIONS: Our review shows that the current machine learning-based breast cancer risk prediction models have some technical pitfalls and that their clinical feasibility and reliability are unsatisfactory.

Association of anaplastic lymphoma kinase variants and alterations with ensartinib response duration in non-small cell lung cancer.

BACKGROUND: Here, we aimed to assess the association of ALK variants and alterations with ensartinib response duration in NSCLC, and explore the potential value of computed tomography (CT) radiomic features in predicting progression-free survival (PFS). METHODS: We enrolled 88 patients with identified ALK variant NSCLC in a multicenter phase 2 trial, and assessed the impact of ALK variants and secondary ALK alterations on the clinical outcome (response duration) of patients receiving ensartinib. We also established a multifactorial model of clinicopathological and quantitative CT radiomic features to predict PFS and risk stratification. Kaplan-Meier analysis was conducted to identify risk factors for tumor progression. RESULTS: Univariate analysis indicated a statistical difference (p = 0.035) in PFS among ALK variants in three classifications (V1, V3, and other variants). Secondary ALK alterations were adversely associated with PFS both in univariate (p = 0.008) and multivariate (p = 0.04) analyses and could identify patients at high risk for early progression in the Kaplan-Meier analysis (p = 0.002). Additionally, response duration to crizotinib <1 year and liver metastasis were adversely associated with PFS. The combined model, composed of clinicopathological signature and CT radiomic signature, showed good prediction ability with the area under the receiver operating characteristic curve being 0.85, and 0.89 in the training and validation dataset respectively. CONCLUSIONS: Our study showed that secondary ALK alterations were adversely associated with ensartinib efficacy, and that ALK variants might not correlate with PFS. The quantitative radiomic signature provided added prognostic prediction value to the clinicopathological features.

MRI radiomic signature predicts intracranial progression-free survival in patients with brain metastases of ALK-positive non-small cell lung cancer.

BACKGROUND: Intracranial progression is considered an important cause of treatment failure in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) patients. Recent advances in targeted therapy and radiomics have generated considerable interest for the exploration of prognostic imaging biomarkers to predict the clinical course. Here, we developed a magnetic resonance imaging (MRI) radiomic signature that can stratify survival and intracranial progression. METHODS: We analyzed 87 brain metastatic lesions in 24 ALK-positive NSCLC patients undergoing ALK-inhibitor ensartinib therapy and divided them into training (n=61) and validation (n=26) sets. Radiomic features were extracted and screened from contrast-enhanced MR images. Combined with these selected features, the Rad-score was calculated with multivariate logistic regression. The predictive model and Rad-score performance were assessed in the training set and validated in the validation set; decision curve analysis was performed with the combined training and validation sets to estimate Rad-score's patient-stratification ability. RESULTS: The prediction model constructed with nine selected radiomic features could predict intracranial progression within 51 weeks (AUC =0.84 and 0.85 in the training and validation sets, respectively), while clinical and regular MRI characteristics were independent of progression (P>0.05). The decision-curve analysis showed that the radiomic prediction model was clinically useful. The Kaplan-Meier analysis showed that the progression-free survival (PFS) difference between the high- and low-risk groups distinguished by the Rad-score was significant (P=0.017). CONCLUSIONS: Radiomics may provide prognostic information and improve pretreatment risk stratification in ALK-positive NSCLC patients with brain metastases undergoing ensartinib treatment, allowing follow-up and treatment to be tailored to the patient's individual risk profile.

Natural history of pathologically confirmed pulmonary subsolid nodules with deep learning-assisted nodule segmentation.

