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Phytochemical investigation of Gynostemma pentaphyllum led to the purification of five novel dammarane-type triterpene isolates, gypenosides B1 - B5 ( 1 - 5 ). Their structures were determined through comprehensive 1D and 2D NMR spectroscopic analyses and HRESIMS data. Of note, 1-3 are inseparable mixtures of epimers due to their unstable nature, and a total of eight dammarane-type triterpene saponins were identified. Additionally, the protective activities of these new compounds against PC12 cell injury induced by hypoxia were evaluated.

Background: Pulmonary nodular consolidation (PN) and pulmonary cavity (PC) may represent the two most promising imaging signs in differentiating multidrug-resistant (MDR)-pulmonary tuberculosis (PTB) from drug-sensitive (DS)-PTB. However, there have been concerns that literature described radiological feature differences between DS-PTB and MDR-PTB were confounded by that MDR-PTB cases tend to have a longer history. This study seeks to further clarify this point., Methods: All cases were from the Guangzhou Chest Hospital, Guangzhou, China. We retrieved data of consecutive new MDR cases [n=46, inclusive of rifampicin-resistant (RR) cases] treated during the period of July 2020 and December 2021, and according to the electronic case archiving system records, the main PTB-related symptoms/signs history was ≤3 months till the first computed tomography (CT) scan in Guangzhou Chest Hospital was taken. To pair the MDR-PTB cases with assumed equal disease history length, we additionally retrieved data of 46 cases of DS-PTB patients. Twenty-two of the DS patients and 30 of the MDR patients were from rural communities. The first CT in Guangzhou Chest Hospital was analysed in this study. When the CT was taken, most cases had anti-TB drug treatment for less than 2 weeks, and none had been treated for more than 3 weeks., Results: Apparent CT signs associated with chronicity were noted in 10 cases in the DS group (10/46) and 9 cases in the MDR group (10/46). Thus, the overall disease history would have been longer than the assumed <3 months. Still, the history length difference between DS patients and MDR patients in the current study might not be substantial. The lung volume involvement was 11.3%±8.3% for DS cases and 8.4%±6.6% for MDR cases (P=0.022). There was no statistical difference between DS cases and MDR cases both in PN prevalence and in PC prevalence. For positive cases, MDR cases had more PN number (mean of positive cases: 2.63 vs. 2.28, P=0.38) and PC number (mean of positive cases: 2.14 vs. 1.38, P=0.001) than DS cases. Receiver operating characteristic curve analysis shows, PN ≥4 and PC ≥3 had a specificity of 86% (sensitivity 25%) and 93% (sensitivity 36%), respectively, in suggesting the patient being a MDR cases., Conclusions: A combination of PN and PC features allows statistical separation of DS and MDR cases., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-694/coif). Y.X.J.W. serves as the Editor-in-Chief of Quantitative Imaging in Medicine and Surgery. The other authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Tuberculosis (TB) remains one of the major infectious diseases in the world with a high incidence rate. Drug-resistant tuberculosis (DR-TB) is a key and difficult challenge in the prevention and treatment of TB. Early, rapid, and accurate diagnosis of DR-TB is essential for selecting appropriate and personalized treatment and is an important means of reducing disease transmission and mortality. In recent years, imaging diagnosis of DR-TB has developed rapidly, but there is a lack of consistent understanding. To this end, the Infectious Disease Imaging Group, Infectious Disease Branch, Chinese Research Hospital Association; Infectious Diseases Group of Chinese Medical Association of Radiology; Digital Health Committee of China Association for the Promotion of Science and Technology Industrialization, and other organizations, formed a group of TB experts across China. The conglomerate then considered the Chinese and international diagnosis and treatment status of DR-TB, China's clinical practice, and evidence-based medicine on the methodological requirements of guidelines and standards. After repeated discussion, the expert consensus of imaging diagnosis of DR-PB was proposed. This consensus includes clinical diagnosis and classification of DR-TB, selection of etiology and imaging examination [mainly X-ray and computed tomography (CT)], imaging manifestations, diagnosis, and differential diagnosis. This expert consensus is expected to improve the understanding of the imaging changes of DR-TB, as a starting point for timely detection of suspected DR-TB patients, and can effectively improve the efficiency of clinical diagnosis and achieve the purpose of early diagnosis and treatment of DR-TB., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-1223/coif). The authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Co 60 Fe 20 Sm 20 thin films were deposited onto glass substrates in a high vacuum setting. The films varied in thickness from 10 to 50 nm and underwent annealing processes at different temperatures: room temperature (RT), 100, 200, and 300 °C. Our analysis encompassed structural, magnetic, electrical, nanomechanical, adhesive, and optical properties in relation to film thickness and annealing temperature. X-ray diffraction (XRD) analysis did not reveal characteristic peaks in Co 60 Fe 20 Sm 20 thin films due to insufficient growth-driving forces. Electrical measurements indicated reduced resistivity and sheet resistance with increasing film thickness and higher annealing temperatures, owing to hindered current-carrier transport resulting from the amorphous structure. Atomic force microscope (AFM) analysis showed a decrease in surface roughness with increased thickness and annealing temperature. The low-frequency alternating current magnetic susceptibility (χ ac ) values increased with film thickness and annealing temperature. Nanoindentation analysis demonstrated reduced film hardness and Young's modulus with thicker films. Contact angle measurements suggested a hydrophilic film. Surface energy increased with greater film thickness, particularly in annealed films, indicating a decrease in contact angle contributing to this increase. Transmittance measurements have revealed intensified absorption and reduced transmittance with thicker films. In summary, the surface roughness of CoFeSm films at different annealing temperatures significantly influenced their magnetic, electrical, adhesive, and optical properties. A smoother surface reduced the pinning effect on the domain walls, enhancing the χ ac value. Additionally, diminished surface roughness led to a lower contact angle and higher surface energy. Additionally, smoother surfaces exhibited higher carrier conductivity, resulting in reduced electrical resistance. The optical transparency decreased due to the smoother surface of Co 60 Fe 20 Sm 20 films.

Background: Magnetic resonance imaging (MRI) plays an important role in the diagnosis of leptomeningeal metastases (LM); however, some sub-centimeter lesions may be missed. Positron emission tomography/computed tomography (PET/CT) has a high sensitivity and may play a synergistic role with MRI in diagnosing spinal LM (SLM). We aimed to retrospectively evaluate the detection of SLM with 18 F-fluorodeoxyglucose PET/CT ( 18 F-FDG PET/CT) compared to that of whole spinal cord MRI in a single center., Methods: Patients with SLM who had undergone 18 F-FDG PET/CT and MRI were enrolled. 18 F-FDG PET/CT imaging findings were independently reviewed by 2 nuclear medicine physicians. 18 F-FDG PET/CT findings of SLMs were described. A consistency test was conducted to assess the patient-based diagnostic results obtained by the 2 physicians. Patient-based sensitivity, accuracy, and specificity in diagnosing SLM between 18 F-FDG PET/CT and MRI of the whole spinal cord were compared using the chi-square or Fisher's exact test. A P value of <0.05 was considered statistically significant. The receiver operating characteristic (ROC) curve was obtained to assess the diagnostic performance of maximum standardized uptake value (SUVmax) to diagnose SLM., Results: A total of 16 patients with SLM were included in this study from October 2010 to April 2022. The primary tumor involved the lungs, liver, ovaries, prostate, esophagus, and unknown primary site. The mean age of patients, including 13 males and 3 females, was 57.8±11.2 (range, 34-73) years. Of 16 patients with SLM, 10 had nodular diseases, 2 had linear diseases, and 4 had mixed diseases. The kappa value of the consistency test of the 2 radiologists' diagnostic results was 0.765. The patient-based sensitivity, specificity, and accuracy of 18 F-FDG PET/CT in diagnosing SLM were 87.5%, 89.2%, and 88.7%, respectively and those of whole spinal cord MRI were 75.0%, 100.0%, and 92.5%, respectively. There were no significant differences in sensitivity, specificity, and accuracy between the 2 methods, with P values of 0.654, 0.115, and 0.506, respectively. However, more nodular diseases were observed on PET/CT. The area under the ROC curve (AUC) for the prediction of SLM by SUVmax was 0.907 [95% confidence interval (CI): 0.831-0.983]. When SUVmax ≥2.45, the Youden index was the largest, and the sensitivity and specificity were 89.3% and 75.7%, respectively., Conclusions: 18 F-FDG PET/CT is a good choice of imaging modality for assessing SLM. In the diagnosis of SLMs, PET/CT and enhanced MRI can play a better synergistic role., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-286/coif). The authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

