Publications by authors named "Xiaoguang Li"

422 Publications

Study on Concrete Deterioration in Different NaCl-NaSO Solutions and the Mechanism of Cl Diffusion.

Materials (Basel) 2021 Sep 3;14(17). Epub 2021 Sep 3.

Department of Civil Engineering, School of Civil Engineering, Chang'an University, Xi'an 710064, China.

The diffusion of sulfate (SO) and chloride (Cl) ions from rivers, salt lakes and saline soil into reinforced concrete is one of the main factors that contributes to the corrosion of steel reinforcing bars, thus reducing their mechanical properties. This work experimentally investigated the corrosion process involving various concentrations of NaCl-NaSO leading to the coupled erosion of concrete. The appearance, weight, and mechanical properties of the concrete were measured throughout the erosion process, and the Cl and SO contents in concrete were determined using Cl rapid testing and spectrophotometry, respectively. Scanning electron microscopy, energy spectrometry, X-ray diffractometry, and mercury porosimetry were also employed to analyze microstructural changes and complex mineral combinations in these samples. The results showed that with higher NaSO concentration and longer exposure time, the mass, compressive strength, and relative dynamic elastic modulus gradually increased and large pores gradually transitioned to medium and small pores. When the NaSO mass fraction in the salt solution was ≥10 wt%, there was a downward trend in the mechanical properties after exposure for a certain period of time. The Cl diffusion rate was thus related to NaSO concentration. When the NaSO mass fraction in solution was ≤5 wt% and exposure time short, SO and cement hydration/corrosion products hindered Cl migration. In a concentrated NaSO environment (≥10 wt%), the Cl diffusion rate was accelerated in the later stages of exposure. These experiments further revealed that the Cl migration rate was higher than that of SO.
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http://dx.doi.org/10.3390/ma14175054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434449PMC
September 2021

Extranodal Extension in Bilateral Cervical Metastases: A predictor of Undesirable Survival Outcomes despite Aggressive Salvage Treatment in Oral Cancer Patients.

J Cancer 2021 3;12(19):5848-5863. Epub 2021 Aug 3.

Department of Dermatology, Huashan Hospital affiliated by Fudan University, No.12, Wulumuqi Middle Road, Shanghai, China.

Despite the inclusion of extranodal extension (ENE) in the recent staging system, the presence of ENE alone is not sufficient to depict all clinical situations, as ENE is frequently found in multiple nodes. Thus, the purpose of this study was to evaluate the surgery-based treatment outcomes and clinicopathological features of oral cavity squamous cell carcinoma (OCSCC) patients with ENE found in bilateral multiple cervical metastases. A retrospective single-institutional study of OCSCC patients with bilateral ENE nodes was performed from January 2011 to December 2018. OCSCC patients of different admission statuses (with primary lesions (PL), recurrent lesions (RL) and isolated neck metastases (INM)) were included for subgroup comparisons. All patients received surgical treatment with/without adjuvant therapies and had complete follow-up data. Disease-free survival (DFS) was regarded as the main outcome. Time-to-relapse data were also collected for comparison. A total of 128 patients were included, of whom 97 (75.8%) were male. The mean follow-up period reached 15 months. Among the patients, 85 (66.4%) were treated for PLs, followed by 26 (20.3%) treated for RLs after failed prior therapy and 17 (13.3%) treated for INMs (concurrent or sequential). The DFS rate was merely 35.2%. Treatment-related factors such as surgical margin (p=0.003), postoperative adjuvant therapy (p=0.014) and perioperative complications (p=0.036) were significantly associated with patient outcomes. In addition, oral lesion-related variables such as oral subsites (p=0.037), T classification (p=0.026) and skull base involvement (p=0.040) were indicators of a worse prognosis. For bilateral ENE features, ENE subclassification (p=0.036), maximum size of ENE nodes (p=0.039) and arterial nodal encasement (p=0.025) tended to predict the surgery-based treatment outcomes of these patients. Bilateral cervical metastases with ENE features, though uncommon, are a serious regional burden, and these patients have lower-than-expected treatment outcomes, especially those with RLs or INMs. A fairly large number of OCSCC patients with advanced oral lesions gain little benefit from intensified salvage surgical treatment. Such treatment should instead be offered to select patients with smaller bilateral ENE nodes (<3 cm) and those with lower ENE subclassifications and no arterial nodal encasement.
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http://dx.doi.org/10.7150/jca.60152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408102PMC
August 2021

Direct Observation of Interface-Dependent Multidomain State in the BaTiO Tunnel Barrier of a Multiferroic Tunnel Junction Memristor.

ACS Appl Mater Interfaces 2021 Sep 2;13(36):43641-43647. Epub 2021 Sep 2.

National Center for Electron Microscopy in Beijing, School of Materials Science and Engineering, The State Key Laboratory of New Ceramics and Fine Processing, Key Laboratory of Advanced Materials (MOE), Tsinghua University, Beijing 100084, People's Republic of China.

Multiferroic tunnel junctions (MFTJs), normally consisting of a four-state resistance, have been studied extensively as a potential candidate for nonvolatile memory devices. More interestingly, the MFTJs whose resistance can be tuned continuously with applied voltage were also reported recently. Since the performance of MFTJs is closely related to their interfacial structures, it is necessary to investigate MFTJs at the atomic scale. In this work, atomic-resolution HAADF, ABF, and EELS of the LaSrMnO/BaTiO/LaSrMnO MFTJ memristor have been obtained with aberration-corrected scanning transmission electron microscopy (STEM). These results demonstrate varied degree of interfacial cation intermixing at the bottom BTO/LSMO interface, which has a direct influence on the polarization of the ferroelectric barrier BTO and the electronic structure of Mn near the interfaces. We also took advantage of a simplified model to explain the relation between the interfacial behavior and polarization states, which could be a contributing factor to the transport properties of this MFTJ.
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http://dx.doi.org/10.1021/acsami.1c11661DOI Listing
September 2021

LRRK2 plays essential roles in maintaining lung homeostasis and preventing the development of pulmonary fibrosis.

Proc Natl Acad Sci U S A 2021 Aug;118(35)

Institute for Immunology, Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China;

Perturbation of lung homeostasis is frequently associated with progressive and fatal respiratory diseases, such as pulmonary fibrosis. Leucine-rich repeat kinase 2 (LRRK2) is highly expressed in healthy lungs, but its functions in lung homeostasis and diseases remain elusive. Herein, we showed that LRRK2 expression was clearly reduced in mammalian fibrotic lungs, and LRRK2-deficient mice exhibited aggravated bleomycin-induced pulmonary fibrosis. Furthermore, we demonstrated that in bleomycin-treated mice, LRRK2 expression was dramatically decreased in alveolar type II epithelial (AT2) cells, and its deficiency resulted in profound dysfunction of AT2 cells, characterized by impaired autophagy and accelerated cellular senescence. Additionally, LRRK2-deficient AT2 cells showed a higher capacity of recruiting profibrotic macrophages via the CCL2/CCR2 signaling, leading to extensive macrophage-associated profibrotic responses and progressive pulmonary fibrosis. Taken together, our study demonstrates that LRRK2 plays a crucial role in preventing AT2 cell dysfunction and orchestrating the innate immune responses to protect against pulmonary fibrosis.
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http://dx.doi.org/10.1073/pnas.2106685118DOI Listing
August 2021

Salvage surgery for patients with residual/persistent diseases after improper or insufficient treatment of oral squamous cell carcinoma: can we rectify these mistakes?

