Publications by authors named "Li Kang"

961 Publications

Nucleolar protein 6 promotes cell proliferation and acts as a potential novel prognostic marker for hepatocellular carcinoma.

Chin Med J (Engl) 2021 Sep 21. Epub 2021 Sep 21.

National Engineering Research Center for Miniaturized Detection Systems, The College of Life Sciences, Northwest University, Xi'an, Shaanxi 710069, China Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.

Background: Nucleolar protein 6 (NOL6) is a nucleolar RNA-associated protein that is highly conserved between species. It has been proved to be associated with the prognosis of liver cancer. However, the underlying mechanism has not been fully established. This study aimed to assess the relationship between NOL6 and liver cancer prognosis.

Methods: We constructed an NOL6-short hairpin RNA (shRNA)-expressing lentivirus. Through viral transfection, cell growth assay and fluorescence-activated cell sorting, we evaluated the effect of shRNA-mediated NOL6 knockdown on the proliferation, colony formation, and apoptosis of hepatocellular carcinoma (HCC) cells. The relationship between NOL6 expression and HCC patient survival has been established through bioinformatics analysis. We also explored the downstream molecular regulatory network of NOL6 in HCC by performing an Ingenuity Pathway Analysis in the database.

Results: Increased NOL6 expression was detected in HCC cells compared to normal controls; HCC patients with high NOL6 expression had poorer prognoses than those with low expression. NOL6 knockdown inhibited HCC cell proliferation, apoptosis, and colony formation. Also, MAPK8, CEBPA, and FOSL1 were selected as potential downstream genes of NOL6.

Conclusions: NOL6 up-regulates HCC cell proliferation and affects downstream expression of related genes. Moreover, NOL6 is considered to be associated with poor prognosis in HCC patients.
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http://dx.doi.org/10.1097/CM9.0000000000001655DOI Listing
September 2021

Characterization of the chicken T cell receptor γ repertoire by high-throughput sequencing.

BMC Genomics 2021 Sep 21;22(1):683. Epub 2021 Sep 21.

Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, 61 Daizong Street, Shandong Province, 271018, Taian City, People's Republic of China.

Background: As one of "γδ-high" species, chicken is an excellent model for the study of γδ T cells in non-mammalian animals. However, a comprehensive characterization of the TCRγδ repertoire is still missing in chicken. The objective of this study was to characterize the expressed TCRγ repertoire in chicken thymus using high-throughput sequencing.

Methods: In this study, we first obtained the detailed genomic organization of the TCRγ locus of chicken based on the latest assembly of the red jungle fowl genome sequences (GRCg6a) and then characterized the TCRγ repertoire in the thymus of four chickens by using 5' Rapid Amplification of cDNA Ends (5' RACE) along with high-throughput sequencing (HTS).

Results: The chicken TCRγ locus contains a single Cγ gene, three functional Jγ segments and 44 Vγ segments that could be classified into six subgroups, each containing six, nineteen, nine, four, three and three members. Dot-plot analysis of the chicken TCRγ locus against itself showed that almost all the entire zone containing Vγ segments had arisen through tandem duplication events, and the main homology unit, containing 9 or 10 Vγ gene segments, has tandemly duplicated for four times. For the analysis of chicken TCRγ repertoire, more than 100,000 unique Vγ-region nucleotide sequences were obtained from the thymus of each chicken. After alignment to the germline Vγ and Jγ segments identified above, we found that the four chickens had similar repertoire profile of TCRγ. In brief, four Vγ segments (including Vγ3.7, Vγ2.13, Vγ1.6 and Vγ1.3) and six Vγ-Jγ pairs (including Vγ3.7-Jγ3, Vγ2.13-Jγ1, Vγ2.13-Jγ3, Vγ1.6-Jγ3, Vγ3.7-Jγ1 and Vγ1.6-Jγ1) were preferentially utilized by all four individuals, and vast majority of the unique CDR3γ sequences encoded 4 to 22 amino acids with mean 12.90 amino acids, which exhibits a wider length distribution and/or a longer mean length than CDR3γ of human, mice and other animal species.

Conclusions: In this study, we present the first in-depth characterization of the TCRγ repertoire in chicken thymus. We believe that these data will facilitate the studies of adaptive immunology in birds.
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http://dx.doi.org/10.1186/s12864-021-07975-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456604PMC
September 2021

WaveICA 2.0: a novel batch effect removal method for untargeted metabolomics data without using batch information.

Metabolomics 2021 Sep 20;17(10):87. Epub 2021 Sep 20.

Interdisciplinary Research Center on Biology and Chemistry, and Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.

Introduction: Untargeted metabolomics based on liquid chromatography-mass spectrometry is inevitably affected by batch effects that are caused by non-biological systematic bias. Previously, we developed a novel method called WaveICA to remove batch effects for untargeted metabolomics data. To detect batch effect information, the method relies on a batch label. However, it cannot be used in the scenario in which there is only one batch of data or the batch label is unknown.

Objectives: We aim to improve the WaveICA method to remove batch effects for untargeted metabolomics data without using batch information.

Methods: We improved the WaveICA method by developing WaveICA 2.0 to remove batch effects for metabolomics data, and provided an R package WaveICA_2.0 to implement this method.

Results: The performance of the WaveICA 2.0 method was evaluated on real metabolomics data. For metabolomics data with three batches, the performance of the WaveICA 2.0 method was similar to that of the WaveICA method in terms of gathering quality control samples (QCSs) and subject samples together in principle component analysis score plots, increasing the similarity of QCSs, increasing differential peaks, and improving classification accuracy. For metabolomics data with only one batch, the WaveICA 2.0 method had a strong ability to remove intensity drift and reveal more biological information and outperformed the QC-RLSC and QC-SVRC methods in our study using our metabolomics data.

Conclusion: Our results demonstrated that the WaveICA 2.0 method can be used in practice to remove batch effects for untargeted metabolomics data without batch information.
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http://dx.doi.org/10.1007/s11306-021-01839-7DOI Listing
September 2021

In situ remediation of Cr(VI) contaminated groundwater by ZVI-PRB and the corresponding indigenous microbial community responses: a field-scale study.

Sci Total Environ 2021 Sep 11;805:150260. Epub 2021 Sep 11.

Nanjing Kangdi Environmental Protection Technology Co., LTD, Nanjing 21000, China.