The importance of mitochondria in regulation of aging has been extensively recognized and confirmed. Gynostemma pentaphyllum (Thunb.) Makino, a homology of medicine and food, has been widely utilized as dietary supplement. In this study, the transcriptome of normal cells (wild type mouse embryo fibroblasts) regulated by the 30% aqueous EtOH extract of G. pentaphyllum was firstly evaluated by RNA sequencing and the results revealed that the G. pentaphyllum could up-regulate the genes involved in oxidative phosphorylation (OXPHOS) and sirtuin (SIRT) signaling pathways, indicating its effect in promoting cell viability might be attributed to the role of improving mitochondrial functions. To further discover the bioactive compounds, sixteen undescribed dammarane-type saponins along with twenty-eight known analogues were isolated from the active extract of G. pentaphyllum. Their structures were elucidated by means of comprehensive analysis of NMR and HRMS spectroscopic data. All isolates were evaluated for the regulatory effects on SIRT3 and translocase of the outer membrane 20 (TOM20), and thirteen of them exhibited satisfactory agonist activities on both SIRT3 and TOM20 at 5 μM. Furthermore, the preliminary structure-activity relationships analysis demonstrated the additional hydroxymethyl and carbonyl groups or less sugar residues in saponins could contribute positively to the up-regulatory effect on SIRT3 and TOM20. These findings encouraged the potential roles of G. pentaphyllum and its bioactive saponins in the development of natural drugs for the treatment of aging-related diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Gypenosides (Gps) are the major bioactive components in Gynostemma species. They include neutral Gps and acidic malonylgypenosides (MGps). MGps are abundant in Gynostemma species and can be transformed into corresponding Gps via extraction, concentration, and drying. If only the Gps were quantified and MGps were ignored, the quality of Gynostemma species would be underestimated. This study aimed to develop a sample preparation method involving demalonylation and ultrahigh-performance liquid chromatography-charged aerosol detector (UHPLC-CAD) analysis to determine the contents of gypenoside XLIX (Gp XLIX) and gypenoside A (Gp A). First, the optimized ultrasonic extraction method was established to extract G. longipes powder ultrasonically. Then, the extracted solution was put into a closed container (centrifuge tube) and heated in a water bath at 95 °C. Then, MGps were converted into corresponding Gps. The proposed preparation method was compared with the other three methods, including water bath reflux heating, alkali hydrolysis, and extraction of heated powder, and was shown to exhibit higher conversion and better convenience. Subsequently, an UHPLC-CAD method was established and validated. Gp XLIX and Gp A showed excellent linear correlations between 15.55 and 248.8 μg/mL and 24.10-385.5 μg/mL, respectively (R 2 > 0.999). The limit of detection was 1.40 ng (Gp XLIX) and 2.41 ng (Gp A), and the limit of quantification was 7.77 ng and 14.46 ng, respectively. The relative standard deviation for precision, stability, and repeatability was 0.63-3.15%. The average recovery of Gp XLIX and Gp A was 98.97% and 98.23%, respectively. The established method was applied for determining Gp XLIX and Gp A contents in wild or cultivated G. longipes samples collected from the Qinba Mountains area. The contents of Gp XLIX and Gp A were 5.16-23.02 mg/g and 15.78-54.55 mg/g, respectively. Conclusively, the proposed sample preparation and analysis method could be used for the quality control and evaluation of G. longipes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Endoscopic biopsy is the pivotal procedure for the diagnosis of gastric cancer. In this study, we applied whole-slide images (WSIs) of endoscopic gastric biopsy specimens to develop an endoscopic gastric biopsy assistant system (EGBAS)., Methods: The EGBAS was trained using 2373 WSIs expertly annotated and internally validated on 245 WSIs. A large-scale, multicenter test dataset of 2003 WSIs was used to externally evaluate EGBAS. Eight pathologists were compared with the EGBAS using a man-machine comparison test dataset. The fully manual performance of the pathologists was also compared with semi-manual performance using EGBAS assistance., Results: The average area under the curve of the EGBAS was 0·979 (0·958-0·990). For the diagnosis of all four categories, the overall accuracy of EGBAS was 86·95%, which was significantly higher than pathologists (P< 0·05). The EGBAS achieved a higher κ score (0·880, very good κ) than junior and senior pathologists (0·641 ± 0·088 and 0·729 ± 0·056). With EGBAS assistance, the overall accuracy (four-tier classification) of the pathologists increased from 66·49 ± 7·73% to 73·83 ± 5·73% (P< 0·05). The length of time for pathologists to manually complete the dataset was 461·44 ± 117·96 minutes; this time was reduced to 305·71 ± 82·43 minutes with EGBAS assistance (P = 0·00)., Conclusions: The EGBAS is a promising system for improving the diagnosis ability and reducing the workload of pathologists., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhu, Yuan, Xie, Xu, Wang, Feng, Wu, Lu, Geng, Lv, Li, Hou, Chen and Zhou.)

Developments in deep learning techniques have led to significant advances in automated abnormality detection in radiological images and paved the way for their potential use in computer-aided diagnosis (CAD) systems. However, the development of CAD systems for pulmonary tuberculosis (TB) diagnosis is hampered by the lack of training data that is of good visual and diagnostic quality, of sufficient size, variety, and, where relevant, containing fine region annotations. This study presents a collection of annotations/segmentations of pulmonary radiological manifestations that are consistent with TB in the publicly available and widely used Shenzhen chest X-ray (CXR) dataset made available by the U.S. National Library of Medicine and obtained via a research collaboration with No. 3. People's Hospital Shenzhen, China. The goal of releasing these annotations is to advance the state-of-the-art for image segmentation methods toward improving the performance of fine-grained segmentation of TB-consistent findings in digital Chest X-ray images. The annotation collection comprises the following: 1) annotation files in JSON (JavaScript Object Notation) format that indicate locations and shapes of 19 lung pattern abnormalities for 336 TB patients; 2) mask files saved in PNG format for each abnormality per TB patient; 3) a CSV (comma-separated values) file that summarizes lung abnormality types and numbers per TB patient. To the best of our knowledge, this is the first collection of pixel-level annotations of TB-consistent findings in CXRs. Dataset: https://data.lhncbc.nlm.nih.gov/public/Tuberculosis-Chest-X-ray-Datasets/Shenzhen-Hospital-CXR-Set/Annotations/index.html., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest.

Background: Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm that can involve multisystem organs. Positron emission tomography/computed tomography (PET/CT) has been widely used in tumor staging and efficacy evaluation. However, at present, there are few 18 F-fluorodeoxyglucose (FDG) PET/CT studies on LCH. This study aimed to explore the possible role of 18 F-FDG PET/CT in the diagnosis and management of patients with LCH., Methods: 18 F-FDG PET/CT images of 22 Chinese patients diagnosed with LCH on biopsy or surgery histopathology between January 2011 and December 2020 were retrospectively analyzed. The incidence of LCH in each system was assessed by a PET/CT scan. The imaging characteristics were analyzed semiquantitatively and qualitatively. The discrepancies between PET/CT and conventional imaging modalities were recorded. Evaluations of curative effect according to RECIST1.1 and PERCIST1.0 were compared using Fisher's exact chi-squared test, and P values <0.05 were considered significant., Results: Eight (36.4%) of the 22 patients presented with single system involvement (4 isolated site involvement, 4 multiple site involvement), and 14 (63.6%) presented with multiple system involvement. Twenty-one (95.5%) patients had hypermetabolic lesions. Musculoskeletal, lymphatic, respiratory, liver, skin-soft tissue and thyroid involvement were seen in 14 (63.6%), 13 (59.1%), 5 (22.7%), 4 (18.2%), 5 (22.7%) and 1 (4.5%) patient, respectively. Cranial and facial bones were the most common sites of musculoskeletal involvement. Ten patients underwent PET/CT follow-up, and there was no significant difference in curative effect evaluations according to RECIST1.1 and PERCIST1.0. However, among the complete remission cases assessed by RECIST1.1, three were partial metabolic responses assessed by PERCIST1.0, while among the partial response cases assessed by RECIST1.1, one was metabolic progressive disease assessed by PERCIST1.0., Conclusions: 18 F-FDG PET/CT is an imaging modality option for the diagnosis and assessment of the curative effect of LCH., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-21-823/coif). The authors have no conflicts of interest to declare., (2022 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

In this paper, a Co 60 Fe 20 Y 20 film was sputtered onto Si (100) substrates with thicknesses ranging from 10 to 50 nm under four conditions to investigate the structure, magnetic properties, and surface energy. Under four conditions, the crystal structure of the CoFeY films was found to be amorphous by an X-ray diffraction analyzer (XRD), suggesting that yttrium (Y) added into CoFe films and can be refined in grain size and insufficient annealing temperatures do not induce enough thermal driving force to support grain growth. The saturation magnetization (M S ) and low-frequency alternate-current magnetic susceptibility (χ ac ) increased with the increase of the thicknesses and annealing temperatures, indicating the thickness effect and Y can be refined grain size and improved ferromagnetic spin exchange coupling. The highest Ms and χ ac values of the Co 60 Fe 20 Y 20 films were 883 emu/cm 3 and 0.26 when the annealed temperature was 300 °C and the thickness was 50 nm. The optimal resonance frequency (f res ) was 50 Hz with the maximum χ ac value, indicating it could be used at a low frequency range. Moreover, the surface energy increased with the increase of the thickness and annealing temperature. The maximum surface energy of the annealed 300 °C film was 30.02 mJ/mm 2 at 50 nm. Based on the magnetic and surface energy results, the optimal thickness was 50 nm annealed at 300 °C, which has the highest Ms, χ ac , and a strong adhesion, which can be as a free or pinned layer that could be combined with the magnetic tunneling layer and applied in magnetic fields.

