Publications by authors named "Xiaohong Wu"

228 Publications

Research on nondestructive identification of grape varieties based on EEMD-DWT and hyperspectral image.

J Food Sci 2021 Apr 22. Epub 2021 Apr 22.

School of Electrical and Information Engineering of Jiangsu University, Zhenjiang, China.

Grape varieties are directly related to the quality and sales price of table grapes and consumed products (raisin, wine, grape juice, etc.). To satisfy the identification requirements of rapid, accurate, and nondestructive detection, an improved denoising algorithm based on ensemble empirical mode decomposition (EEMD) and discrete wavelet transform (DWT) is proposed to couple with the hyperspectral image (HSI) of grape varieties in this study. First, the hyperspectral data of grape varieties are collected by using HSI instrument, and denoised by the proposed EEMD-DWT and other denoising algorithms. CARS-SPA (competitive adaptive reweighed sampling coupled with successive projections algorithm) is introduced to select the effective wavelengths and a discriminative model is constructed by using support vector machine (SVM). Finally, Monte Carlo experiments verified that EEMD-DWT was an effective and powerful spectra denoising method, and the SVM model constructed by combining with CARS-SPA had an excellent identification accuracy (99.3125%). The results suggested that the key wavelengths selected by using CARS-SPA and EEMD-DWT could be an alternative to the deal with HSI, and its potential to become a method for identifying grape varieties. PRACTICAL APPLICATION: Traditional grape varieties identification methods are destructive and time consuming. Therefore, HSI technology is applied to realize fast and nondestructive identification of grape varieties in this study. The research results indicate that it is feasible to combine HSI technology with machine learning algorithm to discriminate grape varieties. It is of great significance for grape grading and the promotion of excellent varieties, and also provides reference for grape industry producers to identify grape varieties quickly and accurately.
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http://dx.doi.org/10.1111/1750-3841.15715DOI Listing
April 2021

Augmenting ATG14 alleviates atherosclerosis and inhibits inflammation via promotion of autophagosome-lysosome fusion in macrophages.

Autophagy 2021 May 4:1-13. Epub 2021 May 4.

Department of Cardiovascular Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.

Dysfunction of macroautophagy/autophagy in macrophages contributes to atherosclerosis. Impaired autophagy-lysosomal degradation system leads to lipid accumulation, facilitating atherosclerotic plaque. ATG14 is an essential regulator for the fusion of autophagosomes with lysosomes. Whether ATG14 plays a role in macrophage autophagy dysfunction in atherosclerosis is unknown. To investigate the effects of ATG14 on macrophage autophagy, human atherosclerotic plaque, mice and cultured mouse macrophages were evaluated. Overexpression of ATG14 by adenovirus was used to reveal its function in autophagy, inflammation and atherosclerotic plaque formation. Results showed that impaired autophagy function with reduction of ATG14 expression existed in macrophages of human and mouse atherosclerotic plaques. Ox-LDL impaired autophagosome-lysosome fusion with reduction of ATG14 expression in macrophages. Overexpression of ATG14 in macrophages enhanced fusion of autophagosomes with lysosomes and promoted lipid degradation, decreasing Ox-LDL-induced apoptosis and inflammatory response. Augmenting ATG14 expression reversed the autophagy dysfunction in macrophages of mice plaque, blunted SQSTM1/p62 accumulation, inhibited inflammation, and upregulated the population of Treg cells, resulting in alleviating atherosclerotic lesions.ABCC1: ATP-binding cassette, sub-family C (CFTR/MRP), member 1; ABCA1: ATP-binding cassette, sub-family A (ABC1), member 1; Ad-: adenovirus vector carrying the mouse gene; Ad-: adenovirus vector carrying the gene for bacterial β-galactosidase; : apolipoprotein E knockout; ATG14: autophagy-related 14; CD68: CD68 antigen; DAPI: 4',6-diamidino-2-phenylindole; Dil-ox-LDL: Dil-oxidized low density lipoprotein; ELISA: enzyme-linked immunosorbent assay; HFD: high-fat diet (an atherogenic diet); IL: interleukin; LAMP2: lysosomal-associated membrane protein 2; LDL-C: low density lipoprotrein cholesterol; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; ND: normal diet; Ox-LDL: oxidized low density lipoprotein; PBMC: peripheral blood mononuclear cells; SQSTM1/p62: sequestosome 1; SREBF1/SREBP1c: sterol regulatory element binding transcription factor 1; SREBF2/SREBP2: sterol regulatory element binding factor 2; STX17: syntaxin 17; TC: serum total cholesterol; TG: triglyceride; TNF: tumor necrosis factor; IFN: interferon; Treg cell: regulatory T cell.
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http://dx.doi.org/10.1080/15548627.2021.1909833DOI Listing
May 2021

Ancient Xinjiang mitogenomes reveal intense admixture with high genetic diversity.

Sci Adv 2021 Mar 31;7(14). Epub 2021 Mar 31.

Key Laboratory of Vertebrate Evolution and Human Origins, Institute of Vertebrate Paleontology and Paleoanthropology, Chinese Academy of Sciences, Beijing 100044, China.

Xinjiang is a key region in northwestern China, connecting East and West Eurasian populations and cultures for thousands of years. To understand the genetic history of Xinjiang, we sequenced 237 complete ancient human mitochondrial genomes from the Bronze Age through Historical Era (41 archaeological sites). Overall, the Bronze Age Xinjiang populations show high diversity and regional genetic affinities with Steppe and northeastern Asian populations along with a deep ancient Siberian connection for the Tarim Basin Xiaohe individuals. In the Iron Age, in general, Steppe-related and northeastern Asian admixture intensified, with North and East Xinjiang populations showing more affinity with northeastern Asians and South Xinjiang populations showing more affinity with Central Asians. The genetic structure observed in the Historical Era of Xinjiang is similar to that in the Iron Age, demonstrating genetic continuity since the Iron Age with some additional genetic admixture with populations surrounding the Xinjiang region.
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http://dx.doi.org/10.1126/sciadv.abd6690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011967PMC
March 2021

Electrosprayed minocycline hydrochloride-loaded microsphere/SAIB hybrid depot for periodontitis treatment.

Drug Deliv 2021 Dec;28(1):620-633

Stomatological Hospital of Chongqing Medical University, Chongqing, China.