The performance of a permeable reactive barrier (PRB) for the in situ remediation of hexavalent chromium [Cr(VI)] contaminated groundwater, and the resulted responses in the indigenous microbial community, were investigated in a field-scale study. The PRB consisted of a mixture of zero-valent iron (ZVI), gravel and sand. The results showed that the PRB segment with 20% active reaction medium (ZVI) was able to successfully reduce Cr(VI) via chemical reduction from 27.29-242.65 mg/L to below the clean-up goal of 0.1 mg/L, and can be scaled-up under field conditions. It was found that the ZVI induced significant changes in the indigenous microbial community structure and compositions in the area of the PRB and those areas downgradient. The competitive growth among Cr(VI)-reducing bacteria (the reduced abundance of Hydrogenophaga, Pseudomonas, Exiguobacterium and Rhodobacter, along with the enrichment of Rivibacter and Candidatus_Desulforudis) were observed in PRB. In addition, Cr(VI)-reducing bacteria (Hydrogenophaga, Pseudomonas, Exiguobacterium and Rhodobacter) were enriched in the downgradient of PRB, indicating that Cr(VI) can be further bio-reduced to Cr(III). The Cr(VI) bio-reduction could serve as a secondary mechanism for further removal of Cr(VI) from contaminated groundwater, suggesting that the actual lifetime of a PRB can be prolonged, which is important for the design and economic assessment of a PRB. Further analysis revealed that pH, dissolved oxygen, Cr(VI) level, the oxidation-reduction potential, and temperature were the main environmental factors influencing the subsurface microbial community compositions.
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http://dx.doi.org/10.1016/j.scitotenv.2021.150260DOI Listing
September 2021

Next-generation sequencing assisted diagnosis of cervical metastasis in EGFR-mutated lung adenocarcinoma: A case report.

Thorac Cancer 2021 Sep 9. Epub 2021 Sep 9.

Second Department of Thoracic Medicine, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.

EGFR mutation has been detected in more than half of non-small cell lung cancer (NSCLC) patients in Asia. Lung cancer is the main cause of malignant tumor-related death worldwide. Although distant metastases often occurs in patients with advanced NSCLC, uterine cervical metastasis is rare. Here, we report a case of EGFR-mutated lung adenocarcinoma with cervical metastasis. A 63-year-old female with known lung adenocarcinoma was found to have abnormal vaginal bleeding during osimertinib follow-up visits. Immunohistochemical (IHC) staining and next-generation sequencing (NGS) of the biopsy sample from the uterine cervical tumor confirmed metastatic dissemination from the primary lung malignancy. NGS assisted the diagnosis of uterine cervical metastasis from the primary lung. This is another major clinical application of NGS in addition to medication guidance and identification of drug resistance mechanisms.
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http://dx.doi.org/10.1111/1759-7714.14143DOI Listing
September 2021

Terahertz Sensor via Ultralow-Loss Dispersion-Flattened Polymer Optical Fiber: Design and Analysis.

Materials (Basel) 2021 Aug 29;14(17). Epub 2021 Aug 29.

School of Physics and Astronomy, Cardiff University, Cardiff CF24 3AA, UK.

A novel cyclic olefin copolymer (COC)-based polymer optical fiber (POF) with a rectangular porous core is designed for terahertz (THz) sensing by the finite element method. The numerical simulations showed an ultrahigh relative sensitivity of 89.73% of the x-polarization mode at a frequency of 1.2 THz and under optimum design conditions. In addition to this, they showed an ultralow confinement loss of 2.18 × 10 cm, a high birefringence of 1.91 × 10, a numerical aperture of 0.33, and an effective mode area of 1.65 × 10 μm was obtained for optimum design conditions. Moreover, the range dispersion variation was within 0.7 ± 0.41 ps/THz/cm, with the frequency range of 1.0-1.4 THz. Compared with the traditional sensor, the late-model sensor will have application value in THz sensing and communication.
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http://dx.doi.org/10.3390/ma14174921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434055PMC
August 2021

HIV-1 CRF07_BC Transmission Dynamics in China: Two Decades of National Molecular Surveillance.

Emerg Microbes Infect 2021 Sep 9:1-27. Epub 2021 Sep 9.

State Key Laboratory for Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.

By analyzing an unprecedentedly large, longitudinal HIV-1 CRF07_BC sequence dataset collected from China in the past two decades, we sought to build CRF07_BC lengthwise transmission networks, and understand its transmission dynamics. We divided CRF07_BC into two clusters based on phylogenetic analysis and an estimation of the pairwise genetic distance at 0.7%. Of 6,213 sequences, 3,607 (58.1%) linked to ≥1 other sequence. CRF07_BC was divided into two clusters: 07BC_O and 07BC_N. The 07BC_O is the original CRF07_BC, circulating in people who inject drugs (PWID) and heterosexuals, predominantly in southwestern and northwestern provinces of China. The 07BC_N is a new cluster, identified mostly in men having sex with men (MSM) in northern provinces of China. Bayesian analysis indicates that CRF07_BC has experienced two phases of exponential growth, which was first driven by 07BC_O then 07BC_N. Compared to 07BC_O, the proportion of the parameter of population transmission risk (TR) of 07BC_N has risen constantly. The power-law function analyses reveal that 07BC_N has increased over years with higher degree. In 07BC_N, only 13.16% of MSM were linked to other risk groups, but these links represent 41.45%, 54.25%, and 55.07% of links among heterosexual females, heterosexual males, and male PWID respectively. This study indicates that CRF07_BC has evolved into two clusters in China, and their distributions are distinct across risk groups and geographical regions. 07BC_N shows greater risk of transmission, and has gradually replaced 07BC_O. Furthermore, the results show that strengthening the MSM interventions could lower the rapidity of 07BC_N transmission in all risk groups.
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http://dx.doi.org/10.1080/22221751.2021.1978822DOI Listing
September 2021

Distinct tumour antigen-specific T-cell immune response profiles at different hepatocellular carcinoma stages.

BMC Cancer 2021 Sep 8;21(1):1007. Epub 2021 Sep 8.

Biomedical Information Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China.

Background: Cancer-testis antigens (CTAs) and tumour-associated antigens (TAAs) are frequently expressed in hepatocellular carcinoma (HCC); however, the role of tumour-antigen-specific T cell immunity in HCC progression is poorly defined. We characterized CTA- and TAA-specific T cell responses in different HCC stages and investigated their alterations during HCC progression.

