Publications by authors named "Jie Mei"

280 Publications

Comparison Between Portal Vein Perfusion Chemotherapy and Neoadjuvant Hepatic Arterial Infusion Chemotherapy for Resectable Intermediate to Advanced Stage Hepatocellular Carcinoma.

Ann Surg Oncol 2021 Oct 12. Epub 2021 Oct 12.

Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.

Background: Patients with intermediate to advanced stage hepatocellular carcinoma (HCC; Barcelona Clinic Liver Cancer [BCLC] stage B/C) have few choices of curable treatments and thus suffer from dismal outcomes. Although surgical resection could prolong survival in certain selected patients with BCLC stage B/C HCC, the frequent postoperative recurrence and poor survival of these patients need to be improved by combining other therapies perioperatively.

Objective: This study was conducted to investigate the survival associations of adjuvant portal vein perfusion chemotherapy (PVC) and neoadjuvant hepatic arterial infusion chemotherapy (HAIC) in patients with resectable BCLC stage B/C HCC.

Methods: A retrospective study was conducted in consecutive patients who underwent R0 resection for intermediate to advanced stage HCC, combined with either PVC or HAIC perioperatively between January 2017 and December 2018. Patients treated with PVC or HAIC were analyzed according to intention-to-treat (ITT) and per protocol (PP) principles, respectively. The chemotherapy regimen of adjuvant PVC and neoadjuvant HAIC included 5-fluorouracil/leucovorin/oxaliplatin. Survival analysis and Cox regression for overall survival (OS) and event-free survival (EFS) were used to compare the outcomes.

Results: Among all 64 patients enrolled in this study, 28 received perioperative PVC and 36 received HAIC for ITT analysis. Age (median 44.00 vs. 46.50 years; p = 0.364), sex (male: 25/28 vs. 35/36; p = 0.435), and tumor size (median 9.55 vs. 8.10 cm; p = 0.178) were comparable between the two groups. In the ITT analysis, the median OS was significantly longer in patients in the HAIC group compared with the PVC group (median OS not reached vs. 19.47 months; p = 0.004); in the PP analysis, patients who received neoadjuvant HAIC followed by hepatectomy presented with much better EFS than patients in the PVC group (modified EFS 16.90 vs. 3.17 months; p = 0.022); and in the multivariate analysis, neoadjuvant HAIC presented as a significant predictor for enhanced EFS (hazard ratio [HR] 0.296; p = 0.007) and OS (HR 0.095; p = 0.007) for BCLC stage B/C HCC patients who received hepatectomy.

Conclusions: Compared with adjuvant PVC, neoadjuvant HAIC treatment was associated with better survival and fewer recurrences in HCC patients who received R0 resection at the intermediate to advanced stage. These results need to be further validated prospectively.
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http://dx.doi.org/10.1245/s10434-021-10903-4DOI Listing
October 2021

DCLK1 might be a therapeutic target of osthole against cervical cancer.

Pharmazie 2021 Oct;76(10):503-506

Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; com.

Discovering compounds with anti-cervical cancer effect and clarifying their targets will help promoting the precise treatment of cervical cancer. The present study intended to clarify the effect of osthole on cervical cancer cells, and to explore the possibility of DCLK1 as its target. Annexin V-PE staining and flow cytometry methods were used to determine cell apoptosis. Meanwhile, apoptosis related biomarkers were probed by immunoblotting. The MTT assay was employed to study the effect of osthole in combined with or without LRRK2-IN-1 (a DCLK1 inhibitor) on cell proliferation. Then, combination index was determined. To examine the interaction of osthole with DCLK1, molecular docking was carried out. Based on the biological database from cBioPortal, the association between DCLK1 and clinical manifestations of cervical cancer were evaluated. The results showed that osthole can significantly induce apoptosis of HeLa and Me-180. When combined with LRRK2-IN-1, the effect of osthole on cell proliferation was antagonized, suggesting that it might competitive binding to DCLK1. Furthermore, molecular docking showed that osthole interacts with Val468 residues of DCLK1 to form hydrogen bonds. The analysis of database showed that DCLK1 frequently mutant and deleted in cervical cancer, and is related to cell survival, tumor progression and recurrence. However, no obvious correlations were found between DCLK1 and lymphatic metastasis/differentiation. In conclusion, osthole significantly inhibits the survival of cervical cancer cells. It's probably target DCLK1 mechanistically via interacting with Val468. DCLK1 could be a potential therapeutic target for cervical cancer.
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http://dx.doi.org/10.1691/ph.2021.1641DOI Listing
October 2021

CoANet: Connectivity Attention Network for Road Extraction From Satellite Imagery.

IEEE Trans Image Process 2021 13;30:8540-8552. Epub 2021 Oct 13.

Extracting roads from satellite imagery is a promising approach to update the dynamic changes of road networks efficiently and timely. However, it is challenging due to the occlusions caused by other objects and the complex traffic environment, the pixel-based methods often generate fragmented roads and fail to predict topological correctness. In this paper, motivated by the road shapes and connections in the graph network, we propose a connectivity attention network (CoANet) to jointly learn the segmentation and pair-wise dependencies. Since the strip convolution is more aligned with the shape of roads, which are long-span, narrow, and distributed continuously. We develop a strip convolution module (SCM) that leverages four strip convolutions to capture long-range context information from different directions and avoid interference from irrelevant regions. Besides, considering the occlusions in road regions caused by buildings and trees, a connectivity attention module (CoA) is proposed to explore the relationship between neighboring pixels. The CoA module incorporates the graphical information and enables the connectivity of roads are better preserved. Extensive experiments on the popular benchmarks (SpaceNet and DeepGlobe datasets) demonstrate that our proposed CoANet establishes new state-of-the-art results. The source code will be made publicly available at: https://mmcheng.net/coanet/.
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http://dx.doi.org/10.1109/TIP.2021.3117076DOI Listing
October 2021

Floquet anomalous Hall effect in ferromagnetic multiorbital tight-binding models.

J Phys Condens Matter 2021 Sep 29. Epub 2021 Sep 29.

Chinese Academy of Sciences, Nanjing Institute of Astronomical Optics & Technology , Bancang street 188, Nanjing, Jiangsu, 210042, CHINA.