Footpad dermatitis (FPD) is a major foot disease in modern poultry production, and it affects both poultry health and animal welfare. It refers to inflammation and necrotizing lesions on the plantar surface of the footpads and toes. We investigated the effects of providing a swimming pool and different floor types on growth performance and FPD score in indoor-reared White Roman geese. Forty-eight male and 48 female White Roman geese were randomly allocated to pens with or without a swimming pool and with either mud or perforated plastic floor and reared from 15 to 84 days of age. Growth performance measurements included feed intake (FI), weight gain (WG), and feed conversion ratio (FCR). FI, WG, and FCR were significantly decreased at various growth periods in geese provided with a pool. Lower WG and bodyweight for the perforated plastic floor group were found at 15-28 and 28 days of age, respectively. The geese reared on the perforated plastic floors without a pool had higher FPD scores at 70 and 84 days of age than those with other rearing conditions. A higher incidence of FPD score 1 was observed in geese raised without a pool. In conclusion, providing a pool can improve footpad health in indoor-reared White Roman geese but may not benefit growth performance.

Background: Non-magnifying endoscopy with narrow-band imaging (NM-NBI) has been frequently used in routine screening of esophagus squamous cell carcinoma (ESCC). The performance of NBI for screening of early ESCC is, however, significantly affected by operator experience. Artificial intelligence may be a unique approach to compensate for the lack of operator experience., Aim: To construct a computer-aided detection (CAD) system for application in NM-NBI to identify early ESCC and to compare it with our previously reported CAD system with endoscopic white-light imaging (WLI)., Methods: A total of 2167 abnormal NM-NBI images of early ESCC and 2568 normal images were collected from three institutions (Zhongshan Hospital of Fudan University, Xuhui Hospital, and Kiang Wu Hospital) as the training dataset, and 316 pairs of images, each pair including images obtained by WLI and NBI (same part), were collected for validation. Twenty endoscopists participated in this study to review the validation images with or without the assistance of the CAD systems. The diagnostic results of the two CAD systems and improvement in diagnostic efficacy of endoscopists were compared in terms of sensitivity, specificity, accuracy, positive predictive value, and negative predictive value., Results: The area under receiver operating characteristic curve for CAD-NBI was 0.9761. For the validation dataset, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of CAD-NBI were 91.0%, 96.7%, 94.3%, 95.3%, and 93.6%, respectively, while those of CAD-WLI were 98.5%, 83.1%, 89.5%, 80.8%, and 98.7%, respectively. CAD-NBI showed superior accuracy and specificity than CAD-WLI ( P = 0.028 and P ≤ 0.001, respectively), while CAD-WLI had higher sensitivity than CAD-NBI ( P = 0.006). By using both CAD-WLI and CAD-NBI, the endoscopists could improve their diagnostic efficacy to the highest level, with accuracy, sensitivity, and specificity of 94.9%, 92.4%, and 96.7%, respectively., Conclusion: The CAD-NBI system for screening early ESCC has higher accuracy and specificity than CAD-WLI. Endoscopists can achieve the best diagnostic efficacy using both CAD-WLI and CAD-NBI., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background and Aims: Somatic mutation R249S in TP53 is highly common in hepatocellular carcinoma (HCC). We aim to investigate the effects of R249S in ctDNA on the prognosis of HCC., Methods: We analysed three cohorts including 895 HCC patients. TP53 mutation spectrum was examined by direct sequencing of genomic DNA from tissue specimens in HCC patients with hepatectomy (Cohort 1, N = 260). R249S and other recurrent missense mutations were assessed for their biological functions and associations with overall survival (OS) and progression-free survival (PFS) of HCC patients in Cohort 1. R249S within circulating tumour DNA (ctDNA) was detected through droplet digital polymerase chain reaction (ddPCR) and its association with OS and PRS was analysed in HCC patients with (Cohort 2, N = 275) or without (Cohort 3, N = 360) hepatectomy., Results: In Cohort 1, R249S occupied 60.28% of all TP53 mutations. Overexpression of R249S induced more serious malignant phenotypes than those of the other three identified TP53 recurrent missense mutations. Additionally, R249S, but not other missense mutations, was significantly associated with worse OS (P = .006) and PFS (P = .01) of HCC patients. Consistent with the results in Cohort 1, HCC patients in Cohorts 2 and 3 with R249S had worse OS (P = 8.291 × 10 -7 and 2.608 × 10 -7 in Cohorts 2 and 3, respectively) and PFS (P = 5.115 × 10 -7 and 5.900 × 10 -13 in Cohorts 2 and 3, respectively) compared to those without this mutation., Conclusions: TP53 R249S mutation in ctDNA may serve as a promising prognosis biomarker for HCC patients with or without hepatectomy., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Gallbladder carcinoma (GBC) is always diagnosed at an advanced stage, and patients often miss the opportunity for surgery. Gemcitabine (GEM) and platinum-based drugs, including oxaliplatin (OXA), are mainstays of chemotherapy. However, drug resistance causes treatment failure. Hence, salvage mechanisms are critical to improve outcomes. This study revealed the positive correlation between placenta-specific protein 8 (PLAC8) overexpression and PD-L1 overexpression in GBC. Given the roles of PLAC8 and PD-L1 in chemotherapy resistance, GEM-resistant and OXA-resistant cell lines (SGC966GR and SGC966OR, respectively) were established to test whether and how PLAC8 and PD-L1 function in chemotherapy resistance. Drug-insensitive SGC966GR and SGC966OR cells upregulated MRP and MDR1 and had high expression of PLAC8. PLAC8 blockade using siRNA reversed chemotherapy resistance and downregulated MRP and MDR1 in SGC966GR and SGC966OR cells, suggesting that PLAC8 mediates chemotherapy resistance in GBC. Consistent with the increased mRNA levels of PD-L1 after the acquisition of resistance, PLAC8 knockdown reduced PD-L1 mRNA expression in SGC966GR and SGC966OR cells. In conclusion, PLAC8 overexpression in GBC patients positively correlated with PD-L1 expression. PLAC8 conferred resistance to GEM and OXA by upregulating PD-L1 expression, and PLAC8 or PD-L1 blockade may have potential for overcoming chemotherapy resistance, providing therapeutic options for chemotherapy-refractory GBC patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Traumatic brain injury (TBI) is a major cause of motor and cognitive impairment in young adults. It is associated with high mortality rates and very few effective treatment options. Bisperoxovanadium (pyridine-2-carboxyl) [bpV(pic)] is an commercially available inhibitor of Phosphatase and tensin homolog (PTEN). Previous studies have shown that bpV(pic) has protective effects in central nervous system. However, the role of bpV(pic) in TBI is unclear. In this study we aimed to investigate the neuroprotective role of bpV(pic) in rat TBI model. We found that injection of bpV(pic) significantly reduces brain edema and neurological dysfunction after TBI and this is mediated by AKT pathway. TBI is known to promote the M1 pro-inflammatory phenotype of microglial polarization and this effect is inhibited by bpV(pic) treatment which, instead promotes M2 microglial polarization in vivo and in vitro. We also found evidence of bpV(pic)-regulated neuroinflammation mediated by AKT activation and NF-κB p65 inhibition. BpV(pic) treatment also suppressed microglia in the peri-TBI region. MCP-1 is known to recruit monocytes and macrophages to promote inflammation, we show that bpV(pic) can inhibit TBI-induced up-regulation of MCP-1 via the AKT/NF-κB p65 signaling pathway. Taken together, our findings demonstrate that bpV(pic) plays a neuroprotective role in rat TBI, which may be achieved by inhibiting M1 microglia polarization and MCP-1 expression by modulating AKT/NF-κB p65 signaling pathway., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The flexible organic amine cations on the interfaces of two-dimensional (2D) hybrid organic-inorganic perovskite nanosheets could form relaxed structures, which would lead to exotic optoelectronic properties but are hard to understand. Here, the unusual interfacial relaxation of nanosheets exfoliated from an orthorhombic 2D lead halide perovskite, [(C 6 H 5 CH 2 NH 3 ) 2 ]PbCl 4 , is interrogated via ultrafast second-harmonic generation (SHG) spectroscopy. The in-plane SHG intensity anisotropy of these nanosheets is found to decrease with reducing layer thickness. Combined first-principles calculations and Monte Carlo simulations reveal that the induced second-order polarization arises primarily from the (C 6 H 5 CH 2 NH 3 ) + cations; and these organic amine cations form significantly reorganized conformations with decreasing nanosheet thickness due to weakened van der Waals interactions. Because the orientations of organic components at the interface determine their electric properties and specifically the dipolar susceptibility, the resulting structure leads to striking changes in the SHG properties.