BMC Cancer 2021 Jul 31;21(1):878. Epub 2021 Jul 31.

Department of Oral & Maxillofacial - Head & Neck Oncology, 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Key Laboratory of Stomatology, No. 639, Zhi Zao Ju Road, Shanghai, 200011, Shanghai, China.

Background: Patterns of failure after treatment of oral and squamous cell carcinomas (OSCC) are diversified, with recurrences being one of the common causes. A special group of patients are sometimes encountered in the outpatient clinic for improper or insufficient initial treatment with reports of positive margins, implying residual/persistent diseases. The question of whether these patients can be surgically salvaged remain unanswered.

Methods: A retrospective study was performed between January 2013 and December 2017 for patients with residual or rapid recurrent (within 3 months) OSCCs, who received salvage surgeries in our institution. The patients with residual/persistent OSCCs were those with microscopic or macroscopic positive surgical margins, while those with rapid recurrent OSCCs were those with close or negative margins, but unabated painful symptoms right after treatment. Both clinicopathological and prognostic variables were analyzed. The focus was also directed towards lessons for possible initial mistakes, resulting in these residual/persistent diseases.

Results: Of 103 patients, 68 (66%) were men, with mean age of 56.3 years. The overall survival reached 60.2%. Regarding the primary OSCC status, most of our patients (n = 75, 72.8%) were diagnosed with ycT2-3 stages. Besides, most patients were found with macroscopic residual diseases (52.4%) before our salvage surgery. The sizes of the residual/persistent OSCCs were generally under 4 cm (87.3%) with minimally residual in 21 (20.4%). Among all the variables, primary T stage (p = 0.003), and residual lesion size (p < 0.001) were significantly associated with the prognosis in multivariate analysis. Though the causes for the initial surgical failure were multifactorial, most were stemmed from poor planning and unstandardized execution.

Conclusions: Cases with residual/persistent OSCCs were mostly due to mistakes which could have been avoided under well-round treatment plans and careful surgical practice. Salvage surgery for cases with smaller residual/persistent OSCCs is still feasible with acceptable outcomes.
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http://dx.doi.org/10.1186/s12885-021-08600-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325844PMC
July 2021

Mechanism of Cr(VI) reduction by Lysinibacillus sp. HST-98, a newly isolated Cr (VI)-reducing strain.

Environ Sci Pollut Res Int 2021 Jul 30. Epub 2021 Jul 30.

College of Biomass Science and Engineering, Sichuan University, Chengdu, 610065, China.

Facing the increasingly severe Cr(VI) pollution, bioreduction has proved to be an eco-friendly remediation method. An isolated strain identified as Lysinibacillus can relatively reduce Cr(VI) well. Even if the concentration of Cr(VI) increased to 250mg/L, the strain HST-98 could also grow and remove Cr(VI) well. After optimization of reaction conditions, the optimal pH, temperature, and electron donor are 8~9, 36°C, and sodium lactate, respectively. Coexisting metal ions such as Cu, Co, and Mn are beneficial to reduce Cr(VI), while Zn, Ni, and Cd are just the opposite. What is more, the mechanism of the reduction by the strain HST-98 is chiefly mediated by intracellular enzymes. After gene sequence homology blast and analysis, the genes and enzymes related to chromium metabolism in strain HST-98 have been annotated, which helps us to further understand the reduction mechanism of the strain HST-98. In general, Lysinibacillus sp. HST-98 is a potential candidate to repair the Cr(VI)-contaminated sites.
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http://dx.doi.org/10.1007/s11356-021-15424-xDOI Listing
July 2021

Rebalancing TGF-β/Smad7 signaling via Compound kushen injection in hepatic stellate cells protects against liver fibrosis and hepatocarcinogenesis.

Clin Transl Med 2021 Jul;11(7):e410

State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Liver fibrosis and fibrosis-related hepatocarcinogenesis are a rising cause for morbidity and death worldwide. Although transforming growth factor-β (TGF-β) is a critical mediator of chronic liver fibrosis, targeting TGF-β isoforms and receptors lead to unacceptable side effect. This study was designed to explore the antifibrotic effect of Compound kushen injection (CKI), an approved traditional Chinese medicine formula, via a therapeutic strategy of rebalancing TGF-β/Smad7 signaling.

Methods: A meta-analysis was performed to evaluate CKI intervention on viral hepatitis-induced fibrosis or cirrhosis in clinical randomized controlled trials (RCTs). Mice were given carbon tetrachloride (CCl ) injection or methionine-choline deficient (MCD) diet to induce liver fibrosis, followed by CKI treatment. We examined the expression of TGF-β/Smad signaling and typical fibrosis-related genes in hepatic stellate cells (HSCs) and fibrotic liver tissues by qRT-PCR, Western blotting, RNA-seq, immunofluorescence, and immunohistochemistry.

Results: Based on meta-analysis results, CKI improved the liver function and relieved liver fibrosis among patients. In our preclinical studies by using two mouse models, CKI treatment demonstrated promising antifibrotic effects and postponed hepatocarcinogenesis with improved liver function and histopathologic features. Mechanistically, we found that CKI inhibited HSCs activation by stabilizing the interaction of Smad7/TGF-βR1 to rebalance Smad2/Smad3 signaling, and subsequently decreased the extracellular matrix formation. Importantly, Smad7 depletion abolished the antifibrotic effect of CKI in vivo and in vitro. Moreover, matrine, oxymatrine, sophocarpine, and oxysophocarpine were identified as material basis responsible for the antifibrosis effect of CKI.

Conclusions: Our results unveil the approach of CKI in rebalancing TGF-β/Smad7 signaling in HSCs to protect against hepatic fibrosis and hepatocarcinogenesis in both preclinical and clinical studies. Our study suggests that CKI can be a candidate for treatment of hepatic fibrosis and related oncogenesis.
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http://dx.doi.org/10.1002/ctm2.410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255064PMC
July 2021

Surgical Management of Bilateral Osteoradionecrosis of the Mandible.

J Craniofac Surg 2021 Jul 27. Epub 2021 Jul 27.