In this work, we study the band structures and intrinsic anomalous Hall conductivity (AHC) of the ferromagnetic multiorbital tight-binding (TB) model derived from the transition metal compound Sr$_2$RuO$_4$ under periodic driving of monochromatic polarized light. Within the framework of the Floquet theory, we adopt the continued fraction technique to attain the effective Hamiltonian valid in the weak-driving and low-frequency regimes, and the related Green's functions which are further employed for the transport calculations based on the Kubo formalism. The high-frequency circularly and linearly polarized (LP) light has limited impacts on the band structures, while the low-frequency light with the photon energy smaller than the bandwidth of the system opens up bandgaps at the edges of the Floquet-Brillouin zone (FBZ) since the transitions between Floquet sidebands become significant. For intrinsic AHC, the left-handed circularly polarized (LCP) light plays a distinct role on AHC compared to the right-handed circularly polarized (RCP) light. Furthermore, it reveals that the roles of LCP and RCP light can be interchanged by altering the incident plane of light. Finally, the intrinsic AHC with the interplay between the short-range disorder and circularly polarized light is also investigated.
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http://dx.doi.org/10.1088/1361-648X/ac2acfDOI Listing
September 2021

Glutamine Metabolism Regulators Associated with Cancer Development and the Tumor Microenvironment: A Pan-Cancer Multi-Omics Analysis.

Genes (Basel) 2021 Aug 25;12(9). Epub 2021 Aug 25.

Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.

Background: In recent years, metabolic reprogramming has been identified as a hallmark of cancer. Accumulating evidence suggests that glutamine metabolism plays a crucial role in oncogenesis and the tumor microenvironment. In this study, we aimed to perform a systematic and comprehensive analysis of six key metabolic node genes involved in the dynamic regulation of glutamine metabolism (referred to as GLNM regulators) across 33 types of cancer.

Methods: We analyzed the gene expression, epigenetic regulation, and genomic alterations of six key GLNM regulators, including , , , , , and , in pan-cancer using several open-source platforms and databases. Additionally, we investigated the impacts of these gene expression changes on clinical outcomes, drug sensitivity, and the tumor microenvironment. We also attempted to investigate the upstream microRNA-mRNA molecular networks and the downstream signaling pathways involved in order to uncover the potential molecular mechanisms behind metabolic reprogramming.

Results: We found that the expression levels of GLNM regulators varied across cancer types and were related to several genomic and immunological characteristics. While the immune scores were generally lower in the tumors with higher gene expression, the types of immune cell infiltration showed significantly different correlations among cancer types, dividing them into two clusters. Furthermore, we showed that elevated GLNM regulators expression was associated with poor overall survival in the majority of cancer types. Lastly, the expression of GLNM regulators was significantly associated with PD-L1 expression and drug sensitivity.

Conclusions: The elevated expression of GLNM regulators was associated with poorer cancer prognoses and a cold tumor microenvironment, providing novel insights into cancer treatment and possibly offering alternative options for the treatment of clinically refractory cancers.
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http://dx.doi.org/10.3390/genes12091305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466418PMC
August 2021

Integrated, Highly Flexible, and Tailorable Thermoelectric Type Temperature Detectors Based on a Continuous Carbon Nanotube Fiber.

Small 2021 Oct 9;17(40):e2102825. Epub 2021 Sep 9.

Beijing National Laboratory for Condensed Matter Physics and Institute of Physics, Chinese Academy of Sciences, Beijing, 100190, China.

As possible alternatives to traditional thermoelectric (TE) materials, carbon nanomaterials and their hybrid materials have great potential in the future application of flexible and lightweight temperature detection. In this work, an integrated, highly flexible, and tailorable TE temperature detector with high performance has been fabricated based on a continuous single-walled carbon nanotube (SWCNT) fiber. The detector consists of more than one pairs of thermocouples composed of p-type SWCNT fiber and n-type SWCNT hybrid fiber in situ doped by polyethylenimine. Due to the node contact mechanism of the detection, the sensitivity of the detector can be improved with the increase of the number of p-n thermocouples, independent of the length of the thermocouple. The temperature detection process of the detector has been studied in detail. In particular, the integrated and flexible detector can be divided into several sub-detectors easily by cutting, illustrating the prospect of large-scale preparation of this kind of novel temperature detectors. Its high flexibility ensures the detector to maintain excellent detection performance after 15 000 bending circles. Furthermore, the as-designed TE type temperature detector demonstrates a great application promise for real-time temperature detection and temperature change sensing even in complex surface and harsh environment.
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http://dx.doi.org/10.1002/smll.202102825DOI Listing
October 2021

Expression pattern and prognostic value of N6-methyladenosine RNA methylation key regulators in hepatocellular carcinoma.

Mutagenesis 2021 Oct;36(5):369-379

Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.

Hepatocellular carcinoma (HCC) is still one of the most common malignancies worldwide. The accuracy of biomarkers for predicting the prognosis of HCC and the therapeutic effect is not satisfactory. N6-methyladenosine (m6A) methylation regulators play a crucial role in various tumours. Our research aims further to determine the predictive value of m6A methylation regulators and establish a prognostic model for HCC. In this study, the data of HCC from The Cancer Genome Atlas (TCGA) database was obtained, and the expression level of 15 genes and survival was examined. Then we identified two clusters of HCC with different clinical factors, constructed prognostic markers and analysed gene set enrichment, proteins' interaction and gene co-expression. Three subgroups by consensus clustering according to the expression of the 13 genes were identified. The risk score generated by five genes divided HCC patients into high-risk and low-risk groups. In addition, we developed a prognostic marker that can identify high-risk HCC. Finally, a novel prognostic nomogram was developed to accurately predict HCC patients' prognosis. The expression levels of 13 m6A RNA methylation regulators were significantly upregulated in HCC samples. The prognosis of cluster 1 and cluster 3 was worse. Patients in the high-risk group show a poor prognosis. Moreover, the risk score was an independent prognostic factor for HCC patients. In conclusion, we reveal the critical role of m6A RNA methylation modification in HCC and develop a predictive model based on the m6A RNA methylation regulators, which can accurately predict HCC patients' prognosis and provide meaningful guidance for clinical treatment.
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http://dx.doi.org/10.1093/mutage/geab032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493108PMC
October 2021

Interferon-Induced Transmembrane Protein 3 Shapes an Inflamed Tumor Microenvironment and Identifies Immuno-Hot Tumors.

Front Immunol 2021 11;12:704965. Epub 2021 Aug 11.

Department of Oncology, Nantong Third People's Hospital Affiliated to Nantong University, Nantong, China.