Minocycline hydrochloride (MINO) has been one of the most frequently used antibiotics in the treatment of periodontitis due to its antibacterial activity and osteogenesis effects; however, high levels of MINO administered during the treatment halt the formation of new bone. Therefore, the purpose of the present study was to prepare a MINO-microsphere/sucrose acetate isobutyrate (SAIB) hybrid depot to reduce the burst release of MINO and ensure antibacterial and osteogenesis effects of MINO in the treatment of periodontitis. Uniform microspheres, approximately 5 µm size, with a slightly rough surface and different MINO loading (10, 12, and 14%) were prepared, and the microspheres were added into SAIB, after which the burst release significantly decreased from 66.18 to 2.92%, from 71.82 to 3.82%, and from 73.35 to 4.45%, respectively, and the release from all the MINO-microspheres/SAIB hybrid depots lasted for 77 days. In addition, cytotoxicity test showed that the MINO-microsphere with 12% drug loading promoted the proliferation of osteoblasts the most and was subsequently used in vivo experiments. Moreover, in the model of ligatured-induced periodontitis in SD rats, the MINO-microsphere/SAIB hybrid depot not only significantly increased the alveolar bone height and bone volume but also reduced the inflammation of the periodontal tissue. Additionally, it also inhibited the expression of the receptor activator of nuclear factor-kappa B ligand (RANKL) and promoted the expression of osteoprotegerin (OPG).. These results indicated that the MINO-microsphere/SAIB hybrid depot might be promising in the treatment of periodontitis.
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http://dx.doi.org/10.1080/10717544.2021.1902020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008938PMC
December 2021

A Retrospective Study on the Use of Chinese Patent Medicine in 24 Medical Institutions for COVID-19 in China.

Front Pharmacol 2020 30;11:574562. Epub 2020 Nov 30.

Beijing University of Traditional Chinese Medicine, Beijing, China.

This research aims to analyze the application regularity of Chinese patent medicine during the COVID-19 epidemic by collecting the names of the top three Chinese patent medicines used by 24 hospitals in 14 provinces of China in four time periods (January 20-22, February 16-18, March 01-03, April 01-03, 2020), and explore its contribution to combating the disease. 1) We built a database of the top three Chinese patent medicines used by 24 hospitals. 2) The frequency and efficacy distribution of Chinese patent medicine were analyzed with risk areas, regions, and hospitals of different properties as three factors. 3) Finally, we analyzed the differences in the use of heat-clearing and non-heat-clearing medicines among the three factors (χ test) and the correlation between the Chinese patent medicine and COVID-19 epidemic (correlation analysis) with SPSS 23.0 statistical software. 1) The heat-clearing medicine was the main use category nationwide during January 20-22, 2020. Meanwhile, there was a significant difference in the utilization rate of heat-clearing and non-heat-clearing medicine in different risk areas ( < 0.01). 2) The variety of Chinese patent medicine was increased nationwide during February 16-18, 2020, mainly including tonics, blood-activating and resolving-stasis, and heat-clearing medicines. Meanwhile, there was a significant difference in the utilization rate of heat-clearing and non-heat-clearing medicine in the southern and northern regions ( < 0.05). 3) Tonics, and blood-activating and resolving-stasis medicines became the primary use categories nationwide during March 01-03, 2020. 4) The tonics class, and blood-activating and resolving-stasis medicine were still the primary categories nationwide during April 01-03, 2020. Meanwhile, there was a significant difference in the utilization rate of heat-clearing and non-heat-clearing medicine in different risk areas ( < 0.01). Chinese patent medicine has a certain degree of participation in fighting against the COVID-19. The efficacy distribution is related to the risk area, region, and hospital of different properties, among which the risk area is the main influencing factor. It is hoped that future research can further collect the application amount of Chinese patent medicine used in hospitals all over the country, so as to perfectly reflect the relationship between Chinese patent medicine and the epidemic situation.
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http://dx.doi.org/10.3389/fphar.2020.574562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990099PMC
November 2020

Silencing of PGK1 Promotes Sensitivity to Paclitaxel Treatment by Upregulating XAF1-Mediated Apoptosis in Triple-Negative Breast Cancer.

Front Oncol 2021 4;11:535230. Epub 2021 Mar 4.

Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China.

Triple negative breast cancer (TNBC) is known to have aggressive clinical course and a high risk of recurrence. Given the lack of effective targeted therapy options, paclitaxel-based chemotherapy is still the primary option for TNBC patients. However, patients who fail to achieve a complete response during neoadjuvant chemotherapy may be mainly due to sensitivity and resistance to chemotherapy. Thus, we concentrated the present research on the role of PGK1 in the sensitivity to paclitaxel treatment and the possible underlying mechanisms in TNBC. After exposure to paclitaxel, a cell viability analysis was made to investigate the influence of PGK1 silencing on cell death. The effect of PGK1 on apoptosis induced by paclitaxel treatment was examined by flow cytometry cell apoptosis assays. Western blotting was performed to examine the impact of PGK1 on paclitaxel-induced apoptosis. The correlation of PGK1 with apoptosis-associated protein X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1) was analyzed in 39 specimens by immunohistochemistry analysis. We observed that silencing PGK1 sensitized triple-negative breast cancer (TNBC) cell lines to paclitaxel treatment as a result of increased drug-induced apoptosis. Furthermore, mechanistic investigations suggested that XAF1 was increased in PGK1-knockdown cells along with the expression of the apoptotic proteins including cleaved caspase-3 and Bax. Immunohistochemistry analysis showed that PGK1 was negatively related to XAF1. Moreover, we found that downregulation of XAF1 reduced paclitaxel-induced apoptosis in PGK1-silenced triple-negative cell lines. Our results identified PGK1 as a potential biomarker for the treatment of TNBC, and inhibition of PGK1 expression might represent a novel strategy to sensitize TNBC to paclitaxel treatment.
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http://dx.doi.org/10.3389/fonc.2021.535230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969978PMC
March 2021

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition).

Autophagy 2021 Jan 8;17(1):1-382. Epub 2021 Feb 8.

University of Crete, School of Medicine, Laboratory of Clinical Microbiology and Microbial Pathogenesis, Voutes, Heraklion, Crete, Greece; Foundation for Research and Technology, Institute of Molecular Biology and Biotechnology (IMBB), Heraklion, Crete, Greece.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
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http://dx.doi.org/10.1080/15548627.2020.1797280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996087PMC
January 2021

Effectiveness of Standardized Nursing Terminologies for Nursing Practice and Healthcare Outcomes: A Systematic Review.

Int J Nurs Knowl 2021 Feb 12. Epub 2021 Feb 12.

Jinan University, Guangzhou, P. R. China.

Purpose: This review evaluates the effectiveness of using standardized terminologies in nursing.