Department of Oral Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine National Clinical Research Center for Oral Disease Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai, China.

Purpose: The purpose of this study was to evaluate our 10 years clinical experience in surgical management of patients with bilateral osteoradionecrosis (BORN) of the mandible in head and neck malignancies patients.

Materials And Methods: The authors reviewed 22 patients with bilateral mandibular bone mineral density changed in image who had failed to respond to conservative treatments. They were treated by radical resection and reconstruction with free flaps immediately or second-stage at our institution between January 2008 and January 2018.

Results: Nine patients received immediate bilateral mandibular radical resection. Six bone flaps (4 fibula osteocutaneous [fibular OC], 1 fibular OC + pectoralis major myocutaneous flap [PMMF] and 1 fibular OC + anterolateral thigh flap [ALTF]) and 3 soft flaps (1 PMMF, 1 PMMF + titanium plate and 1 ALTF) were used. Three (33.3%) of these patients complications occurred in the immediate postoperative period, but all patients have an acceptable follow-up outcomes. In remaining 13 patients who only experienced immediate unilateral mandible resection for the first time. Complications occurred in 1 patient (7.7%), and all patients have a good outcome in the immediate postoperative period. In follow-up, 1 patient titanium plate exposed, and 6 patients (46.2%) contralateral mandible ORN developed that underwent radical resection in second time. Three fibular OC, 2 PMMF, and 1 latissimus dorsi myocutaneous flap were used. The overall outcome of our experience with the use of bone or soft tissue transfers in managing BORN of mandible is encouraging.

Conclusions: An individualized management plan should be given for each patient depending on their own local and general condition. Radical resection followed by vascularized flaps reconstruction is an acceptable and reliable procedure for patients with BORN of the mandible.
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http://dx.doi.org/10.1097/SCS.0000000000007906DOI Listing
July 2021

sp. nov., isolated from chromium-containing chemical plant soil.

Int J Syst Evol Microbiol 2021 Jul;71(7)

College of Biomass Science and Engineering, Sichuan University, Chengdu 610065, PR China.

A Gram-stain-positive, rod-shaped, aerobic, non-motile, non-sporulating bacterial strain, designated CSA1, was isolated from chromium-containing soil sampled at a chemical plant. Growth of strain CSA1 occurred at pH 6-10 (optimum, pH 7), 15-45 °C (optimum, 30 °C) and in the presence of 0.5-6.5 % (w/v) NaCl (optimum, 2 %). The 16S rRNA gene sequence of strain CSA1 revealed the highest similarity to A2 (97.5 %), K 70/01 (97.3 %), Re6 (96.6 %), F3-P9 (96.2 %), CC-MF41 (96.1 %) and S27 (96.0 %). The draft genome of CSA1 was approximately 3 350 931 bp in size with a G+C content of 70.6 mol%. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values among strain CSA1 and the selected species were 74.0-79.2 % (ANIb), 84.3-87.1 % (ANIm) and 21.5-25.4 % (dDDH), which are below the recommended cutoff values for species delineation. The major fatty acids were anteiso-C, iso-C and anteiso-C. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol and an unknown glycolipid. The predominant menaquinones were MK-11, MK-8 and MK-6. The cell-wall amino acids were 2,4-diaminobutyric acid, alanine, glycine, glutamic acid and threonine. From the phenotypic, chemotaxonomic and molecular features, strain CSA1 was considered to represent a novel species of the genus , for which the name sp. nov. is proposed. The type strain is CSA1 (=JCM 34359=CGMCC 1.18746).
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http://dx.doi.org/10.1099/ijsem.0.004923DOI Listing
July 2021

Combination of thermal ablation and activated functional killer cells immunotherapy for cancer: A retrospective study.

J Cancer Res Ther 2021 Jul;17(3):797-802

Department of Minimally Invasive Tumor Therapies Center, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences; Graduate School of Perking Union Medical College, China Academy of Medical Sciences, Beijing, China.

Purpose: The purpose was to evaluate the effect of thermal ablation combined with activated functional killer (AFK) cells immunotherapy for patients with malignant tumors.

Materials And Methods: A cohort of 10 patients with malignancies received thermal ablation combined with AFK cells immunotherapy. Progression-free survival (PFS), overall survival, laboratory test, and postoperative complications were assessed.

Results: The success rate of the combination therapy was 100% and no severe complications occurred. Five patients maintained in PFS (50%) during the follow-up. The median PFS was 11 months (range 3.5-16.75 months). The hemoglobin (P = 0.023), hematocrit (P = 0.034), and lymphocyte ratio (P = 0.023); neutrophil-to-lymphocyte ratio (P = 0.038), neutrophil ratio (P = 0.016), albumin (P = 0.006), and alkaline phosphatase (P = 0.029); CA-125 (P = 0.033); and D-dimer (P = 0.011) changed significant after ablation. Whereas the white blood cell count (P = 0.003), neutrophil count (P = 0.024), lymphocyte count (P =0.003), monocyte ratio (P = 0.008), and eosinophil ratio (P = 0.005) changed significantly after combination therapy. The lymphocytes (P = 0.001) in the surviving patients increased more significantly after treatment. After the combination therapy, the percentage of CD3 + cells (P = 0.016) and CD3 CD8 cells (P = 0.002) increased, while CD3CD16 CD56 (P = 0.002) and CD4/CD8 (P = 0.016) decreased.

Conclusion: Combination of thermal ablation and AFK cells immunotherapy is a safe and effective method for patients with malignancy. And adoptive immunotherapy with AFK cells may be helpful to prevent recurrence after thermal ablation in patients with advanced cancer.
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http://dx.doi.org/10.4103/jcrt.jcrt_26_21DOI Listing
July 2021

Influenza colloidal gold method and blood routine tests combination for rapid diagnosis of influenza: a decision tree-based analysis.

NPJ Prim Care Respir Med 2021 07 15;31(1):39. Epub 2021 Jul 15.

Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, People's Republic of China.

Rapid influenza diagnosis can facilitate targeted treatment and reduce antibiotic misuse. However, diagnosis efficacy remains unclear. This study examined the efficacy of a colloidal gold rapid test for rapid influenza diagnosis. Clinical characteristics of 520 patients with influenza-like illness presenting at a fever outpatient clinic during two influenza seasons (2017-2018; 2018-2019) were evaluated. The clinical manifestations and results of routine blood, colloidal gold, and nucleic acid tests were used to construct a decision tree with three layers, nine nodes, and five terminal nodes. The combined positive predictive value of a positive colloidal gold test result and monocyte level within 10.95-12.55% was 88.2%. The combined negative predictive value of a negative colloidal gold test result and white blood cell count > 9.075 × 10/L was 84.9%. The decision-tree model showed the satisfactory accuracy of an early influenza diagnosis based on colloidal gold and routine blood test results.
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http://dx.doi.org/10.1038/s41533-021-00251-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282862PMC
July 2021

Value of Conventional MRI Texture Analysis in the Differential Diagnosis of Phyllodes Tumors and Fibroadenomas of the Breast.