Interferon-induced transmembrane protein 3 (IFITM3) is an interferon-induced membrane protein, which has been identified as a functional gene in multiple human cancers. The role of IFITM3 in cancer has been preliminarily summarized, but its relationship to antitumor immunity is still unclear. A pancancer analysis was conducted to investigate the expression pattern and immunological role of IFITM3 based on transcriptomic data downloaded from The Cancer Genome Atlas (TCGA) database. Next, correlations between IFITM3 and immunological features in the bladder cancer (BLCA) tumor microenvironment (TME) were assessed. In addition, the role of IFITM3 in estimating the clinical characteristics and the response to various therapies in BLCA was also evaluated. These results were next confirmed in the IMvigor210 cohort and a recruited cohort. In addition, correlations between IFITM3 and emerging immunobiomarkers, such as microbiota and N6-methyladenosine (m6A) genes, were assessed. IFITM3 was enhanced in most tumor tissues in comparison with adjacent tissues. IFITM3 was positively correlated with immunomodulators, tumor-infiltrating immune cells (TIICs), cancer immunity cycles, and inhibitory immune checkpoints. In addition, IFITM3 was associated with an inflamed phenotype and several established molecular subtypes. IFITM3 expression also predicted a notably higher response to chemotherapy, anti-EGFR therapy, and immunotherapy but a low response to anti-ERBB2, anti-ERBB4, and antiangiogenic therapy. In addition, IFITM3 was correlated with immune-related microbiota and m6A genes. In addition to BLCA, IFITM3 is expected to be a marker of high immunogenicity in most human cancers. In conclusion, IFITM3 expression can be used to identify immuno-hot tumors in most cancers, and IFITM3 may be a promising pancancer biomarker to estimate the immunological features of tumors.
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http://dx.doi.org/10.3389/fimmu.2021.704965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385493PMC
August 2021

YWHAZ interacts with DAAM1 to promote cell migration in breast cancer.

Cell Death Discov 2021 Aug 27;7(1):221. Epub 2021 Aug 27.

Department of Physiology, Nanjing Medical University, Nanjing, 211166, China.

Dishevelled-associated activator of morphogenesis 1 (DAAM1) is a critical driver in facilitating metastasis in breast cancer (BrCa). However, molecular mechanisms for the regulation of DAAM1 activation are only partially elucidated. In this research, the expression levels of YWHAZ and DAAM1 were examined by immunohistochemistry (IHC) staining in BrCa tissues. The functional roles of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ)-DAAM1 axis and their regulator microRNA-613 (miR-613) in BrCa cells and associated molecular mechanisms were demonstrated in vitro. As results, the expression levels of DAAM1 and YWHAZ were significantly upregulated in BrCa tissues compared with normal tissues and remarkably associated with poor prognosis. Besides, DAAM1 and YWHAZ were positively correlated with each other in BrCa tissues. YWHAZ interacted and colocalized with DAAM1 in BrCa cells, which was essential for DAAM1-mediated microfilament remodeling and RhoA activation. Moreover, miR-613 directly targeted both YWHAZ and DAAM1, contributing to inhibiting BrCa cells migration via blocking the complex of YWHAZ-DAAM1. To sum up, these data reveal that YWHAZ regulates DAAM1 activation, and the YWHAZ-DAAM1 complex is directly targeted by the shared post-transcriptional regulator miR-613.
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http://dx.doi.org/10.1038/s41420-021-00609-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397740PMC
August 2021

Chemosensory Dysfunctions Induced by COVID-19 Can Persist up to 7 Months: A Study of Over 700 Healthcare Workers.

Chem Senses 2021 01;46

Department of Anatomy, Université du Québec à Trois-Rivières, Trois-Rivières, QC, Canada.

Several studies have revealed either self-reported chemosensory alterations in large groups or objective quantified chemosensory impairments in smaller populations of patients diagnosed with COVID-19. However, due to the great variability in published results regarding COVID-19-induced chemosensory impairments and their follow-up, prognosis for chemosensory functions in patients with such complaints remains unclear. Our objective is to describe the various chemosensory alterations associated with COVID-19 and their prevalence and evolution after infection. A cross-sectional study of 704 healthcare workers with a RT-PCR-confirmed SARS-CoV-2 infection between 2020 February 28 and 2020 June 14 was conducted 3-7 months after onset of symptoms. Data were collected with an online questionnaire. Outcomes included differences in reported chemosensory self-assessment of olfactory, gustatory, and trigeminal functions across time points and Chemosensory Perception Test scores from an easy-to-use at-home self-administered chemosensory test. Among the 704 participants, 593 (84.2%) were women, the mean (SD) age was 42 (12) years, and the questionnaire was answered on average 4.8 (0.8) months after COVID-19. During COVID-19, a decrease in olfactory, gustatory, and trigeminal sensitivities was reported by 81.3%, 81.5%, and 48.0%, respectively. Three to 7 months later, reduced sensitivity was still reported by 52.0%, 41.9%, and 23.3%, respectively. Chemosensory Perception Test scores indicate that 19.5% of participants had objective olfactory impairment. These data suggest a significant proportion of COVID-19 cases have persistent chemosensory impairments at 3-7 months after their infection, but the majority of those who had completely lost their olfactory, gustatory, and trigeminal sensitivities have improved.
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http://dx.doi.org/10.1093/chemse/bjab038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8499810PMC
January 2021

Comparison of the Prognostic Value of Inflammation-Based Scores in Patients with Hepatocellular Carcinoma After Anti-PD-1 Therapy.

J Inflamm Res 2021 11;14:3879-3890. Epub 2021 Aug 11.

Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.

Background: Inflammatory response is related to cancer progression and patient survival. However, the value in predicting survival in hepatocellular carcinoma (HCC) patients who received anti-PD-1 therapy has not been elucidated. This study aimed to compare the predictive ability of inflammation-based scores for the prognosis of HCC patients after anti-PD-1 therapy.

Methods: A total of 442 patients who received anti-PD-1 therapy were included in the study. Representative inflammation-based prognostic scores, including the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-C-reactive protein (CRP) ratio (LCR), lymphocyte-to-monocyte ratio (LMR), systemic immune inflammation index (SII), CRP-to-albumin ratio (CAR), prognostic nutritional index (PNI), Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), and prognostic index (PI), were assessed for prediction accuracy using Kaplan-Meier survival curves, time-dependent receiver operating characteristic (ROC) and Harrell's concordance index (C-index) analyses.

Results: All the inflammation-based prognostic scores exhibited good discriminatory ability in overall survival (OS) (all P < 0.01), while the PNI score was a unique independent predictor for OS in multivariate analysis (hazard ratio, 1.770; confidence interval, 1.309-2.393; P < 0.001). The areas under the ROC curves at 6, 12, 18 and 24 months and the C-index (0.65) demonstrated that the predictive accuracy of the PNI score was superior to that of the other inflammation-based scores.