Methods: A systematic literature review was performed via PubMed, Web of Science, CINAHL, and OVID databases for articles published between January 1973 and September 2020. The Effective Public Health Practice Project's Quality Assessment Tool for Quantitative Studies was used to assess the quality of all included studies.

Results: Fourteen studies were selected for data extraction and analysis, which included a total of 24,243 patients and 99 nurses. Of the studies that met the inclusion criteria, the quality of five were of high quality, one was of moderate quality, and eight was of weak quality. All articles were summarized according to two themes: the identification of common outcomes or interventions, and the validation or evaluation of the effectiveness of standard nursing terminology sets.

Conclusion: Standardized terminologies in nursing help nurses to implement care plans according to nursing procedures, supervise changes in patients' sensitive indicators, improve patients' health outcomes, and contribute to evidence-based nursing practices and global data resource sharing.

Implications For Nursing Practice: Standardized nursing terminologies have positive effects on clinical practice, are essential for enriching nurses' knowledge, and alter nurses' attitudes regarding education and guidance, which promotes the clinical application of these terminologies.
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http://dx.doi.org/10.1111/2047-3095.12315DOI Listing
February 2021

DNA methylome profiling of circulating tumor cells in lung cancer at single base-pair resolution.

Oncogene 2021 Mar 9;40(10):1884-1895. Epub 2021 Feb 9.

Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.

DNA methylation plays a pivotal role in regulating cellular processes, and altered DNA methylation pattern is a general hallmark of cancer. However, DNA methylome in circulating tumor cells (CTCs) is still a mystery due to the lack of proper analytical techniques. We introduced an efficient workflow, LCM-µWGBS, which can efficiently profile the DNA methylation of microdissected CTC samples. LCM-µWGBS combines the laser capture microdissection (LCM)-based CTC capture method and whole-genome bisulfite sequencing in very small CTC population (µWGBS) to gain insight into the DNA methylation landscape of CTCs. We herein profiled the DNA methylome of CTCs from lung cancer patients. Deriving from a comprehensive analysis of CTC methylome, a unique "CTC DNA methylation signature" that is distinct from primary lung cancer tissues was identified. Further analysis showed that promoter hypermethylation of epithelial genes is a hallmark of stable epithelial-mesenchymal transition process. Moreover, it has been suggested that CTCs are endowed with a stemness-related feature during dissemination and metastasis. This work constitutes a unique DNA methylation analysis of CTCs at single base-pair resolution, which might facilitate to propose noninvasive CTC DNA methylation biomarkers contributing to clinical diagnosis.
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http://dx.doi.org/10.1038/s41388-021-01657-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946637PMC
March 2021

Utilization of circulating cell-free DNA profiling to guide first-line chemotherapy in advanced lung squamous cell carcinoma.

Theranostics 2021 1;11(1):257-267. Epub 2021 Jan 1.

Department of Oncology, Qingdao Municipal Hospital, Qingdao, Shandong, China.

Platinum-based chemotherapy is one of treatment mainstay for patients with advanced lung squamous cell carcinoma (LUSC) but it is still a "one-size fits all" approach. Here, we aimed to investigate the predictive and monitoring role of circulating cell-free DNA (cfDNA) profiling for the outcome of first-line chemotherapy in patients with advanced LUSC. Peripheral blood samples of 155 patients from a phase IV trial and 42 cases from an external real-world cohort were prospectively collected. We generated a copy number variations-based classifier via machine learning algorithm to integrate molecular profiling of cfDNA, named RESPONSE SCORE (RS) to predict the treatment outcome. To monitor the treatment efficacy, cfDNA samples collected at different time points were subjected to an ultra-deep sequencing platform. The results showed that patients with high RS showed substantially higher objective response rate than those with low RS in training set ( < 0.001), validation set ( < 0.001) and real-world cohort ( = 0.019). Furthermore, a significant difference was observed in both progression-free survival (training set, < 0.001; validation set: < 0.001; real-world cohort: = 0.019) and overall survival (training set, < 0.001; validation set: = 0.037) between high and low RS group. Notably, variant allele frequency (VAF) calculated from an ultra-deep sequencing platform significantly reduced in patients experienced a complete or partial response after 2 cycles of chemotherapy ( < 0.001), while it significantly increased in these of non-responder ( < 0.001). Moreover, VAF undetectable after 2 cycles of chemotherapy was correlated with markedly better objective response rate ( < 0.001) and progression-free survival ( < 0.001) than those with detectable VAF. These findings indicated that the RS, a circulating cfDNA sequencing-based stratification index, could help to guide first-line chemotherapy in advanced LUSC. The change of VAF is valuable to monitor the treatment response.
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http://dx.doi.org/10.7150/thno.51243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681090PMC
January 2021

Identification of Potential Long Non-coding RNA Expression Quantitative Trait Methylations in Lung Adenocarcinoma and Lung Squamous Carcinoma.

Front Genet 2020 9;11:602035. Epub 2020 Dec 9.

Department of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin, China.

There are associations between DNA methylation and the expression of long non-coding RNA (lncRNA), also known as lncRNA expression quantitative trait methylations (lnc-eQTMs). Lnc-eQTMs may induce a wide range of carcinogenesis pathways. However, lnc-eQTMs have not been globally identified and studied, and their roles in lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) are largely unknown. In the present study, we identified some differential methylation sites located in genes of long intergenic non-coding RNAs (lincRNAs) and other types of lncRNAs in LUAD and LUSC. An integrated pipeline was established to construct two global cancer-specific regulatory networks of lnc-eQTMs in LUAD and LUSC. The associations between eQTMs showed common and specific features between LUAD and LUSC. Some lnc-eQTMs were also related with survival in LUAD- and LUSC-specific regulatory networks. Lnc-eQTMs were associated with cancer-related functions, such as lung epithelium development and vasculogenesis by functional analysis. Drug repurposing analysis revealed that these lnc-eQTMs may mediate the effects of some anesthesia-related drugs in LUAD and LUSC. In summary, the present study elucidates the roles of lnc-eQTMs in LUAD and LUSC, which could improve our understanding of lung cancer pathogenesis and facilitate treatment.
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http://dx.doi.org/10.3389/fgene.2020.602035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756030PMC
December 2020

The effect of rehabilitation in patients with polyneuropathy induced by occupational intoxication with n-hexane: a report of 9 cases.

Ann Palliat Med 2020 Nov;9(6):4179-4186

Department of Rehabilitation Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.

Background: Polyneuropathy caused by n-hexane in its occupational settings is diagnosed with bilaterally symmetrical sensory and motor abnormalities. However, no effective treatments are available.