Tuberculosis (TB) is currently the world's leading cause of infectious mortality. The complex immune response of the human body to Mycobacterium tuberculosis ( M.tb ) results in a wide array of clinical manifestations, thus the clinical and radiological diagnosis can be challenging. 18 F-fluorodeoxyglucose positron emission tomography ( 18 F-FDG-PET) scan with/without computed tomography (CT) component images the whole body and provides a metabolic map of the infection, enabling clinicians to assess the disease burden. 18 F-FDG-PET/CT scan is particularly useful in detecting the disease in previously unknown sites, and allows the most appropriate site of biopsy to be selected. 18 F-FDG-PET/CT is also very valuable in assessing early disease response to therapy, and plays an important role in cases where conventional microbiological methods are unavailable and for monitoring response to therapy in cases of multidrug-resistant TB or extrapulmonary TB. 18 F-FDG-PET/CT cannot reliably differentiate active TB lesion from malignant lesions and false positives can also be due to other infective or inflammatory conditions. 18 F-FDG PET is also unable to distinguish tuberculous lymphadenitis from metastatic lymph node involvement. The lack of specificity is a limitation for 18 F-FDG-PET/CT in TB management., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Glycine is a simple nonessential amino acid known to have neuroprotective properties. Treatment with glycine results in reduced infarct volume of the brain, neurologic function scores, and neuronal and microglial death in ischemic stroke injury. Neuroinflammation has been considered a major contributor to cerebral ischemia-induced brain damage. However, the role of glycine in neuroinflammation following ischemic stroke is unclear. The present study aimed to determine whether neuroinflammation is involved in the neuroprotective effects of glycine in cerebral ischemia injury. Ischemic stroke promotes M1 microglial polarization. Interestingly, we found that the injection of glycine in rats after injury can inhibit ischemia-induced inflammation and promote M2 microglial polarization in vivo (Sprague-Dawley rats) and in vitro (cortical microglia and BV-2 cells). We show that glycine suppresses Hif-1α by inhibiting the upregulation of NF-κB p65 after ischemia-reperfusion injury, resulting in the inhibition of proinflammatory activity. The activation of AKT mediates the inhibition of NF-κB p65/Hif-1α signaling by glycine. Moreover, we confirm that glycine-regulated AKT activation is mediated by the inhibition of PTEN in a PTEN depletion cell line, U251 cells. Glycine modulates microglial polarization after ischemic stroke, which indirectly inhibits ischemia-induced neuronal death and functional recovery. Taken together, our findings provide a new understanding of glycine in neuroprotection by inhibiting M1 microglial polarization and promoting anti-inflammation by suppressing NF-κB p65/Hif-1α signaling., (Copyright © 2019 by The American Association of Immunologists, Inc.)

Objective: To analyze the genotypes and the hematological phenotypic characteristics of α-thalassemia in different areas of Fujian and to evaluate the values of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), hemoglobin (Hb), RBC distribution width/red blood cell (RDW/RBC) for screening α-thalassemia in this area., Methods: The Gap-PCR assay was applied for detecting 3 common deletional mutations of patients with α-thalassemia, and the reverse dot-blot (RDB) assay was adopted to detect the foci of 3 common non-deletional gene mutations.Then,the hematological parameters of individuals with α-thalassemia were analyzed. Finally, the optimal cut-off value in hematological indexes for screening α-thalassemia were determined by the ROC curve., Results: Altogether 16 types of gene mutations were found in 772 patients with α-thalassemia. Among them, the -SEA/αα deletion mutation was the most common which was observed in 521 cases(67.49%). Compared with the control group, the differences in MCV, MCH, and Hb were statistically significant between the patients of the same sex but no same type. In male groups, the RDW/RBC ratio was statistically significant in individuals of light type and HbH disease as compared with the healthy control group. But in female groups, the statistical different of RDW/RBC ratio was found between only HbH disease group and control group. MCV<81.25 fl, MCH<27.30 pg, Hb(male)<128.5 g/L, and Hb(female) <123.5 g/L, with the highest specificity and the highest sensitivity, were the best cut-off points for screening α-thalassemia in the laboratory., Conclusion: Due to the difference of regional heterogeneity and hospital equipment environment, the different laboratories need to establish cut-off value for screening α-thalassemia suitable for its local region. In future, our laboratory can use MCV<81.25 fl, MCH<27.30 pg, Hb(male)<128.5 g/L, and Hb(female) <123.5 g/L for value for clinical screening, of α-thalassemia.

Background: Severe hand, foot, and mouth disease (HFMD) is a common childhood illness caused by various enteroviruses. The disease has imposed increased burden on children younger than 5 years old. We aimed to determine the epidemiology, CNS complication, and etiology among severe HFMD patients, in Jiangsu, China., Methods: Epidemiological, clinical, and laboratory data of severe HFMD cases were extracted from 2009 to 2015. The CNS complication, annually severe illness rates, mortality rates, severity-PICU admission rates, severity-hospitalization rates, and so on were analyzed to assess the disease burden of severe HFMD. All analyses were stratified by time, region, population, CNS involvement and serotypes. The VP1 gene from EV-A71, CV-A16, CV-A6, CV-A10 and other enteroviruses isolates was amplified. Phylogenetic analysis was performed using MEGA5.0., Results: Seven thousand nine hundred ninety-four severe HFMD cases were reported, of them, 7224 cases were inpatients, 611 were PICU inpatients, and 68 were fatal. The average severe illness rate, mortality rate, severity-fatality rate, severity-PICU admission rate, and severity-hospitalization rate were 14.54, 0.12,8506, 76,430, and 903,700 per 1 million, respectively. The severe illness rate was the highest in the 12-23 months age group, and the greatest mortality rate was in the 6-11 months age group. Geographical difference in severe illness rate and mortality were found. Patients infected with EV-A71 were at a higher proportion in different CNS involvement even death. EV-A71, CV-A16 and other enteroviruses accounted for 79.14, 6.49, and 14.47%, respectively. A total of 14 non-EV-A71/ CV-A16 genotypes including CV-A2, CV-A4, CV-A 6, CV-A9, CV-A10, CV-B1, CV-B2, CV-B3, CV-B4, CV-B5, E-6, E-7, E-18, and EV-C96 were identified. Phylogentic analyses demonstrated that EV-A71 strains belonged to subgenotype C4a, while CV-A16 strains belonged to sub-genotype B1a and sub-genotype B1b of genotype B1. CV-A6 strains were assigned to genogroup F, and CV-A10 strains belonged to genogroup D., Conclusions: Future mitigation policies should take into account the age, region heterogeneities, CNS conditions and serotype of disease. Additional a more rigorous study between the mild and severe HFMD should be warranted to elucidate the difference epidemiology, pathogen spectrum and immunity patterns and to optimize interventions in the following study.

Objective: To explore the difference of 18F-FDG PET/CT images between the symptomatic and asymptomatic pulmonary tuberculosis, as well as the correlation between the standard uptake value (SUV) and the symptomatic/asymptomatic pulmonary tuberculosis., Methods: A study dataset of 57 pulmonary tuberculosis cases was retrospectively assembled and analyzed. Among these cases, 30 were diagnosed having symptomatic pulmonary tuberculosis and 27 were asymptomatic pulmonary tuberculosis. PET/CT was performed in all 57 cases. The clinical data, CT images and PET/CT radioactive uptake data were analyzed using statistical data analysis software., Results: All 57 cases showed radioactively high uptake, with the maximum standard uptake value (SUVmax) of the lesion ranging from 1.60 to 27.30 and a mean value of 6.63±4.82. The symptomatic cases had an SUVmax of 8.76±4.97 and the asymptomatic cases had an SUVmax of 4.27±3.39. The SUVmax as well as singular or multiple lesions showed statistical differences between symptomatic and asymptomatic cases., Conclusion: The symptomatic pulmonary tuberculosis cases show significantly higher SUVmax than the asymptomatic cases. Based on the criteria of SUVmax greater than 2.0 to define active lesions, 100% of symptomatic cases might have active lesions while 70.4% of asymptomatic cases might have active lesions. Therefore, focused attention should be clinically paid on the asymptomatic cases of pulmonary tuberculosis to avoid miss diagnosis and delayed treatment.