Conclusion: The PNI score is a discriminatory prognostic indicator for OS in HCC patients with anti-PD-1 therapy and is superior to the other inflammation-based prognostic scores in terms of predictive ability.
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http://dx.doi.org/10.2147/JIR.S325600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364914PMC
August 2021

Prognostic nomogram predicting survival of patients with unresectable hepatocellular carcinoma after hepatic arterial infusion chemotherapy.

Eur J Radiol 2021 Sep 4;142:109890. Epub 2021 Aug 4.

Department of Liver Surgery of the Sun Yat-sen University Cancer Center, China; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China. Electronic address:

Background And Aim: Hepatic arterial infusion chemotherapy (HAIC) has shown encouraging efficacy in the treatment of hepatocellular carcinoma (HCC). This study aims to establish and validate a novel nomogram to predict individualized survival outcomes for patients with unresectable HCC after HAIC.

Methods: Between January 2016 and December 2018, 463 patients diagnosed with HCC who initially received HAIC were included in this study (training cohort: n = 308; validation cohort: n = 153). The prognostic nomogram was constructed based on the training cohort using the independent predictors assessed by the multivariate Cox proportional hazards model. The predictive accuracy and discriminative ability of the model were evaluated by the concordance index (C-index), calibration curve and area under the time-dependent receiver operating characteristic (tdAUC) curve.

Results: After a median follow-up of 35.4 months, 358 patients had died. Six factors, including C-reactive protein, albumin-bilirubin grade, alpha fetoprotein, extrahepatic metastasis, portal vein invasion and tumor size, were selected to establish the nomogram. In the training cohort, the C-index of the nomogram was 0.710, which was significantly better than that of six conventional staging systems (P < 0.001), and the nomogram had a higher tdAUC over time. The calibration curve showed good agreement between the predicted probability and actual outcome. According to specified values, the nomogram stratified patients into three or four risk groups (P < 0.001). Similar findings could be observed in the validation cohort.

Conclusion: The nomogram in this study accurately predicted the OS of patients with unresectable HCC after HAIC.
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http://dx.doi.org/10.1016/j.ejrad.2021.109890DOI Listing
September 2021

Identification of a Novel Immune Landscape Signature for Predicting Prognosis and Response of Endometrial Carcinoma to Immunotherapy and Chemotherapy.

Front Cell Dev Biol 2021 23;9:671736. Epub 2021 Jul 23.

Department of Gynecology and Obstetrics, Wuxi Maternal and Child Health Hospital, The Affiliated Hospital to Nanjing Medical University, Wuxi, China.

Uterine Corpus Endometrial Carcinoma (UCEC) is the most common gynecological cancer. Here, we have investigated the significance of immune-related genes in predicting the prognosis and response of UCEC patients to immunotherapy and chemotherapy. Based on the Cancer Genome Atlas (TCGA) database, the single-sample gene-set enrichment analysis (ssGSEA) scores was utilized to obtain enrichment of 29 immune signatures. Univariate, multivariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were performed to generate an immune-related prognostic signature (IRPS). The biological functions of IRPS-associated genes were evaluated using GSEA, Tumor Immune Estimation Resource (TIMER) Database analysis, Mutation analysis, Immunophenoscore (IPS) analysis, Gene Expression Profiling Interactive Analysis (GEPIA), Genomics of Drug Sensitivity in Cancer (GDSC) and Immune Cell Abundance Identifier (ImmuCellAI). Potential small molecule drugs for UCEC were predicted using the connectivity map (Cmap). The mRNA and protein expression levels of IRPS-associated genes were tested via quantitative real-time PCR (qPCR) and immunohistology. Two immune-related genes (CCL13 and KLRC1) were identified to construct the IRPS. Both genes were related to the prognosis of UCEC patients ( < 0.05). The IRPS could distinguish patients with different prognosis and was closely associated with the infiltration of several types of immune cells. Our findings showed that patients with low IRPS benefited more from immunotherapy and developed stronger response to several chemotherapies, which was also confirmed by the results of ImmuCellAI. Finally, we identified three small molecular drugs that might improve the prognosis of patients with high IRPS. IRPS can be utilized to predict the prognosis of UCEC patients and provide valuable information about their therapeutic response to immunotherapy and chemotherapy.
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http://dx.doi.org/10.3389/fcell.2021.671736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343236PMC
July 2021

Expression and significance of serum soluble fms-like tyrosine kinase 1 (sFlt-1), CXC chemokine ligand 16 (CXCL16), and lipocalin 2 (LCN-2) in pregnant women with preeclampsia.

Ann Palliat Med 2021 Jul;10(7):7866-7871

Department of Gynaecology and Obstetrics, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China; Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China.

Background: To explore the value of serum soluble fms-like tyrosine kinase 1 (sFlt-1), CXC chemokine ligand 16 (CXCL16), and lipocalin 2 (LCN-2) in the diagnosis and grading of preeclampsia (PE).

Methods: A total of 186 patients with PE diagnosed and treated in our hospital were included. According to the disease severity, the patients were divided into the mild PE group (99 cases) and the severe PE group (87 cases). A total of 72 healthy pregnant women who underwent antenatal care were selected as the healthy control group. The levels of serum sFlt-1, CXCL16, and LCN-2 before medication were compared among the patients, and the diagnosis and grading value of the above 3 indicators were analyzed.

Results: For PE patients vs. healthy controls, the levels of sFlt-1 (132.71±14.49 vs. 68.43±9.28 µg/L), CXCL16 (2.15±0.35 vs. 0.61±0.12 µg/L), and LCN-2 (70.81±8.25 vs. 19.22±3.14 µg/L) were all significantly higher in PE patients than in the healthy controls (P<0.05). For severe PE vs. mild PE, the levels of sFlt-1 (142.16±20.23 vs. 124.41±10.36 µg/L), CXCL16 (2.87±0.59 vs. 1.51±0.28 µg/L), and LCN-2 (90.76±10.16 vs. 53.27±6.19 µg/L) in the severe PE group were higher than those in the mild PE group (P<0.05). Receiver operating characteristic curve (ROC) analysis showed that when the cut-off values of sFlt-1, CXCL16, and LCN-2 were 99.65, 1.36, and 0.84 µg/L, respectively, the diagnostic efficacy of PE was the highest. With these cut-off values, the diagnostic sensitivities of sFlt-1, CXCL16, and LCN-2 were 86.67%, 73.33%, and 93.33%, respectively. The specificities of sFlt-1, CXCL16, and LCN-2 were 80.00%, 86.67%, and 60.00%, respectively. The areas under the curves (AUC) of sFlt-1, CXCL16, and LCN-2 were 0.764, 0.769, and 0.831, respectively. When the cut-off values for sFlt-1, CXCL16, and LCN-2 were 135.16, 2.24, and 70.38 µg/L, respectively, the efficacy was the highest in distinguishing mild and severe PE. With these cut-off values, the AUC values of sFlt-1, CXCL16, and LCN-2 were 0.837, 0.808, and 0.869, respectively.