Methods: Fifty-eight HCC patients, 15 liver cirrhosis patients, 15 chronic hepatitis B patients and 10 heathy controls were enrolled in total. IFN-γ ELSPOT using CTAs, including MAGE-A1, MAGE-A3, NY-ESO-1, and SSX2, and two TAAs, SALL4 and AFP, was performed to characterize the T-cell immune response in the enrolled individuals. The functional phenotype of T cells and the responsive T cell populations were analyzed using short-term T-cell culture.

Results: T cell responses against CTAs and TAAs were specific to HCC. In early-stage HCC patients, the SALL4-specific response was the strongest, followed by MAGE-A3, NY-ESO-1, MAGE-A1 and SSX2. One-year recurrence-free survival after transcatheter arterial chemoembolization plus radiofrequency ablation treatment suggested the protective role of CTA-specific responses. The four CTA- and SALL4-specific T cell responses decreased with the progression of HCC, while the AFP-specific T cell response increased. A higher proportion of CD4+ T cells specific to CTA/SALL4 was observed than AFP-specific T cell responses.

Conclusions: The IFN-γ ELISPOT assay characterized distinct profiles of tumour-antigen-specific T cell responses in HCC patients. CTA- and SALL4-specific T cell responses may be important for controlling HCC in the early stage, whereas AFP-specific T cell responses might be a signature of malignant tumour status in the advanced stage. The application of immunotherapy at an early stage of HCC development should be considered.
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http://dx.doi.org/10.1186/s12885-021-08720-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428121PMC
September 2021

Author Correction: pH-sensitive micelles for the intracellular co-delivery of curcumin and Pluronic L61 unimers for synergistic reversal effect of multidrug resistance.

Sci Rep 2021 Sep 6;11(1):18061. Epub 2021 Sep 6.

Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Dongling Road 120, Shenyang, 110866, Liaoning Province, People's Republic of China.

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http://dx.doi.org/10.1038/s41598-021-97676-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421502PMC
September 2021

Treatment and longitudinal follow-up of CNV associated with pattern dystrophy with novel variant.

Ophthalmic Genet 2021 Sep 5:1-5. Epub 2021 Sep 5.

Department of Ophthalmology, Beijing Hospital, Beijing, China.

Background: Peripherin-2 (PRPH2) is a transmembrane glycoprotein crucial for the morphogenesis and stabilization of the photoreceptor outer segments. Variations in gene are associated with vision-threatening diseases.

Methods: Clinical manifestations and multimodal imaging were presented, as well as treatment history and six-year follow-up. In addition, genetic testing was performed to confirm the diagnosis.

Results: In this report, we present an extremely rare case of choroidal neovascularization (CNV) secondary to pattern dystrophy simulating fundus flavimaculatus (PDSFF). Multimodal imaging showed typical symmetric yellow flecks in posterior pole and choroidal neovascularization requiring timely treatment. A novel nonsense variant of c.552 C > G; p.Y184X in gene was detected. The patient received intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment and maintained a good vision after six years.

Conclusion: We described a novel variant (Y184X) associated with PDSFF, its multimodal imaging, and long-term prognosis. Intravitreal anti-VEGF treatment can offer excellent visual prognosis in patients with PDSFF-associated CNV.
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http://dx.doi.org/10.1080/13816810.2021.1952617DOI Listing
September 2021

Preparation of multicolor luminescence Schiff-base compound based on solvent control and its application in the detection of pentachloronitrobenzene.

Anal Chim Acta 2021 Sep 23;1178:338794. Epub 2021 Jun 23.

School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China. Electronic address:

Fluorescent materials with tunable optical properties are critical to their potential application. So far, the tuning of double-color luminescence has been easily achieved for many organic materials, but there are very few reports on multicolor luminescence materials. In this work, a multicolor emissions Schiff-base fluorescent compound 1,1'-{4,4'-Biphenyldiylbis[nitrilo(E)methylylidene]}di(2-naphthol) (BPDN) with an aggregation induced emission (AIE) characteristic was synthesized, and its luminescent characteristic was investigated. The BPDN molecules with low concentration in solution can emit faint light, but a new AIE phenomenon will appear when the BPDN molecules are aggregated in the solvent with low solubility or high concentration. The color and efficiency of the AIE of BPDN can be tuned by changing its aggregation state: the luminescence of the aggregate gradually redshifts (blue, green, to orange) as the solvent with poor solubility in the mixture increases or increasing the concentration of the BPDN. Based on the multicolor luminescence BPDN, a molecularly imprinted ratiometric fluorescent probe test strip (MIRF test strip) had been prepared and successfully applied to visual detection of pentachloronitrobenzene (PCNB). The color of test strip could change gradually from orange to yellow to green with the increase of the concentration of PCNB. This work shows the characteristic and application of multicolor luminescence BPDN.
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http://dx.doi.org/10.1016/j.aca.2021.338794DOI Listing
September 2021

Resilient Optimal Defensive Strategy of TSK Fuzzy-Model-Based Microgrids' System via a Novel Reinforcement Learning Approach.

IEEE Trans Neural Netw Learn Syst 2021 Aug 31;PP. Epub 2021 Aug 31.

With consideration of false data injection (FDI) on the demand side, it brings a great challenge for the optimal defensive strategy with the security issue, voltage stability, power flow, and economic cost indexes. This article proposes a Takagi-Sugeuo-Kang (TSK) fuzzy system-based reinforcement learning approach for the resilient optimal defensive strategy of interconnected microgrids. Due to FDI uncertainty of the system load, TSK-based deep deterministic policy gradient (DDPG) is proposed to learn the actor network and the critic network, where multiple indexes' assessment occurs in the critic network, and the security switching control strategy is made in the actor network. Alternating direction method of multipliers (ADMM) method is improved for policy gradient with online coordination between the actor network and the critic network learning, and its convergence and optimality are proved properly. On the basis of security switching control strategy, the penalty-based boundary intersection (PBI)-based multiobjective optimization method is utilized to solve economic cost and emission issues simultaneously with considering voltage stability and rate-of-change of frequency (RoCoF) limits. According to simulation results, it reveals that the proposed resilient optimal defensive strategy can be a viable and promising alternative for tackling uncertain attack problems on interconnected microgrids.
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http://dx.doi.org/10.1109/TNNLS.2021.3105668DOI Listing
August 2021

Recovering large-scale battery aging dataset with machine learning.