Background: Intravoxel incoherent motion (IVIM) tissue parameters depend on the threshold b-value., Purpose: To explore how threshold b-value impacts PF ( f), D slow ( D), and D fast ( D*) values and their performance for liver fibrosis detection., Material and Methods: Fifteen healthy volunteers and 33 hepatitis B patients were included. With a 1.5-T magnetic resonance (MR) scanner and respiration gating, IVIM data were acquired with ten b-values of 10, 20, 40, 60, 80, 100, 150, 200, 400, and 800 s/mm 2 . Signal measurement was performed on the right liver. Segmented-unconstrained analysis was used to compute IVIM parameters and six threshold b-values in the range of 40-200 s/mm 2 were compared. PF, D slow , and D fast values were placed along the x-axis, y-axis, and z-axis, and a plane was defined to separate volunteers from patients., Results: Higher threshold b-values were associated with higher PF measurement; while lower threshold b-values led to higher D slow and D fast measurements. The dependence of PF, D slow , and D fast on threshold b-value differed between healthy livers and fibrotic livers; with the healthy livers showing a higher dependence. Threshold b-value = 60 s/mm 2 showed the largest mean distance between healthy liver datapoints vs. fibrotic liver datapoints, and a classification and regression tree showed that a combination of PF (PF < 9.5%), D slow (D slow  < 1.239 × 10 -3 mm 2 /s), and D fast (D fast  < 20.85 × 10 -3 mm 2 /s) differentiated healthy individuals and all individual fibrotic livers with an area under the curve of logistic regression (AUC) of 1., Conclusion: For segmented-unconstrained analysis, the selection of threshold b-value = 60 s/mm 2 improves IVIM differentiation between healthy livers and fibrotic livers.

This study investigated a combined use of intravoxel incoherent motion (IVIM) parameters, Dslow ( D), PF ( f), and Dfast ( D*), for liver fibrosis evaluation. Sixteen healthy volunteers (F0) and 33 hepatitis-b patients (stage F1 = 15, stage F2-4 = 18) were included. With a 1.5 T MR scanner and respiration gating, IVIM diffusion-weighted imaging was acquired using a single-shot echo-planar imaging sequence with 10 b values of 10, 20, 40, 60, 80, 100, 150, 200, 400, and 800 s/mm 2 . Signal measurement was performed on right liver parenchyma. With a three-dimensional tool, Dslow, PF, and Dfast values were placed along the x axis, y axis, and z axis, and a plane was defined to separate healthy volunteers from patients. The three-dimensional tool demonstrated that healthy volunteers and all patients with liver fibrosis could be separated. Classification and regression tree showed that a combination of PF (PF < 12.55%), Dslow (Dslow < 1.152 × 10 -3 mm 2 /s), and Dfast (Dfast < 13.36 × 10 -3 mm 2 /s) could differentiate healthy subjects and all fibrotic livers (F1-4) with an area under the curve of logistic regression (AUC) of 0.986. The AUC for differentiation of healthy livers versus F2-4 livers was 1. PF offered the best diagnostic value, followed by Dslow; however, all three parameters of PF, Dslow, and Dfast contributed to liver fibrosis detection.

Objectives: To investigate normative value and age-related change of brain magnetic resonance T1ρ relaxation at 1.5T., Methods: This study was approved by the local ethical committee with participants' written consent obtained. There were 42 adults healthy volunteers, including 20 males (age: 41±16 (mean±standard deviation) years, range: 22-68years,) and 22 females (age: 39±15years, range: 21-62years). MRI was performed at 1.5T using 3D fluid suppressed turbo spin echo sequence. Regions-of-interests (ROIs) were obtained by atlas-based tissue segmentation and T1ρ was calculated by fitting the mean value to mono-exponential model. Correlation between T1ρ relaxation of brain gray matter regions and age was investigated., Results: A regional difference among individual gray matter areas was noted; the highest values were observed in the hippocampus (98.37±5.37ms, median: 97.88ms) and amygdala (94.95±4.34ms, median: 94.73ms), while the lowest values were observed in the pallidum (83.81±5.49ms, median: 83.77ms) and putamen (83.93±4.76ms, median: 83.99ms). Gray matter T1ρ values decreased slowly (mean slope: -0.256) and significantly (p<0.05) with age in gray matter for subjects younger than 40years old, while for subjects older than 40years old there was no apparent correlation between T1ρ relaxation and age. Global white matter measured T1ρ value of 88.65±3.47ms (median: 87.86ms), and the correlation with age was not significant (p=0.18)., Conclusion: Gray matter T1ρ relaxation demonstrates a bi-phase change with age in adults of 22-68years., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The aim of our study was to determine the impact of genetic polymorphisms in the caspase (CASP) genes on prognosis of hepatocellular carcinoma (HCC). We genotyped 7 potentially functional polymorphisms in CASP3, CASP7, CASP8, CASP9, CASP10 genes in 362 HCC patients of receiving surgical resection of HCC tumor. The associations of genotype and haplotype with overall survival (OS) and disease free survival (DFS) were analyzed by using the Cox proportional hazards model. We found that the CASP9 rs4645981 C allele was significantly associated with positive effect on DFS (P = 0.011 and 0.016 for CT+CC vs. TT in univariate and multivariate analysis, respectively), CT genotype was associated with a better OS of HCC than the TT genotype both in univariate and multivariate analysis (P = 0.048 and 0.041, respectively). Moreover, the CASP3 rs2705897 GT genotype showed marginally significant association with decreased OS and DFS, compared with the GG genotype. One haplotype TT/TG in CASP3 (constructed by rs12108497 T>C and rs2705897 T>G) was significantly associated with decreased OS and DFS, compared to the common haplotype TT/TT both in univariate analysis (P = 0.021 and 0.026, respectively) and multivariate analysis (P = 0.025 and 0.030, respectively). The haplotype GT/GT in CASP9 (constructed by rs4645978 A>G and rs4645981 C>T) was significantly associated with decreased DFS both in univariate and multivariate analysis (P = 0.012 and 0.010, respectively). In conclusion, the CASP9 rs4645981 polymorphism, CASP3 and CASP9 haplotypes may be useful prognosis markers for HCC patients with surgical resection of tumor.

Single-nucleotide polymorphisms (SNPs) of microRNAs (miRNAs) are considered potential markers of cancer risk and prognosis in various cancers. In the current study, the primary aim is to determine whether the miR-492G>C polymorphism (rs2289030) altered hepatocellular carcinoma (HCC) prognosis. The SNP rs2289030 of miR-492 was genotyped using DNA from blood samples of 362 HCC patients that had undergone surgical resection of a HCC tumor. The associations between overall survival and demographic characteristics, clinical features, and the SNP rs2289030 were estimated using the Cox proportional hazards model. Results showed that patients who carried the CG genotype (P  = 0.015, hazard ratio [HR] = 0.704, 95 % confidence interval [CI] 0.530-0.934) and CG+GG genotype (P = 0.011, HR = 0.703, 95 % CI 0.536-0.924) had significantly decreased risk of death compared to those with the CC genotype. Similar results were found in the multivariate analysis adjusted by tumor size and venous invasion. Further stratification analysis indicated that the effect of rs2289030 had more prominence in patients ≤50 years old and that reported ever using alcohol, male gender, a family history of HCC, being HbsAg or alpha fetoprotein (AFP) positive, differentiation I + II, presence of venous invasion or cirrhosis, multiple tumors, and pTNM stage I + II. Results from this study illustrate the potential use of miR-492 rs2289030 as a prognostic marker for HCC patients that have undergone a surgical resection of the tumor.