Conclusions: sFlt-1, CXCL16, and LCN-2 have certain significance in the diagnosis and grading of PE. Among them, LCN-2 has the highest correlation with the diagnosis and grading of PE.
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http://dx.doi.org/10.21037/apm-21-1553DOI Listing
July 2021

Effects of acute hypoxia and reoxygenation on oxygen sensors, respiratory metabolism, oxidative stress, and apoptosis in hybrid yellow catfish "Huangyou-1".

Fish Physiol Biochem 2021 Oct 27;47(5):1429-1448. Epub 2021 Jul 27.

College of Marine Science and Engineering, Jiangsu Province Engineering Research Center for Aquatic Animals Breeding and Green Efficient Aquacultural Technology, Nanjing Normal University, Nanjing, 210023, Jiangsu, China.

The regulation mechanism of the hybrid yellow catfish "Huangyou-1" was assessed under conditions of hypoxia and reoxygenation by examination of oxygen sensors and by monitoring respiratory metabolism, oxidative stress, and apoptosis. The expressions of genes related to oxygen sensors (HIF-1α, HIF-2α, VHL, HIF-1β, PHD2, and FIH-1) were upregulated in the brain and liver during hypoxia, and recovered compared with control upon reoxygenation. The expressions of genes related to glycolysis (HK1, PGK1, PGAM2, PFK, and LDH) were increased during hypoxia and then recovered compared with control upon reoxygenation. The mRNA levels of CS did not change during hypoxia in the brain and liver, but increased during reoxygenation. The mRNA levels of SDH decreased significantly only in the liver during hypoxia, but later increased compared with control upon reoxygenation in both tissues. Under hypoxic conditions, the expressions of genes related to oxidative stress (SOD1, SOD2, GSH-Px, and CAT) and the activity of antioxidant enzymes (SOD, CAT, and GSH-Px) and MDA were upregulated compared with control. The expressions of genes related to apoptosis (Apaf-1, Bax, Caspase 3, Caspase 9, and p53) were higher than those in control during hypoxic exposure, while the expressions of Bcl-2 and Cyt C were decreased. The findings of the transcriptional analyses will provide insights into the molecular mechanisms of hybrid yellow catfish "Huangyou-1" under conditions of hypoxia and reoxygenation. Overall, these findings showed that oxygen sensors of "Huangyou-1" are potentially useful biomarkers of environmental hypoxic exposure. Together with genes related to respiratory metabolism, oxidative stress and apoptosis occupy a quite high position in enhancing hypoxia tolerance. Our findings provided new insights into the molecular regulatory mechanism of hypoxia in "Huangyou-1."
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http://dx.doi.org/10.1007/s10695-021-00989-8DOI Listing
October 2021

Up-regulation of microRNA-135 or silencing of PCSK6 attenuates inflammatory response in preeclampsia by restricting NLRP3 inflammasome.

Mol Med 2021 07 23;27(1):82. Epub 2021 Jul 23.

Genaecology and Obstetrics Department, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, No. 32, West Second Section First Ring Rd, Chengdu, 610072, China.

Objective: Numerous studies have confirmed the correlation of microRNAs (miRNAs) with human disease, yet few have explored the role of miR-135 in preeclampsia (PE). This study intends to discuss miR-135's function in inflammatory response in PE by modulating proprotein convertase subtilisin/kexin-6 (PCSK6) and NLR pyrin domain containing 3 (NLRP3).

Methods: The venous blood and placental tissues were collected from PE pregnant women and 25 normal ones. The levels of miR-135, PCSK6 and NLRP3 in placenta tissues of patients were detected. Hypoxia/reoxygenation HTR-8/SVneo and HPT-8 models were established to mimic PE in vitro, and cell proliferation, colony formation, apoptosis rate, invasion, migration and inflammation were detected through gain-of and loss-of-function assays.

Results: MiR-135 was down-regulated, and PCSK6 and NLRP3 were up-regulated in PE patients. Up-regulating miR-135 or silencing PCSK6 strengthened colony formation ability, viability, invasion and migration ability, and weakened apoptosis and inflammation of H/R-treated HTR-8/SVneo and HPT-8 cells. Inhibition of NLRP3 negated the effects of silenced PCSK6 in H/R-treated HTR-8/SVneo and HPT-8 cells.

Conclusions: Altogether, we demonstrate that up-regulated miR-135 or reduced PCSK6 attenuates inflammatory response in PE by restricting NLRP3 inflammasome, which provides novel therapy for PE treatment.
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http://dx.doi.org/10.1186/s10020-021-00335-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299578PMC
July 2021

Bioinformatics Analysis of Expression Profiles and Prognostic Values of the Signal Transducer and Activator of Transcription Family Genes in Glioma.

Front Genet 2021 2;12:625234. Epub 2021 Jul 2.

Department of Neurosurgery, Wuxi People's Hospital of Nanjing Medical University, Wuxi, China.

Signal transducer and activator of transcription () family genes-of which there are seven members: , and -have been associated with the progression of multiple cancers. However, their prognostic values in glioma remain unclear. In this study, we systematically investigated the expression, the prognostic value, and the potential mechanism of the family genes in glioma. The expression of 1/2/3/5A/6 members were significantly higher and positively correlated with mutations, while the expression of was lower and negatively correlated with mutations in glioma. Survival analysis indicated that the upregulation of and downregulation of expression was associated with poorer overall survival in glioma. Joint effects analysis of expression suggested that the prognostic value of the group was more significant than that of each individual gene. Thus, we constructed a risk score model to predict the prognosis of glioma. The receiver operating characteristic curve and calibration curves showed good performance as prognostic indicators in both TCGA (The Cancer Genome Atlas) and the CGGA (Chinese Glioma Genome Atlas) databases. Furthermore, we analyzed the correlation between expression with immune infiltration in glioma. The Protein-protein interaction network and enrichment analysis showed that members and co-expressed genes mainly participated in signal transduction activity, Hepatitis B, the Jak-STAT signaling pathway, transcription factor activity, sequence-specific DNA binding, and the cytokine-mediated signaling pathway in glioma. In summary, our study analyzed the expression, prognostic values, and biological roles of the gene family members in glioma, based on which we developed a new risk score model to predict the prognosis of glioma more precisely.
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http://dx.doi.org/10.3389/fgene.2021.625234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283826PMC
July 2021

Reductions in AFP and PIVKA-II can predict the efficiency of anti-PD-1 immunotherapy in HCC patients.