Patterns (N Y) 2021 Aug 30;2(8):100302. Epub 2021 Jun 30.

Department of Chemical and Biological Engineering, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR 999077, China.

Batteries are crucial for building a clean and sustainable society, and their performance is highly affected by aging status. Reliable battery health assessment, however, is currently restrained by limited access to sufficient aging data, resulting from not only complicated battery operations but also long aging experimental time (several months or even years). Refining industrial datasets (e.g., the field data from electric vehicle batteries) unlocks opportunities to acquire large-volume aging data with low experimental efforts. We introduce the potential of combining industrial data with accelerated aging tests to recover high-quality battery aging datasets, through a migration-based machine learning. A comprehensive dataset containing 8,947 aging cycles with 15 operational modes is collected for evaluation. While saving up to 90% experimental time, aging data can be recovered with ultra-low error within 1%. It provides an alternative solution to significantly improve data shortage issues for assessment of battery and energy storage aging.
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http://dx.doi.org/10.1016/j.patter.2021.100302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369168PMC
August 2021

Decreased Spp1 Expression in Acute Myocardial Infarction after Ischemia and Reperfusion Injury.

Cardiol Res Pract 2021 13;2021:3925136. Epub 2021 Aug 13.

Department of Cardiovascular Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.

Background: With the progress of shock therapy and the establishment and promotion of methods such as thrombolytic therapy and percutaneous coronary intervention (PCI), many tissues and organs have been reperfused after ischemia which may cause even worse disorder called ischemia-reperfusion injury (IRI). mRNAs have been found to have significant impacts on ischemia-reperfusion through various mechanisms. In view of the accessibility of mRNAs from blood, we aimed to find the association between mRNA and ischemia-reperfusion.

Methods: We used the GSE83472 dataset from the Gene Expression Omnibus (GEO) database to find differential RNA expression between ischemia-reperfusion tissue and control samples. In addition, Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to find the biological property of 449 RNAs from GSE83472 via the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Besides, Gene Set Enrichment Analysis (GSEA), a tool to find the pathway orientation of a gene set, was used for further study in the four most significant KEGG pathways. Furthermore, we constructed a protein-protein interaction (PPI) network. In the end, we used quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting to measure and compare the expression of Spp1 in patients who accepted percutaneous coronary intervention.

Results: The bioinformatics analyses suggested that Spp1 was a hub gene in reperfusion after ischemia. The qRT-PCR result showed that the Spp1 expression was significantly downregulated in ischemia-reperfusion cells after PCI compared with normal samples and so as the western blotting.

Conclusion: Spp1 might play an essential role in acute myocardial infarction after ischemia and reperfusion injury.
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http://dx.doi.org/10.1155/2021/3925136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380156PMC
August 2021

A novel attention-guided convolutional network for the detection of abnormal cervical cells in cervical cancer screening.

Med Image Anal 2021 10 10;73:102197. Epub 2021 Aug 10.

Department of Biostatistics, School of Public Health, Peking University, Beijing 100191, China. Electronic address:

Early detection of abnormal cervical cells in cervical cancer screening increases the chances of timely treatment. But manual detection requires experienced pathologists and is time-consuming and error prone. Previously, some methods have been proposed for automated abnormal cervical cell detection, whose performance yet remained debatable. Here, we develop an attention feature pyramid network (AttFPN) for automatic abnormal cervical cell detection in cervical cytology images to assist pathologists to make a more accurate diagnosis. Our proposed method consists of two main components. First, an attention module mimicking the way pathologists reading a cervical cytology image. It learns what features to emphasize or suppress by refining extracted features effectively. Second, a multi-scale region-based feature fusion network guided by clinical knowledge to fuse the refined features for detecting abnormal cervical cells at different scales. The region proposals in the multi-scale network are designed according to the clinical knowledge about size and shape distribution of real abnormal cervical cells. Our method, trained and validated with 7030 annotated cervical cytology images, performs better than the state of art deep learning-based methods. The overall sensitivity, specificity, accuracy, and AUC of an independent testing dataset with 3970 cervical cytology images is 95.83%, 94.81%, 95.08% and 0.991, respectively, which is comparable to that of an experienced pathologist with 10 years of experience. Besides, we further validated our method on an external dataset with 110 cases and 35,013 images from a different organization, the case-level sensitivity, specificity, accuracy, and AUC is 91.30%, 90.62%, 90.91% and 0.934, respectively. Average diagnostic time of our method is 0.04s per image, which is much quicker than the average time of pathologists (14.83s per image). Thus, our AttFPN is effective and efficient in cervical cancer screening, and improvement of clinical workflows for the benefit of potential patients. Our code is available at https://github.com/cl2227619761/TCT_Detection.
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http://dx.doi.org/10.1016/j.media.2021.102197DOI Listing
October 2021

Functional correlation of ATP1A2 mutations with phenotypic spectrum: from pure hemiplegic migraine to its variant forms.

J Headache Pain 2021 Aug 12;22(1):92. Epub 2021 Aug 12.

Department of Neurology, The First Medical Center of Chinese PLA General Hospital, Fuxing Road 28, Haidian District, 100853, Beijing, China.

Background: Mutations in ATP1A2, the gene encoding the α2 subunit of Na/K-ATPase, are the main cause of familial hemiplegic migraine type 2 (FHM2). The clinical presentation of FHM2 with mutations in the same gene varies from pure FHM to severe forms with epilepsy and intellectual disability, but the correlation of these symptoms with different ATP1A2 mutations is still unclear.

Methods: Ten ATP1A2 missense mutations were selected according to different phenotypes of FHM patients. They caused pure FHM (FHM: R65W, R202Q, R593W, G762S), FHM with epilepsy (FHME: R548C, E825K, R938P), or FHM with epilepsy and intellectual disability (FHMEI: T378N, G615R, D718N). After ouabain resistance and fluorescence modification, plasmids carrying those mutations were transiently transfected into HEK293T and HeLa cells. The biochemical functions were studied including cell survival assays, membrane protein extraction, western blotting, and Na/K-ATPase activity tests. The electrophysiological functions of G762S, R938P, and G615R mutations were investigated in HEK293T cells using whole-cell patch-clamp. Homology modeling was performed to determine the locational distribution of ATP1A2 mutations.