Methods: We use the detailed physical, neurological examinations, rehabilitation assessment scale, and electrophysiological examinations at hospital admission and six months' follow up to assess the effect of a rehabilitation program on peripheral nerve injury caused by n-hexane nine patients.

Results: We found that all patients complained about sensory issues of numbness in the distal extremities and decreasing strength with a decreased locomotion speed and gait abnormalities on admission, which is following the result of electrophysiological examinations. After they underwent a hospitalized rehabilitation program for 6 months, all of them showed a significant improvement in muscle strength, balance, deep tendon reflex, walking speed, and Barthel index, which showed a significant improvement in their athletic ability, although some patients still had gait abnormalities. According to the electrophysiological test results, nine patients had increased motor conduction velocities and amplitudes and shortened distal latencies in the four limbs compared with the results upon admission or one month later. However, only some indexes of sensory nerve conduction showed significant differences. With the recovery of movement and sensory function, they could live entirely independently and even return to work.

Conclusions: We suggest that early general physical evaluation with electrophysiological examinations and comprehensive rehabilitation, including different modalities, therapeutic exercise, nerve mobilization, gait training, occupational therapy, traditional Chinese medicine treatment, and patient education, are essential so that patients can perform activities of daily living independently and return to work early.
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http://dx.doi.org/10.21037/apm-20-2176DOI Listing
November 2020

The Effect and Optimal Dosage of Dexmedetomidine Plus Sufentanil for Postoperative Analgesia in Elderly Patients With Postoperative Delirium and Early Postoperative Cognitive Dysfunction: A Single-Center, Prospective, Randomized, Double-Blind, Controlled Trial.

Front Neurosci 2020 23;14:549516. Epub 2020 Oct 23.

Department of Anesthesiology, The Third Affiliated Hospital, Harbin Medical University, Harbin, China.

Background: Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are common complications after major surgery among elderly patients. Dexmedetomidine (DEX) is less frequently explored for its effects in patients with postoperative neurocognitive disorders. This study investigated the effect and optimal dosage of DEX for patient-controlled analgesia (PCA) on POD and early POCD after major surgery among elderly patients.

Methods: Patients in four groups received continuous infusion of DEX 0, 100, 200, and 400 μg with sufentanil 150 μg for PCA immediately after surgery. POD and POCD were assessed on postoperative days 1, 2, 3, and 7 by using the Confusion Assessment Method (CAM) and Mini-Mental State Examination (MMSE) scales. Furthermore, the incidence of POD and POCD of all the four groups in postoperative 7 days classified by high risk factors (age, education, surgical site, and surgical category), sedation level, postoperative pain intensity, and side effects were assessed.

Results: The overall incidence rates of POD and early POCD 7 days after surgery were lower in the DEX 200 μg 400 μg groups than in the DEX 0 μg and 100 μg groups ( < 0.05). Compared with DEX 200 μg, DEX 400 μg reduced early POCD in patients who underwent open surgery ( < 0.05). There were no intergroup differences in the postoperative sedation level, pain intensity, and side effects.

Conclusion: The continuous infusion of DEX 200 μg or DEX 400 μg in PCA significantly decreased the incidence of POD and early POCD after major surgery without increasing any side effects. Compared with DEX 200 μg, DEX 400 μg was preferred for reducing early POCD in patients who underwent open surgery.
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http://dx.doi.org/10.3389/fnins.2020.549516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645155PMC
October 2020

Intracranial Arterial Calcification Relates to Long-Term Risk of Recurrent Stroke and Post-stroke Mortality.

Front Neurol 2020 9;11:559158. Epub 2020 Oct 9.

Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Hong Kong.

Intracranial arterial calcification (IAC) is highly prevalent in ischemic stroke patients. However, data on the association of IAC with stroke recurrence and mortality remains limited. We examined the effect of IAC on the long-term recurrence of stroke and the risk of post-stroke mortality. Using a prospective stroke registry, we recruited 694 patients (mean age 71.6 ± 12.4; male sex 50.3%) since December 2004. IAC was visualized using the computed tomography exam that was made at hospital admission and was quantified with the Agatston method. All patients were regularly followed up till July 2016. The impacts of IAC on stroke recurrence and mortality were assessed using Cox-regression models with adjustments for age, sex, and relevant cardiovascular risk factors. During a median follow-up period of 8.8 years, 156 patients (22.5%) suffered a recurrent stroke and 84 died (12.1%). We found that a higher IAC Agatston score related to a higher risk of stroke recurrence (HR per 1-SD increase in IAC: 1.30; 95% CI, 1.08-1.56, = 0.005) and a higher risk of post-stroke mortality (HR per 1-SD increase, 1.44; 95% CI, 1.06-1.96, = 0.019). After investigating etiology-specific risks of stroke-recurrence, we found that a higher IAC Agatston score specifically associated with small-vessel occlusive stroke. IAC is a strong risk factor for recurrent stroke and post-stroke mortality. Among stroke subtypes, IAC relates to higher risk of stroke recurrence among patients with small-vessel disease, which indicates chronic calcification detected in large cerebral arteries may have potential effects on the cerebrovascular beds extending to small vessels.
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http://dx.doi.org/10.3389/fneur.2020.559158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581678PMC
October 2020

Optically Induced Molecular Logic Operations.

ACS Nano 2020 Nov 3;14(11):15248-15255. Epub 2020 Nov 3.

School of Engineering and Applied Sciences, Harvard University, 9 Oxford Street, Cambridge, Massachusetts 02138, United States.

Molecular electronics is a promising route for down-sizing electronic devices. Tip-enhanced Raman spectroscopy provides us a setup to probe current-driven molecular junctions that are considered as prototypes of molecular electronic devices. In this setup, the plasmonic tip concentrates optical fields to a degree that allows observing optical response of single molecules. Simultaneously, the tip can also induce a localized optical angular momentum, which has been seldomly considered in previous studies. Here, we propose that the induced optical angular momentum can interact with the probed molecule and strongly modify the response signal. Specifically, we demonstrate the ability to control the vibrational resonance of current-driven molecular junctions with the optical angular momentum. This precise control of light-matter interactions at the nanoscale allows us to demonstrate multiple logic operations. These results provide a fundamental understanding of future molecular electronics applications.
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http://dx.doi.org/10.1021/acsnano.0c05513DOI Listing
November 2020

Upregulation of μ-Opioid Receptor in the Rat Spinal Cord Contributes to the α2-Adrenoceptor Agonist Dexmedetomidine-Induced Attenuation of Chronic Morphine Tolerance in Cancer Pain.