OBJECTIVE: To explore the natural history of pulmonary subsolid nodules (SSNs) with different pathological types by deep learning-assisted nodule segmentation. METHODS: Between June 2012 and June 2019, 95 resected SSNs with preoperative long-term follow-up were enrolled in this retrospective study. SSN detection and segmentation were performed on preoperative follow-up CTs using the deep learning-based Dr. Wise system. SSNs were categorized into invasive adenocarcinoma (IAC, n = 47) and non-IAC (n = 48) groups; according to the interval change during the preoperative follow-up, SSNs were divided into growth (n = 68), nongrowth (n = 22), and new emergence (n = 5) groups. We analyzed the cumulative percentages and pattern of SSN growth and identified significant factors for IAC diagnosis and SSN growth. RESULTS: The mean preoperative follow-up was 42.1 ± 17.0 months. More SSNs showed growth or new emergence in the IAC than in the non-IAC group (89.4% vs. 64.6%, p = 0.009). Volume doubling time was non-significantly shorter for IACs than for non-IACs (1436.0 ± 1188.2 vs. 2087.5 ± 1799.7 days, p = 0.077). Median mass doubling time was significantly shorter for IACs than for non-IACs (821.7 vs. 1944.1 days, p = 0.001). Lobulated sign (p = 0.002) and SSN mass (p = 0.004) were significant factors for differentiating IACs. IACs showed significantly higher cumulative growth percentages than non-IACs in the first 70 months of follow-up. The growth pattern of SSNs may conform to the exponential model. The initial volume (p = 0.042) was a predictor for SSN growth. CONCLUSIONS: IACs appearing as SSNs showed an indolent course. The mean growth rate was larger for IACs than for non-IACs. SSNs with larger initial volume are more likely to grow. KEY POINTS: • Invasive adenocarcinomas (IACs) appearing as subsolid nodules (SSNs), with a mean volume doubling time (VDT) of 1436.0 ± 1188.2 days and median mass doubling time (MDT) of 821.7 days, showed an indolent course. • The VDT was shorter for IACs than for non-IACs (1436.0 ± 1188.2 vs. 2087.5 ± 1799.7 days), but the difference was not significant (p = 0.077). The median MDT was significantly shorter for IACs than for non-IACs (821.7 vs. 1944.1 days, p = 0.001). • SSNs with lobulated sign and larger mass (> 390.5 mg) may very likely be IACs. SSNs with larger initial volume are more likely to grow.

Should Waste Separation Be Mandatory? A Study on Public's Response to the Policies in China.

The implementation of effective waste separation policy is an important pathway to guide the public to actively participate in the waste separation action. This study focused on exploring the Chinese public's response to the rigid and flexible waste separation policies from the perspectives of understanding, willingness to support, and willingness to implement. We used a big data mining technique to obtain 10,057 entries of the Chinese public's response to the mandatory waste separation policy. The results showed that "public's understanding-support willingness-implement willingness" regarding mandatory waste separation policy was characterized by a U-shaped response. Specifically, the public's understanding and willingness to implement the rigid waste separation policy were relatively high in the short term, but their willingness to support this policy was relatively low and became increasingly low over time. Particularly, "troublesome" implementation was deemed to the main reason for the public's low willingness to support the rigid waste separation policy. In addition, we further obtained the sample data of the Chinese public regarding the flexible waste separation policy through the situational survey. Contrary to the response characteristics of mandatory waste separation policy, the results showed that "public's understanding-support willingness-implement willingness" regarding flexible waste separation policy was characterized by an inverted U-shaped response, and the Chinese public showed more positive sentiment regarding the willingness to support and implement. The results have important implications for guiding the public to actively participate in the waste separation action.

Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas harboring KRAS and BRCA mutations: case report and whole exome sequencing analysis.

BACKGROUND: Undifferentiated carcinoma with osteoclast-like giant cells (UC-OGC) is an extremely uncommon pancreatic neoplasm that comprises less than 1% of all exocrine pancreatic tumors. To date, cases and data from whole-exome sequencing (WES) analysis have been reported by specific studies. We report a case of pancreatic UC-OGC with a literature review, and provide novel insights into the molecular characteristics of this tumor entity. CASE PRESENTATION: A 31-year-old male presented with intermittent abdominal pain for several months, and positron emission tomography (PET) showed isolated high metabolic nodules during the pancreatic uncinate process that were likely to be malignant disease. Pathological examination after radical excision revealed UC-OGC associated with poorly differentiated adenocarcinoma at the head of the pancreas. The disease recurred 7.4 months after radical surgery. The KRAS p.G12D (c.35G > A) and somatic BRCA2 p.R2896C (c.8686C > T) mutations were detected by subsequent WES analysis. The patient showed no response to platinum-based systemic chemotherapy, and his condition quickly worsened. He finally died, with an overall survival of 1 year. CONCLUSIONS: As an extremely uncommon tumor entity, UC-OGC is really a unique variant of conventional pancreatic ductal adenocarcinoma due to its similarities, as shown by genomic WES analysis. Clinical examination and molecular analysis by WES could further indicate potential treatment strategies for UC-OGC.

[Therapeutic effect of acupuncture on dysphagia in children with severe hand foot and mouth disease].