Results: Compared with wild-type pumps, all mutations showed a similar level of protein expression and decreased cell viability in the presence of 1 µM ouabain, and there was no significant difference among the mutant groups. The changes in Na/K-ATPase activity were correlated with the severity of FHM phenotypes. In the presence of 100 µM ouabain, the Na/K-ATPase activity was FHM > FHME > FHMEI. The ouabain-sensitive Na/K-ATPase activity of each mutant was significantly lower than that of the wild-type protein, and there was no significant difference among all mutant groups. Whole-cell voltage-clamp recordings in HEK293T cells showed that the ouabain-sensitive pump currents of G615R were significantly reduced, while those of G762S and R938P were comparable to those of the wild-type strain.

Conclusions: ATP1A2 mutations cause phenotypes ranging from pure FHM to FHM with epilepsy and intellectual disability due to varying degrees of deficits in biochemical and electrophysiological properties of Na/K-ATPase. Mutations associated with intellectual disability presented with severe impairment of Na/K-ATPase. Whether epilepsy is accompanied, or the type of epilepsy did not seem to affect the degree of impairment of pump function.
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http://dx.doi.org/10.1186/s10194-021-01309-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8359390PMC
August 2021

Methyltransferase like 13 mediates the translation of Snail in head and neck squamous cell carcinoma.

Int J Oral Sci 2021 Aug 11;13(1):26. Epub 2021 Aug 11.

Center for Translational Medicine, Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Methyltransferase like 13 (METTL13), a kind of methyltransferase, is implicated in protein binding and synthesis. The upregulation of METTL13 has been reported in a variety of tumors. However, little was known about its potential function in head and neck squamous cell carcinoma (HNSCC) so far. In this study, we found that METTL13 was significantly upregulated in HNSCC at both mRNA and protein level. Increased METTL13 was negatively associated with clinical prognosis. And METTL13 markedly affected HNSCC cellular phenotypes in vivo and vitro. Further mechanism study revealed that METTL13 could regulate EMT signaling pathway by mediating enhancing translation efficiency of Snail, the key transcription factor in EMT, hence regulating the progression of EMT. Furthermore, Snail was verified to mediate METTL13-induced HNSCC cell malignant phenotypes. Altogether, our study had revealed the oncogenic role of METTL13 in HNSCC, and provided a potential therapeutic strategy.
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http://dx.doi.org/10.1038/s41368-021-00130-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357922PMC
August 2021

On-line SERS detection of bilirubin based on the optofluidic in-fiber integrated GO/Ag NPs for rapid diagnosis of jaundice.

Talanta 2021 Nov 6;234:122692. Epub 2021 Jul 6.

Wireless & Optoelectronics Research & Innovation Centre, Faculty of Computing, Engineering & Science, University of South Wales, Wales, CF37 1DL, UK.

In this paper, we propose a self-assembled graphene oxide (GO)/Ag NPs SERS Raman sensor based on a novel type of optofluidic MHF as a point-of-care testing (POCT) device. This device is used to diagnose jaundice and its related diseases through on-line detection of free bilirubin content in human serum. This optofluidic Raman sensor is composed of a microstructured hollow fiber (MHF) with a microstructured channel and a suspended core, which allows the sample solution to flow in the channel while interacting with the strong evanescent field on the suspended core. Here, the suspended core was modified by a GO/Ag NPs SERS substrate. When the sample flows through the channel, and interacts with the strong evanescent field generated by the suspended core, the on-line SERS signal is generated and can be coupled back to the suspended core to be detected. In addition, both the electrostatic interaction and interference between GO/Ag NPs with the target enriched bilirubin. The results show that the detection concentration range of bilirubin aqueous, bilirubin in albumin and bilirubin in human blood are all in the range of 2 μM-100 μM, and all have a good linear response. The limit of detection reaches the order of 10 M. This rapid, sensitive and label-free SERS Raman sensor of free bilirubin in blood can detect excessive levels of bilirubin in the actual blood environment of the human body, providing a broad prospect for clinically accurate diagnosis of jaundice and related diseases.
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http://dx.doi.org/10.1016/j.talanta.2021.122692DOI Listing
November 2021

Re-evaluation of jumping purse-string suturing in pediatric laparoscopic hernia repair.

Surg Endosc 2021 Jul 29. Epub 2021 Jul 29.

Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Reported recurrence rates using jumping purse-string suturing in laparoscopic hernia repair (LH) are higher than that of intact purse-string. This study aims to compare the outcomes of LH using transabdominal jumping purse-string suturing (TJS) with those using transabdominal intact purse-string suturing (TIS) and percutaneous extraperitoneal intact purse-string suturing (PEIS).

Methods: A total of 3340 patients from three centers who have undergone laparoscopic hernia repair from January 2016 to June 2019 were retrospectively reviewed. Of these, 1460 patients received TJS, 724 patients received TIS, and 1006 patients received PEIS. One hundred and fifty patients were excluded due to the loss of follow-up. Demographic characteristics, intraoperative findings, and postoperative complications were analyzed.

Results: The hernia distribution characteristics and mean length of hospital stay were similar among the three groups (p > 0.05, p > 0.05). While the overall complication rates were similar among the three groups (0.34% in TJS vs. 0.41% in TIS vs. 0.50% in PEIS, TJS & TIS p = 0.502; TJS & PEIS p = 0.813), the incidence of intraoperative hematoma in TIS group and postoperative subcutaneous knot in PEIS group was significantly higher ((0.83% in TIS and 0.34% in TJS vs. 0.2% in PEIS, TJS & TIS p = 0.018; TJS & PEIS p = 0.163), (0% in TIS and 0% in TJS vs. 0.2% in PEIS, TJS & TIS p = 0.415; TJS & PEIS p = 0.025)). There were no differences in the recurrent rate in both unilateral and bilateral cases.

Conclusions: Transabdominal jumping purse-string suturing is not associated with a higher recurrence rate and is the recommended surgical approach.
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http://dx.doi.org/10.1007/s00464-021-08640-6DOI Listing
July 2021

Biodegradable scaffolds facilitate epiretinal transplantation of hiPSC-Derived retinal neurons in nonhuman primates.