Single nucleotide polymorphisms (SNPs) within microRNAs (miRNAs) are considered potential markers for risk and prognosis of various cancers. In the current study, we aimed to determine whether miR-608 rs4919510 affected hepatocellular carcinoma (HCC) prognosis. We genotyped rs4919510 using DNA from blood samples of 362 HCC patients receiving surgical resection of HCC tumor. Associations between rs4919510 and overall survival (OS) and demographic characteristics and clinical features were estimated using the Cox proportional hazards model. Results showed that HCC patients who carried the rs4919510 CC genotype had a significantly longer OS compared to those who carried the GG genotype (P = 0.013, hazard ratio [HR] = 0.600, 95 % confidence interval [CI] 0.402-0.897) and the CG + GG genotype (P = 0.033, HR = 0.681, 95 % CI 0.479-0.970) in univariate analysis. Similar results were obtained in multivariate analysis. Further stratification analysis indicated that rs4919510 was significantly associated with OS in patients who were satisfied with one of the following criteria: male gender, HbsAg-positive, α-fetoprotein (AFP)-positive, tumor size >5 cm, cirrhosis, solitary tumor, I + II pTNM stage, or no tumor capsule. Finally, a significantly higher frequency of rs4919510 CC genotype was observed in patients with cirrhosis (22.9 %, 55/240) than those without cirrhosis (14.0 %, 17/121) (P = 0.047). In conclusion, our results illustrated the potential role of miR-608 rs4919510 as a prognostic marker for HCC patients undergoing surgical resection of the tumor.

The apoptotic pathway is important in the control of vital processes of hepatocellular carcinoma (HCC). In the current study, we aimed to determine whether apoptotic gene-related polymorphisms modified HCC prognosis. We genotyped 16 single nucleotide polymorphisms (SNPs) in 10 core genes (TP53, TP53INP1, TP53BP1, CDKN2A, CDKN1A, CDKN1B, MDM2, BAX, CCDN1 and BCL2) in the apoptotic pathway by using DNA from blood samples of 362 HCC patients receiving surgical resection of HCC tumor. The associations between genotypes/haplotypes of the 10 genes and overall survival (OS) of HCC patients were assessed using the Cox proportional hazards model. We found one CDKN1B haplotype CCT/ACT (constructed by rs36228499 C>A, rs34330 C>T and rs2066827 T>G) significantly associated with decreased OS of HCC patients, compared to the common haplotype ACT/CTT both in univariate analysis (P=0.013, HR=1.198, 95% CI: 1.039-1.381) and multivariate analysis (P=0.006, HR=1.224, 95% CI: 1.059-1.413). We also find two SNPs (rs560191 G>C and rs2602141 T>G) in TP53BP1 shown to be marginally significantly associated with decreased OS of HCC patients. However, none of the other SNPs or haplotypes were significantly associated with HCC OS. Our results illustrated the potential use of CDKN1B haplotype as a prognostic marker for HCC patients with surgical resection of tumor.

Unlabelled: Hepatitis B virus affects more than 2 billion people worldwide, 350 million of which have developed chronic hepatitis B (CHB). The genetic factors that confer CHB risk are still largely unknown. We sought to identify genetic variants for CHB susceptibility in the Chinese population. We undertook a genome-wide association study (GWAS) in 2,514 CHB cases and 1,130 normal controls from eastern China. We replicated 33 of the most promising signals and eight previously reported CHB risk loci through a two-stage validation totaling 6,600 CHB cases and 8,127 controls in four independent populations, of which two populations were recruited from eastern China, one from northern China and one from southern China. The joint analyses of 9,114 CHB cases and 9,257 controls revealed significant association of CHB risk with five novel loci. Four loci are located in the human leukocyte antigen (HLA) region at 6p21.3, including two nonsynonymous variants (rs12614 [R32W] in complement factor B [CFB], Pmeta =1.28 × 10(-34) ; and rs422951 [T320A] in NOTCH4, Pmeta  = 5.33 × 10(-16) ); one synonymous variant (rs378352 in HLA-DOA corresponding to HLA-DOA*010101, Pmeta  = 1.04 × 10(-23) ); and one noncoding variant (rs2853953 near HLA-C, Pmeta  = 5.06 × 10(-20) ). Another locus is located at 20q13.1 (rs1883832 in the Kozak sequence of CD40, Pmeta  = 2.95 × 10(-15) ). Additionally, we validated seven of eight previously reported CHB susceptibility loci (rs3130542 at HLA-C, rs1419881 at TCF19, rs652888 at EHMT2, rs2856718 at HLA-DQB1, rs7453920 at HLA-DQB2, rs3077 at HLA-DPA1, and rs9277535 at HLA-DPA2, which are all located in the HLA region, 9.84 × 10(-71)  ≤ Pmeta  ≤ 9.92 × 10(-7) )., Conclusion: Our GWAS identified five novel susceptibility loci for CHB. These findings improve the understanding of CHB etiology and may provide new targets for prevention and treatment of this disease., (© 2015 by the American Association for the Study of Liver Diseases.)

Objective: To investigate the imaging and pathological findings of severe pneumonia caused by human infected avian influenza (H7N9), and therefore to further understand and improve diagnostic accuracy of severe pneumonia caused by human infected avian influenza (H7N9)., Methods: The relevant clinical and imaging data of 19 cases, including 10 males and 9 females, with pneumonia caused by human infected avian influenza (H7N9) was retrospectively analyzed. One of the cases had received percutaneous lung biopsy, with the clinical, imaging and pathological changes possible to be analyzed., Results: The lesions were mainly located at lower lobes and dorsal of lungs, involving multiple lobes and segments. Ground-glass opacities and/or pulmonary opacities were the more often imaging manifestations of severe pneumonia caused by human infected avian influenza (H7N9) in early and evolving phases (19/19,100%). By biopsy following percutaneous lung puncture, exudation of slurry, cellulose, RBC and neutrophils, formation of hyaline membrane, squamous metaplasia and organizing exudates were observable at the alveolar space. Some of alveoli collapsed, and some responded to show compensatory emphysema., Conclusion: The imaging features of severe pneumonia caused by human infected avian influenza (H7N9) include obvious ground-glass opacity and pulmonary consolidation, mainly at lower lobes and dorsal of lungs, with rapid changes. The cross-analysis of imaging and pathology preliminary can elucidate the pathological mechanisms of ground-glass opacities and pulmonary consolidation of severe pneumonia. Such an intensive study is beneficial to prompt clinicians to observe and evaluate the progress of the disease. In addition, it is also in favor of managing the symptoms and reducing the mortality rate., (© 2015 The Authors.)

The fluorescent carbon dot (C-dot) is a new class of carbon nanomaterials. It has a discrete or quasispherical structure, typically measures less than 10 nm and contains sp(2)/sp(3) carbon, oxygen/nitrogen-based groups and surface-modified functional groups. Compared with semiconductor quantum dots (QDs), C-dots offer much lower toxicity and a better biocompatibility profile. Their other favorable features include easy and inexpensive synthesis and surface modification potential. C-dots can be morphologically classified into graphene-based quantum dots (GQDs) and amorphous carbon nanodots (ACNDs). Numerous methods have been developed to synthesize C-dots, and are mainly divided into 'top-down' and 'bottom-up' routes. In the top-down route, C-dots (mostly GQDs) is derived from the separation of large carbon precursors. The 'bottom-up' method primarily involves the dehydration, polymerization and carbonization of small molecules to form the GQDs and ACNDs through thermal/hydrothermal synthesis, microwave irradiation, and solution chemistry. Potential applications of C-dots have been explored in a number of cellular and in-vivo imaging approaches. However, some difficulties remain, including limited penetration depth and poorly controlled in-vivo pharmacokinetics, which depends on multiple factors such as the morphology, physiochemical properties, surface chemistry and formulation of C-dots. The exact mechanism of in-vivo biodistribution, cellular uptake and long-term toxicological effect of C-dots still need to be elucidated. An integrated multi-disciplinary approach involving chemists, pharmacologists, toxicologists, clinicians, and regulatory bodies at the early stage is essential to enable the clinical application of C-dots.

The EGFR signaling pathway is important in the control of vital processes in the carcinogenesis of hepatocellular carcinoma (HCC), including cell survival, cell cycle progression, tumor invasion and angiogenesis. In the current study, we aim to assess if genetic variants in the genes of the EGFR signaling pathway are associated with the prognosis of HCC. We genotyped 36 single nucleotide polymorphisms (SNP) in four core genes (EGF, EGFR, VEGF, and VEGFR2) by using DNA from blood samples of 363 HCC patients with surgical resection. The associations between genotypes and overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Hazard ratios (HRs) and 95% confident intervals (CIs) were estimated for the multivariate survival analyses by Cox proportional hazards regression models, adjusting for age, gender, family history, HBsAg and AFP. We found that five SNPs in the VEGFR2 gene were significantly associated with clinical outcomes of HCC patients. Among them, four SNPs (rs7692791, rs2305948, rs13109660, rs6838752) were associated with OS (p=0.035, 0.038, 0.029 and 0.028, respectively), and two SNPs (rs7692791 and rs2034965) were associated with DFS (p=0.039 and 0.017, respectively). Particularly, rs7692791 TT genotype was associated with both reduced OS (p=0.037) and DFS (p=0.043). However, only one SNP rs2034965 with the AA genotype was shown to be an independent effect on DFS (p=0.009) in the multivariate analysis. None of the other 31 polymorphisms or 9 haplotypes attained from the four genes was significantly associated with OS or DFS. Our results illustrated the potential use of VEGFR2 polymorphisms as prognostic markers for HCC patients.