OBJECTIVE: To observe the effect of acupuncture combined with conventional symptomatic and supportive treatments on swallowing function and nutritional status in children with severe hand foot and mouth disease complicated with dysphagia. METHODS: A total of 68 children with severe hand foot and mouth disease complicated with dysphagia were randomized into an observation group and a control group, 34 cases in each one. Symptomatic and supportive treatments such as lowering temperature, tranquilizing and mechanical ventilation were adopted in the control group. On the basis of the treatments in the control group, acupuncture was applied at Lianquan (CV 23), Jialianquan (Extra), cervical Jiaji (EX-B 2), Fengfu (GV 16), Fengchi (GB 20), Yamen (GV 15), scalp motor and sensory areas in the observation group, once a day, 6 times a week, one month as a course and totally 3 courses were required. Time spent on restoring swallowing function was observed in both groups. Besides, score of dysphagia disorder survey (DDS) and nutritional status were evaluated before and after treatment, and the clinical effects were compared. RESULTS: The total effective rate was 91.2% (31/34) in the observation group, which was superior to 73.5% (25/34) in the control group (P<0.05). The time of restoring swallowing function in the observation group was advanced than the control group (P<0.05). Compared before treatment, the DDS scores after treatment were decreased in both groups, and the reduction in the observation group was larger than the control group (all P<0.05). After the treatment, the normal rate of nutritional status was 61.8% (21/34) in the observation group, which was superior to 32.4% (11/34) in the control group (P<0.05). CONCLUSION: On the basis of conventional treatment, acupuncture can effectively treat the severe hand foot and mouth disease complicated with dysphagia, improve the swallowing function and nutritional status.

Dual-energy spectral CT characteristics in surgically resected lung adenocarcinoma: comparison between Kirsten rat sarcoma viral oncogene mutations and epidermal growth factor receptor mutations.

BACKGROUND: Kirsten rat sarcoma viral oncogene homolog (KRAS) and epidermal growth factor receptor (EGFR) are the two most frequent and well-known oncogene of lung adenocarcinoma. The purpose of this study is to compare the characteristics measured with dual-energy spectral computed tomography (DESCT) in lung adenocarcinoma patients who have KRAS and EGFR gene mutations. METHODS: Patients with surgically resected lung adenocarcinoma (n = 72) were enrolled, including 12 patients with KRAS mutations and 60 patients with EGFR mutations. DESCT quantitative parameters, including the CT number at 70 keV, the slopes of the spectral attenuation curves (slope λ HU), normalized iodine concentration (NIC), normalized water concentration (NWC), and effective atomic number (effective Z), were analyzed. A multiple logistic regression model was applied to discriminate clinical and DESCT characteristics between the types of mutations. RESULTS: The KRAS mutation was more common in people who smoked than the EGFR mutation. Nodule type differed significantly between the KRAS and EGFR groups (P = 0.035), and all KRAS mutation adenocarcinomas were solid nodules. Most DESCT quantitative parameters differed significantly between solid nodules and subsolid nodules. CT number at 70 keV, slope λ HU, NIC, and effective Z differed significantly between the KRAS and EGFR groups (P = 0.006, 0.017, 0.013 and 0.010) with solid lung adenocarcinoma. Multivariate logistic analysis of DESCT and clinical features indicated that besides smoking history, the CT value at 70 keV (OR = 0.938, P = 0.009) was significant independent factor that could be used to differentiate KRAS and EGFR mutations in solid lung adenocarcinoma. CONCLUSIONS: DESCT would be a potential tool to differentiate lung adenocarcinoma patients with a KRAS mutation from those with an EGFR mutation.

Quantitative features of dual-energy spectral computed tomography for solid lung adenocarcinoma with EGFR and KRAS mutations, and ALK rearrangement: a preliminary study.

BACKGROUND: The present work aimed to evaluate radio-genomic associations of quantitative parameters obtained by dual-energy spectral computed tomography (DESCT) for solid lung adenocarcinoma with epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations, as well as anaplastic lymphoma kinase (ALK) rearrangement. METHODS: Ninety-six cases of solid lung cancer were selected and assessed for EGFR and KRAS mutations, and ALK rearrangement. Then, they underwent chest DESCT, and quantitative parameters, including water concentration (WC), iodine concentration (IC), CT value at 70 keV, effective atomic number (Effective-Z) and spectral Hounsfield unit curve slope (λHU slope) were measured. Finally, the associations of quantitative radiological features with various gene alterations were evaluated. RESULTS: The positive rates were 51.0% (49/96) for EGFR, 13.5% (13/96) for KRAS and 16.7% (16/96) for ALK. In univariate analysis, EGFR mutation was associated with smoking status, CT value at 70 keV, IC, Effective-Z, and λHU slope; KRAS mutation was associated with CT value at 70 keV, IC, Effective-Z, and λHU slope, and ALK rearrangement was correlated with age and WC. In multivariate analysis, smoking status (OR =2.924, P=0.019) and CT value at 70 keV (OR =1.036, P=0.006) were significantly associated with EGFR mutation; Effective-Z and age were significantly associated with KRAS mutation (OR =0.047, P=0.032) and ALK rearrangement (OR =0.933, P=0.008), respectively. CONCLUSIONS: Quantitative analysis of DESCT could help detect solid lung adenocarcinoma harboring EGFR or KRAS mutation, or ALK rearrangement.