Breast Care (Basel) 2021 Jun 23;16(3):283-290. Epub 2020 Jun 23.

Department of Radiology, Daping Hospital, Army Medical University, Chongqing, China.

Background: There is substantial overlap in MRI findings between phyllodes tumors (PTs) and fibroadenomas (FAs). Our study was performed to investigate the value of conventional MRI texture analysis in the differential diagnosis of PTs and FAs.

Methods: Preoperative MRI data - including axial T1WI, T2WI (T2WI with fat suppression), dynamic contrast-enhanced (DCE)-T1WI and DCE-T1WI (T1WI post-strengthened for 2 and 7 min, respectively, on DCE-MRI) - of 45 patients with PTs and 67 patients with FAs were retrospectively analyzed. MaZda 4.7 software was used to manually draw the maximum ROIs at the same lesion level of the above MRI images. The optimized feature selection methods included Fisher's coefficient, probability of classification error and average correction coefficient (POE + ACC), and mutual information (MI) as well as a combination of the above 3 methods (F + POE + ACC + MI [FPM]), respectively. The misclassification rates of PTs and FAs were compared between texture analysis and subjective diagnosis by radiologists.

Results: The DCE-T1WI images had the lowest misclassification rate of 10.71% (12/112). The misclassification rate for the radiologists' analysis (31.25%, 35/112) was higher than that of all the texture analysis, and there was a statistically significant difference between the radiologists' misclassification rates and those from the FPM method in terms of the T2WI and DCE-T1WI images (all < 0.05), and for the DCE-T1WI images by using the Fisher and FPM methods (all < 0.05).

Conclusion: Texture analysis of conventional MRI can be used as an assistant tool in providing a certain objective basis for differentiating PTs from FAs.
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http://dx.doi.org/10.1159/000508456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248772PMC
June 2021

Structural elucidation and physicochemical characteristics of a novel high-molecular-weight fructan from halotolerant Bacillus sp. SCU-E108.

Food Chem 2021 Dec 30;365:130496. Epub 2021 Jun 30.

College of Biomass Science and Engineering, Sichuan University, Chengdu 610065, PR China; Key Laboratory of Leather Chemistry and Engineering (Sichuan University), Ministry of Education, Chengdu 610065, PR China. Electronic address:

An exopolysaccharide, EPS-B108, was isolated from the fermented broth (with a yield of 11.3 g/L) of halotolerant Bacillus sp. SCU-E108 by ethanol precipitation, anion-exchange and gel-filtration chromatography, and well characterized by means of physical, chemical and spectral techniques. Data indicated that EPS-B108 was composed solely of fructose with a high molecular weight of 3.578 × 10 g/mol, and contained a β-(2 → 6)-linked d-Fruf backbone with a single β-d-Fruf at C-1 position. An irregular saccular- or cake-like shape was observed under the enlarged view. It showed no acute oral toxicity in mice, and had good thermal stability (242 °C), solubility in water (91.3%) and oil-holding capacity (1717.0%). Steady-shear flow and dynamical viscoelasticity of aqueous EPS-B108 solutions varied with the polymer concentration, shear rate and temperature, and were described by the Power-law model. Together, these findings support the further application of EPS-B108 as an alternative source of functional food additives and ingredients.
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http://dx.doi.org/10.1016/j.foodchem.2021.130496DOI Listing
December 2021

Trends in Prevalence of Diabetes and Control of Risk Factors in Diabetes Among US Adults, 1999-2018.

JAMA 2021 Jun 25. Epub 2021 Jun 25.

School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Importance: Understanding population-wide trends in prevalence and control of diabetes is critical to planning public health approaches for prevention and management of the disease.

Objective: To determine trends in prevalence of diabetes and control of risk factors in diabetes among US adults between 1999-2000 and 2017-2018.

Design, Setting, And Participants: Ten cycles of cross-sectional National Health and Nutrition Examination Survey (NHANES) data between 1999-2000 and 2017-2018 were included. The study samples were weighted to be representative of the noninstitutionalized civilian resident US population. Adults aged 18 years or older were included, except pregnant women.

Exposures: Survey cycle.

Main Outcomes And Measures: Diabetes was defined by self-report of diabetes diagnosis, fasting plasma glucose level of 126 mg/dL or more, or hemoglobin A1c (HbA1c) level of 6.5% or more. Three risk factor control goals were individualized HbA1c targets, blood pressure less than 130/80 mm Hg, and low-density lipoprotein cholesterol level less than 100 mg/dL. Prevalence of diabetes and proportion of adults with diagnosed diabetes who achieved risk factor control goals, overall and by sociodemographic variables, were estimated.

Results: Among the 28 143 participants included (weighted mean age, 48.2 years; 49.3% men), the estimated age-standardized prevalence of diabetes increased significantly from 9.8% (95% CI, 8.6%-11.1%) in 1999-2000 to 14.3% (95% CI, 12.9%-15.8%) in 2017-2018 (P for trend < .001). From 1999-2002 to 2015-2018, the estimated age-standardized proportion of adults with diagnosed diabetes who achieved blood pressure less than 130/80 mm Hg (P for trend = .007) and low-density lipoprotein cholesterol level less than 100 mg/dL (P for trend < .001) increased significantly, but not individualized HbA1c targets (P for trend = .51). In 2015-2018, 66.8% (95% CI, 63.2%-70.4%), 48.2% (95% CI, 44.6%-51.8%), and 59.7% (95% CI, 54.2%-65.2%) of adults with diagnosed diabetes achieved individualized HbA1c targets, blood pressure less than 130/80 mm Hg, and low-density lipoprotein cholesterol level less than 100 mg/dL, respectively. Only 21.2% of these adults (95% CI, 15.5%-26.8%) achieved all 3. During the entire study period, these 3 goals were significantly less likely to be achieved among young adults aged 18 to 44 years (vs older adults ≥65 years: estimated proportion, 7.4% vs 21.7%; adjusted odds ratio, 0.32 [95% CI, 0.16-0.63]), non-Hispanic Black adults (vs non-Hispanic White adults: estimated age-standardized proportion, 12.5% vs 20.6%; adjusted odds ratio, 0.60 [95% CI, 0.40-0.90]), and Mexican American adults (vs non-Hispanic White adults: estimated age-standardized proportion, 10.9% vs 20.6%; adjusted odds ratio, 0.48 [95% CI, 0.31-0.77]).