Acta Biomater 2021 Jul 24. Epub 2021 Jul 24.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong 510060, China. Electronic address:

Transplantation of stem cell-derived retinal neurons is a promising regenerative therapy for optic neuropathy. However, significant anatomic differences compromise its efficacy in large animal models. The present study describes the procedure and outcomes of human-induced pluripotent stem cell (hiPSC)-derived retinal sheet transplantation in primate models using biodegradable materials. Stem cell-derived retinal organoids were seeded on polylactic-coglycolic acid (PLGA) scaffolds and directed toward a retinal ganglion cell (RGC) fate. The seeded tissues showed active proliferation, typical neuronal morphology, and electrical excitability. The cellular scaffolds were then epiretinally transplanted onto the inner surface of rhesus monkey retinas. With sufficient graft-host contact provided by the scaffold, the transplanted tissues survived for up to 1 year without tumorigenesis. Histological examinations indicated survival, further maturation, and migration. Moreover, green fluorescent protein-labeled axonal projections toward the host optic nerve were observed. Cryopreserved organoids were also able to survive and migrate after transplantation. Our results suggest the potential efficacy of RGC replacement therapy in the repair of optic neuropathy for the restoration of visual function. STATEMENT OF SIGNIFICANCE: In the present study, we generated a human retinal sheet by seeding hiPSC-retinal organoid-derived RGCs on a biodegradable PLGA scaffold. We transplanted this retinal sheet onto the inner surface of the rhesus monkey retina. With scaffold support, donor cells survive, migrate and project their axons into the host optic nerve. Furthermore, an effective cryopreservation strategy for retinal organoids was developed, and the thawed organoids were also observed to survive and show cell migration after transplantation.
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http://dx.doi.org/10.1016/j.actbio.2021.07.040DOI Listing
July 2021

pMGF505-7R determines pathogenicity of African swine fever virus infection by inhibiting IL-1β and type I IFN production.

PLoS Pathog 2021 Jul 26;17(7):e1009733. Epub 2021 Jul 26.

Division of Fundamental Immunology, National African Swine Fever Para-reference Laboratory, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.

Inflammatory factors and type I interferons (IFNs) are key components of host antiviral innate immune responses, which can be released from the pathogen-infected macrophages. African swine fever virus (ASFV) has developed various strategies to evade host antiviral innate immune responses, including alteration of inflammatory responses and IFNs production. However, the molecular mechanism underlying inhibition of inflammatory responses and IFNs production by ASFV-encoded proteins has not been fully understood. Here we report that ASFV infection only induced low levels of IL-1β and type I IFNs in porcine alveolar macrophages (PAMs), even in the presence of strong inducers such as LPS and poly(dA:dT). Through further exploration, we found that several members of the multigene family 360 (MGF360) and MGF505 strongly inhibited IL-1β maturation and IFN-β promoter activation. Among them, pMGF505-7R had the strongest inhibitory effect. To verify the function of pMGF505-7R in vivo, a recombinant ASFV with deletion of the MGF505-7R gene (ASFV-Δ7R) was constructed and assessed. As we expected, ASFV-Δ7R infection induced higher levels of IL-1β and IFN-β compared with its parental ASFV HLJ/18 strain. ASFV infection-induced IL-1β production was then found to be dependent on TLRs/NF-κB signaling pathway and NLRP3 inflammasome. Furthermore, we demonstrated that pMGF505-7R interacted with IKKα in the IKK complex to inhibit NF-κB activation and bound to NLRP3 to inhibit inflammasome formation, leading to decreased IL-1β production. Moreover, we found that pMGF505-7R interacted with and inhibited the nuclear translocation of IRF3 to block type I IFN production. Importantly, the virulence of ASFV-Δ7R is reduced in piglets compared with its parental ASFV HLJ/18 strain, which may due to induction of higher IL-1β and type I IFN production in vivo. Our findings provide a new clue to understand the functions of ASFV-encoded pMGF505-7R and its role in viral infection-induced pathogenesis, which might help design antiviral agents or live attenuated vaccines to control ASF.
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http://dx.doi.org/10.1371/journal.ppat.1009733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341718PMC
July 2021

[Corrigendum] HORMAD1 promotes docetaxel resistance in triple negative breast cancer by enhancing DNA damage tolerance.

Oncol Rep 2021 Sep 23;46(3). Epub 2021 Jul 23.

Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, P.R. China.

Following the publication of this article, the authors realized that the published version of Fig. 4A contained an erroneous label; essentially, the information purported to relate to experiments having been performed with docetaxel should not have been included in this figure. The correctly labelled version of Fig. 4 is shown with the remainder of Fig. 4 on the next page. This change does not affect the data shown in the paper, and the text in the published article did accurately describe the information shown in this figure. The authors sincerely apologize for the error that was introduced during the preparation of this figure, and thank the Editor for allowing them the opportunity to publish a Corrigendum. Furthermore, they regret any inconvenience caused. [the original article was published in Oncology Reports 46: Article no. 138, 2021; DOI: 10.3892/or.2021.8089].
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http://dx.doi.org/10.3892/or.2021.8146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317148PMC
September 2021

Profiles of immune infiltration in the tumor microenvironment of hepatocellular carcinoma.

J Gastrointest Oncol 2021 Jun;12(3):1152-1163

Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Background: Thus far, few studies have systematically analyzed the profiles of immune cells infiltrated in the tumor microenvironment (TME) of hepatocellular carcinoma (HCC). Therefore, the purpose of our study was to comprehensively analyze the 22 tumor-infiltrating immune cells (TIICs) and the immune subtypes of HCC, as well as the factors associated with the prognosis of HCC patients.

Methods: In this study, we evaluated the abundance of 22 tumor-infiltrating immunocytes of 371 HCC patients from The Cancer Genome Atlas (TCGA) database by using the CIBERSORT algorithm, and defined immune subtypes of HCC according to unsupervised cluster analysis. The immune score of HCC patients was calculated by the prognostic regression model, while the survival analysis was evaluated by the Kaplan-Meier method. In addition, the consistency index of TIICs and principal component analysis (PCA) of immunomodulator genes were estimated.

Results: The results of this study showed that three distinct immune subtypes of HCC were stratified, and the C1 subtype and C3 subtype were correlated with a good prognosis. The cellular composition of three immune subtypes was different. Moreover, immunomodulator gene and programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) expression in the C1 subtype was significantly higher (P<0.05).