Identification of epidermal growth factor receptor mutations in pulmonary adenocarcinoma using dual-energy spectral computed tomography.

OBJECTIVES: To explore the role of dual-energy spectral computed tomography (DESCT) quantitative characteristics for the identification of epidermal growth factor receptor (EGFR) mutation status in a cohort of East Asian patients with pulmonary adenocarcinoma. MATERIALS AND METHODS: Patients with lung adenocarcinoma who underwent both DESCT chest examination and EGFR test were retrospectively selected from our institution's database. The DESCT visual morphological features and quantitative parameters, including the CT number at 70 keV, normalized iodine concentration (NIC), normalized water concentration, and slopes of the spectral attenuation curves (slope λ HU [Hounsfield unit]), were evaluated or calculated. The patients were divided into two groups: the EGFR mutation group and EGFR wild-type group. Statistical analyses were performed to identify the DESCT quantitative parameters for diagnosis of EGFR mutation status. RESULTS: EGFR mutations were detected in 66 (55.0%) of the 120 enrolled patients. The univariate analysis revealed that sex, smoking history, CT texture, NIC, and slope λ HU were significantly associated with EGFR mutation status (p = 0.037, 0.001, 0.047, 0.010, and 0.018, respectively). The multivariate logistic analysis revealed that smoking history (odds ratio [OR] = 3.23, p = 0.005) and NIC (OR = 58.026, p = 0.049) were the two significant predictive factors associated with EGFR mutations. Based on this analysis, the smoking history and NIC were combined to determine the predictive value for EGFR mutations with the area under the curve of 0.702. CONCLUSIONS: NIC may be a potential quantitative DESCT parameter for predicting EGFR mutations in patients with pulmonary adenocarcinoma. KEY POINTS: • DESCT can provide multiple quantitative image parameters compared to conventional CT. • Identification of the radio-genomic relation between DESCT and EGFR status can help to define molecular subcategories of lung adenocarcinoma, which is valuable for personalized clinical targeted therapy. • NIC may be a potential DESCT quantitative parameter for predicting EGFR mutations in pulmonary adenocarcinoma.

ROS­mediated autophagy through the AMPK signaling pathway protects INS­1 cells from human islet amyloid polypeptide­induced cytotoxicity.

Oligomerization of human islet amyloid polypeptide (hIAPP) is toxic and contributes to progressive reduction of ß cell mass in patients with type 2 diabetes mellitus. Autophagy is a highly conserved homeostatic mechanism in eukaryotes. Previous studies have confirmed that hIAPP can promote autophagy in ß cells, but the underlying molecular mechanism and cellular regulatory pathway of hIAPP­induced autophagy remains not fully elucidated. Accumulation of reactive oxygen species (ROS) causes hIAPP induced­ß cell death. At present, little is known about the association between hIAPP­induced oxidative stress and autophagy in ß cells. Therefore, the present study investigated the underlying molecular mechanism and regulatory pathway of hIAPP­induced autophagy. Transmission electron microscopy was used to observe the number of autophagosome in cells. Cell viability was determined by an MTT test. A 2',7'­dichlorofluorescin diacetate assay was used to measure the relative levels of reactive ROS. Western blotting was used to detect expression of adenosine monophosphate­activated protein kinase (AMPK) and autophagic markers p62 and microtubule associated protein 1 light chain 3. The results demonstrated that hIAPP induces autophagy through ROS­mediated AMPK signaling pathway in INS­1 cells. Upregulation of autophagy by AMPK activator 5­aminoimidazole­4­carboxamide1­ß­D­ribofuranoside decreased ROS and malondialdehyde generation, whereas inhibition of autophagy by 3­methyladenine and AMPK inhibitor compound C aggravated hIAPP­induced oxidative stress and toxicity in INS­1 cells. Taken together, the present study suggested that hIAPP induces autophagy via a ROS­mediated AMPK signaling pathway. Furthermore, autophagy serves as a cell­protective mechanism against hIAPP­induced toxicity and chemical promotion of autophagy through AMPK signaling pathway attenuates hIAPP induced cytotoxicity and oxidative stress in INS­1 cells.