BMC Cancer 2021 Jul 4;21(1):775. Epub 2021 Jul 4.

Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.

Background: Few biomarkers can predict the efficiency of PD-1 blockade in patients with hepatocellular carcinoma (HCC). This study aimed to investigate the prognostic role of AFP and PIVKA-II in HCC patients receiving anti-PD-1 immunotherapy.

Methods: A total of 235 HCC patients treated with PD-1 blockade were enrolled. Serum AFP and PIVKA-II levels were collected before and after treatments. The patients were divided into groups based on the reduction in AFP and PIVKA-II: AFP reduction ≤50% vs AFP reduction > 50% and PIVKA-II reduction ≤50% vs PIVKA-II reduction > 50%. The primary endpoints included objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Binary logistic regression analyses were used to explore the related factors of ORR. A Cox proportional hazards model was employed to identify the potential prognostic factors of PFS and OS.

Results: Among all the patients, 34.9% (82/235) achieved a complete or partial response. There was a positive correlation between AFP reduction > 50% or PIVKA-II reduction> 50% and the ORR of PD-1 blockade (P < 0.001 and = 0.003). PFS was significantly improved in patients with AFP reduction > 50% and PIVKA-II reduction > 50% (p < 0.001 and = 0.021). In addition, AFP reduction > 50% and PIVKA-II reduction> 50% were positively correlated with longer OS (p = 0.003 and 0.006).

Conclusion: Early reductions in AFP and PIVKA-II can be predictors of the efficacy of PD-1 blockade in HCC patients.
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http://dx.doi.org/10.1186/s12885-021-08428-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254996PMC
July 2021

The predictive value of vessels encapsulating tumor clusters in treatment optimization for recurrent early-stage hepatocellular carcinoma.

Cancer Med 2021 Aug 1;10(16):5466-5474. Epub 2021 Jul 1.

State Key Laboratory of Oncology in South China, Guangzhou, China.

Background: The predictive value of vessels encapsulating tumor clusters (VETC) in recurrent early-stage hepatocellular carcinoma (HCC) remains unclear. Therefore, the aim of the present study was to investigate the prognostic significance of VETC in patients with recurrent early-stage HCC after repeat hepatic resection (RHR) or radiofrequency ablation (RFA).

Methods: From December 2005 to December 2016, 138 patients receiving RHR and 188 patients receiving RFA were recruited. VETC was evaluated by immunohistochemical staining for CD34. The survival outcomes of patients with VETC pattern or not were investigated.

Results: There was no significant difference between the RHR and RFA groups in disease-free survival (DFS) or overall survival (OS) as determined by the univariate analysis of the whole cohort. In the subgroup analysis of the VETC-positive cohort, the patients in the RHR group showed a longer median DFS time in contrast to those in the RFA group (15.0 vs. 5.0 months, p = 0.001). Similarly, the patients in the RHR group showed a longer median OS time in contrast to those in the RFA group (39.5 vs. 19 months, p = 0.001). In the VETC-negative cohort, no significant differences in DFS and OS rates between the RHR and RFA groups were observed (p > 0.05).

Conclusions: The results of our study suggested that RHR was relatively safe and superior to RFA in improving survival outcomes for recurrent early-stage HCC after initial hepatectomy. Furthermore, the VETC pattern may represent a reliable marker for selecting HCC patients who may benefit from RHR.
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http://dx.doi.org/10.1002/cam4.4102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8366089PMC
August 2021

Analytical Modeling of a Doubly Clamped Flexible Piezoelectric Energy Harvester with Axial Excitation and Its Experimental Characterization.

Sensors (Basel) 2021 Jun 3;21(11). Epub 2021 Jun 3.

Institute of Intelligent Manufacturing and Control, Wuhan University of Technology, Wuhan 430063, China.

With the rapid development of wearable electronics, novel power solutions are required to adapt to flexible surfaces for widespread applications, thus flexible energy harvesters have been extensively studied for their flexibility and stretchability. However, poor power output and insufficient sensitivity to environmental changes limit its widespread application in engineering practice. A doubly clamped flexible piezoelectric energy harvester (FPEH) with axial excitation is therefore proposed for higher power output in a low-frequency vibration environment. Combining the Euler-Bernoulli beam theory and the D'Alembert principle, the differential dynamic equation of the doubly clamped energy harvester is derived, in which the excitation mode of axial load with pre-deformation is considered. A numerical solution of voltage amplitude and average power is obtained using the Rayleigh-Ritz method. Output power of 22.5 μW at 27.1 Hz, with the optimal load resistance being 1 MΩ, is determined by the frequency sweeping analysis. In order to power electronic devices, the converted alternating electric energy should be rectified into direct current energy. By connecting to the MDA2500 standard rectified electric bridge, a rectified DC output voltage across the 1 MΩ load resistor is characterized to be 2.39 V. For further validation of the mechanical-electrical dynamical model of the doubly clamped flexible piezoelectric energy harvester, its output performances, including both its frequency response and resistance load matching performances, are experimentally characterized. From the experimental results, the maximum output power is 1.38 μW, with a load resistance of 5.7 MΩ at 27 Hz, and the rectified DC output voltage reaches 1.84 V, which shows coincidence with simulation results and is proved to be sufficient for powering LED electronics.
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http://dx.doi.org/10.3390/s21113861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199891PMC
June 2021

High SGO2 Expression Predicts Poor Overall Survival: A Potential Therapeutic Target for Hepatocellular Carcinoma.

Genes (Basel) 2021 06 7;12(6). Epub 2021 Jun 7.

Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.