Conclusions: This suggested that the low immune score of HCC patients is associated with better clinical outcomes. In addition, the interaction network of cluster of differentiation CD8+ T cells was mainly concentrated in the C1 subtype. Taken together, this study showed that tumor-infiltrating immune cells can perhaps be an important determinant of clinical outcomes of patients with HCC and may provide biomarkers to reflect the immunotherapy response. Notably, the C1 subtype of HCC may be used as an important predictive factor for immunotherapy response.
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http://dx.doi.org/10.21037/jgo-21-291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261307PMC
June 2021

Irisin ameliorates nicotine-mediated atherosclerosis via inhibition of the PI3K pathway.

Ann Transl Med 2021 May;9(9):805

Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China.

Background: Atherosclerosis is a chronic disease, with smoking being an independent risk factor. Irisin, a factor produced by myocytes, is expected to treat smoking-related arteriosclerosis, however its specific mechanism remains unclear.

Methods: Forty -/- mice with nicotine intervention were involved in this study. The atherosclerotic lesions, smooth muscle cell proliferation, and macrophage infiltration induced by nicotine, and the corresponding changes caused by the administration of irisin, were obtained. The integrin αVβ5 inhibitor, cilengitide, was included to determine the cell entry pathway of irisin. Proteins and mRNA levels of phosphatidylinositol 3-kinase (PI3K) and downstreams were detected to clarify the specific molecular mechanism of irisin activity.

Results: H&E staining and Masson staining showed that nicotine could aggravate the intensity of atherosclerosis in mice, and Irisin could reverse the thickening of the vascular media induced by nicotine. Immunohistochemical staining of CD68 and α-SMA suggested that Irisin could inhibit nicotine-mediated macrophage infiltration and smooth muscle cell proliferation. The protective effect of Irisin was partially reduced after the administration of cilengitide, confirming that Irisin enters cells through multiple ways, including integrin αvβ5. Nicotine was confirmed to activate the PI3K pathway to promote media thickening, while Irisin can inhibit the activation of the PI3K pathway, thus playing its anti-atherosclerosis role. Irisin was further observed to reverse nicotine-mediated P27 down-regulation.

Conclusions: Irisin was found to inhibit nicotine-mediated medium thickening, smooth muscle cell proliferation, macrophage infiltration, and atherosclerosis progression via the integrin αVβ5/PI3K/P27 pathway.
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http://dx.doi.org/10.21037/atm-21-2072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246167PMC
May 2021

Get Vaccinated for Loved Ones: Effects of Self-Other Appeal and Message Framing in Promoting HPV Vaccination among Heterosexual Young Men.

Health Commun 2021 Jul 16:1-13. Epub 2021 Jul 16.

College of Communication and Media Sciences, Zayed University.

HPV has long been constructed as a sex-specific virus. Boys and men largely perceive the virus as not related to themselves and thus develop a female-specific schema on HPV. The present study investigates message strategies for promoting HPV vaccination among heterosexual young men in the United States. Through an online experiment, this study examined the effects of reference point (self, other, vs. self-other) and message framing (gain vs. loss) on processing fluency, optimistic bias, and behavioral intentions. The findings showed a schema-matching pattern in facilitating information processing, and a schema-mismatching pattern in attenuating optimistic bias. Specifically, other-referencing messages that related the outcomes of getting vaccinated for HPV to the message recipients' sexual partners promoted processing fluency and widened the self-other gap in perceived susceptibility to HPV, regardless of the message frame. By contrast, self-other-referencing messages that highlighted the outcomes regarding themselves and their sex partners enhanced processing fluency and mitigated optimistic bias. Moreover, the attenuation in optimistic bias increased the participants' information seeking intentions and the likelihood that they would share the messages on social media. The implications for health message design are discussed from a schema-based, message-tailoring perspective.
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http://dx.doi.org/10.1080/10410236.2021.1953728DOI Listing
July 2021

Low urinary iodine is a protective factor of central lymph node metastasis in papillary thyroid cancer: a cross-sectional study.

World J Surg Oncol 2021 Jul 12;19(1):208. Epub 2021 Jul 12.

Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China.

Background: An abrupt increase of thyroid cancer has been witnessed paralleling the supplemented iodine intake in formerly iodine-deficient countries. And increased iodine intake has been linked to the rising incidence rate of papillary thyroid cancer (PTC). However, the correlation between iodine and clinicopathological features of PTC has not been well-characterized. This study aimed to investigate the associations between iodine intake and the clinicopathological features of PTC patients.

Methods: Three hundred and fifty-nine PTC patients who received surgical treatment in Peking Union Medical College Hospital from May 2015 to November 2020 were retrospectively reviewed. The associations between urinary iodine (UI), urinary iodine/creatinine ratio (UI/U-Cr), and the clinicopathological features of PTC were analyzed. Univariate and multivariate analysis were performed to investigate the relationship between UI level and central lymph node metastasis (CLNM).

Results: There were no significant differences in UI in different groups according to the variables studied, except that patients with CLNM had higher UI level than CLNM(-) patients. No associations were found between UI/U-Cr and clinicopathological features except variant subtypes (classic/follicular). After dividing patients into high-iodine group and low-iodine group, more patients were found to have CLNM in the high-iodine group (p = 0.02). In addition, younger age, larger tumor size, and classic variant were positively correlated with CLNM (p < 0.05). Univariate analysis showed that insufficient iodine intake (≤ 99 μg/L) was associated with decreased CLNM risk in PTC. And after defining insufficient iodine intake as ≤ 109 μg/L and above requirements as ≥ 190 μg/L, multivariate analysis showed that lower iodine was associated with CLNM in total population of PTC (OR 0.53, 95% CI 0.31-0.91) and in PTC < 1 cm (papillary thyroid microcarcinoma, PTMC) (OR 0.43, 95% CI 0.21-0.87).

Conclusions: Low iodine was a protective factor for CLNM in papillary thyroid cancer, particularly in those < 1 cm. These results indicated that iodine may not only be an initiator of tumorigenesis, but also a promoter of the development of PTC.
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http://dx.doi.org/10.1186/s12957-021-02302-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276512PMC
July 2021

The internal exposure of bisphenol analogues in South China adults and the associated health risks.

Sci Total Environ 2021 Nov 2;795:148796. Epub 2021 Jul 2.