Adding Prandial Insulin to Basal Insulin Plus Oral Antidiabetic Drugs in Chinese Patients with Poorly Controlled Type 2 Diabetes Mellitus: An Open-Label, Single-Arm Study.

INTRODUCTION: There is relatively little data from China on the efficacy and safety of adding prandial insulin to basal insulin plus oral antidiabetic drugs (OADs) in people with poorly controlled type 2 diabetes mellitus (T2DM). This study assessed the efficacy and safety of basal insulin dose optimization followed by the addition of prandial insulin in Chinese people with T2DM achieving suboptimal glycemic control with basal insulin and OADs. METHODS: In this open-label, single-arm study, adults with T2DM receiving basal insulin plus OADs underwent insulin dose optimization for 12 weeks. At week 12, subjects who achieved fasting blood glucose (FBG) ≤6.5 mmol/L but not HbA1c ≤7% added one injection of prandial insulin at the main meal for an additional 24 weeks. Endpoints included mean HbA1c, the achievement rate of HbA1c ≤7%, hypoglycemia, and other adverse events (AEs). RESULTS: A total of 120 subjects underwent basal insulin optimization; At week 12, 110 study subjects achieved FBG ≤6.5 mmol/L, of whom 66 did not achieve HbA1c ≤7% and therefore initiated prandial insulin. Three patients discontinued prandial insulin due to dissatisfaction with treatment outcome (n = 1), accidental injury (n = 1), or personal reasons (n = 1). After 24 weeks of basal-plus treatment, mean HbA1c significantly decreased (8.06% to 7.17%; p < 0.001), 65.1% of subjects achieved HbA1c ≤7%, there was no change in FBG (6.23-6.20 mmol/L; p = 0.118), and mean post-prandial blood glucose decreased (13.17-10.14 mmol/L; p < 0.001). During basal-plus treatment, three individuals experienced hypoglycemia, and no significant change in the mean subject weight was observed (73.2 vs. 73.3 kg; p = 0.379). CONCLUSIONS: In people with T2DM who are achieving suboptimal glycemic control with basal insulin plus OADs, basal insulin dose optimization followed by the addition of prandial insulin improves glycemic control, is well tolerated, and is associated with a low incidence of hypoglycemia.

Chemical constituents derived from Artocarpus xanthocarpus as inhibitors of melanin biosynthesis.

Twenty-four compounds, including the previously unknown artoxanthocarpuone A, artoxanthocarpuone B, hydroxylakoochin A, methoxylakoochin A, epoxylakoochin A, and artoxanthol, were isolated and characterized spectroscopically. Among them, artoxanthol is stilbene oligomer presumably constructed in a 5,11,12-triphenyl hexahydrochrysene scaffold by a Diels-Alder type of reaction, for which a biosynthetic pathway is proposed. Artoxanthol, alboctalol, steppogenin, norartocarpetin, resveratrol, oxyresveratrol, and chlorophorin potently inhibited mushroom tyrosinase activity with IC50 values from 0.9 to 5.7 µM that were all far stronger than the positive controls. Artoxanthocarpuone A, artoxanthocarpuone B, methoxylakoochin A, lakoochin A, cudraflavone C, artonin A, resveratrol, and chlorophorin reduced tyrosinase activity and inhibited α-melanocyte-stimulating hormone-induced melanin production in B16F10 melanoma cells without affecting cell proliferation. Collectively, the results suggest that the constituents of Artocarpus xanthocarpus have potential to be used as depigmentation agents.

A novel monoterpene-stilbene adduct with a 4,4-dimethyl-2,3-diphenylchromane skeleton from Artocarpus xanthocarpus.

Artoxanthochromane (1), a DielsAlder-type conjugation product of 4-isopropenylresorcinol and oxyresveratrol, was isolated from the heartwood of Artocarpus xanthocarpus and characterized. The structure of 1 was elucidated as 2-(2,4-dihydroxyphenyl)-3-(3,5-dihydroxyphenyl)-7-hydroxy-4,4-dimethylchromane by 1D- and 2D-NMR spectroscopy, and other spectral evidences. A plausible metabolic mechanism was proposed to illustrate the biosynthetic pathway of artoxanthochromane. This compound exhibited mild mushroom tyrosinase inhibitory, and weak free radical-scavenging activities on ABTS(+.) and superoxide anion (O$\rm{{_{2}^{-{^\cdot} }}}$) free radicals.