Conclusions And Relevance: Based on NHANES data from US adults, the estimated prevalence of diabetes increased significantly between 1999-2000 and 2017-2018. Only an estimated 21% of adults with diagnosed diabetes achieved all 3 risk factor control goals in 2015-2018.
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http://dx.doi.org/10.1001/jama.2021.9883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233946PMC
June 2021

The bridging and normal dimensions of sella turcica in Yemeni individuals.

Oral Radiol 2021 Jun 18. Epub 2021 Jun 18.

Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Jiamusi University, Jiamusi, China.

Objective: This study aimed to evaluate and compare sizes, shapes and bridging of the sella turcica (ST) in Yemeni individuals with different skeletal patterns, genders, and ages, and to assess the association between the linear dimension of ST and gender, age, or skeletal patterns. The standard anatomical structure of ST among Yemeni subjects is still unknown and this study can be considered as the first reference regarding ST of Yemeni individuals.

Materials And Methods: Cephalogram images for 234 subjects (167 females and 67 males) were traced and classified for groups by gender, age, and dentofacial skeletal patterns. Size, shape, and bridging of ST were assessed. Multivariate ANOVA (MANOVA) analysis was used to detect the interaction between gender, age, and skeletal patterns on ST dimensions.

Results: The mean values for length, anteroposterior diameter, and depth of ST were 8.02 ± 1.67, 11.37 ± 1.60, and 8.56 ± 1.26 mm, respectively. A significant difference in length of ST between gender and age stages (p < 0.05) was detected while older subjects revealed a greater anteroposterior diameter than younger subjects (p < 0.05). The morphological variations of ST were observed in 55.6% of samples. No significant association between the shape of ST and skeletal patterns (p > 0.05) was found.

Conclusions: ST bridging was highly prevalent in Yemeni subjects (35.9%). Samples showed a higher rate of complete ST bridging in the three skeletal patterns, Class I (17.1%), Class II (18.9%), and Class III (20%). ST dimensions and shape findings in this study can be used as reference standards for further investigation, including the ST area in the Yemeni population.
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http://dx.doi.org/10.1007/s11282-021-00541-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211719PMC
June 2021

Air pollutants and outpatient visits for influenza-like illness in Beijing, China.

PeerJ 2021 2;9:e11397. Epub 2021 Jun 2.

Department of Laboratorial of Science and Technology, School of Public Health, Peking University, Beijing, China.

Background: Air pollution leads to many adverse health conditions, mainly manifested by respiratory or cardiac symptoms. Previous studies are limited as to whether air pollutants were associated to influenza-like illness (ILI). This study aimed to explore the association between air pollutants and outpatient visits for ILI, especially during an outbreak of influenza.

Methods: Daily counts of hospital visits for ILI were obtained from Peking University Third Hospital between January 1, 2015, and March 31, 2018. A generalized additive Poisson model was applied to examine the associations between air pollutants concentrations and daily outpatient visits for ILI when adjusted for the meteorological parameters.

Results: There were 35862 outpatient visits at the fever clinic for ILI cases. Air quality index (AQI), PM, PM, CO and O on lag0 days, as well as nitrogen dioxide (NO) and sulfur dioxide (SO) on lag1 days, were significantly associated with an increased risk of outpatient visits for ILI from January 2015 to November 2017. From December 2017 to March 2018, on lag0 days, air pollutants PM [risk ratio (RR) = 0.971, 95% CI: 0.963-0.979], SO (RR = 0.892, 95% CI: 0.840-0.948) and CO (RR = 0.306, 95% CI: 0.153-0.612) were significantly associated with a decreased risk of outpatient visits for ILI. Interestingly, on the lag2 days, all the pollutants were significantly associated with a reduced risk of outpatient visits for ILI except for O. We did not observe the linear correlations between the outpatient visits for ILI and any of air pollutants, which were instead associated via a curvilinear relationship.

Conclusions: We found that the air pollutants may be associated with an increased risk of outpatient visits for ILI during the non-outbreak period and with a decreased risk during the outbreak period, which may be linked with the use of disposable face masks and the change of outdoor activities. These findings expand the current knowledge of ILI outpatient visits correlated with air pollutants during an influenza pandemic.
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http://dx.doi.org/10.7717/peerj.11397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179240PMC
June 2021

Multicentre study of microwave ablation for pulmonary oligorecurrence after radical resection of non-small-cell lung cancer.

Br J Cancer 2021 Aug 15;125(5):672-678. Epub 2021 Jun 15.

Department of Oncology, Shandong Lung Cancer Institute, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, China.

Background: Microwave ablation (MWA) is an effective minimally invasive technique for lung tumours. We aim to evaluate its role for pulmonary oligorecurrence after radical surgery of non-small-cell lung cancer (NSCLC).

Methods: From June 2012 to Jan 2020, a total of 103 patients with pulmonary oligorecurrence after previous radical surgical resection of NSCLC were retrospectively analysed. The primary endpoint was postoperative progression-free survival (PFS). Secondary endpoints were postoperative overall survival (OS), patterns of failure, complications and predictive factors associated with prognosis.

Results: Of the 103 patients identified, 135 pulmonary oligorecurrences developed at a median interval of 34.8 months. In total, 143 sessions of MWA were performed to ablate all the nodules. The median PFS and OS were 15.1 months and 40.6 months, respectively. After MWA, 15 (14.6%) patients had local recurrence as the first event, while intrathoracic oligorecurrence and distant metastases were observed in 45 (43.7%) and 20 (19.4%) patients, respectively. In the multivariate analysis, local recurrence and intrathoracic oligorecurrence were not significant predictors for OS (P = 0.23 and 0.26, respectively). However, distant metastasis was predictive of OS (HR = 5.37, 95% CI, 1.04-27.84, P = 0.04).

Conclusion: MWA should be considered to be an effective and safe treatment option for selected patients with pulmonary oligorecurrence after NSCLC radical surgical resection.
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http://dx.doi.org/10.1038/s41416-021-01404-yDOI Listing
August 2021

Outcome of mitral valve repair or replacement for non-ischemic mitral regurgitation: a systematic review and meta-analysis.

J Cardiothorac Surg 2021 Jun 15;16(1):175. Epub 2021 Jun 15.

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Province, 430022, China.

Background: Mitral regurgitation (MR) is a rather common valvular heart disease. The aim of this systematic review and meta-analysis was to compare the outcomes, and complications of mitral valve (MV) replacement with surgical MV repair of non-ischemic MR (NIMR) METHODS: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched until October, 2020. Studies were eligible for inclusion if they included patients with MR and reported early (30-day or in-hospital) or late all-cause mortality. For each study, data on all-cause mortality and incidence of reoperation and operative complications in both groups were used to generate odds ratios (ORs) or hazard ratios (HRs). This study is registered with PROSPERO, CRD42018089608.