Shugoshin2 (SGO2) may participate in the occurrence and development of tumors by regulating abnormal cell cycle division, but its prognostic value in hepatocellular carcinoma (HCC) remains unclear. In this study, we accessed The Cancer Genome Atlas (TCGA) database to get the clinical data and gene expression profile of HCC. The expression of SGO2 in HCC tissues and nontumor tissues and the relationship between SGO2 expression, survival, and clinicopathological parameters were analyzed. The SGO2 expression level was significantly higher in HCC tissues than in nontumor tissues ( < 0.001). An analysis from the Oncomine and Gene Expression Profiling Interactive Analysis 2 (GEPIA2) databases also demonstrated that SGO2 was upregulated in HCC (all < 0.001). A logistic regression analysis revealed that the high expression of SGO2 was significantly correlated with gender, tumor grade, pathological stage, T classification, and Eastern Cancer Oncology Group (ECOG) score (all < 0.05). The overall survival (OS) of HCC patients with higher SGO2 expression was significantly poor ( < 0.001). A multivariate analysis showed that age and high expression of SGO2 were independent predictors of poor overall survival (all < 0.05). Twelve signaling pathways were significantly enriched in samples with the high-SGO2 expression phenotype. Ten proteins and 34 genes were significantly correlated with SGO2. In conclusion, the expression of SGO2 is closely related to the survival of HCC. It may be used as a potential therapeutic target and prognostic marker of HCC.
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http://dx.doi.org/10.3390/genes12060876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226836PMC
June 2021

The next generation therapy for lung cancer: taking medicine by inhalation.

Nanotechnology 2021 Jul 9;32(39). Epub 2021 Jul 9.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, People's Republic of China.

The inhalation administration method which has been applied to treat respiratory diseases has the characteristics of painlessness high efficiency and non-invasiveness, and the drug can also be targeted at the organ level first to reduce the loss of drug during circulation. Therefore, delivering medicine by inhalation administration has brought a new turnaround for lung cancer treatment. Herein from the perspective of combining traditional drug delivery design strategies with new drug delivery methods how to improve lung targeting efficiency and treatment efficacy is discussed. We also discuss the comparative advantages of inhaled drug delivery and traditional administration in the treatment of lung cancer such as intravenous injection. And the researches are divided into different forms of inhalation administration studied in the treatment of lung cancer in recent years, such as single-component loaded and multi-component loaded systems and their advantages. Finally, the obstacles of the application of carrier materials for inhalation administration and the prospects for improvement of lung cancer treatment methods are presented.
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http://dx.doi.org/10.1088/1361-6528/ac0e68DOI Listing
July 2021

The guiding value of microvascular invasion for treating early recurrent small hepatocellular carcinoma.

Int J Hyperthermia 2021 ;38(1):931-938

Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.

Introduction: Hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI) have worse survival. Whether the presence of MVI indicates the necessity of more aggressive locoregional treatments for recurrences remains to be elucidated.

Methods: We reviewed patients who underwent curative hepatectomy for primary HCC in our institution, and 379 patients with recurrent HCC up to three nodules smaller than 3 cm were enrolled. The Kaplan-Meier method was adopted to compare the secondary recurrence-free survival (sRFS) and post-recurrence survival (PRS) among patients undergoing hepatectomy, RFA and transarterial chemoembolization plus RFA (TACE-RFA). Cox regression analyses were performed to identify independent prognostic factors.

Results: Both the sRFS and PRS of the MVI (-) group were significantly longer than those of the MVI (+) group ( = 0.001 and 0.011). For patients with MVI (-), no significant difference was found in sRFS or PRS among recurrent HCC patients receiving hepatectomy, RFA or TACE-RFA ( = 0.149 and 0.821). A similar trend was found in patients with MVI (+) ( = 0.851 and 0.960). Further analysis found that TACE-RFA provided better sRFS than hepatectomy or RFA alone in patients with MVI (+) and early recurrence within two years ( = 0.036 and 0.044).

Conclusion: For HCC patients with MVI (+) and early small recurrence, TACE-RFA could achieve better prognosis than hepatectomy or RFA alone, while RFA alone provided comparable survival benefits compared with hepatectomy or TACE-RFA in other HCC patients with small recurrence.
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http://dx.doi.org/10.1080/02656736.2021.1937715DOI Listing
July 2021

Active components in Ephedra sinica stapf disrupt the interaction between ACE2 and SARS-CoV-2 RBD: Potent COVID-19 therapeutic agents.

J Ethnopharmacol 2021 Oct 5;278:114303. Epub 2021 Jun 5.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 211198, China; Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University, Nanjing, 211198, China; Research Center for Traceability and Standardization of TCMs, China Pharmaceutical University, Nanjing, 211198, China. Electronic address:

Ethnopharmacological Relevance: Ephedra sinica Stapf is a widely used folk medicine in Asia to treat lung diseases, such as cold, cough and asthma. Many efforts have revealed that some traditional Chinese medicine (TCM) prescriptions containing Ephedra sinica could effectively alleviate the symptoms and prevent the fatal deterioration of COVID-19.

Aim Of The Study: The present study aims to discover active compounds in Ephedra sinica disrupting the interaction between angiotensin-converting enzyme 2 (ACE2) and the SARS-CoV-2 spike protein receptor-binding domain (SARS-CoV-2 RBD) to inhibit SARS-CoV-2 virus infection.

Materials And Methods: The ethanol extracts of Ephedra sinica were prepared. Activity guided isolation of constituents was carried out by measuring the inhibitory activity on ACE2-RBD interaction. The structures of active compounds were identified by HPLC-Q-TOF-MS/MS and NMR. To testify the contribution of main components for the inhibitory activity, different samples were prepared by components knock-out strategy. The mechanism of compounds inhibiting protein-protein interaction (PPI) was explored by competition inhibition assays, surface plasmon resonance (SPR) assays and molecular docking. SARS-CoV-2 S protein-pseudoviruses were used to observe the viropexis effect in cells.

Results: Ephedra sinica extracts (ESE) could effectively inhibit the interaction between ACE2 and SARS-CoV-2 RBD (IC = 95.01 μg/mL). Three active compounds, 4,6-dihydroxyquinoline-2-carboxylic acid, 4-hydroxyquinoline-2-carboxylic acid and 4-hydroxy-6-methoxyquinoline-2-carboxylic acid were identified to inhibit ACE2-RBD interaction (IC = 0.58 μM, 0.07 μM and 0.15 μM respectively). And knock-out the three components could eliminate the inhibitory activity of ESE. Molecular docking calculations indicated that the hydrogen bond was the major intermolecular force. Finally, our results also showed that these compounds could inhibit the infectivity of SARS-CoV-2 S protein-pseudoviruses to 293T-ACE2 (IC = 0.44-1.09 μM) and Calu-3 cells.

Conclusion: These findings suggested that quinoline-2-carboxylic acids in Ephedra sinica could be considered as potential therapeutic agents for COVID-19. Further, this study provided some justification for the ethnomedicinal use of Ephedra sinica for COVID-19.
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http://dx.doi.org/10.1016/j.jep.2021.114303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178536PMC
October 2021

Effects of extract on lung adenocarcinoma.