J Pain Res 2020 15;13:2617-2627. Epub 2020 Oct 15.

Department of Anesthesiology, The Fourth Hospital of Harbin Medical University, Harbin, People's Republic of China.

Background: Sustained morphine treatment for cancer pain has been limited due to analgesic tolerance. Opioid receptor internalization and desensitization mediated by downregulation of mu-opioid receptor (MOR) expression have been confirmed as one of the mechanisms of chronic morphine tolerance. In addition to the opiate system, the α2-adrenergic system is involved in the development of morphine tolerance. Several studies reported that co-administration of α2-adrenoceptor agonist dexmedetomidine inhibits morphine tolerance in normal or neuropathic pain animals. However, the effect of dexmedetomidine on morphine tolerance has not been studied in cancer pain. Therefore, we investigated the effect of intrathecal injection of dexmedetomidine on the development of morphine tolerance in cancer pain and on the expression of MOR in the spinal cord of morphine-tolerant cancer pain rats.

Methods: The model was established using a rat's right hind paw injection of Walker 256 cancer cells. Subcutaneous morphine (10mg/kg) was administrated twice daily for 7 days; meanwhile, the rats received intrathecal α2-adrenoceptor agonist dexmedetomidine (10μ/kg) or antagonist MK-467 (0.25mg/kg) in test groups. Rats receiving drug vehicle served as the control group. Antinociception was detected by von Frey filaments and hot-plate tests. The expression of MOR in the spinal cord was examined through real-time reverse transcription polymerase chain reaction and Western blotting. The data were analyzed via analysis of variance followed by Student -test with Bonferroni correction.

Results: Seven-day chronic morphine administration elicited notable analgesic tolerance in the rats with cancer pain. Co-administration of α2-adrenoceptor agonist dexmedetomidine enhanced morphine analgesia and attenuated morphine tolerance, which could be blocked by α2-adrenoceptor antagonist MK-467. Furthermore, pre-treatment of dexmedetomidine significantly upregulated MOR protein expression without a notable change in MOR mRNA expression in the spinal cord.

Conclusion: Our findings suggest that intrathecal injection of dexmedetomidine enhanced morphine analgesia and attenuated morphine tolerance in cancer pain, potentially by upregulating MOR expression in the spinal cord. The α2-adrenoceptor agonist may provide a more versatile analgesia option for morphine treatment for cancer pain.
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http://dx.doi.org/10.2147/JPR.S274225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573317PMC
October 2020

Creation of a Prognostic Risk Prediction Model for Lung Adenocarcinoma Based on Gene Expression, Methylation, and Clinical Characteristics.

Med Sci Monit 2020 Oct 6;26:e925833. Epub 2020 Oct 6.

Department of Medical Oncology, Affiliated Hospital of Jiangnan University and Wuxi 4th People's Hospital, Wuxi, Jiangsu, China (mainland).

BACKGROUND This study aimed to identify important marker genes in lung adenocarcinoma (LACC) and establish a prognostic risk model to predict the risk of LACC in patients. MATERIAL AND METHODS Gene expression and methylation profiles for LACC and clinical information about cases were downloaded from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, respectively. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) between cancer and control groups were selected through meta-analysis. Pearson coefficient correlation analysis was performed to identify intersections between DEGs and DMGs and a functional analysis was performed on the genes that were correlated. Marker genes and clinical factors significantly related to prognosis were identified using univariate and multivariate Cox regression analyses. Risk prediction models were then created based on the marker genes and clinical factors. RESULTS In total, 1975 DEGs and 2095 DMGs were identified. After comparison, 16 prognosis-related genes (EFNB2, TSPAN7, INPP5A, VAMP2, CALML5, SNAI2, RHOBTB1, CKB, ATF7IP2, RIMS2, RCBTB2, YBX1, RAB27B, NFATC1, TCEAL4, and SLC16A3) were selected from 265 overlapping genes. Four clinical factors (pathologic N [node], pathologic T [tumor], pathologic stage, and new tumor) were associated with prognosis. The prognostic risk prediction models were constructed and validated with other independent datasets. CONCLUSIONS An integrated model that combines clinical factors and gene markers is useful for predicting risk of LACC in patients. The 16 genes that were identified, including EFNB2, TSPAN7, INPP5A, VAMP2, and CALML5, may serve as novel biomarkers for diagnosis of LACC and prediction of disease prognosis.
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http://dx.doi.org/10.12659/MSM.925833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549534PMC
October 2020

Response of patients with chest tightness variant asthma with routine asthma treatment regimen: A 1-year multicenter, prospective, real-world study.

Clin Transl Med 2020 Sep;10(5):e178

Department of Pulmonary Medicine, Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Background: Asthmatic patients with chest tightness as their only presenting symptom (chest tightness variant asthma [CTVA]) have clinical characteristics of eosinophilic airway inflammation similar to those of classic asthma (CA); however, whether CTVA has similar response to antiasthma treatment as compared with CA remains unclear.

Objective: The response of 76 CTVA patients to standard asthma treatments with inhaled corticosteroids with long-acting beta-agonists was explored in a 52-week multicenter, prospective, real-world study.

Results: After 52 weeks of treatment with therapy regimens used for CA, the mean 5-point Asthma Control Questionnaire (ACQ-5) score decreased markedly from 1.38(first administration) to 0.71 (52 weeks, mean decrease: 0.674, 95%CI: 0.447-0.900, P<.001).The mean asthma quality-of-life questionnaire (AQLQ) score increased from 5.77 (first administration) to 6.20 (52 weeks, mean increase: 0.441, 95% CI 0.258-0.625, P<.001). Furthermore, at week 52, FVC, FEV %, the diurnal variation in PEFand the PD20-FEV were significantly improved. Subgroup analysis revealed that the patients at first administration in the responsive group had higher ACQ-5 scores than those in the nonresponsive group (P < .05).

Conclusion: In conclusion, patients with CTVA had a good therapeutic response to the guideline-recommended routine treatment (containing inhaled corticosteroids). The association between the treatment response and the severity of CTVA suggested that CTVA patients with higher ACQ-5 scores had better therapeutic effects.
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http://dx.doi.org/10.1002/ctm2.178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503098PMC
September 2020

Application of 3D-print silica bolus for nasal NK/T-cell lymphoma radiation therapy.

J Radiat Res 2020 Nov;61(6):920-928

Department of Radiation Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.