The U.S. National Library of Medicine has made two datasets of postero-anterior (PA) chest radiographs available to foster research in computer-aided diagnosis of pulmonary diseases with a special focus on pulmonary tuberculosis (TB). The radiographs were acquired from the Department of Health and Human Services, Montgomery County, Maryland, USA and Shenzhen No. 3 People's Hospital in China. Both datasets contain normal and abnormal chest X-rays with manifestations of TB and include associated radiologist readings.

Purpose: This study was aimed to determine whether pure molecular-based diffusion coefficient (D) and perfusion-related diffusion parameters (perfusion fraction f, perfusion-related diffusion coefficient D*) differ in healthy livers and fibrotic livers through intra-voxel incoherent motion (IVIM) MR imaging., Material and Methods: 17 healthy volunteers and 34 patients with histopathologically confirmed liver fibrosis patients (stage 1 = 14, stage 2 = 8, stage 3 & 4 = 12, METAVIR grading) were included. Liver MR imaging was performed at 1.5-T. IVIM diffusion weighted imaging sequence was based on standard single-shot DW spin echo-planar imaging, with ten b values of 10, 20, 40, 60, 80, 100, 150, 200, 400, 800 sec/mm2 respectively. Pixel-wise realization and regions-of-interest based quantification of IVIM parameters were performed., Results: D, f, and D* in healthy volunteer livers and patient livers were 1.096±0.155 vs 0.917±0.152 (10(-3) mm2/s, p = 0.0015), 0.164±0.021 vs 0.123±0.029 (p<0.0001), and 13.085±2.943 vs 9.423±1.737 (10(-3) mm2/s, p<0.0001) respectively, all significantly lower in fibrotic livers. As the fibrosis severity progressed, D, f, and D* values decreased, with a trend significant for f and D*., Conclusion: Fibrotic liver is associated with lower pure molecular diffusion, lower perfusion volume fraction, and lower perfusion-related diffusion. The decrease of f and D* in the liver is significantly associated liver fibrosis severity.

Objective: To study the CT characteristics of solitary focal organizing pneumonia (FOP)., Materials and Methods: Chest CT of consecutive 45 patients (34 males and 11 females, median age: 56 years) with confirmed FOP were analyzed. The CT features between large FOP (>3 cm, n=27) and small FOP (≤ 3 cm, n=18) were compared., Results: FOP lesions predominately located in peripheral lungs (86.7%), with the right lower lobe being most common lobe (44.4%). No lesion mainly located in the inner 1/3 of lungs. All large lesions were polygon in shape and had an irregular margin, while small lesions were more likely to be round or oval with an irregular or smooth border. Air bronchogram or small bubble-like lucency was present in majority of the lesions. 42.2% of lesions had incompact internal structure with inhomogeneous density besides air component. Most lesions were associated with a contraction or convergence of surrounding vessels; while no pulmonary vessel was interrupted abruptly by a small FOP lesion. Majority of large lesions had broad contact with the pleura, while only one patient had mild pleural effusion. Mild mediastinal lymph nodes enlargement was present in about 1/5 of the patients., Conclusion: Compared with the known CT features of lung cancer, our results suggest differential diagnosis can often be made for large FOP, while small FOP may resemble lung cancer., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

With biliary duct ligation and CCl4 induced rat liver fibrosis models, recent studies showed that MR T1rho imaging is able to detect liver fibrosis, and the degree of fibrosis is correlated with the degree of elevation of the T1rho measurements, suggesting liver T1rho quantification may play an important role for liver fibrosis early detection and grading. It has also been reported it is feasible to obtain consistent liver T1rho measurement for human subjects at 3 Tesla (3 T), and preliminary clinical data suggest liver T1rho is increased in patients with cirrhosis. In these previous studies, T1rho imaging was used with the rotary-echo spin-lock pulse for T1rho preparation, and number of signal averaging (NSA) was 2. Due to the presence of inhomogeneous B0 field, artifacts may occur in the acquired T1rho-weighted images. The method described by Dixon et al. (Magn Reson Med 1996;36:90-4), which is a hard RF pulse with 135° flip angle and same RF phase as the spin-locking RF pulse is inserted right before and after the spin-locking RF pulse, has been proposed to reduce sensitivity to B0 field inhomogeneity in T1rho imaging. In this study, we compared the images scanned by rotary-echo spin-lock pulse method (sequence 1) and the pulse modified according to Dixon method (sequence 2). When the artifacts occurred in T1rho images, we repeated the same scan until satisfactory. We accepted images if artifact in liver was less than 10% of liver area by visual estimation. When NSA =2, the breath-holding duration for data acquisition of one slice scanning was 8 sec due to a delay time of 6,000 ms for magnetization restoration. If NSA =1, the duration was shortened to be 2 sec. In previous studies, manual region of interest (ROI) analysis of T1rho map was used. In this current study, histogram analysis was also applied to evaluate liver T1rho value on T1rho maps. MRI data acquisition was performed on a 3 T clinical scanner. There were 29 subjects with 61 examinations obtained. Liver T1rho values obtained by sequence 1 (NSA =2) and sequence 2 (NSA =2) showed similar values, i.e., 43.1±2.1 ms (range: 38.6-48.0 ms, n=40 scans) vs. 43.5±2.5 ms (range: 39.0-47.7 ms, 
n=12 scans, P=0.74) respectively. For the six volunteers scanned with both sequences in one session, the intraclass correlation coefficient (ICC) was 0.939. Overall, the success rate of obtaining satisfactory images per acquisition was slightly over 50% for both sequence 1 and sequence 2. Satisfactory images can usually be obtained by asking the volunteer subjects to better hold their breath. However, sequence 2 did not increase the scan success rate. For the nine subjects scanned by sequence 2 with both NSA =2 and NSA =1 during one session, the ICC was 0.274, demonstrated poor agreement. T1rho measurement by ROI method and histogram had an ICC of 0.901 (P>0.05), demonstrated very good agreement. We conclude that by including 135° flip angle before and after the spin-locking RF pulse, the rate of artifacts occurring did not decrease. On the other hand, sequence 1 and sequence 2 measured similar T1rho value in healthy liver. While reducing the breath-holding duration significantly, NSA =1 did not offer satisfactory signal-to-noise ratio. Histogram measurement can be adopted for future studies.

Objective: To study the CT and MR features of xanthogranulomatous cholecystitis (XGC)., Materials and Methods: 49 patients had pathologically confirmed XGC. All patients underwent contrast enhanced CT, and 10 patients had additional plain MRI. The CT and MRI results were retrospectively analyzed., Results: On CT, all patients had thickening of gallbladder wall, with 87.8% cases showed diffuse thickening. 85.7% cases had intramural hypo-attenuated nodules in the thickened wall. Continuous mucosal line and luminal surface enhancement were noted in 79.6% and 85.7% cases, respectively. Gallbladder stones were seen in 69.4% patients. The coexistence of the above 5 CT features was seen in 40% cases, and 80% cases had the coexistence of ≥ 4 features. Diffused gallbladder wall thickening in XGC is more likely to have disrupted mucosal line, and XGC with disrupted mucosal line is more likely to be associated with liver infiltration. In 60% patients the inflammatory process extended beyond gallbladder, with the interface between gallbladder and liver and/or the surrounding fat blurred. 40% cases had an early enhancement of liver parenchyma. Infiltration to other surrounding tissues included bowel (n=3), stomach (n=2), and abdominal wall (n=1). On MR images, 7 of 9 intramural nodules in 7 subjects with T1-weighted dual echo MR images showed higher signal intensity on in-phase images than out-of-phase images., Conclusion: Coexisting of diffuse gallbladder wall thickening, hypo-attenuated intramural nodules, continuous mucosal line, luminal surface enhancement, and gallbladder stone highly suggest XGC. XGC frequently infiltrate liver and surrounding fat. Chemical-shift MRI helps classifying intramural nodules in the gallbladder wall., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