Exp Ther Med 2021 Aug 25;22(2):794. Epub 2021 May 25.

Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.

Lung adenocarcinoma is the most common subtype of non-small cell lung carcinoma. Tanshinone I is an important fat-soluble component in the extract of that has been reported to inhibit lung adenocarcinoma cell proliferation. However, no studies have clearly demonstrated changes in lung adenocarcinoma gene expression and signaling pathway enrichment following Tanshinone I treatment. And it remains unclear whether salvianolate has an effect on lung adenocarcinoma. The present study downloaded the GSE9315 dataset from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) and the underlying signaling pathways involved after Tanshinone I administration in the lung adenocarcinoma cell line CL1-5. The results revealed that there were 28 and 102 DEGs in the low dosage group (0.01 and 0.10 µg/ml Tanshinone I) and medium dosage groups (1 and 10 µg/ml Tanshinone I), respectively. In the low dosage group, DEGs were mainly enriched in 'positive regulation of T-helper cell differentiation' and 'protein complex'. In the medium dosage group, 102 DEGs were enriched in 'MAPK cascade' and 'extracellular exosome'. Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated enrichment of both groups in the PI3K-Akt signaling pathway. Furthermore, there were nine overlapping DEGs [ADP ribosylation factor-interacting protein 2, chemokine (C-X-C motif) ligand 6, SH2 domain-containing adaptor protein B, Src homology 2 domain-containing transforming protein1, collagen type VI α1 chain, elastin, integrin subunit α, endoplasmic reticulum mannosyl-oligosaccharide 1,2-α-mannosidase and sterile α motif domain-containing 9 like] between the two groups, which serve to be potential targets for the treatment of lung adenocarcinoma. The present study also investigated the possible effects of salvianolate on lung adenocarcinoma using nude mouse xenograft models injected with the A549 cell line. The data revealed that salvianolate not only suppressed lung adenocarcinoma tumor growth of in nude mice, but also downregulated the expression levels of ATP7A and ATP7B, which are important proteins in the tumorigenesis and chemotherapy of lung adenocarcinoma. The present study provided evidence for the potential use of extract for treating lung adenocarcinomas in the clinic.
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http://dx.doi.org/10.3892/etm.2021.10226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170645PMC
August 2021

Removal of N-Linked Glycosylation Enhances PD-L1 Detection in Colon Cancer: Validation Research Based on Immunohistochemistry Analysis.

Technol Cancer Res Treat 2021 Jan-Dec;20:15330338211019442

Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.

In recent years, immunotherapies have emerged as effective therapeutic strategies for treating human cancers. However, accumulating evidence has revealed an inconsistency between the response to immune checkpoint inhibitors and programmed death ligand 1 (PD-L1) expression status detected by immunohistochemistry staining. Recent research has revealed that the removal of N-Linked glycosylation significantly enhanced PD-L1 detection, resulting in both more accurate PD-L1 quantification and clinical outcome prediction. In the present study, we evaluated natural and deglycosylated PD-L1 expression in colon cancer using the PD-L1 28-8 antibody. The results of the present study validated the hypothesis that PD-L1 had a higher expression in colon cancer tissues compared with normal tissues. Additionally, colon tumors with defective mismatch repair tended to express higher PD-L1 than those without. Most importantly, the results of the present study indicated that the removal of N-linked glycosylation remarkably enhanced PD-L1 detection. Moreover, the PD-L1 signal intensity of samples with a low natural PD-L1 signal was enhanced more remarkably than that of samples with high signal intensity. Overall, our research provides an improved strategy for patient stratification for anti-PD-1/PD-L1 therapy, which deepens the clinical significance of this established strategy for treatment of colon cancer.
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http://dx.doi.org/10.1177/15330338211019442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173990PMC
June 2021

Machine Learning for the Diagnosis of Parkinson's Disease: A Review of Literature.

Front Aging Neurosci 2021 6;13:633752. Epub 2021 May 6.

Chemosensory Neuroanatomy Lab, Department of Anatomy, Université du Québec à Trois-Rivières (UQTR), Trois-Rivières, QC, Canada.

Diagnosis of Parkinson's disease (PD) is commonly based on medical observations and assessment of clinical signs, including the characterization of a variety of motor symptoms. However, traditional diagnostic approaches may suffer from subjectivity as they rely on the evaluation of movements that are sometimes subtle to human eyes and therefore difficult to classify, leading to possible misclassification. In the meantime, early non-motor symptoms of PD may be mild and can be caused by many other conditions. Therefore, these symptoms are often overlooked, making diagnosis of PD at an early stage challenging. To address these difficulties and to refine the diagnosis and assessment procedures of PD, machine learning methods have been implemented for the classification of PD and healthy controls or patients with similar clinical presentations (e.g., movement disorders or other Parkinsonian syndromes). To provide a comprehensive overview of data modalities and machine learning methods that have been used in the diagnosis and differential diagnosis of PD, in this study, we conducted a literature review of studies published until February 14, 2020, using the PubMed and IEEE Xplore databases. A total of 209 studies were included, extracted for relevant information and presented in this review, with an investigation of their aims, sources of data, types of data, machine learning methods and associated outcomes. These studies demonstrate a high potential for adaptation of machine learning methods and novel biomarkers in clinical decision making, leading to increasingly systematic, informed diagnosis of PD.
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http://dx.doi.org/10.3389/fnagi.2021.633752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134676PMC
May 2021

Nanotechnology: Breaking the Current Treatment Limits of Lung Cancer.

Adv Healthc Mater 2021 06 21;10(12):e2100078. Epub 2021 May 21.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing, 100190, P. R. China.

Lung cancer is one of the most rapidly growing malignancies in terms of morbidity and mortality. Although traditional treatments have been used for more than 50 years, it is still far from solving the problems of postoperative risks and systemic toxicity. Emerging targeting and immunotherapy are developing continuously and are gaining recognition; eventually, they face the inevitable challenge of drug resistance. Nanotechnology has several important effects on lung cancer treatment, owing to its unique properties. Several nanoparticle-based treatments have successfully become cancer treatments. Good biocompatibility with higher specific surface area can carry substantial amounts of lung cancer treatment medications while avoiding medication toxicity; editable and modified characteristics give rise to multifunctional nanomedicines; excellent photoelectric effects make lung cancer a multimodal treatment. This article summarizes the breakthroughs achieved by nanotechnology, targeted therapy, and immunotherapy, reflecting the importance and necessity of nanotechnology in the treatment of lung cancer.
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http://dx.doi.org/10.1002/adhm.202100078DOI Listing
June 2021
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