Results: The literature search yielded 4834 studies, of which 20 studies, including a total of 21,898 patients with NIMR, were included. The pooled analysis showed that lower age, less female inclusion and incident of hypertension, significantly higher rates of diabetes and atrial fibrillation in the MV replacement group than MV repair group. No significant differences in the rates of pre-operative left ventricle ejection fraction (LVEF) and heart failure were observed between groups. The number of patients in the MV repair group was lower than in the MV replacement group. We found that there were significantly increased risks of mortality associated with replacement of MR. Moreover, the rate of re-operation and post-operative MR in the MV repair group was lower than in the MV replacement group.

Conclusions: In patients with NIMR, MV repair achieves higher survival and leads to fewer complications than surgical MV replacement. In light of these results, we suggest that MV repair surgery should be a priority for NIMR patients.
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http://dx.doi.org/10.1186/s13019-021-01563-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207733PMC
June 2021

Tuning the emission color of a quantum emitter by using photonic local density of states.

Opt Lett 2021 Jun;46(11):2750-2753

Quantum emitters characterized by their emission colors constitute important elements in the design of modern nano-optics. Although we can change the emission colors of a quantum emitter by tailoring its chemical component, once selected, the color usually cannot be changed. It will be tempting to find out whether the emission color of an emitter could be tuned without touching its chemical component. In this Letter, we theoretically propose a strategy to externally tune the emission color of a model emitter by changing its electromagnetic environment. We found that the photonic local density of states (PLDOS) strongly affect the competition between various internal radiative and nonradiative channels, thus enabling a selective electronic state to dominate the emission spectrum. Indeed, quantitative calculations show that the emission color of a model emitter could be tuned from red to green and blue as the PLDOS increases. Moreover, due to direct correspondence between the emission color and PLDOS, the emitter can be potentially used as a sensor to characterize the local electromagnetic environment by its emission color at the nanoscale. This simple strategy may prove to be useful in the future design of various nano-optical devices.
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http://dx.doi.org/10.1364/OL.423589DOI Listing
June 2021

Radiation-Induced Soft Tissue Injuries in Patients With Advanced Mandibular Osteoradionecrosis: A Preliminary Evaluation and Management of Various Soft Tissue Problems Around Radiation-Induced Osteonecrosis Lesions.

Front Oncol 2021 28;11:641061. Epub 2021 Apr 28.

Department of Oral Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Objectives: Radiation-induced soft-tissue injuries (STIs) in mandibular osteoradionecrosis (ORN) are not well studied regarding their correlations with nearby bone lesions. The aim of this study is to investigate the severity of radiation-induced STIs in advanced mandibular ORN and its relationship with hard-tissue damage and postoperative outcomes.

Methods: A retrospective study was performed in our institution from January 2017 to December 2019. Aside from demographic factors, the associations between the triad ORN variables (irradiation doses, ORN stages, ORN sizes) and radiation-related STI factors, vascular characteristics, and postoperative functional recovery were assessed. In addition, the severity of STI was also compared with treatment outcomes. Such correlations were established both univariate and multivariable analyses.

Results: A total number of 47 patients were included. The median follow-up reached 27 months. Nasopharyngeal cancer was the histology type among most patients (n = 21, 44.7%). The median irradiation doses reached 62 Gy (range, 40-110 Gy). For STI, the symptom scoring equaled an average of 5.4 (range from 1 to 12), indicative of the severity of STI problems. During preoperative MRI examinations, signs of hypertrophy or edema (n = 41, 87.2%) were frequently discerned. Most patients (n = 23, 48.9%) also had extensive muscular fibrosis and infection, which required further debridement and scar release. Surprisingly, most STI factors, except cervical fibrosis (p = 0.02), were not in parallel with the ORN levels. Even the intraoperative soft-tissue defect changes could not be extrapolated by the extent of ORN damage (p = 0.096). Regarding the outcomes, a low recurrence rate (n = 3, 6.9%) was reported. In terms of soft tissue-related factors, we found a strong correlation (p = 0.004) between symptom scores and recurrence. In addition, when taking trismus into consideration, both improvements in mouth-opening distance (p < 0.001) and facial contour changes (p = 0.004) were adversely affected. Correlations were also observed between the intraoperative soft-tissue defect changes and complications (p = 0.024), indicative of the importance of STI evaluation and management.

Conclusions: The coexistence of hard- and soft-tissue damage in radiation-induced advanced mandibular ORN patients reminds surgeons of the significance in assessing both aspects. It is necessary to take the same active measures to evaluate and repair both severe STIs and ORN bone lesions.
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http://dx.doi.org/10.3389/fonc.2021.641061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113699PMC
April 2021

Neferine promotes the apoptosis of HNSCC through the accumulation of p62/SQSTM1 caused by autophagic flux inhibition.

Int J Mol Med 2021 07 13;48(1). Epub 2021 May 13.

Department of Oral Maxillofacial‑Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Disease, Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai 200011, P.R. China.

Head and neck squamous cell carcinoma (HNSCC), one of the most common malignancies worldwide, often has a poor prognosis due to the associated metastasis and chemoresistance. Hence, the development of more effective chemotherapeutics is critical. Neferine, a bisbenzylisoquinoline alkaloid isolated from the seed embryo of (common name: Lotus), exerts antitumor effects by regulating apoptosis and autophagy pathways, making it a potential therapeutic option for HNSCC. In our study, it was revealed that neferine inhibited the growth and induced the apoptosis of HNSCC cells both and . Furthermore, the results revealed that neferine activated the ASK1/JNK pathway by increasing reactive oxygen species production, resulting in the subsequent induction of apoptosis and the regulation of canonical autophagy in HNSCC cells. Moreover, a novel pro‑apoptotic mechanism was described for neferine via the activation of caspase‑8 following the accumulation of p62, which was caused by autophagic flux inhibition. These findings provided insights into the mechanisms responsible for the anticancer effect of neferine, specifically highlighting the crosstalk that occured between apoptosis and autophagy, which was mediated by p62 in HNSCC. Hence, the neferine‑induced inhibition of autophagic flux may serve as the basis for a potential adjuvant therapy for HNSCC.
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http://dx.doi.org/10.3892/ijmm.2021.4957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128420PMC
July 2021

Bibliometric analysis of zerovalent iron particles research for environmental remediation from 2000 to 2019.

Environ Sci Pollut Res Int 2021 Jul 12;28(26):34200-34210. Epub 2021 May 12.

Affiliation State Environmental Protection Key Laboratory of Simulation and Control of Groundwater Pollution, Chinese Research Academy of Environmental Sciences, Beijing, 100012, China.