The aim of the study was to evaluate the clinical feasibility of a 3D-print silica bolus for nasal NK/T-cell lymphoma radiation therapy. Intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) plans were designed using an anthropomorphic head phantom with a 3D-print silica bolus and other kinds of bolus used clinically, and the surface dose was measured by a metal oxide semiconductor field-effect transistor (MOSFET) dosimeter. Four nasal NK/T patients with or without 3D-print silica bolus were treated and the nose surface dose was measured using a MOSFET dosimeter during the first treatment. Plans for the anthropomorphic head phantom with 3D-print bolus have more uniform dose and higher conformity of the planning target volume (PTV) compared to other boluses; the homogeneity index (HI) and conformity index (CI) of the VMAT plan were 0.0589 and 0.7022, respectively, and the HI and CI of the IMRT plan were 0.0550 and 0.7324, respectively. The MOSFET measurement results showed that the surface dose of the phantom with 3D-print bolus was >180 cGy, and that of patients with 3D-print bolus was higher than patients without bolus. The air gap volume between the 3D-print bolus and the surface of patients was <0.3 cc. The 3D-print silica bolus fitted well on the patient's skin, effectively reducing air gaps between bolus and patient surface. Meanwhile, the 3D-print silica bolus provided patients with higher individuation, and improved the conformity and uniformity of the PTV compared to other kinds of boluses.
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http://dx.doi.org/10.1093/jrr/rraa084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674672PMC
November 2020

Erratum to dexmedetomidine promotes breast cancer cell migration through Rab11-mediated secretion of exosomal TMPRSS2.

Ann Transl Med 2020 08;8(16):1040

Department of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin, China.

[This corrects the article DOI: 10.21037/atm.2020.04.28.].
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http://dx.doi.org/10.21037/atm-2020-26DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475481PMC
August 2020

MAC30 Knockdown Inhibits Proliferation and Enhance Apoptosis of Gastric Cancer by Suppressing Wnt/-Cateninsignaling Pathway.

Gastroenterol Res Pract 2020 21;2020:6358685. Epub 2020 Aug 21.

Department of Gastroenterology, the Affiliated Yixing Hospital of Jiangsu University, Yixing 214200, China.

Gastric cancer is one of the most frequently diagnosed cancer and poses a serious threat to health system in the world. Upregulation of meningioma-associated protein (MAC30) has been found in many solid tumors and can regulate the proliferation, differentiation, and apoptosis of different tumor cells. Quantitative polymerase chain reaction (qPCR) was used to detect the expression of MAC30 in 68 patients with gastric cancer and their adjacent tissues. Lentiviral vector pGCSIL-shMAC30-GFP of the RNA interference (RNAi) of the MAC30 gene was transfected into gastric cancer BGC-823 cell line and the expression of lentivirus label protein GFP was observed via fluorescence microscope, while cell proliferation and apoptosis were determined with flow cytometry and MTT assay, respectively. Also, related protein expressions on Wnt/-catenin signaling pathway were analyzed by Western blot method. The expression of MAC30 was abnormally elevated in gastric cancer tissues, while interfering of its expression could significantly inhibit the proliferation of gastric cancer BGC-823 cell line. However, the promotion of apoptosis by mitochondrial pathway was mediated by Bax/Bcl-2 upregulation. Present work showed the effect of downregulated MAC30 expression on proliferation and apoptosis of gastric cancer cell through Wnt/-catenin signaling pathway. Thus, this investigation provides an experimental basis for future development of chemotherapeutic agent on gastric cancer.
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http://dx.doi.org/10.1155/2020/6358685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456481PMC
August 2020

Prolonging the flush-lock interval of totally implantable venous access ports in patients with cancer: A systematic review and meta-analysis.

J Vasc Access 2020 Sep 1:1129729820950998. Epub 2020 Sep 1.

The First Affiliated Hospital of Shantou University Medical College, Shantou, China.

Background: Recently, some studies have shown that prolonging flush interval is safe and feasible for patients who complete chemotherapy. However, there is no consensus about the optimal flush interval for those patients.

Objective: The purpose of this review was to evaluate whether the flush interval could be prolonged based on monthly interval for regular maintenance and to explore the optimal flush interval.

Data Sources: We searched the following databases for articles published between 1 January 1982 and 21 February 2020: PubMed, Cochrane Library, Web of Science, EMBASE, CINAHL, and Ovid.

Study Eligibility Criteria: Randomized controlled trials, retrospective and prospective cohort studies of flush interval less than 4 weeks versus longer than 4 weeks for patients who completed chemotherapy, were included.

Results: Two reviewers extracted information and assessed the quality of the articles independently. In total, 389 articles were retrieved, and 4 studies including 862 cases fulfilled the inclusion criteria. There was no statistical heterogeneity ( = 0,  > 0.05) among the included studies. Hence, the fixed-effects model was used for the meta-analysis. The meta-analysis showed that the total complication rate associated with longer than 4-week interval was higher than that associated with less than 4-week interval. Nevertheless, there was no significant difference between the two groups (7.2% vs 7.6%,  = 0.83). Moreover, the meta-analysis showed that the total complication and catheter occlusion rates associated with the 4-week interval were higher than those associated with the 8-week interval. However, there was no significant difference between the two groups (total complications: 11.4% vs 9.5%,  = 0.68; catheter occlusions: 4.9% vs 4.1%,  = 0.89).

Limitations: Only four non-randomized controlled studies were included, and the outcomes of the included studies were reported incompletely.

Conclusion: Extending the flush interval to longer than 4 weeks is safe and feasible. Based on previous studies, extending the flush interval to 8 weeks might not increase the incidence of total complications and catheter occlusions. However, there is no conclusion on whether the flush interval could be extended to 3 months or longer.
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http://dx.doi.org/10.1177/1129729820950998DOI Listing
September 2020

Exercise Programs for Muscle Mass, Muscle Strength and Physical Performance in Older Adults with Sarcopenia: A Systematic Review and Meta-Analysis.

Aging Dis 2020 Jul 23;11(4):863-873. Epub 2020 Jul 23.