School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, China. Electronic address:

Bisphenol A (BPA) is widely applied in industrial products and household products, leading to ubiquitous occurrences in environmental and biological samples. However, knowledge on human internal exposure to bisphenol analogues remains limited. Our study determined nine bisphenol analogues in urine samples collected from 1168 South China adults. BPA and bisphenol F (BPF) exhibited the highest detection frequencies in urine, i.e., 99.4% and 74.6%, respectively. BPA dominated over other analogues, with a median concentration of 1.74 μg/L, while BPF had a median concentration of 0.08 μg/L. Significant positive correlation was observed between urinary BPA and BPF (r = 0.201, p < 0.01), indicating similar exposure sources or pathways of these two chemicals. Urinary BPA concentrations were significantly correlated with age, marital status, drinking status and history of hyperlipidemia (p < 0.05). The median estimated daily intake (EDI) of ΣBPs (the sum concentrations of BPA, BPF and BPAF) was determined to be 53.6 ng/kg-bw/day for adults. The EDIs were much lower than the temporary tolerable reference dose of BPA recommended by the European Food Safety Authority, indicating the bisphenol analogues presented no obvious health risks to South China adults.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148796DOI Listing
November 2021

High-resolution magnetic sensors in ferrite/piezoelectric heterostructure with giant magnetodielectric effect at zero bias field.

Rev Sci Instrum 2021 Apr;92(4):045006

Physics Department, Oakland University, Rochester, Michigan 48309, USA.

A dielectric AC magnetic sensor in layered ferrites/piezoelectric composites was fabricated and developed, whereby its high magnetodielectric (MDE) effects, the typical magnetic-sensing parameters, were systematically characterized at zero bias. Polycrystalline ferrites were synthesized by the solid-state sintering technique with a composition of NiZnTbFeO, and the desired spinel structure and soft magnetic properties were confirmed by x-ray diffraction and VSM, respectively. The field-induced charge order insulating state in piezoelectric ceramics accounts for the suppressed permittivity, which enables the possibility of a highly sensitive magnetic sensor at zero bias field. Experimental results exhibit that a small variation in H as low as 100 mOe can be clearly distinguished with a favorable nonlinearity of 2.24%. Meanwhile, the output stability of the presented sensor under 2h of constant and continuous excitation was tested within a favorable fluctuating tolerance range of 6.14-6.28 nF, and the estimated uncertainty of ∼0.063 038 nF was verified by statistical analysis. The presented ferrite/piezoelectric magnetic sensors exhibiting a high MDE response without the requirement for an external magnetic bias are of importance for use in bio-magnetic field detection due to metrics of miniaturization, high sensitivity, and favorable stabilities.
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http://dx.doi.org/10.1063/5.0035059DOI Listing
April 2021

Postoperative oxaliplatin-based hyperthermic intraperitoneal chemotherapy: an effective and safe palliative treatment option for colorectal cancer with peritoneal metastasis.

World J Surg Oncol 2021 Jul 6;19(1):200. Epub 2021 Jul 6.

Department of Surgical Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Yanta west street No.277, Xi'an, 710061, Shaanxi, China.

Background: The prognosis of patients with colorectal cancer and peritoneal metastasis (CRC-PM) after incomplete cytoreductive surgery (CRS) or palliative surgery is poor. Novel and effective therapies are urgently needed. This study aimed to assess the effects of palliative postoperative hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with CRC-PM.

Methods: This retrospective study included patients with CRC-PM at the First Affiliated Hospital of Xi'an Jiaotong University in 05/2014-05/2019. Observation indicators included overall survival (OS), ascites-free survival, peritoneal cancer index (PCI), and completeness of cytoreduction (CC). Kaplan-Meier survival curves and multivariable Cox regression models were used to determine the factors associated with OS and ascites-free survival. The ascites-specific quality of life (QoL) was measured using the Functional Assessment of Chronic Illness Therapy-Ascites Index (FACIT-AI).

Results: Eighty-two patients were included, including 37 and 45 in the HIPEC and non-HIPEC groups, respectively. Mean OS was 10.3±3.7 (95% CI 9.5-11.2) months. Multivariable Cox proportional hazard regression suggested that PCI (HR=6.086, 95% CI 3.187-11.620, P < 0.0001) was independently associated with OS. The degree of ascites (HR=2.059, 95% CI 1.412-3.005, P < 0.0001), PCI (HR=6.504, 95% CI 2.844-14.875, P < 0.0001), and HIPEC (HR=0.328, 95% CI 0.191-0.562, P < 0.0001) were independently associated with ascites-free survival. In patients with survival >6 months, postoperative ascites-specific QoL was significantly improved after HIPEC compared with the non-HIPEC group (P < 0.001). Oxaliplatin-based HIPEC significantly increased the rates of neutropenia and peripheral neurotoxicity (both P < 0.05).

Conclusion: These data indicate that postoperative oxaliplatin-based HIPEC might help increase ascites-free survival in CRC-PM patients after incomplete CRS or palliative surgery, with improved QoL after 6 months of follow-up.
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http://dx.doi.org/10.1186/s12957-021-02320-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262040PMC
July 2021

Sox9-expressing cells promote regeneration after radiation-induced lung injury via the PI3K/AKT pathway.

Stem Cell Res Ther 2021 07 2;12(1):381. Epub 2021 Jul 2.

Oncology Department, Chinese PLA General Hospital, Beijing, 100000, China.

Background: Radiation-induced lung injury (RILI) is considered one of the most common complications of thoracic radiation. Recent studies have focused on stem cell properties to obtain ideal therapeutic effects, and Sox9 has been reported to be involved in stem cell induction and differentiation. However, whether Sox9-expressing cells play a role in radiation repair and regeneration remains unknown.

Methods: We successfully obtained Sox9, Rosa and Rosa mice and identified Sox9-expressing cells through lineage tracing. Then, we evaluated the effects of the ablation of Sox9-expressing cells in vivo. Furthermore, we investigated the underlying mechanism of Sox9-expressing cells during lung regeneration via an online single-cell RNA-seq dataset.

Results: In our study, we demonstrated that Sox9-expressing cells promote the regeneration of lung tissues and that ablation of Sox9-expressing cells leads to severe phenotypes after radiation damage. In addition, analysis of an online scRNA-Seq dataset revealed that the PI3K/AKT pathway is enriched in Sox9-expressing cells during lung epithelium regeneration. Finally, the AKT inhibitor perifosine suppressed the regenerative effects of Sox9-expressing cells and the AKT pathway agonist promotes proliferation and differentiation.

Conclusions: Taken together, the findings of our study suggest that Sox9-expressing cells may serve as a therapeutic target in lung tissue after RILI.
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http://dx.doi.org/10.1186/s13287-021-02465-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254240PMC
July 2021
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