Zerovalent iron (ZVI) has been a major focus of research and has attracted great attention during the last 2 decades by international researchers because of its excellent pollutant removal performance and several other merits in environmental remediation. Based on Web of Science Core Collection data, we present a comprehensive bibliometric analysis of ZVI research from 2000 to 2019. We analyze 4472 publications assuming three stages of growth trend of annual publication totals. We find that "The Chemical Engineering Journal" has been the most productive journal; Noubactep C is identified as the most productive author; China has been the most active country in this field and the Chinese Academy of Science the most productive institution. The timeline of keywords shows seven distinct co-citation clusters. In addition, the top 38 keywords with strong citation bursts are also detected, suggesting that the innovation of green composite synthesis of ZVI and nanoscale ZVI and its efficient removal capacity might be the prevailing research directions in the future.
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http://dx.doi.org/10.1007/s11356-021-13847-0DOI Listing
July 2021

CT Texture Analysis for Differentiating Bronchiolar Adenoma, Adenocarcinoma , and Minimally Invasive Adenocarcinoma of the Lung.

Front Oncol 2021 26;11:634564. Epub 2021 Apr 26.

Department of Nuclear Medicine, Daping Hospital, Army Medical University, Chongqing, China.

This study aimed to investigate the potential of computed tomography (CT) imaging features and texture analysis to distinguish bronchiolar adenoma (BA) from adenocarcinoma (AIS)/minimally invasive adenocarcinoma (MIA). Fifteen patients with BA, 38 patients with AIS, and 36 patients with MIA were included in this study. Clinical data and CT imaging features of the three lesions were evaluated. Texture features were extracted from the thin-section unenhanced CT images using Artificial Intelligence Kit software. Then, multivariate logistic regression analysis based on selected texture features was employed to distinguish BA from AIS/MIA. Receiver operating characteristics curves were performed to determine the diagnostic performance of the features. By comparison with AIS/MIA, significantly different CT imaging features of BA included nodule type, tumor size, and pseudo-cavitation sign. Among them, pseudo-cavitation sign had a moderate diagnostic value for distinguishing BA and AIS/MIA (AUC: 0.741 and 0.708, respectively). Further, a total of 396 quantitative texture features were extracted. After comparation, the top six texture features showing the most significant difference between BA and AIS or MIA were chosen. The ROC results showed that these key texture features had a high diagnostic value for differentiating BA from AIS or MIA, among which the value of a comprehensive model with six selected texture features was the highest (AUC: 0.977 or 0.976, respectively) for BA and AIS or MIA. These results indicated that texture analyses can effectively improve the efficacy of thin-section unenhanced CT for discriminating BA from AIS/MIA. CT texture analysis can effectively improve the efficacy of thin-section unenhanced CT for discriminating BA from AIS/MIA, which has a potential clinical value and helps pathologist and clinicians to make diagnostic and therapeutic strategies.
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http://dx.doi.org/10.3389/fonc.2021.634564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109050PMC
April 2021

Authors' reply: Four novel optineurin mutations in patients with sporadic amyotrophic lateral sclerosis in Mainland China.

Neurobiol Aging 2021 08 11;104:104. Epub 2021 Mar 11.

Department of Neurology, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Beijing, China; Neuroscience Center, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Beijing, China. Electronic address:

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http://dx.doi.org/10.1016/j.neurobiolaging.2021.03.004DOI Listing
August 2021

Sputum cell-free DNA: Valued surrogate sample for the detection of EGFR exon 20 p.T790M mutation in patients with advanced lung adenocarcinoma and acquired resistance to EGFR-TKIs.

Cancer Med 2021 05 1;10(10):3323-3331. Epub 2021 May 1.

Department of Pathology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, P.R. China.

Background: Sputum cell-free DNA (cfDNA) is a valuable surrogate sample for assessing EGFR-sensitizing mutations in patients with advanced lung adenocarcinoma. Detecting EGFR exon 20 p.T790 M (p.T790 M) is much more challenging due to its limited availability in tumor tissues. Exploring sputum cfDNA as an alternative for liquid-based sample type in detecting p.T790 M requires potential improvement in clinical practice.

Methods: A total of 34 patients with EGFR-sensitive mutation-positive lung adenocarcinoma and acquired resistance to the first generation of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) were enrolled. The sputum samples, and paired tumors and/or plasma samples were tested for p.T790 M mutation and concordance of p.T790 M status among the three sample types was analyzed.

Results: The overall concordance rate of p.T790 M mutation between sputum cfDNA and tumor tissue samples was 85.7%, with a sensitivity of 66.7% and a specificity of 100%. The sensitivity for detecting p.T790 M in sputum cfDNA was 100%, 66.7%, and 0% in the three sputum groups of malignant, satisfactory but no malignant cells, and unsatisfactory, respectively. The combined results of plasma cfDNA testing and sputum cfDNA testing further increased the sensitivity to 100% for p.T790 M detection in satisfactory but no malignant cells sputum group.

Conclusion: These findings revealed that cfDNA from malignant or satisfied but no malignant cells sputum is considered suitable for detecting p.T790 M mutation in patients with acquired resistance to first or second-generation EGFR-TKIs. The sputum cytological pathological evaluation-guided sputum cfDNA testing assists in significantly improving the sensitivity of p.T790 M detection, bringing significant value for the maximal application of third-generation EGFR-TKIs in second-line treatment.
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http://dx.doi.org/10.1002/cam4.3817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124129PMC
May 2021

[Expert Consensus for Thermal Ablation of Pulmonary Subsolid Nodules (2021 Edition)].

Zhongguo Fei Ai Za Zhi 2021 May 26;24(5):305-322. Epub 2021 Apr 26.

Department of Oncology, Tengzhou Central People's Hospital, Tengzhou 277500, China.

"The Expert Group on Tumor Ablation Therapy of Chinese Medical Doctor Association, The Tumor Ablation Committee of Chinese College of Interventionalists, The Society of Tumor Ablation Therapy of Chinese Anti-Cancer Association and The Ablation Expert Committee of the Chinese Society of Clinical Oncology" have organized multidisciplinary experts to formulate the consensus for thermal ablation of pulmonary subsolid nodules or ground-glass nodule (GGN). The expert consensus reviews current literatures and provides clinical practices for thermal ablation of GGN. The main contents include: (1) clinical evaluation of GGN, (2) procedures, indications, contraindications, outcomes evaluation and related complications of thermal ablation for GGN and (3) future development directions.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2021.101.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174112PMC
May 2021

transmembrane domain mutation: comprehensive characteristics and real-world evidence of treatment response in Chinese lung adenocarcinoma.

Transl Lung Cancer Res 2021 Mar;10(3):1383-1396

Department of Thoracic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

Background: transmembrane domain (TMD) mutation has been reported as a rare driver mutation associated with advanced stage disease and a poor prognosis in patients with lung adenocarcinoma (LUAD). We aimed to comprehensively profile the genetic landscape and treatment response information of TMD-mutant LUAD.