Department of Rehabilitation Medicine, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Sarcopenia is an age-related condition that is characterized by progressive and generalized loss of muscle mass and function. Exercise treatment has been the most commonly used intervention among elderly populations. We performed a systematic review and meta-analysis to evaluate the available literature related to the effects of exercise interventions/programs on muscle mass, muscle strength and physical performance in older adults with sarcopenia. We searched PubMed, EMBASE, MEDLINE and the Web of Science for randomized controlled trials and controlled clinical trials exploring exercise in older adults with sarcopenia published through July 2019 without any language restrictions. Pooled analyses were conducted using Review Manager 5.3, with standardized mean differences (SMDs) and fixed-effect models. A total of 3898 titles and abstracts were initially identified, and 22 studies (1041 individuals, 80.75% females, mean age ranged from 60.51 to 85.90 years) were included in the meta-analysis. The exercise programs in the studies consisted of 30 to 80 min of training, with 1 to 5 training sessions weekly for 6 to 36 weeks. Muscle strength (grip strength [SMD 0.57, 95 % CI 0.42 to 0.73, P <0.00001] and timed five chair stands [SMD -0.56, 95 % CI -0.85 to -0.28, P < 0.0001]) and physical performance (gait speed [SMD 0.44, 95 % CI 0.26 to 0.61, P < 0.00001] and the timed up and go test [SMD -0.97, 95 % CI -1.22 to -0.72, P < 0.00001]) showed significant improvement following exercise treatment, while no differences in muscle mass (ASM [SMD 0.15, 95 % CI -0.05 to 0.36, P = 0.15] and ASM/height [SMD 0.21, 95 % CI -0.05 to 0.48, P = 0.12]) were detected. Exercise programs showed overall significant positive effects on muscle strength and physical performance but not on muscle mass in sarcopenic older adults.
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http://dx.doi.org/10.14336/AD.2019.1012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390512PMC
July 2020

Mapping endocrine toxicity spectrum of immune checkpoint inhibitors: a disproportionality analysis using the WHO adverse drug reaction database, VigiBase.

Endocrine 2020 09 7;69(3):670-681. Epub 2020 Jun 7.

Department of Endocrinology, The Second Affiliated Hospital of Fujian Medical University, No. 950 Donghai Street, Fengze District, Quanzhou, Fujian Province, China.

Purpose: Our study aimed to map endocrine toxicity spectrum of immune checkpoint inhibitors (ICIs).

Methods: We obtained data from VigiBase, between January 1, 2011 and March 6, 2019. All endocrine adverse drug reactions (ADRs) were classified by group queries according to the Medical Dictionary for Regulatory Activities. Disproportionality analysis was performed with information component (IC) and reporting odds ratio (ROR). We used IC to identify meaningful endocrinopathies associated with ICIs and ROR to compare differences between ICI subgroups of ADRs. IC (lower end of the 95% confidence interval of IC) is considered significant if larger than 0.

Results: In all, 6089 reports for endocrinopathies associated with ICIs were involved, with a male to female ratio of 1.5:1. The disproportionality analysis indicated significance of not only common endocrinopathies: thyroid dysfunction, hypophysitis/hypopituitarism, adrenal insufficiency, T1DM, fulminant T1DM (IC: 4.12-6.62), but also rare endocrinopathies: hypoparathyroidism, diabetes insipidus, hypogonadism (IC: 1.56-2.04). Increased risk of ADR reporting emerged in anti-CTLA-4 (e.g., hypophysitis/hypopituitarism, adrenal insufficiency) or in anti-PD-1/PD-L1 (e.g., thyroid dysfunction, T1DM, fulminant T1DM). In general, combination therapy (anti-CTLA-4 plus anti-PD-1/PD-L1) had a stronger association with endocrinopathies than monotherapy (ROR: 2.8, 95% CI: 2.5-3.1). Onset time of common endocrinopathies differed between different ICI therapies, typically within 12 weeks in anti-CTLA-4 monotherapy but diffusely ranging from 0 to 48 weeks in anti-PD-1 monotherapy.

Conclusions: Our study shows rising reporting frequencies of endocrinopathies caused by ICIs, especially aggravated in combination therapy. Clinicians should be early aware of latent endocrine toxicity and different onset time of endocrinopathies when implementing ICI therapies.
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http://dx.doi.org/10.1007/s12020-020-02355-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447663PMC
September 2020

Ancient genomes from northern China suggest links between subsistence changes and human migration.

Nat Commun 2020 06 1;11(1):2700. Epub 2020 Jun 1.

Henan Provincial Institute of Cultural Heritage and Archaeology, Zhengzhou, 450000, China.

Northern China harbored the world's earliest complex societies based on millet farming, in two major centers in the Yellow (YR) and West Liao (WLR) River basins. Until now, their genetic histories have remained largely unknown. Here we present 55 ancient genomes dating to 7500-1700 BP from the YR, WLR, and Amur River (AR) regions. Contrary to the genetic stability in the AR, the YR and WLR genetic profiles substantially changed over time. The YR populations show a monotonic increase over time in their genetic affinity with present-day southern Chinese and Southeast Asians. In the WLR, intensification of farming in the Late Neolithic is correlated with increased YR affinity while the inclusion of a pastoral economy in the Bronze Age was correlated with increased AR affinity. Our results suggest a link between changes in subsistence strategy and human migration, and fuel the debate about archaeolinguistic signatures of past human migration.
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http://dx.doi.org/10.1038/s41467-020-16557-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264253PMC
June 2020

Implant stability and survival rates of a hydrophilic versus a conventional sandblasted, acid-etched implant surface: Systematic review and meta-analysis.

J Am Dent Assoc 2020 06;151(6):444-453

Background: Modifying the implant surface via enhancing the wettability (hydrophilicity) improves osseointegration, reducing the healing period. In this study, the authors aimed to evaluate the stability and survival rates of implants with a hydrophilic surface compared with those with a sandblasted, acid-etched surface.

Types Of Studies Reviewed: The included studies (randomized controlled trials) were identified through searches of PubMed, ScienceDirect, and Cochrane Library databases without date of publication restrictions. Quality assessment was performed using the Cochrane Collaboration tool. For primary outcome, confidence intervals were set at 95%; weighted means across the studies were calculated using a fixed-effects model or risk ratios and their 95% confidence intervals for secondary outcome.

Results: The authors included 5 randomized controlled trials (246 dental implants) in the systematic review, which compared a hydrophilic with conventional sandblasted, acid-etched implant surface. The implant stability (primary outcome) was measured at baseline and 3, 6, and 8 weeks, and implant survival rates were measured as a secondary outcome. Overall, compared with the control groups, no clinically significant differences in implant stability or survival rates were identified for the hydrophilic surface groups.

Conclusions And Practical Implications: The results did not show any clinically significant effect of a hydrophilic surface on improving implant stability or survival rates. However, these findings must be analyzed carefully owing to the limitations of this review, such as the small samples size and some differences among the included studies.
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http://dx.doi.org/10.1016/j.adaj.2020.03.002DOI Listing
June 2020

Dexmedetomidine promotes breast cancer cell migration through Rab11-mediated secretion of exosomal TMPRSS2.

Ann Transl Med 2020 Apr;8(8):531

Department of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin 150081, China.