The interactions between the concentrations of sulfur, iron and cadmium in the rhizosphere and their uptakes in rice (Oryza sativa L. ) were studied using paddy soil which was contaminated by acid mine drainage under five water-management treatments of 60%, 80%, 100% field moisture capacity (FMC), flooded throughout the entire rice growth period and flooded followed by keeping 80% FMC after heading-flowering period. The water managements had no significant influence on the Fe and Cd concentrations in rhizosphere soil in maturity stage, although the concentration of Cd slightly increased with the increase of soil moisture in the tillering stage. However, the uptake of Fe and Cd in rice was obviously related to water managements. The increase of soil moisture enhanced the uptake of Fe, but decreased the uptake of Cd in different organs of rice (roots, stems and leaves, grains) except for Cd uptake of the root in the 60% FMC treatment. However, aerobic treatment after heading-flowering period enhanced Cd uptake in rice in all treatments, but did not influence the uptake of Fe in rice. On the other hand, the increase of soil moisture reduced the concentrations of total sulfur and available sulfur in the rhizosphere soil except for the 60% FMC treatment, which corresponded with the reduction of Cd uptake in rice. And the aerobic treatment promoted Cd uptake in rice, which was also positively related to the increase of total sulfur and available sulfur in rhizosphere soil. Therefore, it was concluded that the uptake and speciation of sulfur in rhizosphere soil other than the change of Fe concentration induced by water management could play an important role in Cd uptake of rice.

To identify genetic susceptibility loci for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in the Chinese population, we carried out a genome-wide association study (GWAS) in 2,514 chronic HBV carriers (1,161 HCC cases and 1,353 controls) followed by a 2-stage validation among 6 independent populations of chronic HBV carriers (4,319 cases and 4,966 controls). The joint analyses showed that HCC risk was significantly associated with two independent loci: rs7574865 at STAT4, P(meta) = 2.48 × 10(-10), odds ratio (OR) = 1.21; and rs9275319 at HLA-DQ, P(meta) = 2.72 × 10(-17), OR = 1.49. The risk allele G at rs7574865 was significantly associated with lower mRNA levels of STAT4 in both the HCC tissues and nontumor tissues of 155 individuals with HBV-related HCC (P(trend) = 0.0008 and 0.0002, respectively). We also found significantly lower mRNA expression of STAT4 in HCC tumor tissues compared with paired adjacent nontumor tissues (P = 2.33 × 10(-14)).

Objective: To investigate the relationship between respiratory viral load and lung lesion severity of patients with pandemic H1N1 2009 influenza A pneumonia., Study Design: Cross-sectional observation study., Methods: 24 consecutive H1N1 influenza patients with viral pneumonia (13 males, 11 females, mean age: 17.5 years) during their presentation to hospital were retrospectively analysed. Viral load were first measured on average 5.2 days after the onset of symptoms. The initial CT and viral load measurement was carried on the same day in 13 patients. The rest were carried out with a mean interval time of 1.5 days. All patients had viral load follow-up till turned negative. Thirteen patients had radiological follow-up., Results: There was no significant correlation between the initial lung lesion severity and viral load (P=0.4). Both viral load and lung lesion severity decreased over time, being highest value at initial presentation. The patients had higher initial viral load or higher initial lung lesion severity tended to be slower in resolving. The lung lesion decreased at a slower rate than viral load., Conclusions: While there was no correlation between the initial viral load and lung lesion severity, these two indices provide valuable information for epidemiological control.

Objective: To explore the relationship between serum HBV DNA load and hepatocellular carcinogenesis in Qidong HBsAg carriers., Methods: In 1997, 477 HBsAg carriers and 477 age, gender and residence matched HBsAg negative controls were enrolled as a prospective cohort in Qidong city. The entry serum samples were detected for the levels of HBeAg and HBV DNA. The relationship between baseline HBV DNA load and hepatocellular carcinoma (HCC) during the follow-up period from June 1997 to June 2011 were analyzed., Results: The total observed person-years (PY) were 12 200. Eighty-seven patients developed HCC with an incidence of 1498/100 000 PY in the HBsAg positive group versus 6 with an incidence of 94/100 000 PY (P = 0.000) in the HBsAg negative group. The relative risk (RR) was 15.96. N o significant difference existed between the incidences of other tumors in two groups (P = 0.161). Compared with the HBsAg negative group, the RR of HCC was 11.38 (95%CI 4.87 - 26.62, P < 0.01)in the HBsAg+/HBeAg- group and 29.08 (95%CI 12.37 - 68.37, P < 0.01) in the HBsAg+/HBeAg+ group; 5.80 (95%CI 2.29 - 14.70, P < 0.01) in the HBsAg+/HBV DNA- group and 27.75 (95%CI 12.07 - 63.81, P < 0.01) in the HBsAg+/HBV DNA+ group. In HBsAg positive subjects, while the HBV DNA load was classified into 5 levels namely 250 - 10(4), 10(4)-, 10(5)-, 10(6)- and ≥ 10(7) copies/ml, the relative risks for HCC at each level were 2.84 (95%CI 1.44 - 5.61, P < 0.01), 5.75 (95%CI 2.77 - 11.95, P < 0.01), 9.05 (95%CI 4.71 - 17.41, P < 0.01), 6.39 (95%CI 2.79 - 14.64, P < 0.01) and 4.35 (95%CI 2.21 - 8.56, P < 0.01) respectively versus the < 250 copies/ml group., Conclusion: HBV DNA is an important risk predictor of hepatocellular carcinoma. The HBsAg carriers with the serum loads of HBV DNA between 10(5) - 10(6) copies/ml are most likely to present with HCC.

The extreme ultraviolet (EUV) emission characteristics from Sn plasma for lithography produced by a pulse discharge CO2 laser was investigated under different conditions. Extreme ultraviolet spectral measurements were made throughout the wavelength region of 6.5 nm to 16.8 nm using a grazing incidence flat-field spectrograph coupled with an X-ray charge-coupled device camera for detection of time-integrated spectra. The dependence of spectral properties of the EUV emission on pulse duration, incidence pulse energy, and buffer gas pressure was investigated. The results show that the peak of EUV spectra was located at 13.5 nm. The intensity of EUV emission increased with increasing laser energy ranging from 30 mJ to 600 mJ in a nonlinear manner with saturation effect. The critical energy of incident pulse laser for the generation of EUV emission is near 30 mJ in our experiment. The highest conversion efficiency of 1.2% in producing 13.5 nm EUV light with 0.27 nm bandwidth was achieved at pump energy of 425 mJ. The EUV spectra from a plate target produced by laser pulse with full width at half maximum range from 50 ns to 120 ns were recorded and negligible differences in their spectral features noticed even though higher spectral intensity was observed by shorter pulse duration. The 2% in-band EUV intensity with 52 ns pulse duration was 1.6 times higher than that with 120 ns pulse duration due to the increase in laser intensity. It was also found that the detected EUV spectral intensity rapidly decreased with increasing buffer air pressure, and the EUV emission could be totally absorbed at the pressure of 200 Pa, while weak EUV emission could be still detected at the buffer He gas pressure of 7 x 10(4) Pa. The experimental results showed that the absorption coefficient of 13.5 nm light at air buffer gas pressure of 100 Pa was 3.0 m(-1), while the absorption coefficient was 0.96 m(-1) at the same He buffer gas pressure.

Purpose: To investigate the imaging manifestations of Pneumocystis Jiroveci Pneumonitis (PCP) in AIDS patients, and the correlation between imaging features, CD(4) (+) lymphocyte count, and plasma HIV viral load., Materials and Methods: A total of consecutive 50 AIDS patients with PCP were reviewed retrospectively. Chest CT manifestations, CD(4) (+) lymphocyte count, and plasma HIV viral load were analyzed to investigate their correlation., Results: PCP chest CT manifestations included ground-glass opacities dominated in 28 cases (28/50, 56%), lung cysts dominated in 10 cases (10/50, 20%), consolidation dominated in 6 cases (6/50, 12%), interstitial lesion dominated in 3 cases (3/50, 6%), and mixed lesions in 3 cases (3/50, 6%). In these 50 patients, CD(4) (+) lymphocyte count ranged from 2 to 373 cells/µL. Plasma HIV viral load ranged from 500 to 5.28×10(7) copies/mL. CD(4) (+) lymphocyte count in ground-glass opacities dominated patients was higher than that of lung cyst dominated patients (P<0.05). Plasma virus load of lung cysts dominated PCP patients was higher than that of consolidation dominated patients (P<0.05)., Conclusions: The typical chest imaging features of PCP in AIDS patients included lung ground-glass opacities and lung cysts. The chest imaging features were correlated with CD(4) (+) T lymphocyte count and plasma HIV viral load.