Methods: An in-house database of 7,812 LUAD patients was screened for mutation prevalence. A multi-center cohort of 16 V659E-mutant patients and an external cohort of 38 -mutant patients from cBioPortal with overall survival (OS) data were analyzed. Eight patients from the in-house cohort were included in the real-world study of treatment response. Molecular docking simulation and binding affinity prediction were performed.

Results: In Chinese LUAD, the prevalence of TMD mutation was 0.18% (14/7,812), and 0.14% (11/7,812) for the V659E mutation. The most recurrent co-alteration was mutation (n=4, 25%) and amplification (n=2, 12.5%). TMD-mutant patients were diagnosed at more advance stages (P<0.001) and had poorer OS (median OS 10.0 61.6 months, HR =7.9, 95% CI: 1.0-61.0, P<0.001) than non-TMD mutations. The overall response rate of targeted therapy, chemo-based therapy, and immunotherapy was 57.1%, 22.2%, and 0%, respectively. We postulated to challenge the resistance of tyrosine kinase inhibitor (TKI) with another with stronger binding energy to HER2 and supported the conclusion with a successful case. Additionally, we demonstrated a three-month response to the off-label use of pyrotinib in fifth-line therapy.

Conclusions: Comapred with non-TMD mtuations, TMD mutation is a rare driver mutation with poorer prognosis in LUAD. Targeted therapy is the dominant choice for patients harboring this targetable mutation and longer OS could possibly be achieved through rechallenge with TKI of stronger binding affinity. Response to fifth-line pyrotinib was observed.
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http://dx.doi.org/10.21037/tlcr-21-107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044484PMC
March 2021

Relationship Orientation, Justice Perception, and Opportunistic Behavior in PPP Projects: An Empirical Study From China.

Front Psychol 2021 1;12:635447. Epub 2021 Apr 1.

School of Economics, Peking University, Beijing, China.

An equal and high-quality partnership between public and private sectors is essential to the sustainable development of public-private partnership (PPP) projects. However, in the special social circumstance in China, the public sector has a strong voice in PPP projects. According to the existing research on PPP project failure, the government's dishonest performance and negative cooperative attitude and the private sector's speculative behavior of concealing information will lead to termination or even failure of project. The attitude and behavior that reflect the relationship orientation of public sector may determine whether the private sector adopts an opportunistic behavior. However, few studies have revealed the mechanism of relationship orientation on opportunism in PPP projects. This paper proposes the connotation of the public sector's relationship orientation and designs a measurement scale from three aspects: emotional relationship orientation, instrumental relationship orientation, and rent-seeking relationship orientation. Based on the data from large construction enterprises, financial institutions and investors, and scholars with practical experience in PPP projects, this paper explores the mechanism of the public sector's relationship orientation on the private sector's justice perception and opportunistic behavior by using the structural equation model (SEM). The results show that the public sector's relationship orientation significantly affects the formation and development of the private sector's justice perception and opportunistic behavior, justice perception plays a mediating role in the process of relationship orientation acting on opportunistic behavior, and the instrumental relationship orientation is more conducive to reducing the opportunistic behavior. The results provide new ideas for changing the public sector's concept and attitude and regulating behavior in PPP projects.
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http://dx.doi.org/10.3389/fpsyg.2021.635447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047633PMC
April 2021

New insights into restoring microbial communities by side-stream supersaturated oxygenation to improve the resilience of rivers affected by combined sewer overflows.

Sci Total Environ 2021 Aug 6;782:146903. Epub 2021 Apr 6.

State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China. Electronic address:

Combined sewer overflows (CSOs) are a dominant contributor to urban river pollution. Therefore, reducing the environmental impacts of CSOs and improving the self-purification capacity of water bodies are essential. In this study, the side-stream supersaturation (SSS) oxygenation was applied to restore microbial function of rivers which are affected by CSOs to improve the self-purification capacity. The results showed that apart from the dissolved organic matter inputs from CSO event, the sediment had become an important contributor to pollution in the studied river. After the long-term (46 d) implementation of SSS oxygenation, dissolved oxygen and the oxidation-reduction potential of the river water increased by 98% and 238%, respectively, compared to emergency control measures implemented following individual CSO events. The NH-N concentrations and the chemical oxygen demand also decreased by 20% and 45%, respectively. In addition, the occurrence of microbial functions related to information storage and processing, and cellular process and signaling, increased by 1.87% and 0.82% in response to SSS oxygenation, respectively, and the Shannon index of the sediment microbial community increased by more than 15%. The frequencies of genes related to nitrification and sulfur oxidation also increased by 20-450% and >50%, respectively. This research provides new insights into the ecological restoration of rivers affected by CSOs.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146903DOI Listing
August 2021

Efficacy and mechanism of the combination of PARP and CDK4/6 inhibitors in the treatment of triple-negative breast cancer.

J Exp Clin Cancer Res 2021 Apr 8;40(1):122. Epub 2021 Apr 8.

Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.

Background: PARP inhibitors (PARPi) benefit only a fraction of breast cancer patients with BRCA mutations, and their efficacy is even more limited in triple-negative breast cancer (TNBC) due to clinical primary and acquired resistance. Here, we found that the efficacy of the PARPi olaparib in TNBC can be improved by combination with the CDK4/6 inhibitor (CDK4/6i) palbociclib.

Methods: We screened primary olaparib-sensitive and olaparib-resistant cell lines from existing BRCA/TNBC cell lines and generated cells with acquired olaparib resistance by gradually increasing the concentration. The effects of the PARPi olaparib and the CDK4/6i palbociclib on BRCA/TNBC cell lines were examined in both sensitive and resistant cells in vitro and in vivo. Pathway and gene alterations were assessed mechanistically and pharmacologically.

Results: We demonstrated for the first time that the combination of olaparib and palbociclib has synergistic effects against BRCA/TNBC both in vitro and in vivo. In olaparib-sensitive MDA-MB-436 cells, the single agent olaparib significantly inhibited cell viability and affected cell growth due to severe DNA damage. In olaparib-resistant HCC1937 and SUM149 cells, single-agent olaparib was ineffective due to potential homologous recombination (HR) repair, and the combination of olaparib and palbociclib greatly inhibited HR during the G2 phase, increased DNA damage and inhibited tumour growth. Inadequate DNA damage caused by olaparib activated the Wnt signalling pathway and upregulated MYC. Further experiments indicated that the overexpression of β-catenin, especially its hyperphosphorylation at the Ser675 site, activated the Wnt signalling pathway and mediated olaparib resistance, which could be strongly inhibited by combined treatment with palbociclib.

Conclusions: Our data provide a rationale for clinical evaluation of the therapeutic synergy of the PARPi olaparib and CDK4/6i palbociclib in BRCA/TNBCs with high Wnt signalling activation and high MYC expression that do not respond to PARPi monotherapy.
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http://dx.doi.org/10.1186/s13046-021-01930-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028839PMC
April 2021
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