Background: Dexmedetomidine (DEX), a highly selective α2-adrenergic receptor agonist, has been reported to increase the malignancy of breast cancer cells and stimulate tumor growth in mice. Transmembrane protease serine 2 (TMPRSS2) demonstrates proteolytic activity, resulting in degradation of the extracellular matrix (ECM). This study investigated whether and how TMPRSS2 regulates migration of DEX-treated breast cancer cells.

Methods: Breast cancer cell lines MCF-7 and MDA-MB-231 were treated with DEX and scratch assay was performed. Expressions of TMPRSS2, α2-adrenergic receptor, phospho-STAT3, Rab11, and ECM components were assessed using real-time polymerase chain reaction (real-time PCR), Western blotting, and immunofluorescence staining. ELISA and ultracentrifugation were used to quantify secreted exosomal proteins. Knockdown assay was used to inhibit the expression of TMPRSS2 and Rab11.

Results: DEX significantly increased the migration of MCF-7 and MDA-MB-231, which was accompanied by the upregulation and colocalization of TMPRSS2 and α2-adrenergic receptor. Nuclear phospho-STAT3 was increased dramatically following DEX treatment, and TMPRSS2 upregulation was significantly suppressed by the STAT3 inhibitor WP1066. Meanwhile, TMPRSS2 knockdown decreased DEX-induced cellular migration. TMPRSS2 and Rab11 were significantly detected in the media and the isolated exosomes from DEX-treated cells, and their colocalization was also revealed. Rab11 knockdown prevented exosomal TMPRSS2 from increasing in DEX-treated cells. In normal cultured MDA-MB-231, migration was increased by Rab11-positive exosomes isolated from DEX-treated MCF-7. Moreover, transmission electron microscopy showed that Rab11-positive exosomes enriched more components than Rab11-negative exosomes. Additionally, a reduction in ECM components fibronectin, collagen IV, matrix metallopeptidase 16, and Tenascin C was detected after DEX treatment, but was prohibited when TMPRSS2 or Rab11 were knocked down.

Conclusions: This study provides evidence that DEX upregulates TMPRSS2 expression via the activation of α2-adrenergic receptor/STAT3 signaling and promotes TMPRSS2 secretion in exosomes through Rab11, thus resulting in degradation of the ECM, which is responsible for DEX-induced migration of breast cancer cells.
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http://dx.doi.org/10.21037/atm.2020.04.28DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214880PMC
April 2020

Ancient DNA indicates human population shifts and admixture in northern and southern China.

Science 2020 07 14;369(6501):282-288. Epub 2020 May 14.

Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig.

Human genetic history in East Asia is poorly understood. To clarify population relationships, we obtained genome-wide data from 26 ancient individuals from northern and southern East Asia spanning 9500 to 300 years ago. Genetic differentiation in this region was higher in the past than the present, which reflects a major episode of admixture involving northern East Asian ancestry spreading across southern East Asia after the Neolithic, thereby transforming the genetic ancestry of southern China. Mainland southern East Asian and Taiwan Strait island samples from the Neolithic show clear connections with modern and ancient individuals with Austronesian-related ancestry, which supports an origin in southern China for proto-Austronesians. Connections among Neolithic coastal groups from Siberia and Japan to Vietnam indicate that migration and gene flow played an important role in the prehistory of coastal Asia.
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http://dx.doi.org/10.1126/science.aba0909DOI Listing
July 2020

Three diphosphates, α-LiNaPO, LiPbBa(PO) and LiRb(PO): influences of co-substitution on the crystal structure.

Dalton Trans 2020 May 6;49(20):6744-6750. Epub 2020 May 6.

School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, Heilongjiang 150001, China.

Three diphosphates, α-LiNaPO, LiPbBa(PO) and LiRb(PO), were synthesized via a high-temperature solution method. α-LiNaPO crystallized into a non-centrosymmetric space group Ama2, while LiPbBa(PO) and LiRb(PO) crystallized into the centrosymmetric space groups C2/c and P1[combining macron]respectively. α-LiNaPO, LiPbBa(PO) and LiRb(PO) could be obtained by co-substitution from each other. Also, we found that the high valence state and small atomic radius of the substituted cations resulted in a larger cation-cation distance, which led to a lower dimension of the structure. LiNaPO possessed two phases, namely, α- and β-LiNaPO, and their second harmonic generation (SHG) responses were compared. We also reported the syntheses, IR spectra, UV-vis-NIR diffuse reflectance spectroscopy data, thermal properties and first principles calculations of the title compounds.
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http://dx.doi.org/10.1039/d0dt01070gDOI Listing
May 2020

Development and validation of a nomogram to predict survival after curative resection of nonmetastatic colorectal cancer.

Cancer Med 2020 06 21;9(12):4126-4136. Epub 2020 Apr 21.

Department of Medical Oncology, The Affiliated Hospital of Jiangnan University and Wuxi 4th People's Hospital, Wuxi, China.

Background: We aimed to develop a clinical applicable nomogram to predict overall survival (OS) for patients with curatively resected nonmetastatic colorectal cancer.

Methods: Records from a retrospective cohort of 846 patients with complete information were used to construct the nomogram. The nomogram was validated in a prospective cohort of 379 patients. The performance of the nomogram was evaluated with concordance index (c-index), time-dependent receiver operating characteristic (ROC) curves, calibration plots, and decision curve analyses for discrimination, accuracy, calibration ability, and clinical net benefits respectively, and further compared with AJCC 8th TNM staging and the MSKCC nomogram. Risk stratification based on nomogram scores was performed with recursive partitioning analysis.

Results: The nomogram incorporated age, Glasgow prognostic score, pretreatment carcinoembryonic antigen levels, T staging, N staging, number of harvested lymph nodes, and histological grade. Compared with the 8th AJCC staging and MSKCC model, the nomogram had a statistically higher c-index (0.77, 95% CI: 0.73-0.80), bigger areas under the time-dependent ROC curves (AUC at 3 years: 79; at 5 years: 79), and improved clinical net benefits. Calibration plots revealed no deviations from reference lines. All results were reproducible in the validation cohort. Nomogram-based risk stratification successfully discriminated patients within each AJCC stage (all log-rank P < .05).

Conclusion: We established an accurate, reliable, and easy-to-use nomogram to predict OS after curative resection for nonmetastatic colorectal cancer (CRC). The nomogram outperformed the 8th AJCC staging and the MSKCC model and could aid in personalized treatment and follow-up strategy for CRC patients.
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http://dx.doi.org/10.1002/cam4.3010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300391PMC
June 2020